The philosophy of man /

Includes bibliographical references and indexes.

Literary essays /

How to tell a story.--In defence of Harriet Shelley.--Fenimore Cooper's literary offences.--Travelling with a reformer.--Private history of the "Jumping frog" story.-- Mental telegraphy again.--What Paul Bourget thinks of us.--A little note to M. Paul Bourget.--The invalid's story.--The captain's story.--Stirring times in Austria.--Concerning the Jews.--From the London times of 1904.--At the appetite cure.--In memorium.-- Mark Twain: a biographical sketch.

The control of hunger in health and disease,

"A summary of the work on the stomach, with special reference to hunger and appetite, carried out in the Hull physiological laboratory of the University of Chicago during the last four years."--Pref.

Aspergillus clavatus tremorgenic neurotoxicosis in cattle fed sprouted grains

Beef and dairy cattle from four different herds in southern and central Queensland fed hydroponically-produced sprouted barley or wheat grain heavily infested with Aspergillus clavatus developed posterior ataxia with knuckling of fetlocks, muscular tremors and recumbency, but maintained appetite. A few animals variously had reduced milk production, hyperaesthesia, drooling of saliva, hypermetria of hind limbs or muscle spasms. Degeneration of large neurones was seen in the brain stem and spinal cord grey matter. The syndrome was consistent with A clavatus tremorgenic mycotoxicosis of ruminants. The cases are the earliest known to be associated with this fungus in Australia. They highlight a potential hazard of hydroponic fodder production systems, which appear to favour A clavatus growth on sprouted grain, exacerbated in some cases by equipment malfunctions that increase operating temperatures.

Role of oxidative stress in age-associated chronic kidney pathologies

The kidneys exhibit age-associated deterioration in function via a loss of 20% to 25% kidney mass, particularly from the renal cortex and increased fibrosis. Oxidative stress has been found to mediate age-associated renal cell injury and cell death, particularly apoptosis. Oxidative stress results from an imbalance between the levels of free radicals generated during aerobic metabolism, inflammation, and infection and the safe breakdown of these species by endogenous and exogenous scavengers. Other factors may influence these pathologies. For example, growth hormone and caloric restriction have been shown to influence life span, although neither method of prolonging life is likely to find general acceptance in humans. Some genetic knockout models offer promise; for example, knockout of the p66 isoform of the Shc gene in mice increases life span by 30%, but appetite, size, and fertility are retained. Whether the increase in life span is via increased kidney health is not yet clear, but decreasing the age-related renal pathologies will no doubt aid in increasing life span and health in general. This review looks at the role and modulation of factors that influence life span, in particular modulation of oxidative stress, with particular relevance to age-related renal pathologies. (C) 2005 by the National Kidney Foundation, Inc.

Will the new CB1 cannabinoid receptor antagonist SR-147778 have advantages over rimonabant?

Obesity and alcoholism are two common modern-day diseases. The cannabinoid CB, receptor antagonist rimonabant is in Phase III clinical trial for the treatment of obesity with preliminary results showing that it decreases appetite and body weight. Animal studies have shown that rimonabant is effective in the treatment of alcoholism. SR-147778 is a new potent and selective CB1 receptor antagonist. In animals, SR-147778 has been shown to inhibit CB1 receptor-mediated hypothermia, analgesia and slowing of gastrointestinal transit. In rats trained to drink sucrose, the oral administration of SR-147778 3 mg/kg, before the presentation of sucrose, decreased the consumption of sucrose. SR-147778 3 mg/kg also reduced spontaneous feeding in rats deprived of food and also in non-deprived rats. In Sardinian alcohol-preferring (sP) rats, in the alcohol-naive state, SR-147778 slowed the development of a preference for alcohol. in alcohol-experienced sP rats SR-147778 (2.5, 5 and 10 mg/kg p.o.) reduced the alcohol intake. When alcohol-experienced sP rats are deprived of alcohol for 15 days, there is a large intake of alcohol on reintroduction of alcohol, and this response was almost abolished by treatment with SR-147778. From the preclinical studies published to date, there is no obvious major point of difference between rimonabant and SR-147778, and both are promising agents for the treatment of obesity and alcoholism.

Doubling daily inhaled corticosteroid dose is ineffective in mild to moderately severe attacks of asthma in adults

Background: Asthma guidelines recommend increasing or doubling inhaled corticosteroid (ICS) dose to treat mild and moderate exacerbations of asthma in adults. Aim: To: (i) compare the effectiveness of doubling existing daily ICS dose (fluticasone) with maintaining usual ICS dose and usual daily ICS dose accompanied by oral steroids (OS) (dexamethasone) during mild and moderately severe exacerbations of asthma in adults; (ii) examine determinants of success and failure; and (iii) compare side-effect profiles. Methods: A randomized, double-blind, placebo-controlled (double-dummy), triple crossover trial. Participants acted as their own control. Outcome measures included treatment success/failure, peak expiratory flow (PEF) after 7 days therapy or at treatment failure, and side-effects. Results: From 22 participants (nine males and 13 females), 18 pairs of data were available for maintaining usual ICS versus doubling ICS and doubling ICS versus OS, and 19 for maintaining usual ICS versus OS. Median (fifth-95th percentile) age was 46.5 (32-64) years and forced expiratory volume in one second (FEV1) 73% (29-97%) predicted. The outcome after doubling ICS was not superior to maintaining usual ICS, with 11 (61%) failures in both arms (P = 0.66). OS, with only 5 (26%) failures, was superior to maintaining usual ICS with 12 (63%) failures (P = 0.04), and to doubling ICS with 5 (28%) versus 11 (61%) failures (P = 0.07). Median PEF (as percentage of run-in best) at end-points were 90.5% (57.1-177.1) for OS, 78.3% (39.5-103.1) for maintaining usual ICS and 77.9 (27.7-110.3) for doubling ICS. Neither gender nor PEF at exacerbation were predictive of failure. Although doubling ICS was not an effective therapy overall, ICS dose at exacerbation were predictive of success in the doubling ICS arm (P = 0.04). Treatment failures when doubling daily ICS dose were more common if achieved fluticasone dose was less than 2000 mu g (three of 11, 73%) compared to 2000 mu g or greater (eight of eight, 37.5%). Increasing age and the presence of an upper respiratory tract infection (URTI) were predictive of failure with OS. Side-effects were more commonly reported with OS (52.6%) than doubling ICS (42.1%) or maintaining usual ICS (19.1%) with the most common being mood changes (36.8%), sleep disturbance (31.6%) and changes in appetite (26.3%). Conclusions: Doubling daily ICS dose per se is not effective for the treatment of mild to moderately severe exacerbations of asthma in adults. Success may depend on achieved ICS dose. Oral steroids are effective, but side-effects are common. A review of current guidelines may be warranted.

Sex Differences in Symptoms of Depression in Unrelated Individuals and Opposite-Sex Twin and Sibling Pairs

Diagnosis of a major depressive episode by the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association requires 5 out of 9 symptoms to be present. Therefore, individuals may differ in the specific symptoms they experience and reach a diagnosis of depression via different pathways. It has been suggested that depressed women more often report symptoms of sleep disturbance, appetite or weight disturbance, fatigue, feelings of guilt/worthlessness and psychomotor retardation than depressed men. In the current study, we investigate whether depressed men and women differ in the symptoms they report. Two samples were selected from a sample of Dutch and Australian twins and siblings. First, Dutch and Australian unrelated depressed individuals were selected. Second, a matched epidemiological sample was created consisting of opposite-sex twin and sibling pairs in which both members were depressed. No sex differences in prevalence rates for symptoms were found, with the exception of decreased weight in women in the sample of unrelated individuals. In general, the similarities in symptoms seem to far outweigh the differences in symptoms between men and women. This signifies that men and women are alike in their symptom profiles for major depression and genes for depression are probably expressed in the same way in the two sexes.

Symptom prevalence and clustering of symptoms in people living with chronic hepatitis C infection

Quality of life has been shown to be poor among people living with chronic hepatitis C However, it is not clear how this relates to the presence of symptoms and their severity. The aim of this study was to describe the typology of a broad array of symptoms that were attributed to hepatitis C virus (HCV) infection. Phase I used qualitative methods to identify symptoms. In Phase 2, 188 treatment-naive people living with HCV participated in a quantitative survey. The most prevalent symptom was physical tiredness (86%) followed by irritability (75%), depression (70%), mental tiredness (70%), and abdominal pain (68%). Temporal clustering of symptoms was reported in 62% of participants. Principal components analysis identified four symptom clusters: neuropsychiatric (mental tiredness, poor concentration, forgetfulness, depression, irritability, physical tiredness, and sleep problems); gastrointestinal (day sweats, nausea, food intolerance, night sweats, abdominal pain, poor appetite, and diarrhea); algesic (joint pain, muscle pain, and general body pain); and dysesthetic (noise sensitivity, light sensitivity, skin. problems, and headaches). These data demonstrate that symptoms are prevalent in treatment-naive people with HCV and support the hypothesis that symptom clustering occurs.

A PRESENÇA DE DEPRESSÃO EM PACIENTES DURANTE O PERÍODO DE REABILITAÇÃO FÍSICA E O IMPACTO NA QUALIDADE DE VIDA DOS MESMOS

A depressão é um termo que descreve uma série de comportamentos complexos e tem sido empregada para designar tanto um estado afetivo normal, quanto um sintoma, uma síndrome e uma ou várias doenças. É caracterizada por um conjunto de sintomas relacionados a uma dada situação, ou ainda pelo aparecimento destes, de forma repetida e/ou sem nenhuma causa aparente. Os principais sintomas para o diagnóstico da depressão são alteração do apetite, agitação ou retardo psicomotor, diminuição da energia ou cansaço excessivo, sensação de culpa, dificuldade de concentração e pensamentos recorrentes de morte ou suicídio. A qualidade de vida está relacionada ao completo bem-estar físico, psíquico e social do indivíduo. Este estudo tem como objetivo investigar a presença de depressão em pacientes portadores de doenças reumatológicas e neurológicas, que estão em tratamento fisioterapêutico na Clínica Escola de Fisioterapia da Universidade Metodista de São Paulo e analisar o impacto da depressão sobre a qualidade de vida dos mesmos. Foram selecionados indivíduos nos setores de neurologia e reumatologia, em atendimento no período de junho a agosto de 2003, os quais responderam a dois questionários, Inventário de Beck para investigar a presença de depressão e, o SF-36 para avaliar a qualidade de vida. Os resultados obtidos foram analisados pelo teste T-Student, de correlação de Pearson, análise de Cluster, e Lambda de Wilks. Os dados foram analisados no programa STATISTICA, foi adotado um nível de significância de 5% (p≤ 0,05). Concluiu-se que durante o período de reabilitação física dos indivíduos participantes deste estudo, um número significativo de pacientes apresentou depressão em diferentes níveis, com provável incidência no grupo reumatológico e este mesmo grupo, apresentou qualidade de vida inferior a dos indivíduos do grupo neurológico avaliados neste estudo

Ansiedade em situações de convívio social em idosos

A ansiedade é uma experiência normal em qualquer idade, mas merece uma atenção especial no indivíduo idoso. O idoso tem vivido uma vida social mais intensa como freqüentar cursos, festas ou mesmo lidar com novas tecnologias.Sintomas de ansiedade social podem surgir ou se acentuar nestas situações, prejudicando a integração do indivíduo à sociedade e à família. .A depressão é uma grande preocupação para o idoso. A importância do diagnóstico da doença depressão para diferenciar sintomas depressivos de sentimento de tristeza ou síndrome depressiva .Trata-se de um estudo, do tipo caso-controle investigando ansiedade em situações de convívio social em 61indivíduos com 60 anos de idade ou mais e um grupo de 60 jovens até 35 anos.Responderam um questionário, escalas de ansiedade,fobia social ,esquiva e desconforto, medo de avaliação negativa e depressão.De acordo com os resultados obtidos a ansiedade pode estar relacionada a fatores biológicos, psicológicos e sociais que diagnosticados precocemente podem ser tratados por medicamentos , psicoterapia ou uso da estratégia adequada melhorar a adaptação do idoso.A realidade é que o perfil do idoso mudou e a qualidade de vida também,o que gerou necessidades diferentes,novos desafios. É um assunto que requer maiores estudos com o intuito de apontar estratégias que auxiliem na prevenção ou que aponte fatores que melhorem a adaptação do idoso.(AU)

Knowledge management applied to enterprise risk management

Risk and knowledge are two concepts and components of business management which have so far been studied almost independently. This is especially true where risk management (RM) is conceived mainly in financial terms, as for example, in the financial institutions sector. Financial institutions are affected by internal and external changes with the consequent accommodation to new business models, new regulations and new global competition that includes new big players. These changes induce financial institutions to develop different methodologies for managing risk, such as the enterprise risk management (ERM) approach, in order to adopt a holistic view of risk management and, consequently, to deal with different types of risk, levels of risk appetite, and policies in risk management. However, the methodologies for analysing risk do not explicitly include knowledge management (KM). This research examines the potential relationships between KM and two RM concepts: perceived quality of risk control and perceived value of ERM. To fulfill the objective of identifying how KM concepts can have a positive influence on some RM concepts, a literature review of KM and its processes and RM and its processes was performed. From this literature review eight hypotheses were analysed using a classification into people, process and technology variables. The data for this research was gathered from a survey applied to risk management employees in financial institutions and 121 answers were analysed. The analysis of the data was based on multivariate techniques, more specifically stepwise regression analysis. The results showed that the perceived quality of risk control is significantly associated with the variables: perceived quality of risk knowledge sharing, perceived quality of communication among people, web channel functionality, and risk management information system functionality. However, the relationships of the KM variables to the perceived value of ERM are not identified because of the low performance of the models describing these relationships. The analysis reveals important insights into the potential KM support to RM such as: the better adoption of KM people and technology actions, the better the perceived quality of risk control. Equally, the results suggest that the quality of risk control and the benefits of ERM follow different patterns given that there is no correlation between both concepts and the distinct influence of the KM variables in each concept. The ERM scenario is different from that of risk control because ERM, as an answer to RM failures and adaptation to new regulation in financial institutions, has led organizations to adopt new processes, technologies, and governance models. Thus, the search for factors influencing the perceived value of ERM implementation needs additional analysis because what is improved in RM processes individually is not having the same effect on the perceived value of ERM. Based on these model results and the literature review the basis of the ERKMAS (Enterprise Risk Knowledge Management System) is presented.

Orexin-stimulated MAP kinase cascades are activated through multiple G-protein signalling pathways in human H295R adrenocortical cells: diverse roles for orexins A and B

Orexins A and B (ORA and ORB) are neuropeptide hormones found throughout the central nervous system and periphery. They are required for a host of physiological processes including mitogen-activated protein kinase (MAPK) regulation, steroidogenesis, appetite control and energy regulation. While some signalling mechanisms have been proposed for individual recombinant orexin receptors in generic mammalian cell types, it is clear that the peripheral effects of orexin are spatially and temporally complex. This study dissects the different G-protein signalling and MAPK pathways activated in a pluripotent human adrenal H295R cell line capable of all the physiological steps involved in steroidogenesis. Both extracellular receptor kinase 1/2 (ERK1/2) and p38 were phosphorylated rapidly with a subsequent decline, in a time- and dose-dependent manner, in response to both ORA and ORB. Conversely, there was little or no direct activation of the ERK5 or JNK pathway. Analysis using signalling and MAPK inhibitors as well as receptor-specific antagonists determined the precise mediators of the orexin response in these cells. Both ERK1/2 and p38 activation were predominantly Gq- and to a lesser extent Gs-mediated; p38 activation even had a small Gi-component. Effects were broadly comparable for both orexin sub-types ORA and ORB and although most of the effects were transmitted through the orexin receptor-1 subtype, we did observe a role for orexin receptor-2-mediated activation of both ERK1/2 and p38. Cortisol secretion also differed in response to ORA and ORB. These data suggest multiple roles for orexin-mediated MAPK activation in an adrenal cell-line, this complexity may help to explain the diverse biological actions of orexins with wide-ranging consequences for our understanding of the mechanisms initiated by these steroidogenic molecules.

Cachexia in cancer patients

Cachexia — the massive (up to 80%) loss of both adipose tissue and skeletal muscle mass — is a significant factor in the poor performance status and high mortality rate of cancer patients. Although this metabolic defect has been known since cancer was first studied, it is only recently that major advances have been made in the identification of catabolic factors that act to destroy host tissues during the cachectic process. Although anorexia is frequently present, depression of food intake alone seems not to be responsible for the wasting of body tissues, as nutritional supplementation or pharmacological manipulation of appetite is unable to reverse the catabolic process — particularly with respect to skeletal muscle. However, recent clinical studies in cancer patients have shown that nutritional supplementation can be effective when combined with agents that attenuate the action of tumour factors and modifiers of the central effects on appetite might also show promise.

Loss of skeletal muscle in cancer: biochemical mechanisms

Patients with cancer often undergo a specific loss of skeletal muscle mass, while the visceral protein reserves are preserved. This condition known as cachexia reduces the quality of life and eventually results in death through erosion of the respiratory muscles. Nutritional supplementation or appetite stimulants are unable to restore the loss of lean body mass, since protein catabolism is increased mainly as a result of the activation of the ATP-ubiquitin-dependent proteolytic pathway. Several mediators have been proposed. An enhanced protein degradation is seen in skeletal muscle of mice administered tumour necrosis factor (TNF), which appears to be mediated by oxidative stress. There is some evidence that this may be a direct effect and is associated with an increase in total cellular-ubiquitin-conjugated muscle proteins. Another cytokine, interleukin-6 (IL-6), may play a role in muscle wasting in certain animal tumours, possibly through both lysosomal (cathepsin) and non-lysosomal (proteasome) pathways. A tumour product, proteolysis-inducing factor (PIF) is produced by cachexia-inducing murine and human tumours and initiates muscle protein degradation directly through activation of the proteasome pathway. The action of PIF is blocked by eicosapentaenoic acid (EPA), which has been shown to attenuate the development of cachexia in pancreatic cancer patients. When combined with nutritional supplementation EPA leads to accumulation of lean body mass and prolongs survival. Further knowledge on the biochemical mechanisms of muscle protein catabolism will aid the development of effective therapy for cachexia.