Why does low dose morphine augment fentanyl analgesia?

Opioids dominate the field of pain management because of their ability to provide analgesia in many medical circumstances. However, side effects including respiratory depression, constipation, tolerance, physical dependence, and the risk of addiction limit their clinical utility. Fear of these side effects results in the under-treatment of acute pain. For many years, research has focused on ways to improve the therapeutic index (the ratio of desirable analgesic effects to undesirable side effects) of opioids. One strategy, combining opioid agonists that bind to different opioid receptor types, may prove successful.^ We discovered that subcutaneous co-administration of a moderately analgesic dose of the mu-opioid receptor (MOR) selective agonist fentanyl (20μg/kg) with subanalgesic doses of the less MOR-specific agonist morphine (100ng/kg-100μg/kg), augmented acute fentanyl analgesia in rats. Parallel [35S]GTPγS binding studies using naïve rat substantia gelatinosa membrane treated with fentanyl (4μM) and morphine (1nM-1pM) demonstrated a 2-fold increase in total G-protein activation. This correlation between morphine-induced augmentation of fentanyl analgesia and G-protein activation led to our proposal that interactions between MORs and DORs underlie opioid-induced augmentation. We discovered that morphine-induced augmentation of fentanyl analgesia and G-protein activity was mediated by DORs. Adding the DOR-selective antagonist naltrindole (200ng/kg, 40nM) at doses that did not alter the analgesic or G-protein activation of fentanyl, blocked increases in analgesia and G-protein activation induced by fentanyl/morphine combinations. Equivalent doses of the MOR-selective antagonist cyprodime (20ng/kg, 4nM) did not block augmentation. Substitution of the DOR-selective agonist SNC80 for morphine yielded similar results, further supporting our conclusion that interactions between MORs and DORs are responsible for morphine-induced augmentation of fentanyl analgesia and G-protein activation. Confocal microscopy of rat substantia gelatinosa showed that changes in the rate of opioid receptor internalization did not account for these effects.^ In conclusion, fentanyl analgesia augmentation by subanalgesic morphine is mediated by increased G-protein activation resulting from functional interactions between MORs and DORs, not changes in MOR internalization. Additional animal and clinical studies are needed to determine whether side effect incidence changes following opioid co-administration. If side effect incidence decreases or remains unchanged, these findings could have important implications for clinical pain treatment. ^

Parental influence on adolescent smoking initiation among Mexican origin youth

Smoking is often initiated in adolescence through trying or experimenting with cigarettes. Smoking initiation is the beginning critical stage in the smoking trajectory often resulting in addiction. This dissertation examined the effect of parenting variables on smoking initiation behavior among 11–14 year old Mexican origin adolescents, a largely understudied group. The participants in this study were part of a population-based cohort of Mexican origin adolescents residing in Houston, Texas. ^ Aim 1 of this study assessed the appropriateness of the Family Life Questionnaire (FLQ) among Mexican origin adolescents. Second order confirmatory factor analysis (CFA) was performed to examine the factor structure of the FLQ and measurement invariance testing was conducted to evaluate the cross-cultural validity of this scale. Aim 2 analyzed cross-sectional associations between parenting variables and adolescent ever tried smoking behavior while aim 3 focused on prospective examination of changes in parenting variables from baseline to final follow-up on ever tried smoking behavior among never smokers. ^ Overall, the results of the CFA indicated that the original factor structure of the FLQ, with alterations, was a good fit for the Mexican origin adolescents. The measurement invariance analysis of the modified FLQ scale indicated adequate measurement invariance. The aim 2 cross-sectional analyses indicated that family cohesion was significantly associated with lower odds of ever tried smoking. Authoritarian parenting was significantly associated with smoking initiation only at the baseline while family conflict was significantly associated with smoking initiation only at the two-year final home visit. The findings from the aim 3 prospective analysis indicated that changes in levels of family cohesion and conflict are important predictors of smoking initiation among those who have never tried smoking. Specifically, perceiving low levels of family cohesion and a decrease in the family cohesion over two years, as well as perceiving high levels of family conflict and an increase in conflict over two years was associated with smoking initiation among never smokers. ^ In general, the findings of this study provide important insights on the links between parenting and adolescent smoking and assist in designing prevention and intervention programs that emphasize the role of family bonding to prevent adolescent smoking behavior. Family education programs for Mexican culture could also highlight the positive effects of authoritarian practices and good family communication to prevent family conflict and subsequent smoking behavior.^

Behavioral decision making and the levels of change: An application of the transtheoretical model to prenatal smoking in low -income women

Despite continued research and public health efforts to reduce smoking during pregnancy, prenatal cessation rates in the United States have decreased and the incidence of low birth weight has increased from 1985 to 1991. Lower socioeconomic status women who are at increased risk for poor pregnancy outcomes may be resistant to current intervention efforts during pregnancy. The purpose of this dissertation was to investigate the determinants of continued smoking and quitting among low-income pregnant women.^ Using data from cross-sectional surveys of 323 low-income pregnant smokers, the first study developed and tested measures of the pros and cons of smoking during pregnancy. The original decisional balance measure for smoking was compared with a new measure that added items thought to be more salient to the target population. Confirmatory factor analysis using structural equation modeling showed neither the original nor new measure fit the data adequately. Using behavioral science theory, content from interviews with the population, and statistical evidence, two 7-item scales representing the pros and cons were developed from a portion (n = 215) of the sample and successfully cross-validated on the remainder of the sample (n = 108). Logistic regression found only pros were significantly associated with continued smoking. In a discriminant function analysis, stage of change was significantly associated with pros and cons of smoking.^ The second study examined the structural relationships between psychosocial constructs representing some of the levels of and the pros and cons of smoking. The cross-sectional design mandates that statements made regarding prediction do not prove causation or directionality from the data or methods analysis. Structural equation modeling found the following: more stressors and family criticism were significantly more predictive of negative affect than social support; a bi-directional relationship was found between negative affect and current nicotine addiction; and negative affect, addiction, stressors, and family criticism were significant predictors of pros of smoking.^ The findings imply reversing the trend of decreasing smoking cessation during pregnancy may require supplementing current interventions for this population of pregnant smokers with programs addressing nicotine addiction, negative affect, and other psychosocial factors such as family functioning and stressors. ^

Evaluación de conductas adictivas en personal médico y no médico en un hospital de agudos : estudio comparativo

Objetivo: Identificar abuso, dependencia, adicciones (tabaquismo, problemas con alcohol y alimentación) y automedicación en el personal de la salud de un Hospital de agudos.- Material y Métodos: Estudio protocolizado y observacional mediante. encuesta estructurada, autoadministrada y anónima. Se realizó el análisis en 4 grupos: Médicos (M) (MS: Staff y MF: en formación), NO M: enfermeros (E) y otros (O: administración, laboratorio, farmacia, servicios generales). Se realizó un estudio comparativo con una población encuestada en el año 2004. Resultados: Se incluyeron 373 personas: 195 M (73 MS y 122 MF), 83 E y 92 O; 225 mujeres (60,3%); edad promedio grupal: 36.1 años (DS± 9.98). El 77.5% con pareja estable, el 98.1% heterosexuales y 67,3% universitarios. El 67.3% se automedicaba, el 35.1% eran tabaquistas activos; el 28.4% presentaba problemas con el alcohol y el 36.2% con la alimentación. El tabaquismo fue más frecuente entre 40-50 años (42,5%) y en E: 56.6%; MS: 21,9%; MF: 27% y O: 36.9%(p<0.05). Se incrementó la intención de abandonar el cigarrillo comparado con el año 2004 (74.6 vs 56.3%)(p<0.05). Los problemas con el alcohol fueron frecuentes entre 20 y 30 años (47.2%), en personas con pareja inestable (73.6%), sin diferencias entre los grupos y en 51.8% coexistía con tabaquismo. Los problemas de alimentación ocurrieron significativamente en MF (46,9%) comparados con MS (22.5%) (p<0.05). Se detectó automedicación en el 68.3 del Grupo O y en 48.1% del Grupo M (p<0.05). Al comparar la automedicación en las encuestas del año 2004 y 2007, se comprobó una reducción en E (87.8 vs 52.4%) y en O (77.5 vs 48.1%)(p<0.05).- Conclusiones: Se detectó elevada prevalencia de tabaquismo, problemas con el alcohol, alimentación y automedicación en todo el personal hospitalario. El tabaquismo predominó en enfermeros, los trastornos alimentarios en médicos en formación y el alcoholismo en solteros con pareja inestable.

Perfil clínico y social del paciente adicto hospitalizado

Objetivos: Determinar las características clínicas y morbilidad de los pacientes (pac.) adictos ingresados a un Servicio de Clínica Médica. Material y métodos: Estudio protocolizado, observacional, descriptivo y transversal. Criterio de inclusión: pac. adicto con consumo de sustancias ilícitas. Informe preliminar: Periodo: 24 meses. Datos analizados en Epi info 6.4 Resultados: Se incluyeron 40 pac. Prevalencia: 0.2/1000 egresos. El 82.5% eran hombres. Edad media: 31.5 años (DS±9.65). Permanencia media: 11 días (DS±13.98) vs 7.12 (DS±10.1) del Servicio (p=0.016). Consumían cocaína el 82.5% (IC95%67.22-92.66) marihuana el 77.5% (IC95% 61.65- 89.16), tolueno el 10% (IC95%2.79-23.66), floripondio y hachis el 2.5% (IC95% 0.06-13.16) cada uno. En el 2.5% la vía de administración era endovenosa y el 60% eran poliadictos. Solo el 10% recibió tratamiento para abandonar la adicción (100% tratamiento psicológico y 5.13% farmacológico). De clase social pobre el 75%. El 62.5% de los pac. estaban desocupados, tenían antecedentes judiciales el 10% y el 7.5% había estado en prisión. El 92.5% (IC95% 76.34-97.21) era heterosexual, 2.5% hombres que tenían sexo con hombres y bisexuales 5% (IC95% 0.61-16.92). Solo el 10% tenían secundaria completa. El 80% ingreso por Emergencias y por causa infecciosa el 45%. El 12.5% ingreso por complicaciones de la adicción. Las manifestaciones relacionadas con la adicción fueron: manifestaciones del sistema nervioso central: 12.5% (IC95%4.19-26.80); síndrome de abstinencia y temblor 7.5% cada uno y excitación psicomotriz, delirium, signo de foco neurológico y rigidez 5% cada uno. El 100% presentaba alguna comórbida; tabaquismo 80%, depresión 12.8% Y alcoholismo 57.5%, entre otras. Presentaban enfermedades de transmisión sexual 5 pac. (4 HIV, 2 VHC y 1 pediculus pubis). No hubo mortalidad hospitalaria. Conclusión: El paciente adicto internado se caracteriza por ser joven, pertenecer a un grupo social desprotegido, sin trabajo y sin educación, tener poliadicción, con alta carga de comórbidas y de internación, principalmente por complicaciones infecciosas.

"La recuperación es para obedientes" : Algunas articulaciones y ajustes metodológicos para el análisis de un tratamiento de adicción a las drogas

El escrito reflexiona sobre la adecuación teórica y metodológica del recurso a las categorías institución total, dispositivo y disciplina, para investigar problemáticas recientes en el campo de la salud-enfermedad-atención, particularmente las denominadas adicciones a las drogas. De la mano de numerosas investigaciones empíricas, ciertos conceptos se anudan en los análisis, asociándose disciplina-encierro, e institución total-espacio cerrado. El escrito propone el desacople de estas nociones y la recuperación de su productividad analítica, desde la investigación en un dispositivo terapéutico ambulatorio para la adicción a drogas del Area Metropolitana de Buenos Aires. Se aborda esta problemática desde una perspectiva etnográfica, con análisis documental, observación participante y entrevistas realizadas a profesionales de la salud de la institución, personal de apoyo y usuarios. Se concluye que las formulaciones de Goffman y Foucault ayudan a comprender la existencia de modalidades de tratamiento para las adicciones a las drogas que, sin fundarse en el encierro como técnica primordial de control de los cuerpos, sostienen un proceso de clausura y despojo significativos; y que la renuncia a homologar la clausura, y el espacio cerrado a una materialidad, permitió dar realce a una vivencia de despojo subjetivo de parte de quienes se encuentran en tratamiento en la institución

"La recuperación es para obedientes" : Algunas articulaciones y ajustes metodológicos para el análisis de un tratamiento de adicción a las drogas

El escrito reflexiona sobre la adecuación teórica y metodológica del recurso a las categorías institución total, dispositivo y disciplina, para investigar problemáticas recientes en el campo de la salud-enfermedad-atención, particularmente las denominadas adicciones a las drogas. De la mano de numerosas investigaciones empíricas, ciertos conceptos se anudan en los análisis, asociándose disciplina-encierro, e institución total-espacio cerrado. El escrito propone el desacople de estas nociones y la recuperación de su productividad analítica, desde la investigación en un dispositivo terapéutico ambulatorio para la adicción a drogas del Area Metropolitana de Buenos Aires. Se aborda esta problemática desde una perspectiva etnográfica, con análisis documental, observación participante y entrevistas realizadas a profesionales de la salud de la institución, personal de apoyo y usuarios. Se concluye que las formulaciones de Goffman y Foucault ayudan a comprender la existencia de modalidades de tratamiento para las adicciones a las drogas que, sin fundarse en el encierro como técnica primordial de control de los cuerpos, sostienen un proceso de clausura y despojo significativos; y que la renuncia a homologar la clausura, y el espacio cerrado a una materialidad, permitió dar realce a una vivencia de despojo subjetivo de parte de quienes se encuentran en tratamiento en la institución

"La recuperación es para obedientes" : Algunas articulaciones y ajustes metodológicos para el análisis de un tratamiento de adicción a las drogas

El escrito reflexiona sobre la adecuación teórica y metodológica del recurso a las categorías institución total, dispositivo y disciplina, para investigar problemáticas recientes en el campo de la salud-enfermedad-atención, particularmente las denominadas adicciones a las drogas. De la mano de numerosas investigaciones empíricas, ciertos conceptos se anudan en los análisis, asociándose disciplina-encierro, e institución total-espacio cerrado. El escrito propone el desacople de estas nociones y la recuperación de su productividad analítica, desde la investigación en un dispositivo terapéutico ambulatorio para la adicción a drogas del Area Metropolitana de Buenos Aires. Se aborda esta problemática desde una perspectiva etnográfica, con análisis documental, observación participante y entrevistas realizadas a profesionales de la salud de la institución, personal de apoyo y usuarios. Se concluye que las formulaciones de Goffman y Foucault ayudan a comprender la existencia de modalidades de tratamiento para las adicciones a las drogas que, sin fundarse en el encierro como técnica primordial de control de los cuerpos, sostienen un proceso de clausura y despojo significativos; y que la renuncia a homologar la clausura, y el espacio cerrado a una materialidad, permitió dar realce a una vivencia de despojo subjetivo de parte de quienes se encuentran en tratamiento en la institución

Tabulation of multiple responses

Although multiple response questions are quite common in survey research, Stata's official release does not provide much possibility for an effective analysis of multiple response variables. For example, in a study on drug addiction an interview question might be, "Which substances did you consume during the last four weeks?" The respondents just list all the drugs they took if any, e.g., an answer could be "cannabis, cocaine, heroin" or "ecstasy, cannabis" or "none", etc. Usually, the responses to such questions are held as a set of variables and, therefore, cannot be easily tabulated. I will address this issue and present a new module to compute one- and two-way tables of multiple responses. The module supports several types of data structure, provides significance tests, and offers various options to control the computation and display of the results.

Income disparity among persons with disabilities assessed by education and sex : findings from a field survey conducted in Metro Manila, the Philippines

How do persons with disabilities (PWDs) earn a living? From the view point of poverty reduction, this question is quite critical in developing countries. This paper presents an investigation of economic activities of PWDs in the Philippines where, among developing countries, disability-related legislation is relatively progressive. In 2008, a field survey was conducted in cooperation with Disability People’s Organizations (DPOs) using a tailor-made questionnaire in four representative cities of Metro Manila. The level and determinants of income of PWDs were examined with Mincer regression. Conclusions are as follows: (1) The incidence and depth of poverty are greater among sample PWDs than that of the total population in Metro Manila. (2) There is remarkable income disparity among PWDs which is associated with education and sex. (3) After controlling individual, parental, and environmental characteristics, it was found that female PWDs are likely to earn less than male PWDs due to fewer opportunities to participate in economic activities. It is suggested that female PWDs are doubly handicapped in earning income.

The effects of cocaine self-administration on dendritic spine density in the rat hippocampus are dependent on genetic background

Chronic exposure to cocaine induces modifications to neurons in the brain regions involved in addiction. Hence, we evaluated cocaine-induced changes in the hippocampal CA1 field in Fischer 344 (F344) and Lewis (LEW) rats, 2 strains that have been widely used to study genetic predisposition to drug addiction, by combining intracellular Lucifer yellow injection with confocal microscopy reconstruction of labeled neurons. Specifically, we examined the effects of cocaine self-administration on the structure, size, and branching complexity of the apical dendrites of CA1 pyramidal neurons. In addition, we quantified spine density in the collaterals of the apical dendritic arbors of these neurons. We found differences between these strains in several morphological parameters. For example, CA1 apical dendrites were more branched and complex in LEW than in F344 rats, while the spine density in the collateral dendrites of the apical dendritic arbors was greater in F344 rats. Interestingly, cocaine self-administration in LEW rats augmented the spine density, an effect that was not observed in the F344 strain. These results reveal significant structural differences in CA1 pyramidal cells between these strains and indicate that cocaine self-administration has a distinct effect on neuron morphology in the hippocampus of rats with different genetic backgrounds.

A TRAJETÓRIA DO SESCTV: desafios na busca por uma nova linguagem televisiva

O SESCTV, canal de televisão administrado pelo Serviço Social do Comércio de São Paulo, caracteriza-se como uma iniciativa peculiar em seu âmbito midiático por diversos fatores. Estes condicionantes, por terem múltiplas origens - da natureza institucional à linguagem criada - desenham uma emissora que desperta inúmeros pontos de debate em torno dela e do meio televisivo. O objeto configura-se como referência também no que diz respeito ao amadurecimento da televisão por assinatura, sobretudo no campo educativo-cultural. Procura-se, aqui, considerar as variantes basilares do canal, que compreendem a construção de linguagem nele processada e o respectivo modo de produzir sentidos, sendo estes dois eixos analisados mediante uma contextualização social, política, econômica e cultural interna e externa ao objeto. Já o percurso metodológico traçado disseca os pontos convergentes e divergentes das relações estabelecidas pelo canal ao longo de sua trajetória. Trata-se de uma reflexão que mensura, a partir dos condicionantes expostos, os potenciais caminhos para que o SESCTV firme-se na história televisiva brasileira como iniciativa de protagonismo e vanguarda. Uma visão crítica que enxerga o atual como ponto de partida e não como fim.(AU)

A TRAJETÓRIA DO SESCTV: desafios na busca por uma nova linguagem televisiva

O SESCTV, canal de televisão administrado pelo Serviço Social do Comércio de São Paulo, caracteriza-se como uma iniciativa peculiar em seu âmbito midiático por diversos fatores. Estes condicionantes, por terem múltiplas origens - da natureza institucional à linguagem criada - desenham uma emissora que desperta inúmeros pontos de debate em torno dela e do meio televisivo. O objeto configura-se como referência também no que diz respeito ao amadurecimento da televisão por assinatura, sobretudo no campo educativo-cultural. Procura-se, aqui, considerar as variantes basilares do canal, que compreendem a construção de linguagem nele processada e o respectivo modo de produzir sentidos, sendo estes dois eixos analisados mediante uma contextualização social, política, econômica e cultural interna e externa ao objeto. Já o percurso metodológico traçado disseca os pontos convergentes e divergentes das relações estabelecidas pelo canal ao longo de sua trajetória. Trata-se de uma reflexão que mensura, a partir dos condicionantes expostos, os potenciais caminhos para que o SESCTV firme-se na história televisiva brasileira como iniciativa de protagonismo e vanguarda. Uma visão crítica que enxerga o atual como ponto de partida e não como fim.(AU)

REFLEXOS INDIVIDUAIS DO USO PESSOAL E EXCESSIVO DE COMUNICADORES INSTANTÂNEOS NO AMBIENTE DE TRABALHO

A Internet está inserida no cotidiano do indivíduo, e torna-se cada vez mais acessível por meio de diferentes tipos de dispositivos. Com isto, diversos estudos foram realizados com o intuito de avaliar os reflexos do seu uso excessivo na vida pessoal, acadêmica e profissional. Esta dissertação buscou identificar se a perda de concentração e o isolamento social são alguns dos reflexos individuais que o uso pessoal e excessivo de aplicativos de comunicação instantânea podem resultar no ambiente de trabalho. Entre as variáveis selecionadas para avaliar os aspectos do uso excessivo de comunicadores instantâneos tem-se a distração digital, o controle reduzido de impulso, o conforto social e a solidão. Através de uma abordagem de investigação quantitativa, utilizaram-se escalas aplicadas a uma amostra de 283 pessoas. Os dados foram analisados por meio de técnicas estatísticas multivariadas como a Análise Fatorial Exploratória e para auferir a relação entre as variáveis, a Regressão Linear Múltipla. Os resultados deste estudo confirmam que o uso excessivo de comunicadores instantâneos está positivamente relacionado com a perda de concentração, e a variável distração digital exerce uma influência maior do que o controle reduzido de impulso. De acordo com os resultados, não se podem afirmar que a solidão e o conforto social exercem relações com aumento do isolamento social, devido à ausência do relacionamento entre os construtos.

Dopamine-dependent responses to morphine depend on glucocorticoid receptors

Previous work has shown that glucocorticoid hormones facilitate the behavioral and dopaminergic effects of morphine. In this study we examined the possible role in these effects of the two central corticosteroid receptor types: mineralocorticoid receptor (MR), and glucocorticoid receptor (GR). To accomplish this, specific antagonists of these receptors were infused intracerebroventricularly and 2 hr later we measured: (i) locomotor activity induced by a systemic injection of morphine (2 mg/kg); (ii) locomotor activity induced by an infusion of morphine (1 μg per side) into the ventral tegmental area, which is a dopamine-dependent behavioral response to morphine; (iii) morphine-induced dopamine release in the nucleus accumbens, a dopaminergic projection site mediating the locomotor and reinforcing effects of drugs of abuse. Blockade of MRs by spironolactone had no significant effects on locomotion induced by systemic morphine. In contrast, blockade of GRs by either RU38486 or RU39305, which is devoid of antiprogesterone effects, reduced the locomotor response to morphine, and this effect was dose dependent. GR antagonists also reduced the locomotor response to intraventral tegmental area morphine as well as the basal and morphine-induced increase in accumbens dopamine, as measured by microdialysis in freely moving rats. In contrast, spironolactone did not modify dopamine release. In conclusion, glucocorticoids, via GRs, facilitate the dopamine-dependent behavioral effects of morphine, probably by facilitating dopamine release. The possibility of decreasing the behavioral and dopaminergic effects of opioids by an acute administration of GR antagonists may open new therapeutic strategies for treatment of drug addiction.