Contribution of hospital effluents to the load of pharmaceuticals in urban wastewaters: Identification of ecologically relevant pharmaceuticals

The impact of effluent wastewaters from four different hospitals: a university (1456 beds), a general (350 beds), a pediatric (110 beds) and a maternity hospital (96 beds), which are conveyed to the same wastewater treatment plant (WWTP), was evaluated in the receiving urban wastewaters. The occurrence of 78 pharmaceuticals belonging to several therapeutic classes was assessed in hospital effluents and WWTP wastewaters (influent and effluent) as well as the contribution of each hospital in WWTP influent in terms of pharmaceutical load. Results indicate that pharmaceuticals are widespread pollutants in both hospital and urban wastewaters. The contribution of hospitals to the input of pharmaceuticals in urban wastewaters widely varies, according to their dimension. The estimated total mass loadings were 306 g d− 1 for the university hospital, 155 g d− 1 for the general one, 14 g d− 1 for the pediatric hospital and 1.5 g d− 1 for the maternity hospital, showing that the biggest hospitals have a greater contribution to the total mass load of pharmaceuticals. Furthermore, analysis of individual contributions of each therapeutic group showed that NSAIDs, analgesics and antibiotics are among the groups with the highest inputs. Removal efficiency can go from over 90% for pharmaceuticals like acetaminophen and ibuprofen to not removal for β-blockers and salbutamol. Total mass load of pharmaceuticals into receiving surface waters was estimated between 5 and 14 g/d/1000 inhabitants. Finally, the environmental risk posed by pharmaceuticals detected in hospital and WWTP effluents was assessed by means of hazard quotients toward different trophic levels (algae, daphnids and fish). Several pharmaceuticals present in the different matrices were identified as potentially hazardous to aquatic organisms, showing that especial attention should be paid to antibiotics such as ciprofloxacin, ofloxacin, sulfamethoxazole, azithromycin and clarithromycin, since their hazard quotients in WWTP effluent revealed that they could pose an ecotoxicological risk to algae.

Application of green zero-valent iron nanoparticles to the remediation of soils contaminated with ibuprofen

Zero-valent iron nanoparticles (nZVIs) are often used in environmental remediation. Their high surface area that is associated with their high reactivity makes them an excellent agent capable of transforming/degrading contaminants in soils and waters. Due to the recent development of green methods for the production of nZVIs, the use of this material became even more attractive. However, the knowledge of its capacity to degrade distinct types of contaminants is still scarce. The present work describes the study of the application of green nZVIs to the remediation of soils contaminated with a common anti-inflammatory drug, ibuprofen. The main objectives of this work were to produce nZVIs using extracts of grape marc, black tea and vine leaves, to verify the degradation of ibuprofen in aqueous solutions by the nZVIs, to study the remediation process of a sandy soil contaminated with ibuprofen using the nZVIs, and to compare the experiments with other common chemical oxidants. The produced nZVIs had nanometric sizes and were able to degrade ibuprofen (54 to 66% of the initial amount) in aqueous solutions. Similar remediation efficiencies were obtained in sandy soils. In this case the remediation could be enhanced (achieving degradation efficiencies above 95%) through the complementation of the process with a catalyzed nZVI Fenton-like reaction. These results indicate that this remediation technology represents a good alternative to traditional and more aggressive technologies.

Depressive symptoms in institutionalized older adults

OBJECTIVE To estimate the prevalence of depressive symptoms among institutionalized elderly individuals and to analyze factors associated with this condition. METHODS This was a cross-sectional study involving 462 individuals aged 60 or older, residents in long stay institutions in four Brazilian municipalities. The dependent variable was assessed using the 15-item Geriatric Depression Scale. Poisson’s regression was used to evaluate associations with co-variables. We investigated which variables were most relevant in terms of presence of depressive symptoms within the studied context through factor analysis. RESULTS Prevalence of depressive symptoms was 48.7%. The variables associated with depressive symptoms were: regular/bad/very bad self-rated health; comorbidities; hospitalizations; and lack of friends in the institution. Five components accounted for 49.2% of total variance of the sample: functioning, social support, sensory deficiency, institutionalization and health conditions. In the factor analysis, functionality and social support were the components which explained a large part of observed variance. CONCLUSIONS A high prevalence of depressive symptoms, with significant variation in distribution, was observed. Such results emphasize the importance of health conditions and functioning for institutionalized older individuals developing depression. They also point to the importance of providing opportunities for interaction among institutionalized individuals.

Trends in the use of antidepressants among older adults: Bambuí Project

OBJECTIVE To analyze the trends and factors associated with the antidepressant use among older adults. METHODS This population-based study evaluated older adults in 1997 (n = 351, baseline) and the survivors at the 15th follow-up year (n = 462, in 2012) among the aging cohort of Bambuí. The prevalence of antidepressant use was estimated, and the most commonly used antidepressants each year were identified. Prevalence ratios with 95% confidence intervals were estimated using Poisson regression with robust variance to investigate differences in the prevalence of use between 1997 and 2012. RESULTS The overall consumption of antidepressants (PR = 2.87, 95%CI 1.94;4.25) and of selective serotonin reuptake inhibitors (PR = 7.50, 95%CI 3.74;15.02) was significantly higher in 2012. However, no significant difference was observed in the use of tricyclic antidepressants between the two cohorts (PR = 0.89, 95%CI 0.49;1.62). In the 2012 cohort, antidepressant use was associated with females, increased age, increased income (≥ 4 minimum wages), self-assessment of health as reasonable, and attending ≥ 5 medical consultations in the last 12 months. CONCLUSIONS The increased consumption of antidepressants in the period due to increased use of selective serotonin reuptake inhibitors was consistent with results observed in international studies of different population groups and contexts. The positive correlation observed between antidepressant use and family income may be a warning of possible inequalities in access to mental health services.

Aplicações da aprendizagem por problemas no ciclo básico do curso de medicina

Acta Médica Portuguesa 1995, 8: 459-462

Entamoeba histolytica: antigenic characterization of axenic strains from Brazil

Trophozoites from cultures of Entamoeba histolytica strains isolated and grown axenically in Brazil (ICB-CSP, ICB-462 and ICB-32) were used for immune sera production and for characterization of their antigens by using electrophoretic and glycoproteic profiles, in parallel with a standard strain isolated and kept under axenic conditions in USA (HK-9). Hyperimmune sera, presenting high antibody titers with homologous and heterologous antigens, were obtained. The four strains in study revealed similar and complex electrophoretic and glycoproteic profiles showing polypep-tides with molecular weights ranging from 200 to less than 29 kDa. No significant differences were detected between the pathogenic and non-pathogenic strains.

An attemp at reversibility and increase of the virulence of axenic strains of Entamoeba histolytica

In this study we have tried to verify whether the interaction "in vitro" with bacteria or small pieces of normal hamster liver would modify the pathogenic behavior of axenic strains of E. histolytica: avirulent ones (ICB-32 and ICB-RPS), of attenuated virulence (ICB-CSP and HM1) and of mean virulence (ICB-462). Every attempt to render virulent, recover or increase the virulence of axenic strains of E. histolytica has failed

Dor crónica lombar : incapacidada auto-reportada em trabalhadores de saúde e sua relação com variáveis psicossociais e intensidade da dor

RESUMO: A dor crónica lombar, é uma condição de saúde cuja prevalência tem aumentado nas últimas décadas. É uma condição que pode ser bastante incapacitante para o indivíduo e por consequência, ter importante impacto social e económico na sociedade. É um fenómeno complexo, multifactorial e pouco estudado na população portuguesa. Objectivo: Estudar a associação entre a catastrofização da dor, crenças de medo evitamento da dor, intensidade da dor e a incapacidade funcional auto reportada em indivíduos com dor crónica lombar. Metodologia: Estudo observacional analítico de corte transversal, com uma amostra de 38 indivíduos com dor crónica lombar, seleccionados a partir de uma população de 186 trabalhadores de uma unidade local de saúde. A recolha de dados foi realizada através de 4 instrumentos de avaliação: Questionário de caracterização e levantamento de factores de risco e impacto associados à dor crónica lombar; Questionário de incapacidade de Roland e Morris; Escala de catastrofização da dor; e Questionário de crenças de medo evitamento da dor. A análise dos dados foi feita através de estatística descritiva pela distribuição de frequências e medidas de tendência central para análise da prevalência e caracterização da amostra e por estatística inferencial para estudar as relações entre variáveis através do teste de correlação não paramétrico de Spearman. Resultados: A variável catastrofização da dor obteve um valor de correlação com a incapacidade auto-reportada de rs=0,473, para p<0,01; a variável crença de medo evitamento da dor relacionada com o trabalho obteve um valor de correlação com a incapacidade auto-reportada de rs=0,462 para p<0,01, a percepção da intensidade actual de dor e a intensidade percepcionada no ano anterior, obtiveram valores de correlação com a incapacidade auto-reportada de rs=0,327 e rs= 0,359 respectivamente para valor de p<0,05. Conclusão: As variáveis psicossociais catastrofização da dor e crença de medo evitamento da dor relacionada com o trabalho, influenciam de forma moderada a incapacidade em indivíduos com dor crónica lombar. A associação entre a intensidade da dor e a incapacidade parece ter um papel menos importante demonstrando associações baixas.--------------------------ABSTRACT: Chronic low back pain is a health condition whose prevalence has increased in recent decades. It is a condition that can be quite disabling for the individual and therefore have important social and economic impact on society. It is a complex phenomenon, multifactorial and poorly studied in the Portuguese population. Objective: To study the association between pain catastrophizing, fear avoidance beliefs, pain, pain intensity and self-reported functional disability in individuals with chronic low back pain. Methods: Observational analytical cross sectional study of a sample of 38 individuals with chronic low back pain, selected from a population of 186 workers at a local health unit. Data collection was performed through four assessment instruments: questionnaire characterization, evaluation of risk factors and impact associated to chronic low back pain, questionnaire Roland and Morris disability, pain catastrophizing scale and fear avoidance beliefs questionnaire. Data analysis was performed using descriptive statistics for the distribution of frequencies and measures of central tendency to analyze the prevalence and characteristics of the sample and inferential statistics to study the relationships between variables by testing for Spearman nonparametric correlation. Results: The pain catastrophizing variable had a correlation value rs= 0,473, p<0,01 with the self-reported disability, the variable of fear avoidance belief of pain related to the work achived a correlation value with the self-reported disability, rs = 0.462 p <0.01, current pain intensity and in the previous year obtained values of correlation with self-reported disability rs = 0.327 and rs = 0.359 respectively for values of p <0.05 .Conclusion: The psychosocial variables of pain catastrophizing and fear avoidance belief of pain related to the work had a moderate association with disability in individuals with chronic low back pain. The association between pain intensity and disability seems to have a less important role demonstrating low associations.

A guerra numa sociedade democrática em crise: Atenas no final do Séc. V a.C.

Falar sobre a Guerra do Peloponeso é falar sobre a guerra que dividiu a Grécia, opondo Esparta e Atenas, com conseqüências gravíssimas para esta última cidade. Simultaneamente, foi o fim da mais conhecida experiência democrática da antiga Grécia. No entanto, o nosso objectivo não é falar sobre essa experiência, ou sobre as conseqüências da Guerra do Peloponeso, mas sobre o modo como ela foi encarada pelos Atenienses. Importa, em primeiro lugar, recordar a situação de Atenas no início da guerra, o que significa ter em conta dois aspectos: a estrutura política de Atenas e o seu domínio marítimo. Desde Sôlon e das suas reformas, que Atenas caminhava no sentido da consolidação de uma estrutura política que respeitasse os direitos dos seus cidadãos e o aumento da sua participação nos órgãos deliberativos da polis. Em 462 a.C, Efialtes (com o apoio de Péricles) reduziu os poderes do Areópago, privando-o de quaisquer funções legislativas e judiciais e deixando- -Ihe apenas o direito de superintender nos casos de homicídio e nos delitos de caracter religioso. Na verdade, Efialtes e Péricles consideravam que, sendo o Areópago constituído por membros vitalícios provenientes das classes mais elevadas, a concentração nele de tais poderes judiciários era contrária ao espírito democrático, afastando assim da constituição ateniense os últimos vestigios de privilégios da aristocracia.

Grande Queimado em Cuidados Intensivos Pediátricos

O grande queimado é um doente de grande labilidade hidroelectrolítica, que justifica internamento numa unidade de cuidados intensivos até à sua estabilização. Efectuou-se um estudo retrospectivo dos doentes queimados internados na UCIP do HDE, num período de oito anos e meio compreendido entre Abril de 1991 e Setembro de 1999. Foram internadas 33 crianças, 8 das quais tiveram mais do que um internamento. Os agentes causais foram o fogo em 12 crianças, a corrente eléctrica também em 12 crianças e os líquidos quentes em 9. Os doentes queimados por fogo apresentaram área mais extensa de queimadura (46.9 ± 22.6%), e consequentemente maior duração de internamento (462.1 ± 884.1 horas), maior grau de instabilidade fisiológica (pRISM 11.3 ± 4.9) e maior intervenção terapêutica (TISS 31.2 ± 9.0). Nao se observaram reinternamentos no grupo das queimaduras electricas, que globalmente apresentaram menor gravidade nas variáveis estudadas. Dos 8 reinternamentos, 6 ocorreram no grupo dos queimados pelo fogo. Observaram-se 6 óbitos, cinco dos quais no grupo dos reinternamentos. Todos os óbitos foram causados por sépsis e choque séptico.

Marcadores inflamatórios de instabilidade da placa aterosclerótica coronária : caraterização e potencial utilização clínica

RESUMO:Introdução: Reviu-se o conhecimento epidemiológico, fisiopatológico e clínico atual sobre a doença coronária, da sua génese até ao evento agudo, o Enfarte Agudo do Miocárdio (EAM). Valorizou-se, em especial, a teoria inflamatória da aterosclerose, que foi objeto de grandes desenvolvimentos na última década. Marcadores de instabilidade da placa aterosclerótica coronária: Aprofundou-se o conhecimento da placa aterosclerótica coronária instável. Descreveram-se detalhadamente os biomarcadores clínicos e laboratoriais associados à instabilidade da placa, com particular ênfase nos mecanismos inflamatórios. Objetivos:Estão divididos em dois pontos fundamentais:(1) Estudar em doentes com EAM a relação existente entre as moléculas inflamatórias: Interleucina-6 (IL-6), Fator de Necrose Tumoral-α (TNF-α) e Metaloproteinase de Matriz-3 (MMP3), não usados em contexto clínico, com um marcador inflamatório já em uso clínico: a Proteína C-Reativa ultrassensível (hs-CRP). Avaliar a relação de todas as moléculas inflamatórias com um biomarcador de lesão miocárdica: a Troponina Cardíaca I (cTnI). (2) Avaliar, no mesmo contexto de EAM, a Resposta de Fase Aguda (RFA) . Pretende-se demonstrar o impacto deste fenómeno, com repercussão clínica generalizada, no perfil lipídico e nos biomarcadores inflamatórios dos doentes. Métodos:(1) Estudo observacional prospetivo de doentes admitidos consecutivamente por EAM (grupo EAM) numa única unidade coronária, após exclusão de trauma ou infeção. Doseamento no sangue periférico, na admissão, de IL-6, TNF-α, MMP3, hs-CRP e cTnI. Este último biomarcador foi valorizado também nos valores séricos obtidos 6-9 horas depois. Procedeu-se a correlação linear (coeficiente de Pearson, de Rho-Spearman e determinação do R2) entre os 3 marcadores estudados com os valores de hs-CRP e de cTnI (valores da admissão e 6 a 9 horas após). Efetuou-se o cálculo dos coeficientes de regressão linear múltipla entre cTnI da admissão e cTnI 6-9h após, com o conjunto dos fatores inflamatórios estudados. (2) Estudo caso-controlo entre o grupo EAM e uma população aleatória de doentes seguidos em consulta de cardiologia, após exclusão de eventos cardiovasculares de qualquer território (grupo controlo) e também sem infeção ou trauma. Foram doseados os mesmos marcadores inflamatórios no grupo controlo e no grupo EAM. Nos dois grupos dosearam-se, ainda, as lipoproteínas: Colesterol total (CT), Colesterol HDL (HDLc), com as suas subfrações 2 e 3 (HDL 2 e HDL3), Colesterol LDL oxidado (LDLox),Triglicéridos (TG), Lipoproteína (a) [Lp(a)], Apolipoproteína A1 (ApoA1), Apolipoproteína B (ApoB) e Apolipoproteína E (ApoE). Definiram-se, em cada grupo, os dados demográficos, fatores de risco clássicos, terapêutica cardiovascular e o uso de anti-inflamatórios. Procedeu-se a análise multivariada em relação aos dados demográficos, fatores de risco e à terapêutica basal. Compararam-se as distribuições destas mesmas caraterísticas entre os dois grupos, assim como os valores séricos respetivos para as lipoproteínas estudadas. Procedeu-se à correlação entre as moléculas inflamatórias e as lipoproteínas, para todos os doentes estudados. Encontraram-se os coeficientes de regressão linear múltipla entre cada marcador inflamatório e o conjunto das moléculas lipídicas, por grupo. Finalmente, efetuou-se a comparação estatística entre os marcadores inflamatórios do grupo controlo e os marcadores inflamatórios do grupo EAM. Resultados: (1) Correlações encontradas, respetivamente, Pearson, Rho-Spearman e regressão-R2: IL-6/hs-CRP 0,549, p<0,001; 0,429, p=0,001; 0,302, p<0,001; MMP 3/hsCRP 0,325, p=0,014; 0,171, p=0,202; 0,106, p=0,014; TNF-α/hs-CRP 0,261, p=0,050; 0,315, p=0,017; 0,068, p=0.050; IL-6/cTnI admissão 0,486, p<0,001; 0,483, p<0,001; 0,236, p<0,001; MMP3/cTnI admissão 0,218, p=0,103; 0,146, p=0,278; 0,048, p=0,103; TNF-α/cTnI admissão 0,444, p=0,001; 0,380, p=0,004; 0,197, p=0,001; IL-6/cTnI 6-9h 0,676, p<0,001; 0,623, p<0,001; 0,456, p<0,01; MMP3/cTnI 6-9h 0,524, p=0,001; 0,149, p=0,270; 0,275, p<0,001; TNF-α/cTnI 6-9h 0,428, p=0,001, 0,452, p<0,001, 0,183, p<0,001. A regressão linear múltipla cTnI admissão/marcadores inflamatórios produziu: (R=0,638, R2=0,407) p<0,001 e cTnI 6-9h/marcadores inflamatórios (R=0,780, R2=0,609) p<0,001. (2) Significância da análise multivariada para idade (p=0,029), IMC>30 (p=0.070), AAS (p=0,040) e grupo (p=0,002). Diferenças importantes entre as distribuições dos dados basais entre os dois grupos (grupo controlo vs EAM): idade (47,95±11,55 vs 68,53±2,70 anos) p<0.001; sexo feminino (18,18 vs 22,80%) p=0,076; diabetes mellitus (9,09% vs 36,84%) p=0,012; AAS (18,18 vs 66,66%) p<0,001; clopidogrel (4,54% vs 66,66%) p=0,033; estatinas (31,81% vs 66,14%) p=0,078; beta-bloqueadores (18,18% vs 56,14%) p=0,011; anti-inflamatórios (4,54% vs 33,33%) p=0,009. Resultados da comparação entre os dois grupos quanto ao padrão lipídico (média±dp ou mediana/intervalo interquartil, grupo controlo vs EAM): CT (208,45±35,03 vs 171,05±41,63 mg/dl) p<0,001; HDLc (51,50/18,25 vs 42,00/16,00 mg/dl) p=0,007; HDL2 (8,50/3,25 vs 10,00/6,00 mg/dl) p=0,292; HDL3 (41,75±9,82 vs 31,75±9,41 mg/dl) p<0,001; LDLox (70,00/22,0 vs 43,50/21,00 U/L) p<0,001; TG (120,00/112,50 vs 107,00/86,00 mg/dl) p=0,527; Lp(a) (0,51/0,73 vs 0,51/0,50 g/L) p=0,854; ApoA1 (1,38±0,63 vs 1,19±0,21 g/L) p=0,002; ApoB (0,96±0,19 vs 0,78±0,28 g/L) p=0,004; ApoE (38,50/10,00 vs 38,00/17,00 mg/L) p=0,574. Nas correlações lineares entre as variáveis inflamatórias e as variáveis lipídicas para todos os doentes, encontrámos uma relação negativa entre IL-6 e CT, HDLc, HDL3, LDLox, ApoA1 e ApoB. A regressão múltipla marcadores inflamatórios/perfil lipídico (grupo controlo) foi: hs-CRP (R=0,883, R2=0,780) p=0,022; IL-6 (R=0,911, R2=0,830) p=0,007; MMP3 (R=0,498, R2=0,248) p=0,943; TNF-α (R=0,680, R2=0,462) p=0,524. A regressão múltipla marcadores inflamatórios/perfil lipídico (grupo EAM) foi: hs-CRP (R=0,647, R2=0,418) p=0,004; IL-6 (R=0,544, R2=0,300), p=0,073; MMP3 (R=0,539, R2=0,290) p=0,089; TNF-α (R=0,595; R2=0,354) p=0,022. Da comparação entre os marcadores inflamatórios dos dois grupos resultou (mediana/intervalo interquartil, grupo controlo vs EAM): hs-CRP (0,19/0,27 vs 0,42/2,53 mg/dl) p=0,001, IL-6 (4,90/5,48 vs 13,07/26,41 pg/ml) p<0,001, MMP3 (19,70/13,70 vs 10,10/10,40 ng/ml) p<0,001;TNF-α (8,67/6,71 vs 8,26/7,80 pg/dl) p=0,805. Conclusões: (1) Nos doentes com EAM, existe correlação entre as moléculas inflamatórias IL-6, MMP3 e TNF-α, quer com o marcador inflamatório hs-CRP, quer com o marcador de lesão miocárdica cTnI. Esta correlação reforça-se para os valores de cTnI 6-9 horas após admissão, especialmente na correlação múltipla com o grupo dos quatro marcadores inflamatórios. (2) IL-6 está inversamente ligada às lipoproteínas de colesterol; hs-CRP e IL-6 têm excelentes correlações com o perfil lipídico valorizado no seu conjunto. No grupo EAM encontram-se níveis séricos mais reduzidos para as lipoproteínas de colesterol. Para TNF-α não foram encontradas diferenças significativas entre os grupos, as quais foram observadas para a IL-6 e hs-CRP (mais elevadas no grupo EAM). Os valores de MMP3 no grupo controlo estão mais elevados. ABSTRACT: 0,524, p=0,001; 0,149, p=0,270; 0,275, p<0,001; TNF-α/cTnI 6-9h 0,428, p=0,001, 0,452, p<0,001, 0,183, p<0,001. A regressão linear múltipla cTnI admissão/marcadores inflamatórios produziu: (R=0,638, R2=0,407) p<0,001 e cTnI 6-9h/marcadores inflamatórios (R=0,780, R2=0,609) p<0,001. (2) Significância da análise multivariada para idade (p=0,029), IMC>30 (p=0.070), AAS (p=0,040) e grupo (p=0,002). Diferenças importantes entre as distribuições dos dados basais entre os dois grupos (grupo controlo vs EAM): idade (47,95±11,55 vs 68,53±2,70 anos) p<0.001; sexo feminino (18,18 vs 22,80%) p=0,076; diabetes mellitus (9,09% vs 36,84%) p=0,012; AAS (18,18 vs 66,66%) p<0,001; clopidogrel (4,54% vs 66,66%) p=0,033; estatinas (31,81% vs 66,14%) p=0,078; beta-bloqueadores (18,18% vs 56,14%) p=0,011; anti-inflamatórios (4,54% vs 33,33%) p=0,009. Resultados da comparação entre os dois grupos quanto ao padrão lipídico (média±dp ou mediana/intervalo interquartil, grupo controlo vs EAM): CT (208,45±35,03 vs 171,05±41,63 mg/dl) p<0,001; HDLc (51,50/18,25 vs 42,00/16,00 mg/dl) p=0,007; HDL2 (8,50/3,25 vs 10,00/6,00 mg/dl) p=0,292; HDL3 (41,75±9,82 vs 31,75±9,41 mg/dl) p<0,001; LDLox (70,00/22,0 vs 43,50/21,00 U/L) p<0,001; TG (120,00/112,50 vs 107,00/86,00 mg/dl) p=0,527; Lp(a) (0,51/0,73 vs 0,51/0,50 g/L) p=0,854; ApoA1 (1,38±0,63 vs 1,19±0,21 g/L) p=0,002; ApoB (0,96±0,19 vs 0,78±0,28 g/L) p=0,004; ApoE (38,50/10,00 vs 38,00/17,00 mg/L) p=0,574. Nas correlações lineares entre as variáveis inflamatórias e as variáveis lipídicas para todos os doentes, encontrámos uma relação negativa entre IL-6 e CT, HDLc, HDL3, LDLox, ApoA1 e ApoB. A regressão múltipla marcadores inflamatórios/perfil lipídico (grupo controlo) foi: hs-CRP (R=0,883, R2=0,780) p=0,022; IL-6 (R=0,911, R2=0,830) p=0,007; MMP3 (R=0,498, R2=0,248) p=0,943; TNF-α (R=0,680, R2=0,462) p=0,524. A regressão múltipla marcadores inflamatórios/perfil lipídico (grupo EAM) foi: hs-CRP (R=0,647, R2=0,418) p=0,004; IL-6 (R=0,544, R2=0,300), p=0,073; MMP3 (R=0,539, R2=0,290) p=0,089; TNF-α (R=0,595; R2=0,354) p=0,022. Da comparação entre os marcadores inflamatórios dos dois grupos resultou (mediana/intervalo interquartil, grupo controlo vs EAM): hs-CRP (0,19/0,27 vs 0,42/2,53 mg/dl) p=0,001, IL-6 (4,90/5,48 vs 13,07/26,41 pg/ml) p<0,001, MMP3 (19,70/13,70 vs 10,10/10,40 ng/ml) p<0,001;TNF-α (8,67/6,71 vs 8,26/7,80 pg/dl) p=0,805. Conclusões: (1) Nos doentes com EAM, existe correlação entre as moléculas inflamatórias IL-6, MMP3 e TNF-α, quer com o marcador inflamatório hs-CRP, quer com o marcador de lesão miocárdica cTnI. Esta correlação reforça-se para os valores de cTnI 6-9 horas após admissão, especialmente na correlação múltipla com o grupo dos quatro marcadores inflamatórios. (2) IL-6 está inversamente ligada às lipoproteínas de colesterol; hs-CRP e IL-6 têm excelentes correlações com o perfil lipídico valorizado no seu conjunto. No grupo EAM encontram-se níveis séricos mais reduzidos para as lipoproteínas de colesterol. Para TNF-α não foram encontradas diferenças significativas entre os grupos, as quais foram observadas para a IL-6 e hs-CRP (mais elevadas no grupo EAM). Os valores de MMP3 no grupo controlo estão mais elevados. ------------- ABSTRACT: Introduction: We reviewed the epidemiology, pathophysiology and current clinical knowledge about coronary heart disease, from its genesis to the acute myocardial infarction (AMI). The inflammatory theory for atherosclerosis, which has undergone considerable development in the last decade, was especially detailed. Markers of coronary atherosclerotic vulnerable plaque: The clinical and laboratory biomarkers associated with the unstable coronary atherosclerotic plaque vulnerable plaque are detailed. An emphasis was placed on the inflammatory mechanisms. Objectives: They are divided into two fundamental points: (1) To study in AMI patients, the relationship between the inflammatory molecules: Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) and Matrix metalloproteinase-3 (MMP3), unused in the clinical setting, with an inflammatory marker in clinical use: ultrasensitive C-reactive protein (hs-CRP), as well as a biomarker of myocardial injury: cardiac troponin I (cTnI). (2) To study, in the context of AMI, the Acute Phase Response (APR). We intend to demonstrate the impact of that clinical relevant phenomenon in the lipid profile and inflammatory biomarkers of our patients. Methods: (1) Prospective observational study of patients consecutively admitted for AMI (AMI group) in a single coronary care unit, after exclusion of trauma or infection. A peripheral assay at admission for IL-6, TNF-α, MMP3, hs-CRP and cTnI was performed. The latter was also valued in assays obtained 6-9 hours after admission. Linear correlation (Pearson's correlation coefficient, Spearman Rho's correlation coefficient and R2 regression) was performed between the three markers studied and the values of hs-CRP and cTnI (on admission and 6-9 hours after admission). Multiple linear regression was also obtained between cTnI on admission and 6-9h after, with all the inflammatory markers studied. (2) Case-control study between the AMI group and a random population of patients from an outpatient cardiology setting (control group). Cardiovascular events of any kind and infection or trauma were excluded in this group. The same inflammatory molecules were assayed in control and AMI groups. The following lipoproteins were also assayed: total cholesterol (TC), HDL cholesterol (HDLc) and subfractions 2 and 3 (HDL2 and HDL 3), oxidized LDL cholesterol (oxLDL), Triglycerides (TG), Lipoprotein (a) [Lp(a)], Apolipoprotein A1 (apoA1), Apolipoprotein B (ApoB) and Apolipoprotein E (ApoE). Demographics, classical risk factors, cardiovascular therapy and the use of anti-inflammatory drugs were appreciated in each group. The authors conducted a multivariate analysis with respect to demographics, risk factors and baseline therapy. The distribution of the same baseline characteristics was compared between the two groups, as well as the lipoprotein serum values. A correlation was performed between each inflammatory molecule and each of the lipoproteins, for all the patients studied. Multiple linear regression was determined between each inflammatory marker and all the lipid molecules per group. Finally, the statistical comparison between the inflammatory markers in the two groups was performed. Results: (1) The correlation coefficients recorded, respectively, Pearson, Spearman's Rho and regression-R2, were: IL-6/hs-CRP 0.549, p <0.001; 0.429, p=0.001; 0.302, p <0.001; MMP 3/hsCRP 0.325, p=0.014; 0.171, p=0.202; 0.106, p=0.014; TNF-α/hs-CRP 0.261, p=0.050; 0.315, p=0.017; 0.068, p=0.050; IL-6/admission cTnI 0.486, p<0.001; 0.483, p<0.001; 0.236, p<0.001; MMP3/admission cTnI 0.218, p=0.103; 0.146, p=0.278; 0.048, p=0.103; TNF-α/admission cTnI 0.444, p=0.001; 0.380, p=0.004; 0.197, p=0.001; IL-6/6-9 h cTnI 0.676, p<0.001; 0.149, p<0.001; 0.456, p <0.01; MMP3/6-9h cTnI 0.428, p=0.001; 0.149, p<0.001; 0.183, p=0.001; TNF-α/6-9 h cTnI 0.676, p<0,001; 0.452, p<0.001; 0.183, p<0,001. The multiple linear regression admission cTnI/inflammatory markers produced: (R=0.638, R2=0.407) p<0.001 and 6-9 h cTnI/inflammatory markers (R=0.780, R2=0.609) p<0.001. (2) Significances of the multivariate analysis were found for age (p=0.029), IMC>30 (p=0.070), Aspirin (p=0.040) and group (p=0.002). Important differences between the baseline data of the two groups (control group vs AMI): age (47.95 ± 11.55 vs 68.53±12.70 years) p<0.001; gender (18.18 vs 22.80%) p=0.076; diabetes mellitus (9.09% vs 36. 84%) p=0.012; Aspirin (18.18 vs. 66.66%) p<0.001; Clopidogrel (4, 54% vs 66.66%) p=0.033; Statins, 31.81% vs 66.14%, p=0.078, beta-blockers 18.18% vs 56.14%, p=0.011; anti-inflammatory drugs (4.54% vs 33.33%) p=0.009. Significant differences in the lipid pattern of the two groups (mean±SD or median/interquartile range, control group vs AMI): TC (208.45±35.03 vs 171.05±41.63 mg/dl) p<0.001; HDLc (51.50/18.25 vs 42.00/16.00 mg/dl) p=0.007; HDL2 (8.50/3.25 vs 10.00/6.00 mg/dl) p=0.292; HDL3 (41.75±9.82 vs 31.75±9.82 mg/dl) p<0.01; oxLDL (70.00/22.0 vs 43.50/21.00 U/L) p <0.001; TG (120.00/112.50 vs 107.00/86.00 mg/dl) p=0.527; Lp(a) (0.51/0.73 vs 0,51/0.50 g/L) p=0.854; apoA1 (1.38±0.63 vs 1.19±0.21 g/L) p=0.002; ApoB (0.96± 0.39 vs 0.78±0.28 g/L) p=0.004; ApoE (38.50/10,00 vs 38.00 /17,00 mg/L) p=0.574. In the linear correlations between inflammatory variables and lipid variables for all patients, we found a negative relationship between IL-6 and TC, HDLc, HDL3, ApoA1 and ApoB. The multiple linear regression inflammatory markers/lipid profile (control group) was: hs-CRP (R= 0.883, R2=0.780) p=0.022; IL6 (R=0.911, R2=0.830) p=0.007; MMP3 (R=0.498, R2=0.248) p=0.943; TNF-α (R=0.680, R2=0.462) p=0.524. For the linear regression inflammatory markers/lipid profile (AMI group) we found: hs-CRP (R=0.647, R2=0.418) p=0.004; IL-6 (R=0.544, R2=0.300) p=0.073; MMP3 (R=0.539, R2 =0.290) p=0.089; TNF-α (R=0.595, R2=0.354) p=0.022. The comparison between inflammatory markers in both groups (median/interquartile range, control group vs AMI) resulted as: hs-CRP (0.19/0.27 vs 0.42/2.53 mg/dl) p=0.001; IL-6 (4.90/5.48 vs 13.07/26.41 pg/ml) p<0.001; MMP3 (19.70/13.70 vs 10.10/10.40 ng/ml) p<0.001; TNF-α (8.67/6.71 vs 8.26/7.80 pg/dl) p=0.805. Conclusions: (1) In AMI patients there is a correlation between the inflammatory molecules IL-6, TNF-α and MMP3 with both the inflammatory marker hs-CRP and the ischemic marker cTnI. This correlation is strengthened for the cTnI at 6-9h post admission, particularly in the multiple linear regression to the four inflammatory markers studied. (2) IL-6 correlates negatively with the cholesterol lipoproteins. Hs-CRP and IL-6 are strongly correlated to the whole lipoprotein profile. AMI patients display reduced serum lipid levels. For the marker TNF-α no significant differences were found between groups, which were observed for IL-6 and hs-CRP (higher in the AMI group). MMP3 values are higher in the control group.

Locally Advanced and Metastatic Prostate Cancer Treated with Intermittent Androgen Monotherapy or Maximal Androgen Blockade: Results from a Randomised Phase 3 Study by the South European Uroncological Group

BACKGROUND: Few randomised studies have compared antiandrogen intermittent hormonal therapy (IHT) with continuous maximal androgen blockade (MAB) therapy for advanced prostate cancer (PCa). OBJECTIVE: To determine whether overall survival (OS) on IHT (cyproterone acetate; CPA) is noninferior to OS on continuous MAB. DESIGN, SETTING, AND PARTICIPANTS: This phase 3 randomised trial compared IHT and continuous MAB in patients with locally advanced or metastatic PCa. INTERVENTION: During induction, patients received CPA 200 mg/d for 2 wk and then monthly depot injections of a luteinising hormone-releasing hormone (LHRH; triptoreline 11.25 mg) analogue plus CPA 200 mg/d. Patients whose prostate-specific antigen (PSA) was <4 ng/ml after 3 mo of induction treatment were randomised to the IHT arm (stopped treatment and restarted on CPA 300 mg/d monotherapy if PSA rose to ≥20 ng/ml or they were symptomatic) or the continuous arm (CPA 200 mg/d plus monthly LHRH analogue). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome measurement was OS. Secondary outcomes included cause-specific survival, time to subjective or objective progression, and quality of life. Time off therapy in the intermittent arm was recorded. RESULTS AND LIMITATIONS: We recruited 1045 patients, of which 918 responded to induction therapy and were randomised (462 to IHT and 456 to continuous MAB). OS was similar between groups (p=0.25), and noninferiority of IHT was demonstrated (hazard ratio [HR]: 0.90; 95% confidence interval [CI], 0.76-1.07). There was a trend for an interaction between PSA and treatment (p=0.05), favouring IHT over continuous therapy in patients with PSA ≤1 ng/ml (HR: 0.79; 95% CI, 0.61-1.02). Men treated with IHT reported better sexual function. Among the 462 patients on IHT, 50% and 28% of patients were off therapy for ≥2.5 yr or >5 yr, respectively, after randomisation. The main limitation is that the length of time for the trial to mature means that other therapies are now available. A second limitation is that T3 patients may now profit from watchful waiting instead of androgen-deprivation therapy. CONCLUSIONS: Noninferiority of IHT in terms of survival and its association with better sexual activity than continuous therapy suggest that IHT should be considered for use in routine clinical practice.

Epidemiological aspects of dengue in Aracaju, State of Sergipe, Brazil

INTRODUCTION: The dengue fever remains to be a disease of serious public health concern, and its incidence has increased in the past decades. This study aimed to characterize the epidemiological incidence of dengue in the period 2001-2010. METHODS: This is an epidemiological study of dengue in the municipality of Aracaju, state of Sergipe, in the period between 2001 and 2010, whose data were obtained from the Information System of Diseases Notifications. A descriptive analysis of the number of confirmed cases of dengue, according to year, semester, sanitary district, age, and sex, was performed. RESULTS: There were 16,462 confirmed cases, especially in 2008, which obtained the highest incidence of the disease, with 10,485 confirmed cases. The first semester obtained the highest registration of cases during the years of research; this was predominated by females between 15 and 49 years old. With regard to the territorial distribution, the second district of the municipality obtained the highest number of cases. CONCLUSIONS: In 2008, in the City of Aracaju, SE, a significant increase in the proportion of dengue cases compared with other years was verified. However, a fast decline in the other years was observed, possibly because of the intensification of preventive actions to combat the mosquito that transmits the dengue virus.

Transplantação hepática no C. H. Porto

RESUMO - Contexto: a actividade de transplantação hepática envolve um número considerável de profissionais multidisciplinares e, possui uma alocação de verbas importante do ponto de vista do administrador hospitalar. Estudar e analisar a actividade de transplantação hepática no Centro Hospitalar do Porto (CHP), é por isso, objecto do trabalho. Objectivos: Efectuar uma análise custo/proveito do processo de transplantação hepática para o CHP nos anos de 2010, 2011 e 2012 e, caracterizar a população em estudo com o maior número de variáveis possível. Metodologia: Seleccionou-se para análise os pacientes com o Grupo de Diagnóstico Homogéneo (GDH) 480 que realizaram transplante hepático entre 1 de Janeiro de 2010 até 30 de Junho de 2012 de modo a quantificar os custos e proveitos dos 161 pacientes desde a fase pré-transplante, passando pelo internamento até aos 6 meses após a alta hospitalar da fase pós-transplante. Na análise de custos da fase pré-transplante consideraram-se os custos com recursos humanos (RH) médicos das consultas e o custo com meios complementares de diagnóstico e terapêutica (MCDT’s). Na fase de internamento considerou-se os custos relativos à cirurgia (RH e material de consumo clinico e farmacológico) e diárias de internamento. Para a fase pós-transplante contabilizou-se os custos relativos a RH médicos das consultas, o custo com MCDT’s e fármacos. O apuramento de proveitos decorreu do contrato programa da instituição, da Portaria 839-A/2009 de 31 de Julho para o cálculo pelo peso relativo do transplante hepático, pelo Despacho nº 19964/2008 de 28 de Julho para a comparticipação dos fármacos. Considerou-se ainda o incentivo à transplantação pelos Despachos nº6155/2006, de 15 de Março e nº 10485/2011, de 19 de Agosto. Resultados: Da análise global dos 161 GDH’s o verificado foi um custo total para o CHP de 7.505.518,89euro (um custo médio de 46.618,13euro por paciente). Quanto aos proveitos utilizando o contrato programa do CHP bem como os Despachos relativos ao incentivo à transplantação e à comparticipação de fármacos, existiu proveitos de 7.089.462,77euro (proveito médio de 44.033,93euro). Se o cálculo dos proveitos de internamento fosse pelo peso relativo do transplante hepático os proveitos seriam de 21.834.655,50euro (proveito médio de 135.618,98euro).

Presence of oOrganophosphate Insecticides in fish of the Amazon River

Trace levels of three organophosphate insecticides (OPI) were detected in eight fish species from the region of Santarém, State of Pará, Brazil. Individual concentrations of OPI in fish ranged from less than the detection limit to 2,1 ppb. Mean concentrations of chlorpyrifos, malathion, and methyl-parathion were 0,3 ± 0,3, 0,1 ± 0,1, and 0,3 ± 0,3 ppb, respectively. Pellona flavipinnis, the largest and fattest piscivorous species analyzed, was the most contaminated. Since an inhabitant of this Amazonian region consumes 220 g of fish per day on average, ingested doses of chlorpyrifos, malathion, and methyl-parathion may reach up to 308, 220, and 462 ng·d-1, respectively. Compared to acceptable daily intakes (ADI), quantities of OPI absorbed via fish consumption on a daily basis are far below deleterious levels. We estimated that even considering the highest OPI contents detected, the average daily fish consumption of anadult of 60 kg would have to increase by ca. 1 950, 5 450, and 2 600 times to reach ADI of chlorpyrifos, malathion, and methyl-parathion, respectively. Neither fish diet nor fish lipid content enabled us to completely explain the interspecific differences observed.