Epidemiología de la urgencia psiquiátrica en el Instituto Psiquiátrico Doctor José Horwitz: un nuevo estudio comparativo / Epidemiology of psychiatric emergency consultations psychiatric Institute Doctor José Horwitz: a new comparative study

Introducción: Una urgencia psiquiátrica es cualquier alteración del afecto, conducta o pensamiento que puede producir daños a terceros o al consultante. La consulta de urgencia ido en aumento en los últimos años. Objetivos: Determinar la prevalencia de las distintas patologías, describir su distribución según sexo, edad, sector de residencia, estado civil, ocupación, previsión y derivación en las consultas de urgencia psiquiátrica en el Hospital Psiquiátrico "Dr. JoséHorwitz" de Santiago y comparar estos resultados con publicaciones previas de estudios en el mismo centro. Material y Método: Muestra representativa de 1999 casos, escogidos aleatoriamente de las consultas realizadas entre el Iº de julio de 2005 y el 30 de junio de 2006. Se agruparon los diagnósticos de acuerdo a la nomenclatura CIE-10. Resultados: 48,7 por ciento de las consultas fueron realizadas por pacientes de sexo masculino. La media de edad fue 39 años. 76,7 por ciento de las consultas fueron realizadas en horario diurno. El 48,3 por ciento de los pacientes no tiene ocupación. 48 por ciento eran solteros. Abuso de sustancias y alcohol, trastornos esquizoides, afectivos y neuróticos congregan el 73,9 por ciento de las consultas. La más prevalente fue la de trastornos asociados al abuso de sustancias y alcohol con un 19,7 por ciento del total. Conductas autoagresivas (74 por ciento) y trastornos afectivos (74 por ciento) se asoció más a mujeres, en cambio el abuso de sustancias y alcohol más con hombres (76 por ciento). Discusión: Las consultas por trastornos esquizoides han disminuido a lo largo de los años. En cambio las consultas por el abuso de sustancias y alcohol y los trastornos afectivos han aumentado. Se hacen sugerencias para enfrentar el nuevo perfil epidemiológico.

Introduction: A psychiatric emergency is any alteration of affection, thought or behavior that may cause harm to others or to the same consultant. These consultations have increased over the last years. Objectives: Determine the prevalence of the various pathologies, describing their distribution according to sex, age, area of residence, marital status, occupation, health insurance, and referral in psychiatric emergency consultations at "Dr. José Horwitz" Hospital of Santiago, and to compare these results with previously published studies in the same center. Material and Method: We used a representative sample of 1999 cases, chosen randomly from consultations held between July 1,2005 and June 30,2006. Diagnoses were grouped according to the nomenclature of the ICD-10. Results: 48.7 percent of the consultations were carried out by male patients and. Average age of consultation was 39. 76.7 percent of consultations were carried out in daytime. The 48.3 percent of people who consulted didn't have any occupation. 48 percent were singles. Abuse of substances and alcohol, schizoid, afective and neurotic disorders congregate 73.9 percent of total consultations. The most prevalent were the disorders associated with abuse of substances and alcohols with a 19.7 percent overall. Autoagressive behaviors (74 percent) and affective disorders (74 percent) were associated with females, while abuse of substances and alcohol was associated with males (76 percent). Discussion: Schizoid disorders have proportionally declined in importance over the years. In contrast, abuse of substances and alcohol, and affective disorders have increased their frecuency. Suggestions are made to FACE the new epidemiological profile.

Spatial memory of heterozygous staggerer (Rora(+)/Rora(sg)) versus normal (Rora(+)/Rora(+)) mice during aging.

Heterozygous staggerer mice (Rora(+)/Rora(sg)) and control mice (Rora(+)/Rora(+)) of the same C57BL/6J strain background were tested in a spontaneous alternation task at 3 to 24 months old. The results demonstrated a decrement in long-term working memory as early as 6 months in Rora(+)/Rora(+) mice and at 3 months in Rora(+)/Rora(sg) mice. Previous studies showed that in both cases, neuronal number in the cerebellar cortex was normal. This suggests that age-dependent decrease in long-term working memory would be due to fine structural or biochemical changes preceding neuronal death in the cerebellum. Such subtle changes would occur more precociously in Rora(+)/Rora(sg) than in Rora(+)/Rora(+) mice. Also, short-term working memory was preserved in Rora(+)/Rora(+) mice as old as 24 months, but was impaired in 6-month-old Rora(+)/Rora(sg) mice.

Effect of training on motor abilities of heterozygous staggerer mutant (Rora(+)/Rora(sg)) mice during aging.

Heterozygous cerebellar mutant (Rora(+)/Rora(sg)) mice and control (Rora(+)/Rora(+)) mice of the same C57Bl6/J strain, 3-24 months old, were subjected to motor training on a rotorod for 10 days. Falling latency and percentage of time spent walking were measured. A good correlation was found between falling latency and walking time: the mice which maintained equilibrium for a long time were those which were walking, and the mice which fell early were those which were gripping suggesting that walking is obviously the most adapted strategy to keep balance on the rotorod. In Rora(+)/Rora(+) mice, scores before training were altered very precociously (from 6 months of age). Moreover, scores of Rora(+)/Rora(sg) mice were lower than those of Rora(+)/Rora(+) mice from the age of 3 months, while neuronal number in the cerebellar cortex of these mutants was quite normal and similar to that of Rora(+)/Rora(+) mice. This suggests that the motor skill disability would be due to fine structural and/or biochemical changes preceding neuronal death. Such subtle changes would begin several months earlier in Rora(+)/Rora(sg) than in Rora(+)/Rora(+) mice. Training on the rotorod resulted in increased scores in both genotypes at all ages. Motor learning abilities were therefore preserved in animals with a moderate neuronal loss in the cerebellum. It may be that motor learning is partly compensated by the striatum, which is known to play a major role in learning of motor skills.

Angiogenesis induced in muscle by a recombinant adenovirus expressing functional isoforms of basic fibroblast growth factor.

The present work studies the effects of a replication-deficient adenovirus (Ad), Ad-RSVbFGF, bearing the human basic fibroblast growth factor (bFGF) cDNA, as a potential vector for therapeutic angiogenesis of ischemic diseases. The different isoforms of the protein were expressed from the viral vector in various cell types and, although the cytoplasmic isoform does not possess a signal peptide, we observed its release from a muscle cell line. The proteins were fully functional when tested in a long-term survival assay of quiescent fibroblasts. After endothelial cell infection with Ad-RSVbFGF, we observed an 80&percnt increase in the mean length of the capillary-like tubes that differentiated in a three-dimensional model of angiogenesis. We evaluated angiogenesis directly in mice 14 days after subcutaneous injection of Matrigel plugs containing Ad-RSVbFGF. A marked neovascularization was observed in the Matrigel plugs and in the surrounding tissues. Finally, the recombinant virus was injected into the hindlimb muscles of mdx mice. A 2.5-fold increase in bFGF content of the muscle was observed 6 days after injection, without any significant variations detected in the animal sera. Immunohistological detection showed an increased number of large-caliber vessels in the treated muscles as compared with control muscles. These results demonstrate that Ad-mediated transfer of the human bFGF gene can induce angiogenesis in muscle, making this tissue a potential target for the treatment of ischemic diseases.

Efficient, repeated adenovirus-mediated gene transfer in mice lacking both tumor necrosis factor alpha and lymphotoxin alpha.

The efficiency of adenovirus-mediated gene transfer is now well established. However, the cellular and the humoral immune responses triggered by vector injection lead to the rapid elimination of the transduced cells and preclude any efficient readministration. The present investigation focuses on the role of tumor necrosis factor alpha (TNF-alpha), a proinflammatory cytokine, and the related cytokine lymphotoxin alpha (LTalpha), in mounting an immune reaction against recombinant adenovirus vectors. After gene transfer in the liver, mice genetically deficient for both cytokines (TNF-alpha/LTalpha-/-), in comparison with normal mice, presented a weak acute-phase inflammatory reaction, a reduction in cellular infiltrates in the liver, and a severely impaired T-cell proliferative response to both Adenoviral and transgene product antigens. Moreover, we observed a strong reduction in the humoral response to the vector and the transgene product, with a drastic reduction of anti-adenovirus immunoglobulin A and G antibody isotypes. In addition, the reduction in antibody response observed in TNF-alpha/LTalpha-/- and TNF-alpha/LTalpha+/- mice versus TNF-alpha/LTalpha+/+ mice links antibody levels to TNF-alpha/LTalpha gene dosage. Due to the absence of neutralizing antibodies, the TNF-alpha/LTalpha knockout mice successfully express a second gene transduced by a second vector injection. The discovery of the pivotal role played by TNF-alpha in controlling the antibody response against adenovirus will allow more efficient adenovirus-based strategies for gene therapy to be proposed.

Role of the cerebellum in exploration behavior.

Compared to +/+ mice, Lurcher (+/Lc) mutant mice whose cerebellar cortex is lacking almost all Purkinje cells and granule cells, exhibit a low level of exploration; this deficit is not due to a low level of activity but to both a decreased motivation to explore a novel environment and to spatial deficits. The characteristics of exploration in cerebellectomized +/+ and +/Lc mice suggest that the cerebellum is involved not only in cognitive but also in motivational processes.

Enhanced endocrine response to novel environment stress and endotoxin in Lurcher mutant mice.

Lurcher mutant mice which are mainly known for their cerebellar degeneration, also display a hyperinducibility of proinflammatory cytokines, such as interleukin-1alpha and beta (IL-1) and tumor necrosis factor alpha (TNF-alpha), in peripheral macrophages. To assess whether this increased responsiveness to inflammatory stimuli is accompanied by a higher pituitary-adrenal response, we compared the adrenocorticotropic hormone (ACTH) and corticosterone response of Lc and wild-type mice to intraperitoneal (i.p.) administration of a cytokine inducer, lipopolysaccharide (LPS). Lurcher mice display resting levels of ACTH and corticosterone similar to those of wild-type mice. LPS (1.25 microg/g) induces a corticosterone surge 2-fold higher in Lurcher than in wild-type mice. By contrast, the response to IL-1alpha (10 ng/g, i.p.) is similar in both genotypes, suggesting that a differential reactivity of the hypothalamo-pituitary adrenal axis to IL-1 does not account for the higher reactivity of Lurcher mice to LPS. To test whether the increased responsiveness of the pituitary-adrenal axis of Lurcher mice generalizes accross stressors, mice were exposed to a novel environment. This condition also induced a surge of ACTH and corticosterone 3.5- and 2-fold higher in Lurcher than in wild-type mice. Prior blockade of IL-1 receptors by injection of IL-1 receptor antagonist (10 microg/g, i.p.) failed to block the response to LPS injection and exposure to novelty. In contrast, immunoneutralization of hypothalamic corticotropin-releasing hormone (CRH) significantly attenuated the ACTH surge and abrogated the difference between Lurcher and wild-type mice in their responses to a novel environment, suggesting that hypothalamic CRH neurons are involved in this excessive response.

Expression from cardiomyocyte-specific promoter after adenovirus-mediated gene transfer in vitro and in vivo.

Adenoviruses are very attractive vectors for gene transfer into the cardiac muscle; however, their promiscuous tissue tropism, leading to an ectopic expression of the transgene, is a considerable practical limitation. To restrict expression of a reporter gene in cultured cardiomyocytes and in the heart of the rat, we have constructed a recombinant adenovirus (Ad-MLC2 beta gal) containing the beta-galactosidase gene under the control of the rat ventricle-specific cardiac myosin light chain 2 (MLC-2v) promoter. We show in this work that the MLC-2v promoter inside the adenoviral genome retains its cardiac specificity in vitro in cultured cardiomyocytes as well as in vivo in the animal heart. Northern blot studies after Ad-MLC2 beta gal infection show significant transcription only in cells derived from the cardiac muscle and not from the skeletal muscle. Quantitative analysis of the beta-galactosidase activity in a number of cell lines also confirms this result. The level of beta-galactosidase expression in rat neonatal cardiomyocytes infected with Ad-MLC2 beta gal is 8% of that found when primary cells are infected with Ad-RSV beta gal (containing a beta-galactosidase gene under the control of the Rous sarcoma virus promoter). The cardiomyocytes-specific expression is also found after injection of Ad-MLC2 beta gal directly into the rat myocardium, although the viral genome can be detected by polymerase chain reaction (PCR) in other tissues. Lack of expression after direct injection into liver and skeletal muscle confirms these results. The use of a tissue-specific promoter is a first step to restrict transgene expression to a particular cell type of the targeted tissue.

Over-expression of interleukin-1 beta-converting enzyme mRNA in staggerer cerebellum.

Interleukin-1 beta-converting enzyme (ICE), involved in the maturation process of interleukin-1 beta (IL-1 beta, is a homologue of ced-3, a protease required for programmed cell death in Caenorhabditis elegans. Over-expression of ICE induces programmed cell death in certain mammalian cell types, whereas in neurones of the central nervous system such a role has yet to be established. We show that ICE mRNA expression is increased 4-fold in the cerebellum of homozygous staggerer mice, where IL-1 beta mRNA is overexpressed and programmed neuronal cell death occurs. Intraperitoneal injection of endotoxin (LPS) induced a strong phasic increase in IL mRNA levels in the cerebellum, whereas the ICE mRNA level increased only moderately. Involvement of ICE in neuronal cell death in the cerebellum of staggerer mice is suspected.

Differential roles of cerebellar cortex and deep cerebellar nuclei in the learning of the equilibrium behavior: studies in intact and cerebellectomized lurcher mutant mice.

Three- to 6-month-old lurcher mutant mice (+/lc), which exhibit a massive loss of neurons in the cerebellar cortex and in the inferior olivary nucleus but whose deep cerebellar nuclei are essentially intact, were trained daily, for 9 days, to maintain their equilibrium upon a rota rod rotating at 20 or 30 revolutions per minute (rpm). Their scores were measured and their behavior upon the rotating rod quantified in comparison to those of matched control (+/+) mice. Lurcher mice were able to learn to maintain their equilibrium efficiently when rotated at 20 rpm but were not when rotated at 30 rpm. After cerebellectomy, the equilibrium capabilities of the animals were much altered, especially in +/lc. These results show that the deep cerebellar nuclei are sufficient for motor learning, provided the task is not too difficult (20 rpm), but that the cerebellar cortex is required when the task is more difficult (30 rpm). Therefore, it can be concluded that the adaptive motor capabilities of lurcher mice are less developed than those of control animals.

Reduced incidence of spontaneous mammary tumors in C3H/He mice after treatment with polyadenylate-polyuridylate.

The effect of treatment with the double-stranded polynucleotide complex polydenylate with polyuridylate [poly(A) with poly(U)] on tumor development in C3H/He mice was evaluated. Poly(A) with poly(U) was injected in newborn females, and mice were observed for 380 days. During this experimental period 42 percent of treated mice developed tumors, while the incidence in the control group was 63 percent. This difference was statistically significant.