[Migraine and evolutionary theory: paths for a clinical approach]. / Migraña y teoria evolutiva: vias para un acercamiento clinico.

INTRODUCTION: Migraine is a very common disorder with a raising incidence. The theory of evolution allow us to explain the emergence of the disorder, due to the advantages that the overreactivity to stimulus provided to ancestral groups of Homo sapiens, and a greater presence of the disorder in modern societies, based in the interactions with external factors. Herein we analyze these points. DEVELOPMENT: Design of organisms and their responses to environmental factors emerge to improve survival. Thus pain and headache can be contemplated as homeostatic and adaptative responses. Below 10% of the population has no experience with headache and the migrainous phenotype is quite frequent in secondary headaches and in syndromic forms of migraine. These features can be understood under the next undergrounds: specific neurophysiological data (lack of habituation, sensibilization and low preactivation), genetic features (polygenic disorder with the implication of many gens with a low penetrance, that interact with the environment and are shared with comorbid disorders such as depression and anxiety); and environmental interactions in modern societies (increase in the number of estrogenic cycles and particularly overexposition to stress). CONCLUSIONS: A feature that was an evolutionary advantage has been transformed in a highly prevalent and disabling disorder in modern societies. It is the result of the interaction with internal (estrogenic cycles) and external (stress) stimuli. As a consequence, it becomes a mismatch disorder. The effects appear in childhood through epigenetics. Therefore, therapeutic interventions would yield greater benefits if whole populations were included in educative interventions incorporating these aspects.

TITLE: Migraña y teoria evolutiva: vias para un acercamiento clinico.Introduccion. La migraña es un trastorno muy comun, con incidencia en aumento. La teoria evolutiva permite explicar su aparicion, dadas las ventajas que aportaba a grupos originarios de Homo sapiens una mayor reactividad a estimulos, y la presencia creciente de interaccion con factores ambientales. Analizamos estos aspectos a traves de los mecanismos potenciales que los explican. Desarrollo. El diseño de los organismos y sus respuestas ambientales surgen para mejorar la supervivencia. Asi, el dolor y la cefalea pueden entenderse como respuestas homeostaticas y adaptativas. Menos del 10% de la poblacion no tiene experiencia de cefalea, y el fenotipo migrañoso es una repuesta dolorosa comun en formas secundarias y sindromicas de cefalea. Estas caracteristicas se entienden segun rasgos neurofisiologicos especificos (falta de habituacion, sensibilizacion y baja preactivacion), caracteristicas geneticas (trastorno poligenico con multiples genes de baja penetrancia, que interaccionan con el ambiente y que son comunes a los de los trastornos comorbidos, como depresion-ansiedad) e interaccion ambiental en las sociedades modernas (aumento del numero de ciclos estrogenicos, y especialmente sobreexposicion al estres). Conclusiones. Lo que fue una ventaja evolutiva se ha transformado en la sociedad moderna en un trastorno muy prevalente y frecuentemente incapacitante. Es el resultado de una interaccion con sobrecarga de estimulos externos (estres) e internos (hormonales), lo que, de acuerdo con la teoria evolutiva, convertiria a la migraña en una enfermedad por desajuste. Los efectos ocurririan precozmente, en la infancia, a traves de mecanismos de epigenetica. Se obtendria un gran beneficio terapeutico mediante intervenciones poblacionales y educativas que incorporen estos aspectos.

[3T tractography imaging: anatomy and clinical applications]. / Imagen de tractografía 3T: anatomía y aplicaciones clínicas.

Tractography (TG) is the only non-invasive technique that enables the fibres of the white substance to be dissected. This technique can study the projection, association, and commissural fibres, and is an improvement and an important complement to conventional MR imaging. TG is an important tool for preoperative sub-cortical mapping, and there is a good correlation between TG and the direct sub-cortical stimulation technique. TG can have false positives in regions infiltrated by the tumour or with a mass effect. Furthermore, a negative TG does not exclude functional fibre persistence. TG is capable of demonstrating changes in other pathologies (congenital malformations, ischaemic disease and demyelinating diseases).

A 13-year molecular epidemiological analysis of tuberculosis in San Francisco.

BACKGROUND: We examined the molecular epidemiology of tuberculosis (TB) in San Francisco during a 13-year period encompassing the peak of TB resurgence and subsequent decline to historic low levels. OBJECTIVE: To compare rates of TB caused either by rapid progression of recent Mycobacterium tuberculosis infection or by reactivation of latent infection. METHODS: All TB cases reported from 1991 to 2003 were included. Genotyping was performed to identify clustered cases. RESULTS: The annual TB case rate decreased significantly from 50.8 to 28.8 cases/100000 persons from 1992 to 1999 (P < 0.0001). After 1999, no significant decrease was observed for the population as a whole or in any subgroup examined. Similarly, the rate of clustered cases decreased significantly from 1992 to 1999 (11.4 to 3.1 cases/100000, P < 0.0001). Although the rate of non-clustered cases also declined significantly (25.6 to 17.6 cases/100,000, P < 0.0001), there was a disproportionate reduction in clustered cases (94.7% vs. 50.8%, P < 0.0001). Neither clustered nor non-clustered cases decreased significantly after 1999. CONCLUSIONS: TB case rates reached a plateau despite ongoing application of control measures implemented in 1993. These data suggest that intensification of measures designed to identify and treat persons with latent TB infection will be necessary to further reduce TB incidence.

Análisis coste-efectividad en procesos que requieren ventilación mecánica. Estudio de los GRD 475 y 483 / Cost-effectiveness analysis in conditions that require mechanical ventilation. A DRGs 475 and 483 study

Objetivo. Evaluar la relación coste-efectividad del tratamiento en procesos complejos predefinidos que precisan ventilación mecánica (VM). Diseño. Estudio de cohorte retrospectivo con análisis coste-efectividad y estimación del porcentaje de pacientes sometidos a cuidados potencialmente ineficientes (CPI). Ámbito. Unidad de Cuidados Intensivos (UCI) de un hospital general. Pacientes. Pacientes ingresados entre los años 1997 y 2001, asignados al alta hospitalaria a los GRD 475 (diagnósticos del sistema respiratorio con ventilación asistida) y 483 (traqueostomía excepto trastornos de la boca, laringe o faringe). Intervenciones. Ninguna. Variables de interés principales. Edad, sexo, gravedad (mediante APACHE II), estado crónico de salud, grupo patológico de base, estancia en UCI, estancia hospitalaria, duración de la VM, mortalidad hospitalaria predicha y observada. Estimación del coste-efectividad mediante cociente entre costes totales hospitalarios y años de vida ganados (avg). Porcentaje de pacientes sometidos a CPI, definido como pacientes con costes totales superiores al percentil 90 y destino exitus. Resultados. Se estudiaron 247 pacientes, 142 del GRD 475 y 105 del GRD 483. Los dos grupos poseían características similares, salvo mayor predominio de pacientes médicos, menor estancia y duración de VM en el GRD 475. El costeefectividad fue favorable en todos los subgrupos estudiados, y mostró un incremento en ambos grupos de GRD según aumentaba la edad, la gravedad y la duración de la VM. La distribución del coste-efectividad por estado crónico de salud no mostró diferencias en el GRD 475, mientras que en el GRD 483 se producía un incremento del mismo según empeoraba el estado de salud. En el GRD 483 y grupo patológico de base cardiológico, se observaron los peores valores de costeefectividad. El porcentaje de CPI fue del 7,0 por ciento en GRD 475 y del 5,4 por ciento en GRD 483. Conclusiones. El tratamiento de los pacientes críticos agrupables a los GRD 475 y 483, se ha mostrado coste-efectivo de forma global y en todos los subgrupos analizados. La estimación del coste-efectividad y del porcentaje de pacientes sometidos a CPI, en procesos con similar complejidad de la casuística, ofrece información médica y económica del funcionamiento de una UCI (AU)

Absceso prostático como causa poco frecuente de shock séptico / Prostatic abscess as a unusual cause of septic shock

El absceso prostático es una enfermedad poco frecuente, asociada generalmente a prostatitis, y cuyo diagnóstico puede retrasarse por lo inespecífico de la clínica. Es aún más raro que aparezcan complicaciones graves sistémicas. Será preciso un alto nivel de sospecha y la realización de técnicas de imagen para llegar a un diagnóstico de certeza. Presentamos el caso de un paciente en situación de shock séptico secundario a un absceso de próstata. Tras revisar la bibliografía comprobamos que son escasos los casos documentados de complicaciones sistémicas graves de este tipo de pacientes (AU)

Neuroactive steroids influence peripheral myelination: a promising opportunity for preventing or treating age-dependent dysfunctions of peripheral nerves.

The process of aging deeply influences morphological and functional parameters of peripheral nerves. The observations summarized here indicate that the deterioration of myelin occurring in the peripheral nerves during aging may be explained by the fall of the levels of the major peripheral myelin proteins [e.g., glycoprotein Po (Po) and peripheral myelin protein 22 (PMP22)]. Neuroactive steroids, such as progesterone (PROG), dihydroprogesterone (5alpha-DH PROG), and tetrahydroprogesterone (3alpha,5alpha-TH PROG), are able to stimulate the low expression of these two myelin proteins present in the sciatic nerve of aged male rats. Since Po and PMP22 play an important physiological role in the maintenance of the multilamellar structure of PNS myelin, we have evaluated the effect of PROG and its neuroactive derivatives, 5alpha-DH PROG and 3alpha,5alpha-TH PROG, on the morphological alterations of myelinated fibers in the sciatic nerve of 22-24-month-old male rats. Data obtained clearly indicate that neuroactive steroids are able to reduce aging-associated morphological abnormalities of myelin and aging-associated myelin fiber loss in the sciatic nerve.

[Orbital vasculonervous network and orbital surgical compartments by high field magnetic resonance]. / Dotación vasculonerviosa y espacios anatomoquirúrgicos de la órbita por resonancia magnética de alto campo.

PURPOSE: To elucidate the possibilities and indications of high-resolution magnetic resonance imaging (MRI) in the study of the orbit and its contents. METHODS: Orbital anatomy was studied in sliced specimens of fifteen fresh frozen cadavers and the results were compared with those obtained in thirty asymptomatic subjects who underwent a magnetic resonance with 1.5 Tesla equipment. The information obtained was used to interpret the findings in twenty-two patients with various orbital diseases. RESULTS: High-resolution MRI allows visualization of structures difficult to assess previously, like the cerebrospinal fluid (CSF) surrounding the optic nerve, the complete intraorbital route and the exit of the third cranial nerve, the ophthalmic artery and the intraorbital relationships of the sixth cranial nerve, which can be clearly differentiated from the lateral rectus muscle. CONCLUSIONS: High-resolution MRI is a very useful tool for the study of the orbit and its content. It provides accurate diagnoses through non-invasive procedures and facilitates the planning of the surgical approaches by improving the visualization of pathologic orbital structures. lcarlos@correo.uniovi.es

Effects of neuroactive steroids on myelin of peripheral nervous system.

Peripheral nervous system (PNS) possess both classical (e.g. progesterone receptor, PR, androgen receptor, AR) and non-classical (e.g. GABA(A) receptor) steroid receptors and consequently may represent a target for the action of neuroactive steroids. Our data have indicated that neuroactive steroids, like for instance, progesterone, dihydroprogesterone, tetrahydroprogesterone, dihydrotestosterone and 3alpha-diol, stimulate both in vivo and in vitro (Schwann cell cultures), the expression of two important proteins of the myelin of peripheral nerves, the glycoprotein Po (Po) and the peripheral myelin protein 22 (PMP22). It is important to highlight that the mechanisms by which neuroactive steroids exert their effects on the expression of Po and PMP22 involve different kind of receptors depending on the steroid and on the myelin protein considered. In particular, at least in culture of Schwann cells, the expression of Po seems to be under the control of PR, while that of PMP22 needs the GABA(A) receptor. Because Po and PMP22 play an important physiological role for the maintenance of the multilamellar structure of the myelin of the PNS, the present observations might suggest the utilization of neuroactive steroids as new therapeutically approaches for the rebuilding of the peripheral myelin.

[Inflammatory mechanisms, arteriosclerosis and ischemic stroke: clinical data and perspectives]. / Mecanismos inflamatorios, arteriosclerosis e ictus isquémico: datos de interés clínico y perspectivas.

OBJECTIVE: The atherosclerosis is the most common cause of death and disability in developed countries by causing ischemic cardiopathic and stroke. The ischemic atherotrombotic stroke is the most frequent form of the last one. In this sense we review herein the mechanisms underlying the artherosclerotic process. DEVELOPMENT: It is understood as an inflammatory disease, by taking into account the widely accepted hypothesis by Ross: it was firstly stated in structural terms, as macrophages and T/B linfocities were present in the arterial wall from the first stages of the disease (fatty streak) to the last and complicated ones. The starting point is a functional endothelial damage, secondary to mechanical or vascular risk factors and called response to injury hypothesis . The next step is an inflammatory cascade that involves humoral (citokines, growth factors) and cellular (increased quimiotaxis, adherece and infiltration of inflamatory cells) mechanisms. They interact among them, outbalanced and in a progresssive way that leads to the final fibroproliferative response. Every stage has his own inflammatory components and interactive pathways. The following elements are outstanding in this process: 1) Adhesion molecules, including E selectin, ICAM 1 and VCAM 1, that are increased locally in the plaques and as circulating elements; plaquetary receptors of the type IIb/IIIa are integrins wich belong to the same family; 2) Citokines with either proinflammatory activity like IL 1, the TNF a and linfocitary ligands like the CD 40, or with antiinflammatory activity like the gamma interpheron; 3) Growth factors, with plaquetary (PDGF) and fibroblastic (FGF) variants as the cornerstone; 4) Markers of systemic inflammation, overall plasma C reactive protein and fibrinogen, that predict the risk of stroke and cardiovascular death; IL 6, complement, thrombin and heat shock proteins (HSP) would act in a similar but less conclusive way. CONCLUSIONS: The evidences of the pivotal role of the inflammation in the stroke allow to develop therapeutical strategies to prevent the disease: fostering natural antiinflamatory mechanisms, or inhibiting inflammatory elements by selective (monoclonal antibodies) or non selective (IIb/IIIa receptors, antiinflammatory drugs) pathways are distinctily glimpsed, ongoing or fully developed.

Mecanismos inflamatorios, arteriosclerosis e ictus isquémico: datos de interés clínico y perspectivas / Inflammatory mechanisms, arteriosclerosis and ischemic stroke: clinical data and perspectives

Objetivo. La arteriosclerosis es la causa más común de muerte y discapacidad en los países desarrollados, debido a su papel principal en la cardiopatía isquémica e ictus, del cual la forma aterotrombótica resulta la más frecuente. Revisamos aquí los mecanismos subyacentes a la enfermedad arteriosclerótica. Desarrollo. Consideramos ésta un proceso inflamatorio de acuerdo con la hipótesis de Ross, inicialmente descrita en términos estructurales, ya que macrófagos y linfocitos T/B están presentes en la pared arterial desde los primeros (fatty streak) hasta los últimos y complicados estadios de la enfermedad. El punto de inicio es un daño endotelial funcional, secundario a factores de riesgo vascular o mecánicos, definido como ` response-to-injury hypothesis'. El siguiente paso es una cascada inflamatoria que incluye factores humorales (citocinas y factores de crecimiento) y celulares (aumento de quimiotaxis, adherencia e infiltración de células inflamatorias), que interactúan entre ellos de manera progresiva, dando lugar a la respuesta fibroproliferativa. Cada estadio tiene sus propios componentes inflamatorios e interacciones. Los siguientes elementos destacan en este proceso: 1) Moléculas de adhesión, incluyendo la E-selectina, ICAM-1 y VCAM-1, que están aumentados localmente en las placas y en el plasma; los receptores plaquetarios del tipo IIb/IIIa son integrinas pertenecientes a la misma familia; 2) Citocinas con actividad proinflamatoria -tales como la IL-1 o el TNF-alfa- y ligandos inflamatorios -como el CD-40-, o con actividad antiinflamatoria, como interferón- gama; 3) Factores de crecimiento: las variantes plaquetarias (PDGP) y fibroblástica (FGF) serían los elementos claves; 4) Marcadores de inflamación sistémica, sobre todo la proteína C reactiva plasmática y el fibrinógeno, que predicen el riesgo de ictus y de muerte cardiovascular; la IL-6, complemento, trombina y proteinas de `golpe de calor' (HSP) actuarían de modo similar pero menos decisivo. Conclusiones. Las evidencias del papel fundamental de la inflamación en el ictus permiten desarrollar estrategias terapéuticas para prevenir la enfermedad, ya sea fomentando los mecanismos antiinflamatorios o inhibiendo los elementos inflamatorios por vías selectivas (anticuerpos monoclonales) o no selectivas (receptores IIb/IIIa, fármacos antiinflamatorios); se vislumbra su desarrollo completo en un futuro próximo (AU)

Interactions between GABAergic and aminoacidergic pathways in the control of gonadotropin and GH secretion in pre-pubertal female rats.

Present experiments were carried out in 23-day-old female rats to analyze the interaction between excitatory amino acids (EAAs) and gamma-aminobutyric acid (GABA) in the control of gonadotropin and GH secretion. For this purpose, serum concentrations of LH, FSH and GH were measured after injection of different agonists of EAA receptor subtypes [N-methyl-D-aspartate (NMDA); kainic acid (KA), (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)], antagonists of GABA receptors (bicuculline, phaclofen) or the combined administration of both types of drugs. The results obtained indicated that: 1) GABA has a minor physiological role in the control of LH and GH secretion, since neither LH nor GH serum concentrations changed after administration of bicuculline (antagonist of GABA(A) receptors) or phaclofen (antagonist of GABA(B) receptors); 2) GABA has a sex-specific physiological role in the control of FSH secretion in female rats, in which FSH secretion increases after phaclofen administration; 3) GH secretion was enhanced after administration of NMDA, KA and AMPA, while LH increased only after activation of NMDA receptors; 4) the stimulatory effect of NMDA on LH secretion was counteracted by administration of phaclofen; and 5) bicuculline and phaclofen reduced the ability of NMDA and AMPA to stimulate GH secretion. In conclusion, present experiments evidenced a physiological role of GABA, mediated by GABA(B) receptors, in the control of FSH secretion and a cross-talk between excitatory and inhibitory amino acids in the control of anterior pituitary secretion.

Comparative effects of testosterone propionate, oestradiol benzoate, ICI 182,780, tamoxifen and raloxifene on hypothalamic differentiation in the female rat.

Hypothalamic differentiation in the female rat during the neonatal period is critically dependent on the steroid milieu, as permanent changes in reproductive function are observed after administration of oestradiol and testosterone during such a critical stage. Selective oestrogen modulators (SERMs) constitute a family of drugs that, depending on the tissue, are able to exert oestrogenic or antioestrogenic actions. The present experiments were conducted to analyse whether the SERMs, tamoxifen and raloxifene, can cause oestrogenic actions during the hypothalamic differentiation period. Postnatal female rats were injected between days 1 and 5 with 100 microg/day tamoxifen, raloxifene or ICI 182,780 (a pure antioestrogen). Other groups of animals were injected on day 1 of age with 100 microg oestradiol benzoate (OeB) or 1.25 mg testosterone propionate (TP) alone or in combination with raloxifene (500 microg/day between days 1 and 5). In all experimental groups, the age, body weight and concentrations of serum gonadotrophins at vaginal opening were recorded, whereas vaginal cyclicity and the negative and positive feedback between oestradiol and LH were monitored in adulthood. The results obtained confirmed the ability of high doses of OeB or TP to alter the normal differentiation of the brain permanently. They also reinforced the hypothesis that oestrogens are also necessary for normal brain differentiation in female rats because administration of a pure antioestrogen, such as ICI 182,780 permanently altered the function of the reproductive axis. In addition, our data provided evidence for different actions of the two SERMs under analysis (raloxifene and tamoxifen) upon peripheral targets, as raloxifene advanced vaginal opening whereas tamoxifen did not. In contrast, their actions on brain differentiation appeared similar and analogous to those obtained after neonatal administration of oestradiol, as evidenced by vaginal acyclicity, ovarian atrophy, sterility and abolition of negative and positive feedback between oestradiol and LH, thus suggesting an oestrogenic action of these SERMs on hypothalamic differentiation. Moreover, the oestrogenic activity of raloxifene was supported by its inability to block the effects of OeB and TP administered neonatally. In conclusion, the present results indicated that the SERMs, tamoxifen and raloxifene, exert an oestrogen-like effect upon hypothalamic differentiation of the neonatal female rat.