Estudo dos Princípios da Eficiência Energética de um Edifício

O trabalho aqui desenvolvido tem como objetivos descrever o empreendimento acompanhado durante o estágio, relatar as tarefas realizadas no contexto do estágio e por fim desenvolver um tema adequado ao ramo de Mestrado. Primeiro é apresentado o empreendimento acompanhado durante o estágio. O empreendimento acompanhado foi do Hotel Golden Tulip em Águeda, constituído por um edifício principal e um edifício anexo destinado a spa. São referidas as soluções construtivas, os equipamentos e os serviços que irá proporcionar aos seus utilizadores. Seguidamente são relatadas as tarefas realizadas no contexto do estágio, relacionadas com o acompanhamento da construção do hotel. Estas tarefas foram diversas, desde a direção até à coordenação de segurança em obra. Por último é desenvolvido o tema “Estudo e avaliação de princípios de sustentabilidade de um edifício”, que é aplicado ao edifício principal do hotel. Este tema procura estudar e avaliar soluções aplicadas no edifício, desde soluções construtivas a equipamentos, de forma a propor melhorias ao seu desempenho e a retirada das respetivas conclusões.

Decreased Vascular Endothelial Growth Factor (VEGF) Expression in Focal Segmental Glomeruloesclerosis Lesions of Patients Under Sirolimus

Background: Proteinuria (PT) with SRL appears not only after conversion from a calcineurin inhibitor (CI), but also in de novo patients. The PT may be related to a hemodynamic effect of CI withdrawal or to a direct effect of SRL in glomerulus (GL). Recently an association between PT in SRL patients and FSGS lesions has been described. It is also known that SRL decrease VEGF synthesis and experimental data suggest that VEGF is essential to podocyte survival and differentiation. Aim: To determine if glomerular lesions and PT in SRL patients could be related to altered glomerular VEGF expression. Material and methods: We evaluated glomerular VEGF expression in 10 biopsies: A-allograft kidney in backtable (n=3); B-native normal kidney (n=1); C-native kidney with FSGS lesions (n=2); D-allograft kidney with FSGS lesions from proteinuric patients under SRL after conversion from CI (n=3); E-allograft kidney in proteinuric patient under SRL with a membranous glomerulonephritis (n=1). We employed indirect immunohistochemistry in paraffin-embedded sections using a mouse monoclonal antibody against human VEGF-C1 (Santa Cruz). Results: The controls biopsies (A; B) showed normal global VEGF expression, with strong podocyte staining. The VEGF expression in the group C was similar to the controls, although no FSGS lesions were observed in the stained GL. The group D showed normal VEGF expression in the apparently normal GL, hypertrophied podocytes with reduction of VEGF in anomalous GL, and no staining in slcerotic lesions. We observed a gradual reduction of VEGF expression with progressive dedifferentiation of podocytes. In the group E the VEGF was globally reduced, with some hypertrophied podocytes expressing decreased VEGF. Conclusion: We confirmed the diminished VEGF expression in injured podocytes of SRL patients.This decreased expression may result from a direct effect of SRL and precede the appearance of FSGS lesions and PT. Further studies are needed with greater number of cases and controls, including early biopsies of patients under SRL.

Validating Regulatory Sensory Processing Disorders Using the Sensory Profile and Child Behavior Checklist (CBCL 1 –5)

The objective was to validate Regulatory Sensory Processing Disorders’ criteria (DC:0-3R, 2005) using empirical data on the presence and severity of sensory modulation deficits and specific psychiatric symptoms in clinical samples. Sixty toddlers who attended a child mental health unit were diagnosed by a clinical team. The following two groups were created: toddlers with RSPD(N = 14) and those with ‘‘other diagnoses in Axis I/II of the DC:0-3R00(OD3R) (N = 46). Independently of the clinical process, parents completed the Infant Toddler Sensory Profile (as a checklist for sensory symptoms) and the Achenbach Behavior Checklist for ages 1/2–5 (CBCL 1/2–5). The scores from the two groups were compared. The results showed the following for the RSPD group: a higher number of affected sensory areas and patterns than in the OD3R group; a higher percentage of sensory deficits in specific sensory categories; and a higher severity of behavioral symptoms such as withdrawal, inattention, other externalizing problems and pervasive developmental problems in CBCL 1/2–5. The results confirmed our hypotheses by indicating a higher severity of sensory symptoms and identifying specific behavioral problems in children with RSPD. The results revealed convergent validity between the instruments and the diagnostic criteria for RSPD and supported the validity of RSPD as a unique diagnosis. The findings also suggested the importance of identifying sensory modulation deficits in order to develop an early intervention to enhance the sensory capacities of children who do not fully satisfy the criteria for some DSM-IV-TR disorders.

Economic analysis in health care regulation : three essays

ABSTRACT - It is the purpose of the present thesis to emphasize, through a series of examples, the need and value of appropriate pre-analysis of the impact of health care regulation. Specifically, the thesis presents three papers on the theme of regulation in different aspects of health care provision and financing. The first two consist of economic analyses of the impact of health care regulation and the third comprises the creation of an instrument for supporting economic analysis of health care regulation, namely in the field of evaluation of health care programs. The first paper develops a model of health plan competition and pricing in order to understand the dynamics of health plan entry and exit in the presence of switching costs and alternative health premium payment systems. We build an explicit model of death spirals, in which profitmaximizing competing health plans find it optimal to adopt a pattern of increasing relative prices culminating in health plan exit. We find the steady-state numerical solution for the price sequence and the plan’s optimal length of life through simulation and do some comparative statics. This allows us to show that using risk adjusted premiums and imposing price floors are effective at reducing death spirals and switching costs, while having employees pay a fixed share of the premium enhances death spirals and increases switching costs. Price regulation of pharmaceuticals is one of the cost control measures adopted by the Portuguese government, as in many European countries. When such regulation decreases the products’ real price over time, it may create an incentive for product turnover. Using panel data for the period of 1997 through 2003 on drug packages sold in Portuguese pharmacies, the second paper addresses the question of whether price control policies create an incentive for product withdrawal. Our work builds the product survival literature by accounting for unobservable product characteristics and heterogeneity among consumers when constructing quality, price control and competition indexes. These indexes are then used as covariates in a Cox proportional hazard model. We find that, indeed, price control measures increase the probability of exit, and that such effect is not verified in OTC market where no such price regulation measures exist. We also find quality to have a significant positive impact on product survival. In the third paper, we develop a microsimulation discrete events model (MSDEM) for costeffectiveness analysis of Human Immunodeficiency Virus treatment, simulating individual paths from antiretroviral therapy (ART) initiation to death. Four driving forces determine the course of events: CD4+ cell count, viral load resistance and adherence. A novel feature of the model with respect to the previous MSDEMs is that distributions of time to event depend on individuals’ characteristics and past history. Time to event was modeled using parametric survival analysis. Events modeled include: viral suppression, regimen switch due virological failure, regimen switch due to other reasons, resistance development, hospitalization, AIDS events, and death. Disease progression is structured according to therapy lines and the model is parameterized with cohort Portuguese observational data. An application of the model is presented comparing the cost-effectiveness ART initiation with two nucleoside analogue reverse transcriptase inhibitors (NRTI) plus one non-nucleoside reverse transcriptase inhibitor(NNRTI) to two NRTI plus boosted protease inhibitor (PI/r) in HIV- 1 infected individuals. We find 2NRTI+NNRTI to be a dominant strategy. Results predicted by the model reproduce those of the data used for parameterization and are in line with those published in the literature.

Portugal Telecom’s strategic partnership with Oi: The value creation potential

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Optimização do processo de devolução de medicamentos fora do prazo de validade

RESUMO - Durante todo o seu ciclo de vida, o medicamento está sujeito a padrões de qualidade, segurança e eficácia, alicerçados numa atuação conjunta dos responsáveis pela sua colocação no mercado, das autoridades competentes nacionais e comunitárias. Os diferentes intervenientes estão sujeitos a um conjunto de obrigações e procedimentos que englobam também a sua fase final de retirada do mercado, devolução, recolha e valorização ou reciclagem. Neste trabalho é caracterizada a cadeia de distribuição do medicamento assim como o seu fluxo físico no sentido inverso, ou seja, o processo de devolução e de tratamento ambientalmente adequado para os resíduos de medicamentos. A maioria da literatura a respeito das devoluções de medicamentos enfatiza a vertente ecológica do sistema de logística inversa. Neste trabalho, as questões ambientais são discutidas , mas o objectivo primário focaliza questões económicas relacionadas com o processo de devoluções. São apresentadas as possíveis vantagens teóricas da criação de um sistema centralizado de gestão de devoluções, por oposição ao atual sistema de circuitos dispersos. Com a aplicação de um inquérito a armazenistas com larga responsabilidade no processo de devoluções, pretendeu-se avaliar os custos inerentes ao atual modelo. Os resultados obtidos indicam que existe margem potencial para reduzir custos neste processo, para a grande maioria dos armazenistas. Na área específica dos medicamentos fora de prazo de validade, o crescente desenvolvimento e aperfeiçoamento dos processos de devolução poderá direcionar-se no sentido da criação de centrais de devolução centralizadas.

O direito de arrependimento nos contratos celebrados à distância e fora do estabelecimento

This dissertation aims to analyze the right of withdrawal and its implications on distance and off-premises contracts, due to the importance of these contracts in our society. Our main goal is, first of all, to explain the meaning and characteristics of both distance and off-premises contracts and the reason why a right of withdrawal is granted. Secondly, we intend to explain all of the relevant aspects related to this right, such as its legal concept and main characteristics, the origin and evolution of the right of withdrawal on both European and Portuguese legislation, its implications in the contracting parties and, finally, a brief analysis of the applicable law. In a nutshell, the right of withdrawal allows the consumer to withdraw from a distance or off-premises contract, unilaterally, without having to indicate any motive to justify the decision, after a cooling-off period of 14 calendar days. In these two types of contracts such right exists due to the reasons or circumstances that lead to the conclusion of the contract.

Estigma e percepções dos médicos de Clínica Geral sobre a doença mental e o suicídio

RESUMO: INTRODUÇÃO: A OMS (2001) revela que cerca de 450 milhões de pessoas sofrem de perturbações mentais ou comportamentais em todo o mundo, mas apenas uma pequena minoria tem tratamento, ainda que elementar. Transformam-se em vítimas por causa da sua doença e convertem-se em alvos de estigma e discriminação. O suicídio é considerado como um grande problema de saúde pública em todo o mundo, é uma das principais causas de morte de jovens adultos e situa-se entre as três maiores causas de morte na população entre 15-34 anos (OMS, 2001). As perturbações mentais aumentam o risco de suicídio. A depressão, esquizofrenia, e a utilização de substâncias incrementam o risco de suicídio. Estudos (Sartorius, 2002; Magliano et al., 2012) mostram que os profissionais de saúde, tal como o público em geral, podem ter atitudes negativas e estigma em relação às pessoas com perturbações mentais, podendo agir em conformidade, uma vez feito e conhecido o diagnóstico psiquiátrico. Os clínicos gerais são os receptores das perturbações mentais e tentativas de suicídio nas principais portas de entrada no acesso a cuidados de saúde. As crenças, conhecimentos e contacto com a doença mental e o suicídio, podem influenciar a atenção clínica. OBJECTIVOS: Avaliar o estigma e as percepções dos médicos de clínica geral em relação às tentativas de suicídio, o suicídio e perturbações mentais bem como os possíveis factores associados a estes fenómenos. MATERIAIS E MÉTODOS: Estudo do tipo transversal, combinando métodos quantitativos e qualitativos. A amostra é constituída por 125 sujeitos, médicos de clínica geral. Utilizaram-se as versões adaptadas dos seguintes instrumentos: Questionário sobre Percepções e Estigma em Relação à Saúde Mental e ao Suicídio (Liz Macmin e SOQ, Domino, 2005) e a Escala de Atitudes sobre a Doença Mental (Amanha Hahn, 2002). Para o tratamento estatístico dos dados usou-se a estatística 1) descritiva e 2) Análise estatística das hipóteses formuladas (Qui Quadrado - 2) a correlação entre variáveis (Spearman: ρ, rho). Os dados conectados foram limpos de inconsistências com base no pacote informático e estatístico SPSS versão 20. Para a aferição da consistência interna foi usado o teste de Alfa de Cronbach. RESULTADOS: Uma boa parte da amostra (46.4%) refere que não teve formação formal ou informal em saúde mental e (69.35%) rejeitam a ideia de que “grupos profissionais como médicos, dentistas e psicólogos são mais susceptíveis a cometer o suicídio”. Já (28.0%) têm uma perspectiva pessimista quanto a possibilidade de recuperação total dos sujeitos com perturbação mental. Sessenta e oito(54.4%) associa sujeitos com perturbação mental, a comportamentos estranhos e imprevisíveis, 115 (92.0%) a um baixo QI e 35 (26.7%) a poderem ser violentas e e perigosas. Os dados mostram uma associação estatisticamente significativa (p0.001) entre as variáveis: tempo de serviço no SNS, recear estar perto de sujeitos com doença mental e achar que os sujeitos com doença mental são mais perigosos que outros. Em termos estatísticos, existe uma associação estatitisticamente significativa entre as duas variáveis(X2=9,522; p0.05): percepção de que “é vergonhoso ter uma doença mental” e os conhecimentos em relação à doença mental. Existe uma correlação positiva, fraca e estatisticamente significativa entre os conhecimentos dos clínicos gerais(beneficiar-se de formação em saúde mental) e a percepção sobre os factores de risco (0,187; P0,039). DISCUSSÃO E CONCLUSÕES: A falta de conhecimento sobre as causas e factores de risco para os comportamentos suicidários, opções de intervenção e tratamento, particularmente no âmbito da doença mental, podem limitar a procura de ajuda individual ou dos próximos. Percepções negativas como o facto de não merecerem prioridade nos serviços, mitos (frágeis e cobarde, sempre impulsivo, chamadas de atenção, problemas espirituais) podem constituir-se como um indicador de que os clínicos gerais podem sofrer do mesmo sistema de estigma e crenças, de que sofre o público em geral, podendo agir em conformidade (atitudes de afastamento ereceio). As atitudes são influenciadas por factores como a formação, cultura e sistema de crenças. Sujeitos com boa formação na área da saúde mental têm uma percepção positiva e optimista sobre os factores de risco e uma atitude positiva em relação aos sujeitos com doença mental e comportamentos suicidários.-------------ABSTRACT: INTRODUCTION: The WHO (2001) reveals that about 450 million people suffer from mental or behavioral disorders worldwide, but only a small minority have access to treatment, though elementary. They become victims because of their disease and they become the targets of stigma and discrimination. Suicide is seen as a major public health problem worldwide, is a leading cause of death for young adults and is included among the three major causes of death in the population aged 15-34 years (WHO, 2001). Mental disorders increase the risk of suicide. Depression, schizophrenia, and the substances misuse increase the risk of suicide. Studies (Sartorius, 2002; Magliano et al, 2012) show that health professionals, such as the general public, may have negative attitudes and stigma towards people with mental disorders, and can act accordingly after psychiatric diagnosis is known. General practitioners are the main entry points of mental disorders and suicide attempts in the health sistem. Beliefs, knowledge and contact with mental illness and suicide, may influence clinical care. OBJECTIVES: To assess stigma and perceptions of general practitioners in relation to suicide attempts, suicide and mental disorders as well as possible factors associated with these phenomena. MATERIAL AND METHODS: This was a descriptive cross-sectional study, combining quantitative and qualitative methods. The sample consisted of 125 subjects, general practitioners. We used adapted versions of the following instruments: Questionnaire of Perceptions and Stigma in Relation to Mental Health and Suicide (Liz Macmin and SOQ, Domino, 2005) and the Scale of Attitudes on Mental Illness (Tomorrow Hahn, 2002). For the statistical treatment of the data we used: 1) descriptive (Data distribution by absolute and relative frequencies for each of the variables under study (including mean and standard deviation measures of central tendency and deviation), 2) statistical analysis of hypotheses using (Chi Square - 2, a hypothesis test that is intended to find a value of dispersion for two nominal variables, evaluating the association between qualitative variables) and the correlation between variables (Spearman ρ, rho), a measure of non-parametric correlation, which evaluates an arbitrary monotonic function can be the description of the relationship between two variables, without making any assumptions about the frequency distribution of the variables). For statistical analysis of the correlations were eliminated subjects who did not respond to questions. The collected data were cleaned for inconsistencies based on computer and statistical package SPSS version 20. To measure the internal consistency was used the Cronbach's alpha test. RESULTS: A significant part of the sample 64 (46.4%) reported no formal or informal training in mental health and 86 (69.35%) reject the idea that "professional groups such as doctors, dentists and psychologists are more likely to commit suicide." On the other hand, 42 (28.0%) have a pessimistic view of the possibility of full recovery of individuals with mental disorder. Sixty-eight ( 54.4 % ) of them associates subjects with mental disorder to strange and unpredictable behavior, 115 ( 92.0 % ), to low IQ, 35 ( 26.7 % ) and even to violent and dangerous behavior, 78 ( 62.4 % ) The data show a statistically significant (p = 0.001) relationship between the following variables: length of service in the NHS, fear of being close to individuals with mental illness and considering individuals with mental illness more dangerous than others. In statistical terms, there is a dependency between the two variables (X2 = 9.522, p> 0.05): the perception that "it is shameful to have a mental illness" and knowledge regarding mental illness. There is a positive and statistically significant weak correlation between knowledge of general practitioners (benefit from mental health training) and the perception of the risk factors (0,187; P0,039). DISCUSSION AND CONCLUSIONS: The lack of knowledge about the causes and risk factors for suicidal behavior, intervention and treatment, particularly in the context of mental illness options, may decreaseseeking for help by individual and their relatives. Negative perceptions such as considering that they dont deserve priority in services, myths (weak and cowards, always impulsive, seeking for attentions, spirituals problems) may indicate that general practitioners, may suffer the same stigma and beliefs systems as the general public, and can act accordingly (withdrawal and fear attitudes). Attitudes are influenced by factors such as education, culture and belief system. Subjects with good training in mental health have a positive and optimistic perception of the risk factors and a positiveattitude towards individuals with mental illness and suicidal behaviour.

Immune reconstitution inflammatory syndrome in HIV and sporotrichosis coinfection: report of two cases and review of the literature

We report 2 cases of patients with immune reconstitution inflammatory syndrome (IRIS) associated with cutaneous disseminated sporotrichosis and human immunodeficiency virus (HIV) coinfection. The patients received specific treatment for sporotrichosis. However, after 4 and 5 weeks from the beginning of antiretroviral therapy, both patients experienced clinical exacerbation of skin lesions despite increased T CD4+ cells (T cells cluster of differentiation 4 positive) count and decreased viral load. Despite this exacerbation, subsequent mycological examination after systemic corticosteroid administration did not reveal fungal growth. Accordingly, they were diagnosed with IRIS. However, the sudden withdrawal of the corticosteroids resulted in the recurrence of IRIS symptoms. No serious adverse effects could be attributed to prednisone. We recommend corticosteroid treatment for mild-to-moderate cases of IRIS in sporotrichosis and HIV coinfection with close follow-up.

Ethical aspects in the management of the terminally ill patient in the pediatric intensive care unit

OBJECTIVE: To identify the prevalence of management plans and decision-making processes for terminal care patients in pediatric intensive care units. METHODOLOGY: Evidence-based medicine was done by a systematic review using an electronic data base (LILACS, 1982 through 2000) and (MEDLINE, 1966 through 2000). The key words used are listed and age limits (0 to 18 years) were used. RESULTS: One hundred and eighty two articles were found and after selection according to the exclusion/inclusion criteria and objectives 17 relevant papers were identified. The most common decisions found were do-not-resuscitation orders and withdrawal or withholding life support care. The justifications for these were "imminent death" and "unsatisfatory quality of life". CONCLUSION: Care management was based on ethical principles aiming at improving benefits, avoiding harm, and when possible, respecting the autonomy of the terminally ill patient.

Urethral catheter removal 7 or 14 days after radical retropubic prostatectomy: clinical implications and complications in a randomized study

PURPOSE: To evaluate the hypothesis that a 7-day period of indwelling catheter after radical retropubic prostatectomy is effective and safe without the need of performing cystography. METHODS: In the period from January of 2000 to July of 2002, 73 patients underwent radical retropubic prostatectomy, and these patients were prospectively randomized in 2 groups: Group 1-37 patients who had the urethral catheter removed 7 days after the procedure, and Group 2-36 patients who had the catheter removed 14 days after the surgery. The 2 groups were similar, the surgeons and the technique were the same, and no cystography was performed to evaluate the presence of leaks. RESULTS: Two patients in Group 1 had bleeding and clot retention after having the catheter taken out in the seventh postoperative day and were managed by putting the catheter back in for 7 more days. Two patients in Group 2 developed bladder neck stricture and were treated by bladder neck incision with success. The continence rate was the same, with 2 cases of incontinence in each group. About 2 pads a day were used by the patients with incontinence. The average follow-up was 17.5 months (12-36 months). No urinary fistula, urinoma, or pelvic abscesses developed after catheter removal. Two patients were excluded from the analysis of this series: 1 died with a pulmonary embolus in the third postoperative day, and 1 developed a urinary suprapubic fistula before catheter withdrawal, which was maintained for 16 days. CONCLUSION: Withdrawal of the urethral catheter 7 days after radical retropubic prostatectomy, without performing cystography, has a low rate of short-term complications that are equivalent to withdrawal 14 days after the surgery.

O setor de distribuição farmacêutica em Portugal estrutura e estratégias

A presente investigação desenvolveu uma análise profunda do setor da distribuição farmacêutica, no período compreendido entre 2000 e 2009, procurando identificar as possíveis relações de interdependência entre o meio envolvente e as opções de estratégia das empresas que constituíram a amostra de estudo e entre as referidas opções de estratégia e as estruturas e o desempenho dessas empresas. A dinâmica do mercado do medicamento na economia nacional, com um valor de 3,2 mil milhões de euros anuais (Infarmed, 2010), apresenta um impacto significativo na esperança de vida e na qualidade de vida dos cidadãos. Segundo a OCDE, os produtos farmacêuticos são responsáveis por quase um quinto de todos os gastos com saúde, em média, nos países da OCDE. Neste contexto, a distribuição farmacêutica representa uma componente crítica. A disponibilização de medicamentos em ambulatório num curto espaço de tempo só é possível devido a uma estrutura logística com características muito específicas. A qualidade do armazenamento e do transporte dos medicamentos desde a saída dos laboratórios até à chegada às farmácias é rigorosamente monitorizada e controlada. O setor da distribuição farmacêutica assume assim uma postura elementar na cadeia do medicamento, contribuindo para a melhoria da qualidade do sistema de saúde que se tem vindo a verificar nas últimas décadas e prestando um serviço com valor para a comunidade, uma vez que se compromete a assegurar um adequado e contínuo fornecimento de medicamentos para que as necessidades dos doentes e das populações em geral sejam satisfeitas. As alterações verificadas ao longo dos últimos anos estimularam a dinâmica concorrencial entre os diferentes agentes neste mercado, bastante regulamentado e com elevado entrosamento financeiro com o Estado, o que obrigou a rápidas mudanças. Neste contexto, a sobrevivência das empresas, o seu crescimento e a sua perenidade futura têm constituído um desafio abordado de forma diversa por cada empresa.

Comorbidities of mental and behavioral disorders in chemically dependent patients in different periods of abstinence

OBJECTIVE: To assess the frequency of comorbidities of mental and behavioral disorders (CMBD) in psychoactive substance (PAS)-dependent patients with different periods of abstinence cared for at Alcohol and Other Drug Psychosocial Care Centers (CAPS-ad). METHOD: All patients under treatment in the two CAPS-ad of the city of Uberlândia-MG, between April and September 2010, were consecutively assessed. The ICD-10 symptom checklist was used to diagnose CMBD; additional information was obtained from interviews and medical records. The patients were divided according to duration of abstinence: < 1 week (Group 1); 1-4 weeks (Group 2); and > 4 weeks (Group 3). RESULTS: Of all patients assessed, 62.8% were diagnosed with CMBD, which were more frequent (p < 0.05) in Group 1 (72%) than Group 3 (54.2%), and both groups were similar to Group 2 (61%). Depressive and anxiety disorders were more frequent among patients of Group 1. Mood disorders were more frequent (p < 0.05) in women [22/34 (65%) vs. 54/154 (35.1%)], whereas psychotic disorders were more frequent (p = 0.05) in men [16/154 (10.4%) vs. 0]. The presence of CMBD was associated with more severe clinical conditions. CONCLUSIONS: The higher frequency of diagnosis of CMBD in patients of Group 1 may have resulted from the difficulties in distinguishing mental disorders that are due to PAS intoxication or withdrawal from those that are not. However, to make the diagnosis of CMBD, even during detoxification, can increase the likelihood of better response to treatment.

Clozapine-induced severe eosinophilia: report of a case with good outcome

INTRODUCTION: Clozapine is the antipsychotic of choice in the treatment of refractory schizophrenia. However, its side effects, such as eosinophilia, may preclude its use. METHODS: Case report and literature review. RESULTS: Young woman, 19 years old, diagnosed with hebefrenic schizophrenia, admitted at Unicamp's psychiatry ward after psychotic symptoms relapse. Clozapine was started after unsuccessful attempts with risperidon and olanzapine. By the fourth week of clozapine use, eosinophils began to increase. Drug titration was stopped, but eosinophils counts continued to rise up, reaching the mark of 5200/mm³. Due to severity of psychotic symptoms and to the good response obtained with clozapine, we decided to investigate organs involvement before withdrawing the medication. As the patient had no organs involvement, clozapine was maintained and one month after eosinophils peak, it was already normalized. CONCLUSION: Eosinophilia should not necessarily lead to clozapine's withdrawal. Patients who present eosinophilia must be at rigorous observation for organs involvement, and if there is no such involvement, clozapine might be maintained, considering the possible benign and transitory nature of the eosinophils count elevation.

Galanin-mediated behavioural hyperalgesia from the dorsomedial nucleus of the hypothalamus involves two independent descending pronociceptive pathways

Activation of the dorsomedial nucleus of the hypothalamus (DMH) by galanin (GAL) induces behavioural hyperalgesia. Since DMH neurones do not project directly to the spinal cord, we hypothesized that the medullary dorsal reticular nucleus (DRt), a pronociceptive region projecting to the spinal dorsal horn (SDH) and/or the serotoninergic raphe-spinal pathway acting on the spinal 5-HT3 receptor (5HT3R) could relay descending nociceptive facilitation induced by GAL in the DMH. Heat-evoked paw-withdrawal latency (PWL) and activity of SDH neurones were assessed in monoarthritic (ARTH) and control (SHAM) animals after pharmacological manipulations of the DMH, DRt and spinal cord. The results showed that GAL in the DMH and glutamate in the DRt lead to behavioural hyperalgesia in both SHAM and ARTH animals, which is accompanied particularly by an increase in heat-evoked responses of wide-dynamic range neurons, a group of nociceptive SDH neurones. Facilitation of pain behaviour induced by GAL in the DMH was reversed by lidocaine in the DRt and by ondansetron, a 5HT3R antagonist, in the spinal cord. However, the hyperalgesia induced by glutamate in the DRt was not blocked by spinal ondansetron. In addition, in ARTH but not SHAM animals PWL was increased after lidocaine in the DRt and ondansetron in the spinal cord. Our data demonstrate that GAL in the DMH activates two independent descending facilitatory pathways: (i) one relays in the DRt and (ii) the other one involves 5-HT neurones acting on spinal 5HT3Rs. In experimental ARTH, the tonic pain-facilitatory action is increased in both of these descending pathways.