Putting the horse before the cart: a pragmatist analysis of knowledge

The definition of knowledge as justified true belief is the best we presently have. However, the canonical tripartite analysis of knowledge does not do justice to it due to a Platonic conception of a priori truth that puts the cart before the horse. Within a pragmatic approach, I argue that by doing away with a priori truth, namely by submitting truth to justification, and by accordingly altering the canonical analysis of knowledge, this is a fruitful definition. So fruitful indeed that it renders the Gettier counterexamples vacuous, allowing positive work in epistemology and related disciplines.

Proposal of abolition of the skin sensitivity test before equine rabies immune globulin application

An epizootic outbreak of rabies occurred in 1995 in Ribeirão Preto, SP, with 58 cases of animal rabies (54 dogs, 3 cats and 1 bat) confirmed by the Pasteur Institute of São Paulo, and one human death. The need to provide care to a large number of people for the application of equine rabies immune globulin (ERIG) prevented the execution of the skin sensitivity test (SST) and often also the execution of desensitization, procedures routinely used up to that time at the Emergency Unit of the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo (EU-UHFMRP-USP), a reference hospital for the application of heterologous sera. In view of our positive experience of several years with the abolition of SST and of the use of premedication before the application of antivenom sera, we used a similar schedule for ERIG application. Of the 1489 victims of animal bites, 1054 (71%) received ERIG; no patient was submitted to SST and all received intravenously anti-histamines (anti-H1 + anti-H2) and corticosteroids before the procedure. The patients were kept under observation for 60 to 180 minutes and no adverse reaction was observed. On the basis of these results, since December 1995 ERIG application has been decentralized in Ribeirão Preto and has become the responsibility of the Emergency Unit of the University Hospital and the Central Basic Health Unit, where the same routine is used. Since then, 4216 patients have received ERIG (1818 at the Basic Health Unit and 2398 at the EU-UHFMRP), with no problems. The ideal would be the routine use of human rabies immune globulin (HRIG) in public health programs, but this is problematic, because of their high cost. However, while this does not occur, the use of SST is no longer justified at the time of application of ERIG, in view of the clinical evidence of low predictive value and low sensitivity of SST involving the application of heterologous sera. It is very important to point out that a negative SST result may lead the health team to a feeling of false safety that no adverse reaction will occur, but this is not true for the anaphylactoid reactions. The decision to use premedication, which is based on knowledge about anaphylaxis and on the pharmacology of the medication used, is left to the judgment of health professionals, who should always be prepared for eventual untoward events.

Candida dubliniensis does not show phospholipase activity: true or false?

INTRODUCTION: The phospholipase activity in Candida albicans and Candida dubliniensis isolated from oral candidiasis cases were studied. METHODS: The phospholipase activity was evaluated in egg yolk agar. RESULTS: All the C. albicans isolates (n = 48) showed phospholipase activity (mean Pz = 0.66). However, none of the C. dubliniensis isolates (n = 24) showed this activity. CONCLUSIONS: The authors discuss whether these findings are a true characteristic of C. dubliniensis or a consequence of the methodology employed, which includes the possibility that NaCl may have inhibited the enzymatic activity of C. dubliniensis.

Levosimendana em pacientes com insuficiência cardíaca descompensada: eficácia em uma coorte brasileira. Resultados do estudo BELIEF

FUNDAMENTO: A levosimendana é um novo agente inodilatador que aumenta a contratilidade cardíaca pela sensibilização ao Ca(2+) e induz vasodilatação por meio da ativação dos canais KATP/BKCa. OBJETIVO: Estudar a eficácia e segurança da levosimendana em uma coorte brasileira portadora de insuficiência cardíaca descompensada e em pacientes resistentes a agonistas b-adrenérgicos. MÉTODOS: O BELIEF (Brazilian Evaluation of Levosimendan Infusion Efficacy) foi um estudo aberto, prospectivo, multicêntrico e observacional realizado com 182 portadores de ICD de alto risco, todos tratados com levosimendana. O desfecho primário do estudo era alta hospitalar sem terapia inotrópica adicional (pacientes que responderam ao tratamento). Os desfechos secundários eram alterações nos parâmetros clínicos e hemodinâmicos e nos níveis de peptídeo natriurético cerebral (BNP). RESULTADOS: A taxa de mortalidade foi de 14,8%, e 139 dos 182 pacientes responderam ao tratamento. Entre os que não responderam, a taxa de mortalidade foi de 62,8%. A pressão arterial sistólica foi um preditor de resposta ao tratamento. No grupo resistente aos agonistas b-adrenérgicos, 55,8% responderam ao tratamento. Ao todo, 54 pacientes tiveram pelo menos um evento adverso, a maioria dos quais desapareceu espontaneamente ou após redução da dose da levosimendana. Houve uma melhora significativa na qualidade de vida entre 2 e 6 meses do acompanhamento (p < 0,0001). CONCLUSÃO: Nossos resultados indicam que a infusão de levosimendana é uma terapia alternativa de curto prazo para tratamento de pacientes com ICD. A gravidade da insuficiência cardíaca pode influenciar a resposta ao tratamento com levosimendana. São necessários estudos prospectivos com uma coorte brasileira que inclua também pacientes com doença de Chagas.

Variation in the cytoadherence characteristics of malaria parasites: is this a true virulence factor?

The sequestration of Plasmodium falciparum-infected erythrocytes to the endothelial cells of brain capillaries is believed to represent one of the determining factors in the pathogenesis of cerebral malaria. In vitro studies of cytoadherence provide an experimental approach to understand the mechanism of sequestration and the respective roles played by parasite and host components in this interaction. This paper critically reviews current studies on cytoadherence, with particular emphasis on the nature of the information provided by such studies and their limitations. The paper also describes how cytoadherence studies using the patient's own monocytes can provide original information on the level of receptor up-regulation in the course of malarial infection.

Chronic Trypanosoma cruzi-elicited cardiomyopathy: from the discovery to the proposal of rational therapeutic interventions targeting cell adhesion molecules and chemokine receptors - how to make a dream come true

One hundred years ago, Carlos Chagas discovered a new disease, the American trypanosomiasis. Chagas and co-workers later characterised the disease's common manifestation, chronic cardiomyopathy, and suggested that parasitic persistence coupled with inflammation was the key underlying pathogenic mechanism. Better comprehension of the molecular mechanisms leading to clinical heart afflictions is a prerequisite to developing new therapies that ameliorate inflammation and improve heart function without hampering parasite control. Here, we review recent data showing that distinct cell adhesion molecules, chemokines and chemokine receptors participate in anti-parasite immunity and/or detrimental leukocyte trafficking to the heart. Moreover, we offer evidence that CC-chemokine receptors may be attractive therapeutic targets aiming to regain homeostatic balance in parasite/host interaction thereby improving prognosis, supporting that it is becoming a non-phantasious proposal.

True believers: the recption of Descartes's meditations by Malebranche and Huet

Both Nicholas Malebranche and Pierre-Daniel Huet were at first positively influenced by Descartes's Meditations, and both came to perceive shortcomings in that work. With respect to mind-body dualism, Malebranche attempted to strengthen Descartes's position by jettisoning clarity and distinctness basing it instead on a principle of intentionality. Huet jettisoned the whole position in favor of skepticism. The source of their different responses lay in their different estimations of Descartes's integrity.

In search of true friendship

The present text proposes a discussion on the concept of true friendship. The argument is grounded mostly on Aristotle's Nicomachean Ethics, Owen Flanagan's ethics as human ecology, and on contemporary authors' works about the Greek philosopher's concept of friendship. Given that human beings flourish through 1) exercising capacities, 2) being moral, and 3) having true friendships, difficulties to establish the level of trust required by true friendships turns the search itself (for them) morally valid.

Use of RAPD-PCR to identify true hybrid plants from crosses between closely related progenitors

RAPD-PCR molecular markers were used to identify common bean and soybean hybrid plants derived from crosses between closely related progenitors, with no apparent phenotypic differences. Primers OP-F12 and OP-0O3 were used to identify true hybrids derived from crosses between common bean cultivars Rudá (A 285) and AN 910408, and soybean cultivars Cristalina and Bossier, respectively. Each primer generated one polymorphic DNA band which was present in the male progenitor and absent in the female progenitor. As RAPD bands are normally inherited as dominant characters, the presence of these bands in the F1 plants confirmed their status.