RESUMEN
Losing a loved one is among the most common and stressful traumatic events that a child or and adolescent can experience and can be associated with mental health and somatic disorders, as well as a range of life issues and potentially negative outcomes that may impact longitudinal development. Complicated grief, a disorder that has been studied primarily among adults, has received increasing recognition among children and adolescents in recent years. The demonstration of the distinctive character of grief reactions in relation to major depressive disorder and posttraumatic stress disorder has resulted in the inclusion of "persistent complex bereavement disorder" in an annex section of DSM-5 and of "prolonged grief disorder" in ICD-11. The grieving process in children and adolescents is not linear and is often characterised by periods of regression. Developmental phases should be taken into account to understand and clinically describe grief reactions occurring during childhood and adolescence. There are currently numerous interventions for bereaved children and adolescents, but little evidence to support them. More research focusing on the understanding of the underlying mechanisms and the risk factors for complicated grief among children and adolescents, as well as the implementation of evidence-based interventions, is definitely warranted.
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Aflicción , Trastorno Depresivo Mayor , Adolescente , Adulto , Niño , Trastorno Depresivo Mayor/epidemiología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Pesar , Humanos , Clasificación Internacional de EnfermedadesRESUMEN
BACKGROUND AND AIM: Psychiatric emergency services (PES) have recently occupied a new and growing place in the landscape of mental health services. However, few data are available on the way psychiatrists practice in the PES. Our aim was to survey psychiatrists working in PES, focusing on their job satisfaction and the theoretical models they use in their everyday practice. METHOD: We sent a survey to a sample of 508 psychiatrists working in PES in France. RESULTS: Two hundred and thirty-seven psychiatrists returned the survey, yielding a response rate of 47%. On a 0 to 10 scale, the mean level of job satisfaction was 6.7 (SD: 1.92). Participants reported that facing a variety of clinical situations and playing a key-coordinating role in the mental health system were the two most specific features of emergency psychiatry. The main sources of dissatisfaction were organizational issues and stressful clinical experiences, including violence or hostility. Sixty-three percent (n=150) of participants reported using more than two theoretical models in their practice, while the use of crisis models was reported by almost 40% of them. When assessed for suggestions to improve the PES, the majority of participants indicated that efforts should be focused on organizational factors. CONCLUSION: While emergency psychiatry could appear as an ungrateful practice, the majority of psychiatrists who responded to our survey reported satisfaction with their work and highlighted its unique particularities. Future research and collaborations are needed to identify organizational models of PES and their better integration in mental health networks.
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Servicios de Urgencia Psiquiátrica , Satisfacción en el Trabajo , Fatiga Mental/psicología , Psiquiatría , Adulto , Agotamiento Profesional , Femenino , Francia , Humanos , Masculino , Fatiga Mental/etiología , Persona de Mediana Edad , Estrés Psicológico/etiología , Estrés Psicológico/psicología , Encuestas y Cuestionarios , Lugar de Trabajo/psicologíaRESUMEN
Eucalypts cover most of Australia. Here, we investigate the relative contribution of climate and geochemistry to the distribution and diversity of eucalypts. Using geostatistics, we estimate major element concentrations, pH, and electrical conductivity at sites where eucalypts have been recorded. We compare the median predicted geochemistry and reported substrate for individual species that appear associated with extreme conditions; this provides a partial evaluation of the predictions. We generate a site-by-species matrix by aggregating observations to the centroids of 100-km-wide grid cells, calculate diversity indices, and use numerical ecology methods (ordination, variation partitioning) to investigate the ecology of eucalypts and their response to climatic and geochemical gradients. We find that ß-diversity coincides with variations in climatic and geochemical patterns. Climate and geochemistry together account for less than half of the variation in eucalypt species assemblages across Australia but for greater than 80% in areas of high species richness. Climate is more important than geochemistry in explaining eucalypts species distribution and change in assemblages across Australia as a whole but there are correlations between the two sets of environmental variables. Many individual eucalypt species and entire taxonomic sections (Aromatica, Longistylus of subgenus Eucalyptus, Dumaria, and Liberivalvae of subgenus Symphyomyrtus) have distributions affected strongly by geochemistry. We conclude that eucalypt diversity is driven by steep geochemical gradients that have arisen as climate patterns have fluctuated over Australia over the Cenozoic, generally aridifying since the Miocene. The diversification of eucalypts across Australia is thus an excellent example of co-evolution of landscapes and biota in space and time and challenges accepted notions of macroecology.
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Biodiversidad , Clima , Eucalyptus/clasificación , Eucalyptus/genética , Suelo/química , Australia , Conductividad Eléctrica , Elementos Químicos , Eucalyptus/crecimiento & desarrollo , Concentración de Iones de Hidrógeno , FilogeografíaRESUMEN
BACKGROUND: Considering the remarkable efficacy of the strategies for preventing mother-to-child transmission of HIV infection (PMTCT), failures are rare in high-resource countries and deserve further investigation. Moreover, infants have been found to be at increased risk of viral failure. We analyzed the factors related to the children's environment, including maternal psychological factors that may be associated with viral failure in children diagnosed before the age of 1 year. PATIENTS AND METHODS: Retrospective study of all HIV-infected infants, born in France between July 2003 and July 2013, diagnosed before the age of 1 year, cared for in a single reference center, comparing the group of children in viral success to the group of children presenting at least one episode of viral failure, using data available in their medical, psychological and social files. RESULTS: Out of 1061 infants included in the prospective PMTCT follow-up, eight infants were found HIV-positive and an additional six cases were referred from other centers before the age of 1 year, for a total of 14 children born to 13 mothers. Seven children presented durable optimal viral control (VL<50 c/mL) whereas seven others did not reach or maintain optimal viral control over time. The main difference between the two groups was the presence among the mothers of children with viral failure of severe psychological disorders, leading to treatment adherence problems in the mothers who were aware of their HIV status before pregnancy, and difficulties in giving their children's treatments correctly. CONCLUSIONS: Although seroconversion during pregnancy is responsible for a significant proportion of residual transmission in high-resource countries, severe psychological or psychiatric conditions in HIV-positive mothers play an important role on the risk of both MTC residual transmission and viral failure in their infants.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/prevención & control , Infecciones por VIH/transmisión , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Femenino , Estudios de Seguimiento , Infecciones por VIH/psicología , VIH-1/efectos de los fármacos , Humanos , Lactante , Recién Nacido , Masculino , Cumplimiento de la Medicación/psicología , Madres/psicología , Embarazo , Estudios Retrospectivos , Factores de Riesgo , Insuficiencia del TratamientoRESUMEN
PURPOSE: Transfusion ratios approaching 1:1 FFP:PRBC for trauma resuscitation have become the de facto standard of care. The aim of this study was to prospectively evaluate the effect of increasing ratios of FFP:PRBC transfusion on survival for massively transfused civilian trauma patients as well as determine if time to reach the target ratio had any effect on outcomes. METHODS: This is a prospective, observational study of all trauma patients requiring a massive transfusion (≥10 PRBC in ≤24 h) at a level 1 trauma center over a 2.5-year period. The ratio of FFP:PRBC was tracked hourly up to 24 h post-initiation of massive transfusion. A logistic regression model was utilized to identify the ideal ratio associated with mortality prediction. A stepwise logistic regression was performed to identify independent predictors of mortality. RESULTS: The study population was predominantly male (89 %) with a mean age of 34.8 ± 16. On admission, 22 % had a systolic blood pressure ≤90 mmHg, 47 % had a heart rate ≥120, and 25 % had a GCS ≤8. The overall mortality was 33 %. The ratio of FFP:PRBC ≥ 1:1.5 was the second most important independent predictor of mortality for this population (R (2) = 0.59). Survivors had a higher FFP:PRBC ratio at all times during the first 24 h of resuscitation. CONCLUSIONS: Achieving a ratio of FFP:PRBC ≥ 1:1.5 after the initial 24 h of resuscitation significantly improves survival in massively transfused trauma patients compared to patients that achieved a ratio <1:1.5.
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Cuidados Críticos/métodos , Transfusión de Eritrocitos , Traumatismo Múltiple/terapia , Resucitación , Centros Traumatológicos/estadística & datos numéricos , Adulto , Transfusión de Eritrocitos/estadística & datos numéricos , Femenino , Mortalidad Hospitalaria , Humanos , Tiempo de Internación , Modelos Logísticos , Los Angeles/epidemiología , Masculino , Traumatismo Múltiple/complicaciones , Traumatismo Múltiple/mortalidad , Estudios Prospectivos , Resucitación/métodos , Resucitación/mortalidad , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVES: While researches focusing on posttraumatic stress disorder (PTSD) symptoms following childbirth tend to develop, few studies have been conducted on French samples. The aim of the current study was to explore the prevalence rate of women developing postpartum PTSD following preterm birth and highlighting associated features. PATIENTS AND METHOD: In the 4weeks following the preterm infant's hospital discharge, a sample of 110 French women (mean age [SD]=29.5 [4.3]years) who delivered prematurely completed questionnaires assessing PTSD symptoms (Impact of Event Scale-Revised) postpartum depressive symptomatology (Edinburgh Postnatal Depression Scale), quality of marital relationship (Dyadic Adjustment Scale) and partner support (Multidimensional Scale of Perceived Social Support). Sociodemographic and gynecologic data were also gathered. RESULTS: Thirty percent of our sample reported a score on the IES-R highlighting a probable posttraumatic stress disorder. Increased postpartum depressive symptoms (ß=0.47, P<0.05), having undergone a caesarian section (ß=0.24, P<0.05), and prior traumatic event (ß=0.20, P<0.05), were independently associated with the intensity of PTSD symptoms. DISCUSSION AND CONCLUSION: Given the traumatic impact of preterm birth on mothers, further studies focusing on the trauma of premature delivery are warranted.
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Nacimiento Prematuro/psicología , Trastornos por Estrés Postraumático/epidemiología , Adulto , Cesárea , Femenino , Francia , Humanos , Matrimonio/psicología , Embarazo , Trastornos Puerperales/psicología , Encuestas y CuestionariosRESUMEN
OBJECTIVE: The authors had for aim to describe the effectiveness and the safety of a saquinavir/ritonavir (SQV/r) regimen, 1000/100mg twice daily, in HIV-infected pregnant patients. PATIENTS AND METHOD: We made a prospective and observational study of HIV positive female patients beginning or going on SQV/r antiretroviral treatment (ART) during pregnancy. RESULTS: Sixty-two patients were enrolled from July 2007 to June 2009 in 10 infectious diseases units in France. Thirty-six women (group 1) were ART naive on inclusion, 20 (group 2) had been previously treated and then switched to SQV/r, six (group 3) were treated with SQV/r before pregnancy. 58 patients delivered while on SQV/r regimen after a median pregnancy duration of 39 WA. Eighty percent had a viral load below 50 copies/mL and 93% below 400 copies/mL: respectively 77% and 93.5% in group 1, 83% and 89% in group 2, 83% and 100% in group 3. The median SQV minimum concentrations (C(min)) measured at the third trimester and at delivery were adequate, respectively 0.91 mg/L and 0.86 mg/L. Most women (52%) had a vaginal delivery; 12 (21%) had an elective caesarean section, for obstetrics factors in eight cases. None of the newborns were HIV-infected at 6 months of age (n = 59, one death at day 3). Only one severe adverse event occurred due to saquinavir (maternal grade 3 hepatotoxicity). CONCLUSION: SQV/r 1000/100mg twice daily seems to be effective and safe in HIV-infected pregnant women with adequate saquinavir C(min).
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Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1 , VIH-2 , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Ritonavir/uso terapéutico , Saquinavir/uso terapéutico , Adulto , Recuento de Linfocito CD4 , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Estudios de Cohortes , Parto Obstétrico/estadística & datos numéricos , Quimioterapia Combinada , Femenino , Infecciones por VIH/congénito , Infecciones por VIH/prevención & control , Infecciones por VIH/transmisión , Inhibidores de la Proteasa del VIH/administración & dosificación , Inhibidores de la Proteasa del VIH/efectos adversos , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Masculino , Embarazo , Resultado del Embarazo , Estudios Prospectivos , Ritonavir/administración & dosificación , Ritonavir/efectos adversos , Saquinavir/administración & dosificación , Saquinavir/efectos adversos , Resultado del Tratamiento , Carga Viral , Viremia/tratamiento farmacológico , Adulto Joven , Zidovudina/administración & dosificación , Zidovudina/uso terapéuticoRESUMEN
BACKGROUND: Borderline personality disorder (BPD) accounts for 10% of outpatient psychiatric practice. The risk of suicide attempts is high and the psychosocial impairment significant. Different theoretical streams have suggested psychotherapeutical approaches for BPD. OBJECTIVE: to examine the efficacy of psychotherapy for BPD patients on affective symptoms, behavioural outcomes, interpersonal and social functioning, as well as BPD criteria. METHODS: We reviewed the medical literature from 1990 to 2008 on Medline by combining the following keywords "borderline personality disorder" and "psychotherapy" (inclusion criteria). We restricted the analysis to "randomised control trial" or "meta analysis". RESULTS: Of the 39 abstracts that came out from the search, we selected 17 (44%) after applying the exclusion criteria. According to our review, different types of psychotherapies have shown some efficacy on reducing affective symptoms and BPD criteria, as well as improving behavioural outcomes and psychosocial functioning. Dialectical behavioural therapy presents the best-documented efficacy, notably on reducing self-mutilating and suicidal behaviours (five randomized controlled trials [RCT]). Mentalization based treatment seems to be efficient on the four types of outcomes, but has been the object of only one RCT. Finally, some evidence suggests that Manual Assisted Cognitive Treatment and Systems Training for Emotional Predictability and Problem Solving are the most cost-effective and easiest to be implemented. CONCLUSION: According to our review, some evidence supports an efficiency of psychotherapies in the management of several features of BPD. It is likely that, depending on the target symptoms, one type of therapy might be more efficient than another. The acceptability of these long-term treatments is however unknown.
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Trastorno de Personalidad Limítrofe/terapia , Psicoterapia/métodos , Afecto , Trastorno de Personalidad Limítrofe/diagnóstico , Trastorno de Personalidad Limítrofe/psicología , Humanos , Relaciones Interpersonales , Cuidados a Largo Plazo , Evaluación de Procesos y Resultados en Atención de Salud , Ensayos Clínicos Controlados Aleatorios como Asunto , Automutilación/prevención & control , Automutilación/psicología , Ajuste Social , Conducta Social , Intento de Suicidio/prevención & control , Intento de Suicidio/psicologíaRESUMEN
BACKGROUND: Although the reliable and valid Peritraumatic Distress Inventory (PDI-C) and Peritraumatic Dissociative Experiences Questionnaire (PDEQ) are useful for identifying adults at risk of developing acute and chronic posttraumatic stress disorder (PTSD), they have not been validated in school-aged children and their predictive values remain unknown in this population. This study aims to assess the psychometric properties of the children versions of these two measures (PDI-C and PDEQ-C) in a sample of French-speaking school-children. METHODS: One-hundred and thirty-three consecutive victims of road traffic accidents, aged 8-15 years, were recruited into this longitudinal study via the emergency room. The peritraumatic reactions were assessed at baseline and PTSD symptoms were assessed 1 month later. RESULTS: Cronbach's alpha coefficients were 0.8 and 0.77 for the PDI-C and PDEQ-C, respectively. The 1-month test-retest correlation coefficient (n=33) was 0.77 for both measures. The PDI-C demonstrated a two-factor structure while the PDEQ-C displayed a one-factor structure. As with adults, the two measures were intercorrelated (r=0.52) and correlated with subsequent PTSD symptoms and diagnosis (r=0.21-0.56; P<0.05). CONCLUSIONS: The children versions of the PDI and PDEQ are reliable and valid in children.
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Accidentes de Tránsito/psicología , Trastornos Disociativos/diagnóstico , Trastornos por Estrés Postraumático/diagnóstico , Encuestas y Cuestionarios/normas , Sobrevivientes/psicología , Accidentes de Tránsito/estadística & datos numéricos , Adolescente , Niño , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Trastornos Disociativos/complicaciones , Trastornos Disociativos/psicología , Femenino , Francia , Humanos , Acontecimientos que Cambian la Vida , Estudios Longitudinales , Masculino , Psicometría/métodos , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Trastornos por Estrés Postraumático/complicaciones , Trastornos por Estrés Postraumático/psicologíaRESUMEN
INTRODUCTION: The therapeutic alliance in psychotherapy refers to the quality of the relationship between therapist and patient, as well as their agreement upon the aims and tasks of the treatment. This concept is widely used in clinical settings and, since the validation of a number of instruments, has become the focus of much research. However, the quantity of experimental evidence now available impedes the dissemination of these findings among clinicians in a concise manner. LITERATURE FINDINGS: The present paper aimed to provide a review of the literature reporting experimental evidence focusing on the therapeutic alliance. In order to do this, findings were organized around four main issues: the relationship between the therapeutic alliance and clinical outcome; the evolution of the therapeutic alliance over time; the mechanism of action by which the therapeutic alliance encourages change, and finally the factors that have been shown to influence the creation and evolution of the alliance. DISCUSSION: This review reveals that the therapeutic alliance is to this day one of the most investigated factors of psychotherapy. The therapeutic alliance enables change to take place during psychotherapy and, along with a number of specific factors, appears to be important for clinical outcome. Over time, the therapeutic alliance has been seen to evolve and several patterns have been identified. A number of characteristics inherent to the patient, the therapist, and even their interaction have been reported to influence the development and strength of the therapeutic alliance. Several hypotheses have been put forward to account for the mechanism by which the therapeutic alliance encourages change. CONCLUSION: The area of research regarding the therapeutic alliance remains dynamic. Despite the present body of knowledge surrounding this concept, a number of research questions await further investigation.
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Investigación Empírica , Relaciones Médico-Paciente , Psicoterapia , Adaptación Psicológica , Estudios de Seguimiento , Humanos , Resultado del TratamientoAsunto(s)
Sarampión/diagnóstico , Adulto , Anticuerpos Antivirales/sangre , Diagnóstico Precoz , Femenino , Francia/epidemiología , Humanos , Inmunoglobulina M/sangre , Sarampión/patología , Sarampión/prevención & control , Vacuna Antisarampión/administración & dosificación , Vacuna Antisarampión/inmunología , Insuficiencia del TratamientoRESUMEN
We report the case of a 27-year-old man presenting with a hepatic abscess and hereditary hemorrhagic telangiectasia (HHT). The association between HHT and an infectious disease seemed to be induced by arteriovenous malformations and maybe also by a deficit of polymorphonuclear cells, a monocyte oxidative burst and phagocytosis. This diagnosis should be suggested in case of serious infections in young patients. Prevention is based on screening for and destroying infection, antibioprophylaxis and embolization of arteriovenous malformations.
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Absceso Hepático/complicaciones , Infecciones Estreptocócicas/complicaciones , Streptococcus anginosus , Telangiectasia Hemorrágica Hereditaria/complicaciones , Adulto , Humanos , MasculinoAsunto(s)
Angioplastia Coronaria con Balón/psicología , Trastornos de Ansiedad/epidemiología , Trastornos de Ansiedad/psicología , Trastorno Depresivo/epidemiología , Trastorno Depresivo/psicología , Isquemia Miocárdica/psicología , Isquemia Miocárdica/terapia , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/psicología , Calidad de Vida/psicología , Anciano , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The term treatment barrier describes obstacles to the treatment process. These obstacles affect the patient: there may be melancholic crypts in encysted trauma ; there may be a link rooted to a dead person in the form of attachment to the internal object: there are different forms of moral masochism. Barriers relating to the therapist may be seen in therapists who take a dogmatic position: the therapist must realise these counter-attitudes and their impatience or irritation movements. In the patient doctor-interaction, understanding previous treatment failures and the relationship style developed with other therapists plays an important role. The concept of the negative therapeutic reaction in which any clinical progress returns to aggravation must also be investigated.
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Trastorno Depresivo Mayor/terapia , Acontecimientos que Cambian la Vida , Aceptación de la Atención de Salud/psicología , Relaciones Médico-Paciente , Antidepresivos/uso terapéutico , Contratransferencia , Mecanismos de Defensa , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Humanos , Apego a Objetos , Pronóstico , Psicoterapia , Trastornos Somatomorfos/diagnóstico , Trastornos Somatomorfos/psicología , Trastornos Somatomorfos/terapia , Resultado del TratamientoRESUMEN
Different cleaning and silanization methods have been applied to bioactive glasses with the aim of covalently bonding bone morphogenetic proteins (BMP-2) to the surface. Several glasses, with different bioactivity index, were cleaned with acidic, basic, or neutral aqueous media to investigate the role of pH in the formation of silanols on glass surfaces of different reactivity. The cleaned glasses were then functionalized using 3-aminopropyl-triethoxysilane (APTS). After the optimization of the silanization procedure, proteins of different complexity were immobilized on the functionalized glasses. To optimize the protein immobilization, a model protein (carnosine) was first used, and the procedure was then used to bind human BMP-2. The glass surfaces were characterized during each step of the treatment by water contact angles and X-ray photoelectron analyses. The APTS functionalization was then used to immobilize bone morphogenetic protein on the bioactive glasses. This result suggested that such a treatment could be successfully used as an efficient alternative to systemic administration of transforming growth factors for the development of local delivery vehicle implants.
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Proteína Morfogenética Ósea 2/química , Vidrio/química , Sistemas de Liberación de Medicamentos/métodos , Humanos , Proteínas Inmovilizadas/química , Prótesis e Implantes , Silanos/química , Propiedades de SuperficieRESUMEN
BACKGROUND: Management of suicide attempters accounts for 10% of the psychiatric activity in the emergency room. In this population, the prevalence of borderline personality disorder (BPD) is high (10 - 55%). These patients present poorer psychosocial outcome and more frequent suicide attempts repetitions. However, the utility of the assessment of BPD in the referral to a specific treatment plan has not been yet studied. OBJECTIVE: To examine the association between the assessment of a diagnosis of BPD after a suicide attempt and the referral from the emergency room to a specific treatment plan. HYPOTHESIS: Suicide attempters with BPD, according to clinicians diagnosis, differ in terms of severity from those without more risk factors of suicide attempt repetitions and poorer psychosocial functioning, and in psychiatric referral from the emergency room. METHOD: Our case-control study took place during 10 months in the Geneva general hospital. We continuously enrolled patients admitted to the emergency room for deliberate self poisoning and separated them into two groups (BPD and control) according to the clinician's diagnosis. Data from medical records were systemically and anonymously gathered. We compared BPD patients' socio-demographic and clinical characteristics, as well as psychiatric referral, with the control group. RESULTS: Of the 478 subjects admitted to the emergency room for deliberate self-poisoning, 99 (22.6%) were diagnosed BPD by clinicians. Compared to controls, they were more frequently female (OR=3.9) and living alone (OR=3.8) and more often resorted to psychiatric care (OR=2.9), notably to emergency care (OR=3.8). Past history of suicide attempt was also more frequent (OR=1.9) as was the use of neuroleptics in the attempt (OR=2.7). No difference was detected in terms of psychiatric referral after emergency room care. CONCLUSION: Even if borderline personality disorder in suicide attempters is associated with more severity criteria, it is not associated with a referral to a specific treatment plan.
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Trastorno de Personalidad Limítrofe/diagnóstico , Determinación de la Personalidad , Derivación y Consulta , Intento de Suicidio/psicología , Adulto , Trastorno de Personalidad Limítrofe/epidemiología , Trastorno de Personalidad Limítrofe/psicología , Estudios de Casos y Controles , Estudios Transversales , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intoxicación/epidemiología , Intoxicación/psicología , Psicopatología , Recurrencia , Ajuste Social , Intento de Suicidio/estadística & datos numéricos , SuizaAsunto(s)
Brucella melitensis , Brucelosis/complicaciones , Absceso del Psoas/etiología , Adulto , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Brucelosis/tratamiento farmacológico , Niño , Doxiciclina/administración & dosificación , Doxiciclina/uso terapéutico , Quimioterapia Combinada , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Absceso del Psoas/diagnóstico , Absceso del Psoas/tratamiento farmacológico , Rifampin/administración & dosificación , Rifampin/uso terapéutico , Factores de Tiempo , Resultado del TratamientoRESUMEN
Phenobarbital, a classical inducer of the drug-metabolizing cytochrome P450 genes, induces alpha1-acid glycoprotein gene expression through a PB-responsive element (PBRE) located at position -142 to -126 from the transcriptional start site. The aim of this study was to investigate nuclear protein binding to the PBRE sequence after PB treatment. Cycloheximide treatment showed that de novo protein synthesis was not required for PB to induce AGP gene expression, pointing to post-translational modifications. Studies of the DNA-protein complex with the PBRE showed that phosphorylation status is a key regulator of the binding capacity of transactivating proteins involved in PB transcriptional activation. This DNA-protein complex, analyzed by southwestern blotting and UV cross-linking, involves three nuclear factors with molecular weights of 43, 52, and 65 kDa. Supershift and competition experiments showed that the 43-kDa factor can be related to C/EBPalpha and the 52- and 65-kDa factors to the two subunits of NF-kappaB.
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Proteínas de Unión al ADN/genética , Regulación de la Expresión Génica/efectos de los fármacos , Hígado/metabolismo , FN-kappa B/genética , Proteínas Nucleares/genética , Animales , Proteínas Potenciadoras de Unión a CCAAT , Proteínas de Unión al ADN/biosíntesis , Masculino , Proteínas Nucleares/biosíntesis , Procesamiento Proteico-Postraduccional , Ratas , Ratas Sprague-DawleyRESUMEN
The gene encoding alpha-1-acid glycoprotein (AGP), one of the major acute-phase proteins, is positively controlled at the transcriptional level by cytokines (interleukin-1 [IL-1], IL-6, and tumor necrosis factor alpha) and glucocorticoids. Here, we show that growth hormone (GH) treatment of isolated rat hepatocytes in vitro reduces AGP messenger RNA (mRNA) expression. AGP gene expression remained inducible by IL-1, IL-6, and phenobarbital (PB) in GH-treated hepatocytes. Interestingly, the repressive effect of GH on AGP gene expression was also observed in vivo: liver AGP mRNA content was strongly increased in hypophysectomized rats, and GH treatment of these animals led to a decrease in mRNA to levels lower than those in untreated control animals. Moreover, the inhibitory effect of GH mainly occurs at the transcriptional level and can be observed as little as 0.5 hours after GH adding in vitro to isolated hepatocytes. These results show negative regulation of AGP gene expression and strongly suggest that GH is a major endogenous regulator of constitutive AGP gene expression. Moreover, transfection assays showed that the region of the AGP promoter located at position -147 to -123 is involved in AGP gene regulation by GH. Furthermore, GH deeply modifies the pattern of nuclear protein binding to this region. GH treatment of hypophysectomized rats led to the release of proteins of 42 to 45 and 80 kd and to the binding of proteins of 48 to 50 and 90 kd.
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Regulación de la Expresión Génica , Hormona del Crecimiento/fisiología , Hígado/metabolismo , Orosomucoide/biosíntesis , Animales , Northern Blotting , Núcleo Celular/metabolismo , Células Cultivadas , Reactivos de Enlaces Cruzados , Dexametasona/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Hormona de Crecimiento Humana/farmacología , Hipofisectomía , Interleucina-1/farmacología , Interleucina-6/farmacología , Hígado/efectos de los fármacos , Hígado/ultraestructura , Masculino , Proteínas Nucleares/metabolismo , Orosomucoide/genética , Fenobarbital/farmacología , Regiones Promotoras Genéticas/efectos de los fármacos , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Transcripción GenéticaRESUMEN
The activities of HIV-specific cytotoxic T lymphocytes (CTLs) were evaluated in 10 HIV-infected children, born to infected mothers who did not receive AZT during pregnancy. CTL activities were present as early as 4 months of age. The five children that progressed to AIDS before 1 year of age had reduced in vivo and in vitro CTL activities, when compared with children who remained AIDS free after 1 year of age. The latter children had weak in vivo activated CTL responses but strong memory CTLs. No relation was found between viral load, lymphocyte populations, and CTL responses between birth and 6 months of age. Between 7 and 12 months old, children with broader in vitro activated CTLs had higher absolute numbers of CD4+ and CD8+ T lymphocytes and lower plasma viral load. These data support a beneficial role of CTLs in pediatric HIV infection.