7 research outputs found
Myocardial infarction in a 28-year-old thalassemia intermedia patient
A 28-year-old Lebanese thalassemia intermedia (TI) patient with homozygous IVS1-110 mutation sustained atypical chest pain of 1 day's duration. The EKG reading revealed ST segment elevation in the chest leads V1 to V 5. Coronary angiography showed 2 plaques in the left anterior descending coronary artery. He underwent subsequent angioplasty with stenting of the left anterior descending coronary artery. An extensive thrombophilia profile was negative. He was started on medication, and his medical condition improved and chest pain ceased. This is the first case report of myocardial infarction in a TI patient among thalassemics. We propose that such cases will emerge more frequently as our population ages, keeping in mind a possible thrombotic mechanism.Fridlender ZG, 2004, AM J HEMATOL, V75, P52, DOI 10.1002-ajh.10454; Karimi M, 2006, ANN HEMATOL, V85, P29, DOI 10.1007-s00277-005-1101-x; Namazi MR, 2002, MED HYPOTHESES, V59, P361, DOI 10.1016-S0306-9877(02)00264-5; Taher A, 2006, THROMB HAEMOSTASIS, V96, P488, DOI 10.1160-TH06-05-0267; Taher A, 2006, BLOOD CELL MOL DIS, V37, P12, DOI 10.1016-j.bcmd.2006.04.0050
Thrombosis of the corpora cavernosa complicating lenalidomide therapy of myelofibrosis
Venous thrombosis is a well-recognized complication of lenalidomide therapy in patients with multiple myeloma, but its occurrence during the treatment of other hematologic malignancies is less well described. In this report, we detail the occurrence of corpora cavernosa thrombosis in a patient receiving lenalidomide for the therapy of myelofibrosis. This case highlights the need for clinical vigilance in patients who present with unusual symptoms during investigational therapy, and indicates that the occurrence of venous thrombosis complicating therapy with lenalidomide or related compounds is not isolated to patients with multiple myeloma.BENNETT CL, 2006, JAMA-J AM MED ASSOC, V296, P2260; Hirsch J, 2007, CHEST, V131, P275, DOI 10.1378-chest.06-2360; Zangari M, 2007, EXPERT REV ANTICANC, V7, P307, DOI 10.1586-14737140.7.3.30712
North American import? Charting the origins of an enigmatic Trypanosoma cruzi domestic genotype.
BACKGROUND: Trypanosoma cruzi, the agent of Chagas disease, is currently recognized as a complex of six lineages or Discrete Typing Units (DTU): TcI-TcVI. Recent studies have identified a divergent group within TcI - TcI(DOM). TcI(DOM). is associated with a significant proportion of human TcI infections in South America, largely absent from local wild mammals and vectors, yet closely related to sylvatic strains in North/Central America. Our aim was to examine hypotheses describing the origin of the TcI(DOM) genotype. We propose two possible scenarios: an emergence of TcI(DOM) in northern South America as a sister group of North American strain progenitors and dispersal among domestic transmission cycles, or an origin in North America, prior to dispersal back into South American domestic cycles. To provide further insight we undertook high resolution nuclear and mitochondrial genotyping of multiple Central American strains (from areas of México and Guatemala) and included them in an analysis with other published data. FINDINGS: Mitochondrial sequence and nuclear microsatellite data revealed a cline in genetic diversity across isolates grouped into three populations: South America, North/Central America and TcI(DOM). As such, greatest diversity was observed in South America (A(r) = 4.851, π = 0.00712) and lowest in TcI(DOM) (Ar = 1.813, π = 0.00071). Nuclear genetic clustering (genetic distance based) analyses suggest that TcI(DOM) is nested within the North/Central American clade. CONCLUSIONS: Declining genetic diversity across the populations, and corresponding hierarchical clustering suggest that emergence of this important human genotype most likely occurred in North/Central America before moving southwards. These data are consistent with early patterns of human dispersal into South America
Estudo da variabilidade intraespecífica do gene do RNA ribossomal (rRNA) em cepas de Trypanosoma rangeli Tejera, 1920 isoladas de diferentes regiões geográficas
Dissertação (mestrado) - Universidade Federal de Santa Catarina. Programa de Pós-Graduação em Biotecnologia.O Trypanosoma rangeli, assim como o T. cruzi, são protozoários hemoflagelados, parasitas de uma grande variedade de mamíferos domésticos e silvestres, incluindo humanos, numa ampla extensão da América do Sul e Central. Apesar da aparente apatogenicidade para mamíferos, o T. rangeli determina reações sorológicas cruzadas com T. cruzi, dificultando desta forma o diagnóstico sorológico da doença de Chagas. Uma grande heterogeneidade intra-populacional destes parasitas foi comprovada pelas marcantes diferenças no comportamento biológico tanto em hospedeiros vertebrado como invertebrados e, mais recentemente, por vários marcadores moleculares. Nesse sentido, o presente estudo avaliou comparativamente os espaçadores ITS-1 e ITS-2 que flanqueiam a subunidade 5,8S do gene do RNA ribossomal (rRNA) entre diferentes cepas de T. rangeli isoladas de hospedeiros e origens geográficas distintas. Tendo revelado um baixo nível de variabilidade de ambos os espaçadores entre as cepas estudadas, os resultados revelaram a existência de polimorfismos de mononucleotídeos (SNP's) na subunidade 5,8S do gene do rRNA. Apesar da observação que o espaçador ITS-1 demonstrou-se menos polimórfico que o ITS-2, não foi possível realizar nenhuma inferência epidemiológica. A inclusão de seqüências homólogas do gene do rRNA de cepas de T. cruzi e Leishmania sp. demonstrou a possível utilização deste marcador na diferenciação interespecífica de tripanosomatídeos
Estado da arte do evento quedas em idosos: uma revisão integrativa de literatura
Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Enfermagem, Florianópolis, 2014.Trata-se de uma pesquisa bibliográfica do tipo Revisão Integrativa de literatura, que objetivou investigar e descrever o estado da arte, na literatura científica, do evento quedas em idosos nos últimos dez anos (2003 a 2012). A busca dos artigos ocorreu entre julho/2012 e julho/2013, em seis bases de dados eletrônicas e o acesso foi online: PubMed/Medline (National Library of Medicine and National Institutes of Health/Medical Literature Analysis and Retrieval System Online); CINAHL (Cumulative Index to Nursing and Allied Health Literatue); Scopus; LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde); BDENF (Base de Dados de Enfermagem); SciELO (Scientific Electronic Library Online). Foram selecionados e submetidos à análise 224 artigos nos idiomas inglês, português e espanhol. O método utilizado para análise dos artigos foi a Proposta operativa de acordo com Minayo. Após o processo de análise emergiram quatro categorias: Análise quantitativa do estado da arte do evento queda em idoso; Epidemiologia do evento queda em idoso: um traçado histórico entre os anos de 2003 a 2012; Estudo dos preditores de quedas em idosos entre os anos de 2003 e 2012; Prevenção de quedas em idosos: um estudo do estado da arte. Por meio dessas quatro categorias foram produzidos quatro manuscritos. Percebemos que há diferentes abordagens dos autores relacionadas às quedas entre idosos, que se afunilam quando se trata de preditores e prevenção das mesmas nessa população. Notamos também a diversidade adotada pelos autores no que se refere aos instrumentos de avaliação de risco de queda e das intervenções propostas pelos programas, o que de fato limita a comparação e nos exige relativizar os resultados. Os profissionais da fisioterapia e da educaçãofísica se destacam quando se trata de quedas de idoso. Observamos que os autores estão certos de que o sexo, a cultura, educação, etnia e as condições sociodemográficas de fato interferem na incidência e prevalência de quedas entre idosos. No entanto é necessário afirmar que as quedas são evitáveis. As ILPs foram os locais com maiores estatísticas de quedas entre idosos. A enfermagem tem relevante papel na prevenção das quedas em qualquer estabelecimento assistencial de saúde, inclusive em ILPs, pois é a equipe de enfermagem que assiste e cuida integralmente e de maneira ininterrupta os idosos. Pontuamos que se faz necessário que os profissionais da área da saúde e os gestores aprimorem seus conhecimentos no desenvolvimento de estratégias e políticas específicas para a saúde do idoso.Abstract : This is a literature integrative review aimed at investigating and describing the state of the art in the literature related to the event of falls in the elderly people in the last ten years (2003 to 2012). The search for the items happened between July/2012 and july/2013 in six electronic databases; the access was online: PubMed/Medline (National Library of Medicine and National Institutes of Health / Medical Literature Analysis and Retrieval System Online); CINAHL (Cumulative Index to Nursing and Allied Health Literature); Scopus; LILACS (Latin American and Caribbean Literature on Health Sciences); BDENF (Database of nursing); SciELO (Scientific Electronic Library Online). Were selected and subjected to analysis 224 articles in the languages of English, Portuguese and Spanish. The method used for the analysis of the items was the Proposed Operative according to Minayo. After the analysis process four themes emerged that were presented and discussed in the form of manuscripts. The first manuscript is a state of the art related to the fall of elderly people; the second manuscript refers to the epidemiology of the fall event in elderly 2003 to 2012. The third manuscript is a study of the predictors of falls in the elderly between 2003 and 2012; and the fourth manuscript is about preventing falls in the elderly. We identify that there are different approaches of the authors listed in the elderly falls, which are reduced in the case of the predictors and prevention of the same in this population. We also note the diversity adopted by the authors with regards the assessment tools fall hazards and interventions proposed by the programs, which effectively limits the comparison and requires us to relativize the results. The professional of physiotherapy and physical education stand out when it comes to falls in the elderly. We note that the authors are confident that gender, culture,education, ethnicity and socio-demographic conditions in fact interfere with the incidence and prevalence of falls among the elderly. Meanwhile it is necessary to state that falls are inevitable. The ILPs were more local statistic falls among the elderly. Nursing has an important role in the prevention of falls in any health care facility, including the ILPs, it is the nursing staff which attending integrally and deliver continuously caring for the elderly people. Punctuate it becomes necessary that professionals in health and managers improve their knowledge in the development of specific strategies and elderly health policies
The effects of host-vector relationships and density dependence on the epidemiology of visceral leishmaniasis
In Latin America, visceral leishmaniasis (VL) is caused by infection with
Leishmania infantum, an endemic but lethal parasite transmitted by Lutzomyia
longipalpis sandflies. Multiple hosts are implicated in VL transmission; therefore
sandfly biting preferences may be pivotal in determining transmission dynamics.
Host preferences are poorly understood with simple preference-host density
relationships being conventionally assumed.
Combined modelling and fieldwork approaches were used to investigate the
preference of sandflies for key host types (dogs, humans and chickens) and force of
infection (FOI) over a range of vector and host densities. In Brazil, variable vector
densities were (i) observed over a period of seasonal variation, and (ii)
experimentally manipulated via “trapping out” (sustained CDCLT capture to reduce
local vector density). Host density was also manipulated by (iii) the incremental
introduction of chickens to experimental sheds.
Results suggest that there is a significant link between alternative host density and
the absolute and relative preference of sandflies for humans and dogs. Investigations
also indicate that host choice has a vector density dependent element, which varies
significantly and nonlinearly depending upon vector density. Meta-analysis and
mathematical modelling of human and canine prevalences across Brazil also point
toward variable transmission rates to these hosts attributable to density-dependent
biting preferences observed in the field. These host choice dynamics ultimately
combine to demonstrate the influence of host and vector densities on FOI on dogs
and humans, but there are significant interactions between host and vector densities
resulting in complex FOI relationships.
Nonlinearities are likely explained by density dependent sandfly aggregation
behaviour upon outdoor living hosts, such as chickens, as vector density rises. This
preference behaviour may have far reaching implications for our understanding of
transmission and control, and potentially indicate host density manipulation as an
intervention measure
Topoisomerase-II mediated biochemical mapping of centromeres and nitroreductase mediated drug metabolism in Trypanosomatids
PhDThe protozoan parasites Trypanosoma cruzi and Trypanosoma brucei are the causative agents of Chagas disease and Human African sleeping sickness respectively. Existing therapies are toxic and ineffective against the later stages of the two diseases, consequently safer, improved therapies are urgently required. Here, two areas of trypanosome biology are explored. In the first section, the process of cell division is approached from a fundamental biology perspective. Centromeres are the region of DNA where kinetochore structures form, allowing the attachment of microtubules to facilitate chromosome segregation. In T. brucei we have characterized the nature and location of centromeres by exploiting the localized activity of topoisomerase-II, a cancer chemotherapy target, at the centromere. Etoposide mediated DNA cleavage mapping revealed the presence of signature AT-rich repeat regions coupled with adjacent retrotransposons at the centromere. Further experiments demonstrate that of the two nuclear T. brucei topoisomerase-II isoforms, only topoisomerase-IIα is essential and active at the centromere. The second section centres on pro-drug development against a trypanosome type I nitroreductase. This enzyme has previously been implicated in activation of nifurtimox and benznidazole, the two therapies in clinical use against Chagas disease. Initially we have developed a luciferase based drug assay system in the clinically relevant intracellular T. cruzi stage and rapidly screened a range of nitroaromatic based compounds for trypanocidal activity. A series of derived nitrofuryl compounds previously developed against Chagas disease were also screened against T. brucei, where most demonstrate trypanocidal activities of less than 1 μM. Further we show that these compounds are active substrates of nitroreductase, and act as pro-drugs within the parasite by specific activation of nitroreductase to generate cytotoxic moieties
