862 resultados para ICU family members


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AIMS An independent, powerful coronary heart disease (CHD) predictor is a low level of high-density lipoprotein cholesterol (HDL-C). Discoidal preβ-HDL particles and large HDL2 particles are the primary cholesterol acceptors in reverse cholesterol transport, a key anti-atherogenic HDL mechanism. The quality of HDL subspecies may provide better markers of HDL functionality than does HDL-C alone. We aimed I) to study whether alterations in the HDL subspecies profile exist in low-HDL-C subjects II) to explore the relationship of any changes in HDL subspecies profile in relation to atherosclerosis and metabolic syndrome; III) to elucidate the impact of genetics and acquired obesity on HDL subspecies distribution. SUBJECTS The study consisted of 3 cohorts: A) Finnish families with low HDL-C and premature CHD (Study I: 67 subjects with familial low HDL-C and 64 controls; Study II: 83 subjects with familial low HDL-C, 65 family members with normal HDL-C, and 133 controls); B) a cohort of 113 low- and 133 high-HDL-C subjects from the Health 2000 Health Examination Survey carried out in Finland (Study III); and C) a Finnish cohort of healthy young adult twins (52 monozygotic and 89 dizygotic pairs) (Study IV). RESULTS AND CONCLUSIONS The subjects with familial low HDL-C had a lower preβ-HDL concentration than did controls, and the low-HDL-C subjects displayed a dramatic reduction (50-70%) in the proportion of large HDL2b particles. The subjects with familial low HDL-C had increased carotid atherosclerosis measured as intima-media-thickness (IMT), and HDL2b particles correlated negatively with IMT. The reduction in both key cholesterol acceptors, preβ-HDL and HDL2 particles, supports the concept of impaired reverse cholesterol transport contributing to the higher CHD risk in low-HDL-C subjects. The family members with normal HDL-C and the young adult twins with acquired obesity showed a reduction in large HDL2 particles and an increase in small HDL3 particles, which may be the first changes leading to the lowering of HDL-C. The low-HDL-C subjects had a higher serum apolipoprotein E (apoE) concentration, which correlated positively with the metabolic syndrome components (waist circumference, TG, and glucose), highlighting the need for a better understanding of apoE metabolism in human atherosclerosis. In the twin study, the increase in small HDL3b particles was associated with obesity independent of genetic effects. The heritability estimate, of 73% for HDL-C and 46 to 63% for HDL subspecies, however, demonstrated a strong genetic influence. These results suggest that the relationship between obesity and lipoproteins depends on different elements in each subject. Finally, instead of merely elevating HDL-C, large HDL2 particles and discoidal preβ-HDL particles may provide beneficial targets for HDL-targeted therapy.

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Biological membranes are tightly linked to the evolution of life, because they provide a way to concentrate molecules into partially closed compartments. The dynamic shaping of cellular membranes is essential for many physiological processes, including cell morphogenesis, motility, cytokinesis, endocytosis, and secretion. It is therefore essential to understand the structure of the membrane and recognize the players that directly sculpt the membrane and enable it to adopt different shapes. The actin cytoskeleton provides the force to push eukaryotic plasma membrane in order to form different protrusions or/and invaginations. It has now became evident that actin directly co-operates with many membrane sculptors, including BAR domain proteins, in these important events. However, the molecular mechanisms behind BAR domain function and the differences between the members of this large protein family remain largely unresolved. In this thesis, the structure and functions of the I-BAR domain family members IRSp53 and MIM were thoroughly analyzed. By using several methods such as electron microscopy and systematic mutagenesis, we showed that these I-BAR domain proteins bind to PI(4,5)P2-rich membranes, generate negative membrane curvature and are involved in the formation of plasma membrane protrusions in cells e.g. filopodia. Importantly, we characterized a novel member of the BAR-domain superfamily which we named Pinkbar. We revealed that Pinkbar is specifically expressed in kidney and epithelial cells, and it localizes to Rab13-positive vesicles in intestinal epithelial cells. Remarkably, we learned that the I-BAR domain of Pinkbar does not generate membrane curvature but instead stabilizes planar membranes. Based on structural, mutagenesis and biochemical work we present a model for the mechanism of the novel membrane deforming activity of Pinkbar. Collectively, this work describes the mechanism by which I-BAR domain proteins deform membranes and provides new information about the biological roles of these proteins. Intriguingly, this work also gives evidence that significant functional plasticity exists within the I-BAR domain family. I-BAR proteins can either generate negative membrane curvature or stabilize planar membrane sheets, depending on the specific structural properties of their I-BAR domains. The results presented in this thesis expand our knowledge on membrane sculpting mechanisms and shows for the first time how flat membranes can be generated in cells.

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The purpose of this study was to find out whether food-related lifestyle guides and explains product evaluations, specifically, consumer perceptions and choice evaluations of five different food product categories: lettuce, mincemeat, savoury sauce, goat cheese, and pudding. The opinions of consumers who shop in neighbourhood stores were considered most valuable. This study applies means-end chain (MEC) theory, according to which products are seen as means by which consumers attain meaningful goals. The food-related lifestyle (FRL) instrument was created to study lifestyles that reflect these goals. Further, this research has adopted the view that the FRL functions as a script which guides consumer behaviour. Two research methods were used in this study. The first was the laddering interview, the primary aim of which was to gather information for formulating the questionnaire of the main study. The survey consisted of two separate questionnaires. The first was the FRL questionnaire modified for this study. The aim of the other questionnaire was to determine the choice criteria for buying five different categories of food products. Before these analyses could be made, several data modifications were made following MEC analysis procedures. Beside forming FRL dimensions by counting sum-scores from the FRL statements, factor analysis was run in order to elicit latent factors underlying the dimensions. The lifestyle factors found were adventurous, conscientious, enthusiastic, snacking, moderate, and uninvolved lifestyles. The association analyses were done separately for each choice of product as well as for each attribute-consequence linkage with a non-parametric Mann-Whitney U test. The testing variables were FRL dimensions and the FRL lifestyle factors. In addition, the relation between the attribute-consequence linkages and the demographic variables were analysed. Results from this study showed that the choice of product is sequential, so that consumers first categorize products into groups based on specific criteria like health or convenience. It was attested that the food-related lifestyles function as a script in food choice and that the FRL instrument can be used to predict consumer buying behaviour. Certain lifestyles were associated with the choice of each product category. The actual product choice within a product category then appeared to be a different matter. In addition, this study proposes a modification to the FRL instrument. The positive towards advertising FRL dimension was modified to examine many kinds of information search including the internet, TV, magazines, and other people. This new dimension, which was designated as being open to additional information, proved to be very robust and reliable in finding differences in consumer choice behaviour. Active additional information search was linked to adventurous and snacking food-related lifestyles. The results of this study support the previous knowledge that consumers expect to get many benefits simultaneously when they buy food products. This study brought detailed information about the benefits sought, the combination of benefits differing between products and between respondents. Household economy, pleasure and quality were emphasized with the choice of lettuce. Quality was the most significant benefit in choosing mincemeat, but health related benefits were often evaluated as well. The dominant benefits linked to savoury sauce were household economic benefits, expected pleasurable experiences, and a lift in self-respect. The choice of goat cheese appeared not to be an economic decision, self-respect, pleasure, and quality being included in the choice criteria. In choosing pudding, the respondents considered the well-being of family members, and indulged their family members or themselves.

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Background—Mutations of the APC gene cause familial adenomatous polyposis (FAP), a hereditary colorectal cancer predisposition syndrome.Aims—To conduct a cost comparison analysis of predictive genetic testing versus conventional clinical screening for individuals at risk of inheriting FAP, using the perspective of a third party payer. Methods—All direct health care costs for both screening strategies were measured according to time and motion, and the expected costs evaluated using a decision analysis model.Results—The baseline analysis predicted that screening a prototype FAP family would cost $4975/£3109 by molecular testingand $8031/£5019 by clinical screening strategy, when family members were monitored with the same frequency of clinical surveillance (every two to three years). Sensitivity analyses revealed that the genetic testing approach is cost saving for key variables including the kindred size, the age of screening onset, and the cost of mutation identification in a proband. However, if the APC mutation carriers were monitored at an increased (annual) frequency, the cost of the genetic screening strategy increased to $7483/ £4677 and was especially sensitive to variability in age of onset of screening, family size, and cost of genetic testing of at risk relatives. Conclusions—In FAP kindreds, a predictive genetic testing strategy costs less than conventional clinical screening, provided that the frequency of surveillance is identical using either strategy. An additional significant benefit is the elimination of unnecessary colonic examinations for those family members found to be noncarriers.

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BACKGROUND Familial diarrhea disorders are, in most cases, severe and caused by recessive mutations. We describe the cause of a novel dominant disease in 32 members of a Norwegian family. The affected members have chronic diarrhea that is of early onset, is relatively mild, and is associated with increased susceptibility to inflammatory bowel disease, small-bowel obstruction, and esophagitis. METHODS We used linkage analysis, based on arrays with single-nucleotide polymorphisms, to identify a candidate region on chromosome 12 and then sequenced GUCY2C, encoding guanylate cyclase C (GC-C), an intestinal receptor for bacterial heat-stable enterotoxins. We performed exome sequencing of the entire candidate region from three affected family members, to exclude the possibility that mutations in genes other than GUCY2C could cause or contribute to susceptibility to the disease. We carried out functional studies of mutant GC-C using HEK293T cells. RESULTS We identified a heterozygous missense mutation (c.2519G -> T) in GUCY2C in all affected family members and observed no other rare variants in the exons of genes in the candidate region. Exposure of the mutant receptor to its ligands resulted in markedly increased production of cyclic guanosine monophosphate (cGMP). This may cause hyperactivation of the cystic fibrosis transmembrane regulator (CFTR), leading to increased chloride and water secretion from the enterocytes, and may thus explain the chronic diarrhea in the affected family members. CONCLUSIONS Increased GC-C signaling disturbs normal bowel function and appears to have a proinflammatory effect, either through increased chloride secretion or additional effects of elevated cellular cGMP. Further investigation of the relevance of genetic variants affecting the GC-C-CFTR pathway to conditions such as Crohn's disease is warranted. (Funded by Helse Vest Western Norway Regional Health Authority] and the Department of Science and Technology, Government of India.)

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Over the past two decades, many ingenious efforts have been made in protein remote homology detection. Because homologous proteins often diversify extensively in sequence, it is challenging to demonstrate such relatedness through entirely sequence-driven searches. Here, we describe a computational method for the generation of `protein-like' sequences that serves to bridge gaps in protein sequence space. Sequence profile information, as embodied in a position-specific scoring matrix of multiply aligned sequences of bona fide family members, serves as the starting point in this algorithm. The observed amino acid propensity and the selection of a random number dictate the selection of a residue for each position in the sequence. In a systematic manner, and by applying a `roulette-wheel' selection approach at each position, we generate parent family-like sequences and thus facilitate an enlargement of sequence space around the family. When generated for a large number of families, we demonstrate that they expand the utility of natural intermediately related sequences in linking distant proteins. In 91% of the assessed examples, inclusion of designed sequences improved fold coverage by 5-10% over searches made in their absence. Furthermore, with several examples from proteins adopting folds such as TIM, globin, lipocalin and others, we demonstrate that the success of including designed sequences in a database positively sensitized methods such as PSI-BLAST and Cascade PSI-BLAST and is a promising opportunity for enormously improved remote homology recognition using sequence information alone.

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Staphylococcus aureus is an opportunistic pathogen that rapidly acquires resistance to frontline antibiotics. The characterization of novel protein targets from this bacterium is thus an important step towards future therapeutic strategies. Here, the crystal structure of an amidohydrolase, SACOL0085, from S. aureus COL is described. SACOL0085 is a member of the M20D family of peptidases. Unlike other M20D peptidases, which are either monomers or dimers, SACOL0085 adopts a butterfly-shaped homotetrameric arrangement with extensive intersubunit interactions. Each subunit of SACOL0085 contains two Mn2+ ions at the active site. A conserved cysteine residue at the active site distinguishes M20D peptidases from other M20 family members. This cysteine, Cys103, serves as bidentate ligand coordinating both Mn2+ ions in SACOL0085.

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Background: A better understanding of the quality of cellular immune responses directed against molecularly defined targets will guide the development of TB diagnostics and identification of molecularly defined, clinically relevant M.tb vaccine candidates. Methods: Recombinant proteins (n = 8) and peptide pools (n = 14) from M. tuberculosis (M.tb) targets were used to compare cellular immune responses defined by IFN-gamma and IL-17 production using a Whole Blood Assay (WBA) in a cohort of 148 individuals, i.e. patients with TB + (n = 38), TB- individuals with other pulmonary diseases (n = 81) and individuals exposed to TB without evidence of clinical TB (health care workers, n = 29). Results: M.tb antigens Rv2958c (glycosyltransferase), Rv2962c (mycolyltransferase), Rv1886c (Ag85B), Rv3804c (Ag85A), and the PPE family member Rv3347c were frequently recognized, defined by IFN-gamma production, in blood from healthy individuals exposed to M.tb (health care workers). A different recognition pattern was found for IL-17 production in blood from M.tb exposed individuals responding to TB10.4 (Rv0288), Ag85B (Rv1886c) and the PPE family members Rv0978c and Rv1917c. Conclusions: The pattern of immune target recognition is different in regard to IFN-gamma and IL-17 production to defined molecular M.tb targets in PBMCs from individuals frequently exposed to M.tb. The data represent the first mapping of cellular immune responses against M.tb targets in TB patients from Honduras.

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N-Alkyl substituted pyrazoloanthrone derivatives were synthesized, characterized and tested for their in vitro inhibitory activity over c-Jun N-terminal kinase (JNK). Among the tested molecules, a few derivatives showed significant inhibitory activity against JNK with minimal off-target effect on other mitogen-activated protein kinase (MAP kinase) family members such as MEK1/2 and MKK3,6. These results suggested that N-alkyl (propyl and butyl) bearing pyrazoloanthrone scaffolds provide promising therapeutic inhibitors for JNK in regulating inflammation associated disorders.

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Staphylococcus aureus is an opportunistic pathogen that rapidly acquires resistance to frontline antibiotics. The characterization of novel protein targets from this bacterium is thus an important step towards future therapeutic strategies. Here, the crystal structure of an amidohydrolase, SACOL0085, from S. aureus COL is described. SACOL0085 is a member of the M20D family of peptidases. Unlike other M20D peptidases, which are either monomers or dimers, SACOL0085 adopts a butterfly-shaped homotetrameric arrangement with extensive intersubunit interactions. Each subunit of SACOL0085 contains two Mn2+ ions at the active site. A conserved cysteine residue at the active site distinguishes M20D peptidases from other M20 family members. This cysteine, Cys103, serves as bidentate ligand coordinating both Mn2+ ions in SACOL0085.

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[Es] Las habilidades sociales, o habilidades interpersonales, han sido objeto de creciente interés durante los últimos años en psicología social, clínica y educativa; y, sin embargo, tanto su evaluación como la intervención psicológica para su mejora se topan con una desconcertante proliferación de clasificaciones o categorías divergentes de las mismas. En este trabajo, y como resultado de sucesivos análisis factoriales, se proponen cinco grandes categorías de habilidades sociales (Interacción con personas desconocidas en situaciones de consumo, Interacción con personas que atraen, Interacción con amigos y compañeros, Interacción con familiares, y Hacer y rechazar peticiones a los amigos/as) que responden a distintos contextos de interacción social. Las cinco escalas, correspondientes a tales categorías, de un nuevo instrumento de medida, el Cuestionario de Dificultades Interpersonales (CDI), con alta consistencia interna (·= 0,896), explican el 47,47% de la varianza total. Los análisis correlacionales entre el CDI y el Test de Autoverbalizaciones en la Interacción Social (SISST) de Glass, Merluzzi, Biever y Larsen (1982) revelan diferencias cognitivas significativas entre los sujetos de alta y baja habilidad social, dándose una mayor frecuencia de autoverbalizaciones positivas y una menor frecuencia de autoverbalizaciones negativas en los sujetos de alta habilidad social que en los sujetos de baja habilidad social.

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Diffusible proteins regulate neural development at a variety of stages. Using a novel neuronal culture assay, I have identified several cytokines that regulate the expression of neurotransmitters and neuropeptides in sympathetic neurons. These cytokines fall into two families. The first group is termed the neuropoietic cytokines, while including CDF/LIF, CNTF, OSM and GPA, induces expression of the same set of neuropeptide mRNAs in cultured sympathetic neurons. These four factors not only exhibit similar biological activities; they also share a predicted secondary structure and bind to a signal-transducing receptor subunit in common with IL-6 and IL-11. The latter two cytokines display a weaker activity in this assay. In addition, I find that several members of the TGF-β superfamily, activin A, BMP-2, and BMP-6, have a selective overlap with the neuropoietic family in the spectrum of neuropeptides that these cytokines induce in sympathetic neurons. Different patterns of neuropeptides induced by the TGF-β family members, however, demonstrate that the activities of these cytokines are distinct from those of the neuropoietic family. Another 30 cytokines are without detectable effect in this neuronal assay.

Activin A induces a set of neurotransmitters and neuropeptides that is somewhat similar to the phenotype of sympathetic neurons innervating sweat glands in rat footpads. In situ hybridization and RNase protection were carried out to test whether activins were involved in the phenotypic transition when sympathetic neurons contact sweat glands. I find that activin mRNA is present in both cholinergic and noradrenergic targets. Moreover, homogenates of footpads do not contain activin-like activity in the neuronal assay in vitro. Taken together, these data do not support activins as the best candidates for the sweat gland factor.

Several novel factors that regulate neuropeptide expression exist in heart cell conditioned medium. I attempted to purify these factors in collaboration with Dr. Jane Talvenheimo. Our results suggest that these factors are sensitive to the storage conditions used. Several modifications of purification strategy are discussed.

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Considerando-se que a família vivencia e partilha junto com o doente todos os sentimentos, emoções e angústias que envolve o diagnóstico e o tratamento do câncer, o presente estudo teve como objetivos descrever as dimensões das representações sociais acerca do câncer para familiares do cliente oncológico em tratamento quimioterápico ambulatorial em uma unidade de referência para o seu tratamento; analisar a representação social do câncer elaborada por familiares do cliente oncológico em tratamento quimioterápico ambulatorial; e discutir as contribuições do enfermeiro junto à família do cliente oncológico em tratamento quimioterápico ambulatorial a partir da construção representacional do câncer para os sujeitos do estudo. De caráter qualitativo, o caminho metodológico foi construído com base na Teoria das Representações Sociais. Os sujeitos foram 30 familiares que estavam acompanhando o doente durante o tratamento quimioterápico. Os dados foram coletados a partir da realização de entrevistas semi-estruturadas e analisados através da análise de conteúdo de Bardin (1979), sistematizada por Oliveira (2008), com o auxílio do software QRS Nvivo 2.0. Da análise dos dados emergiram seis categorias que compõem o campo representacional e se expressa através das dimensões representacionais concretizadas nas seguintes categorias: sentimentos compartilhados por familiares de clientes oncológicos em tratamento quimioterápico, que mostra que, ao se depararem com a doença e sua dura realidade, os familiares são acometidos por diversos tipos de sentimentos; imagens, metáforas e conceitos no existir da família que enfrenta a doença, onde os familiares revelaram que o câncer é percebido, entre outras coisas, como um monstro que invade a vida das pessoas e dela passa a tomar conta e a dominá-la; preconceitos e estigmas na vivência do câncer, que revelou que ainda hoje existem representações e estigmas presentes na sociedade e em suas construções culturais acerca do câncer; diferentes práticas desenvolvidas no contexto da doença e do processo de adoecimento pelo câncer, que evidenciou as diferentes práticas presentes no discurso dos sujeitos, quais sejam, a de religiosidade no contexto do câncer, a de enfrentamento da doença, a de comunicação-ocultamento e de atitudes da família ao estar no mundo frente ao câncer; o processo de ancoragem e o conhecimento adquirido após a experiência do câncer, onde surgiram os conhecimentos que os sujeitos adquiriram acerca do câncer e alguns elementos do processo de ancoragem do câncer; as vivências do enfermeiro que trabalha em oncologia e suas contribuições junto à família que alerta os enfermeiros para a necessidade de intervenções efetivas direcionadas à assistência integral do indivíduo, levando em consideração a importância da família. Conclui-se que ao se descobrir acompanhando um familiar que tem câncer, a família passa a viver um outro mundo, no qual a possibilidade de morte se mostra de forma inevitável e iminente. Diante disso, a família passa a valorizar não apenas o cuidado dispensado ao doente, mas também anseia por uma atenção profissional que contemple seu existir e seu modo de viver.

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Lan honen helburua, Espainiako ekonomiarako fruten eskari sistema estimatzea da. Horretarako, ustez fruten kontsumoan eragina duten aldagaien aukeraketa egin da, zehazki familien ezaugarriei lotutakoak (adina, ikasketa maila, familiaren indibiduo kopurua adin ezberdineko, bizilekua eta nazionalitatea) eta merkatuari lotutakoak (fruten prezioa eta gastua). Bestelako emaitzen artean, faktore ekonomikoak fruten kontsumoan eragin nabarmena dute, familien bizilekua eta kide kopuruarekin batera. Gainera, fruta mota bakoitzarentzat kontsumo ohitura ezberdinak daude, batzuk elkarrekin kontsumitzen dira eta beste batzuk ordezten joaten baitira. EUSKERA

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O controle da Hipertensão Arterial é central para que seja alcançada maior eficiência na redução de eventos adversos secundários ao descontrole crônico da pressão arterial. Os resultados de uma atenção integral aos portadores não se esgotam no acesso e disponibilização de fármacos eficazes no controle da pressão arterial. Ela envolve a rede integrada de serviços, orientada pela atenção primária, com serviços especializados e hospitalares na atenção das intercorrências. O cuidado aos portadores destes agravos crônicos exige dos serviços e profissionais da atenção primária a implantação de estratégias de acolhimento, efetivação de vínculos e projetos terapêuticos e uma intervenção que abrange a promoção, prevenção, assistência e reabilitação. Com esta questão em mente é que este projeto buscou analisar a atenção prestada aos portadores de Hipertensão Arterial no município de Piraí com base nos registros dos prontuários ambulatoriais e hospitalares. Foram computados e analisados os prontuários de pacientes internados por agravos que, direta ou indiretamente, estão relacionados ao descontrole da pressão arterial. Identificaram-se um total de 61 pacientes internados com diagnóstico de internação de Crise Hipertensiva e Acidente Vascular Encefálico no ano de 2010, no Hospital Flávio Leal. A partir dos registros hospitalares foram selecionados 35 pacientes. Estes eram moradores do município de Piraí, adscritos a equipes básicas no município e tiveram seus diagnósticos de internação confirmados na alta hospitalar. A segunda etapa do estudo analisou, na Unidade de Saúde da Família, os prontuários familiares dos casos de internação. Foi observado que não havia uniformidade na forma de registro e de arquivamento dos prontuários entre as unidades básicas. Nos prontuários clínicos não havia campos destinados aos registros de aspectos psicossociais, mudança de comportamento ou adesão. As anotações eram centradas na doença e nos tratamentos farmacológicos. A participação de profissionais não médicos nos registros clínicos era escassa. A Ficha B do SIAB (Ficha de Acompanhamento do Paciente Hipertenso) que contém os dados sobre comportamento e risco cardiovascular foi encontrada apenas em 3 das 8 unidades visitadas. Segundo os dados dos prontuários analisados a distribuição de consultas e visitas domiciliares foi muito irregular. Com um total de 10 prontuários sem registros de consultas no ano em que o pacientes foi internado. A gravidade dos pacientes internados pode ser identificada pelo elevado número de óbitos entre os casos analisados. Muitos dos casos apresentavam sequelas neurológicas e comorbidades que provavelmente dificultava suas idas às unidades de saúde da família. Aspectos psicossociais, familiares e da comunidade estavam, em sua maioria, ausente dos prontuários familiares analisados dos pacientes internados. Também não foram encontrados anotações sobre projetos terapêuticos multidisciplinares que individualizassem e hierarquizassem os agravos e os riscos físicos e psicossociais dos pacientes. A análise evidencia que os registros nos prontuários não traduzem a abrangência de uma atenção integral aos portadores de Hipertensão Arterial no âmbito da Atenção Primária.