Increased sympathetic activity in normotensive offspring of malignant hypertensive parents compared to offspring of normotensive parents

Malignant hypertension seems to be the consequence of very high blood pressure. Furthermore, an increase in sympathetic and renin-angiotensin system activity is considered to be the main mechanisms producing malignant hypertension. In the present study, 10 offspring of malignant hypertensive (OMH) parents (age 28 ± 5 years, 7 males, 3 females, 2 white and 8 non-white) and 10 offspring of normotensive (ONT) parents (age 28 ± 6 years, 2 males, 8 females, 3 white and 7 non-white) were evaluated. The OMH group had significantly higher (P < 0.05) casual blood pressure (125 ± 10/81 ± 5 mmHg) compared with ONT (99 ± 13/67 ± 5 mmHg). The increase in blood pressure was greater in OMH (Δ SBP = 17 ± 2 vs Δ SBP = 9 ± 1 mmHg in ONT) during cold pressor testing, but they had a lower increase in heart rate (Δ HR = 13 ± 2 vs Δ HR = 20 ± 3 bpm in ONT) during isometric exercise (handgrip test). Sympathetic activity, measured by microneurography, was significantly higher (P < 0.05) before exercise in OMH (17 ± 6 vs 11 ± 4 burst/min in ONT) and exhibited a greater increase (Δ = 18 ± 10 vs Δ = 8 ± 3 burst/min in ONT) during isometric exercise. This study showed increased sympathetic activity in OMH before exercise and a greater response during isometric exercise, suggesting an autonomic abnormality before exercise and a greater sympathetic response to physical stress in OMH compared to ONT.

Multigenerational Brazilian family with malignant hyperthermia and a novel mutation in the RYR1 gene

Malignant hyperthermia (MH) is a pharmacogenetic disease triggered in susceptible individuals by the administration of volatile halogenated anesthetics and/or succinylcholine, leading to the development of a hypermetabolic crisis, which is caused by abnormal release of Ca2+ from the sarcoplasmic reticulum, through the Ca2+ release channel ryanodine receptor 1 (RyR1). Mutations in the RYR1 gene are associated with MH in the majority of susceptible families. Genetic screening of a 5-generation Brazilian family with a history of MH-related deaths and a previous MH diagnosis by the caffeine halothane contracture test (CHCT) in some individuals was performed using restriction and sequencing analysis. A novel missense mutation, Gly4935Ser, was found in an important functional and conserved locus of this gene, the transmembrane region of RyR1. In this family, 2 MH-susceptible individuals previously diagnosed with CHCT carry this novel mutation and another 24 not previously diagnosed members also carry it. However, this same mutation was not found in another MH-susceptible individual whose CHCT was positive to the test with caffeine but not to the test with halothane. None of the 5 MH normal individuals of the family, previously diagnosed by CHCT, carry this mutation, nor do 100 controls from control Brazilian and USA populations. The Gly4932Ser variant is a candidate mutation for MH, based on its co-segregation with disease phenotype, absence among controls and its location within the protein.

Use of the caffeine-halothane contracture test for the diagnosis of malignant hyperthermia in Brazil

Malignant hyperthermia (MH) is a pharmacogenetic disease triggered by volatile anesthetics and succinylcholine. Deaths due to MH have been reported in Brazil. The first Malignant Hyperthermia Diagnostic and Research Center in Latin America was inaugurated in 1993 at the Federal University of Rio de Janeiro, Brazil. The center followed the diagnostic protocols of the North America MH Group, in which the contractures of biopsies from the vastus lateralis muscle are analyzed after exposure to caffeine and halothane (CHCT). CHCT was performed in individuals who survived, their relatives and those with signs/symptoms somewhat related to MH susceptibility (MHS). Here, we report data from 194 patients collected over 16 years. The Southeast (N = 110) and South (N = 71) represented the majority of patients. Median age was 25 (4-70) years, with similar numbers of males (104) and females (90). MHS was found in 90 patients and 104 patients were normal. Abnormal responses to both caffeine and halothane were observed in 59 patients and to caffeine or halothane in 20 and 11 patients, respectively. The contracture of biopsies from MHS exposed to caffeine and halothane was 1.027 ± 0.075 g (N = 285) and 4.021 ± 0.255 g (N = 226), respectively. MHS was found in patients with either low or high blood creatine kinase and also, with a low score on the clinical grading scale. Thus, these parameters cannot be used with certainty to predict MHS. We conclude that the CHCT protocol described by the North America MH Group contributed to identification of MHS in suspected individuals at an MH center in Brazil with 100% sensitivity and 65.7% specificity.

Kaurene diterpene induces apoptosis in U87 human malignant glioblastoma cells by suppression of anti-apoptotic signals and activation of cysteine proteases

Gliomas are the most common and malignant primary brain tumors in humans. Studies have shown that classes of kaurene diterpene have anti-tumor activity related to their ability to induce apoptosis. We investigated the response of the human glioblastoma cell line U87 to treatment with ent-kaur-16-en-19-oic acid (kaurenoic acid, KA). We analyzed cell survival and the induction of apoptosis using flow cytometry and annexin V staining. Additionally, the expression of anti-apoptotic (c-FLIP and miR-21) and apoptotic (Fas, caspase-3 and caspase-8) genes was analyzed by relative quantification (real-time PCR) of mRNA levels in U87 cells that were either untreated or treated with KA (30, 50, or 70 µM) for 24, 48, and 72 h. U87 cells treated with KA demonstrated reduced viability, and an increase in annexin V- and annexin V/PI-positive cells was observed. The percentage of apoptotic cells was 9% for control cells, 26% for cells submitted to 48 h of treatment with 50 µM KA, and 31% for cells submitted to 48 h of treatment with 70 µM KA. Similarly, in U87 cells treated with KA for 48 h, we observed an increase in the expression of apoptotic genes (caspase-8, -3) and a decrease in the expression of anti-apoptotic genes (miR-21 and c-FLIP). KA possesses several interesting properties and induces apoptosis through a unique mechanism. Further experiments will be necessary to determine if KA may be used as a lead compound for the development of new chemotherapeutic drugs for the treatment of primary brain tumors.

Relationship between deep venous thrombosis and inflammatory cytokines in postoperative patients with malignant abdominal tumors

Deep venous thrombosis (DVT) is a common surgical complication in cancer patients and evidence that inflammation plays a role in the occurrence of DVT is increasing. We studied a population of cancer patients with abdominal malignancies with the aim of investigating whether the levels of circulating inflammatory cytokines were associated with postoperative DVT, and to determine the levels in DVT diagnoses. The serum levels of C-reactive protein (CRP), interleukins (IL)-6 and IL-10, nuclear transcription factor-κB (NF-κB) and E-selectin (E-Sel) were determined in 120 individuals, who were divided into 3 groups: healthy controls, patients with and patients without DVT after surgery for an abdominal malignancy. Data were analyzed by ANOVA, Dunnet's T3 test, chi-square test, and univariate and multivariate logistic regression as needed. The CRP, IL-6, NF-κB, and E-Sel levels in patients with DVT were significantly higher than those in the other groups (P<0.05). The IL-10 level was higher in patients with DVT than in controls but lower than in patients without DVT. Univariate analysis revealed that CRP, IL-6, NF-κB, and E-Sel were statistically associated with the risk of DVT (OR=1.98, P=0.002; OR=1.17, P=0.000; OR=1.03, P=0.042; and OR=1.38, P=0.003; respectively), whereas IL-10 had a protective effect (OR=0.94, P=0.011). Multivariate analysis showed that E-Sel was an independent risk factor (OR=1.41, P=0.000). Thus, this study indicated that an increased serum level of E-Sel was associated with increased DVT risk in postoperative patients with abdominal malignancy, indicating that E-Sel may be a useful predictor of diagnosis of DVT.

Premières conséquences de la guerre : transformation mentale des peuples... / Dr Gustave Le Bon

Collection : Bibliothèque de philosophie scientifique

Les 5 milliards sont là ! ! ! sans emprunt ni augmentation des charges publiques par la seule transformation de l'impôt... 2e édition

Comprend : Préambule

Gadamer's transformation of hermeneutics : from Dilthey to Heidegger

Abstract: The purpose of this paper is to show how Gadamer's hermeneutics synthesizes the insights of both Heidegger and Dilthey in order to introduce a new hermeneutics. Gadamer's hermeneutics is based not only on the priority of ontology, as Heidegger insists, and neither is it only a product of life which can be objectively understood through study and rigorous method, as Dilthey suggests. For Gadamer, hermeneutics is the bringing together of ontology in terms of history. By this synthesis Gadamer not only places himself within the context of a Lebensphilosophie, but also shows that it is within language that Being can be disclosed according to a lived context. Throughout this paper the philosophies ofDilthey and Heidegger are explicated within a historical context as to bring out how, and why, Gadamer sees the need to surpass these philosophies. Through Gadamer's philosophy of play and the game, language, the dialogical model, application, and the fusion of horizons we can see how Gadamer's critique and questioning of these two philosophy leads to his new hermeneutics. Special attention is paid to the role in which these two contrasting philosophies were used to complement each other in the product of Gadamer' s philosophical hermeneutics as it is presented in his major work Truth andMethod. For Gadamer, the task of understanding is never complete. Therefore, his hermeneutics remains a dynamic structure with which we can always question the past and our traditions. This paper seeks to show his philosophical movements within these questions

The essence of a tacit intersection : a heuristic inquiry into nature-based leisure and personal transformation

There are a considerable number of programs and agencies that count on the existence of a unique relationship between nature and human development. In addition, there are significant bodies of literature dedicated to understanding developmentally focused nature-based experiences. This research project was designed to flirther the understanding of this phenomenon. Consequently, the purpose of this research endeavour was to discover the essence ofthe intersection ofpersonal transformation and nature-based leisure, culminating in a rich and detailed account of this otherwise tacit phenomenon. As such, this research built on the assumption of this beneficial intersection of nature and personal transformation and contributes to the understanding ofhow this context is supporting or generating of selfactualization and positive development. Heuristic methods were employed because heuristics is concerned with the quality and essence of an experience, not causal relationships (Moustakas, 1990). Heuristic inquiry begins with the primary researcher and her personal experience and knowledge of the phenomenon. This study also involved four other coresearchers who had also experienced this phenomenon intensely. Co-researchers were found through purposeful and snowball sampling. Rich narrative descriptions of their experiences were gathered through in-depth, semi-structured interviews, and artifact elicitation was employed as a means to get at co-researchers' tacit knowledge. Each coresearcher was interviewed twice (the first interview focused on personal transformation, the second on nature) for approximately four and a half hours in total. Transcripts were read repeatedly to discern patterns that emerged from the study of the narratives and were coded accordingly. Individual narratives were consolidated to create a composite narrative of the experience. Finally, a creative synthesis was developed to represent the essence of this tacit experience. In conclusion the essence of the intersection of nature-based leisure and personal transformation was found to lie in the convergence of the lived experience of authenticity. The physical environment of nature was perceived and experienced to be a space and context of authenticity, leisure experiences were experienced as an engagement of authenticity, and individuals themselves encountered a true or authentic self that emanated from within. The implications of these findings are many, offering suggestions, considerations and implications from reconsidered approaches to environmental education to support for selfdirected human development.

Words on wisdom: perspective transformation in a "learning in retirement institute" /

In this study, 7 men and women with an average age of 77 were interviewed regarding their experience of attending courses at a Learning in Retirement Institute (LRI) in southern Ontario. The purpose was to explore the role of wisdom in the learning of these retirees. Explicit theories of wisdom developed by selected philosophers, psychologists, and religious thinkers were compared to the implicit theories of wisdom that respondents expressed. Further comparisons were drawn between these implicit theories of wisdom and the act of perspective transformation in transformative learning. Some evidence was found that the development of wisdom compares favourably to perspective transformation, especially with regards to the behavioural changes associated with critical self-reflection. Among all the respondents, those 3 LRI stude.its who had also moderated courses indicated that they had experienced the most opportunities for critical self-reflection. These 3 also expressed deep satisfaction in having been able to put their learnings to use as teachers. A recommendation of this study is that opportunities for sharing and acting upon the results of discourse within Learning in Retirement Institutes should be implemented. In the absence of evaluation, opportunities for praxis (such as coop placements) must be developed so that students can measure their success against objective criteria and hence attach meaning to their studies.

Paradigms and prisons: a narrative of translation and transformation : my hero's journey from "at-risk" youth to teacher/learner in a jail setting /

All life is suffering. Life is the pursuit ofhappiness. These are two foundational Buddhist dictums that, in their simplicity, I have entirely misunderstood regarding their depth, misreading them as contradictory. Indeed, my superficial interpretations led me to Thoreau's life ofquiet desperation and deep depression. We come to know and bring understanding to our lives by storying them. My own Hero's Journey, the path from my egoic selftoward the universal Self, can be understood as the resultant translations and transformations. Inevitably each of us is involved in such a story, though most are unaware of the stages along our own Hero's journey. ' Narrative honours writing as a means of knowing. The contemplative reflection allows insight into our imprisoning paradigms, beliefs, behaviours, and blind spots. My research revisits and explores nodal experiences along my Hero's Journey through 4 categories: self, society, soil, and Self. While the value of this process of narrative inquiry lay in its ability to come to know and understand one's self, perhaps its greater value is of a more universal nature. My inquiry, while adding to the body of academic educational narrative literature, may also illuminate a path to educators, students, and all interested, encouraging a response to the call of their own Hero's journey. I am a teacher/learner in a jail setting, working with youth between the ages of 12 and 18 who have committed crimes such as armed robbery, assault, rape, and murder. As this thesis follows my continual development from egoic self/teacher/learner to universal Self/Teacher/Learner, it also enables me to both consciously and unconsciously open the ways in which I expand my care, compassion, and love to work with at-risk youth.

An exploration of transformation theory and the western tradition: a critical evaluation of a graduate studies class

This qualitative study is an exploration of transformation theory, the Western tradition, and a critical evaluation of a graduate studies class at a university. It is an exploration of assumptions that are embedded in experience, that influence the experience and provide meaning about the experience. An attempt has been made to identify assumptions that are embedded in Western experience and connect them with assumptions that shape the graduate class experience. The focus is on assumptions that facilitate and impede large group discussions. Jungian psychology of personality type and archetype and developmental psychology is used to analyze the group experience. The pragmatic problem solving model, developed by Knoop, is used to guide thinking about the Western tradition. It is used to guide the analysis, synthesis and writing of the experience of the graduate studies class members. A search through Western history, philosophy. and science revealed assumptions about the nature of truth, reality, and the self. Assumptions embedded in Western thinking about the subject-object relationship, unity and diversity are made explicit. An attempt is made to identify Western tradition assumptions underlying transformation theory. The critical evaluation of the graduate studies class experience focuses upon issues associated with group process, self-directed learning, the educator-learner transaction and the definition of adult education. The advantages of making implicit assumptions explicit is explored.