Sanger sequencing is no longer always necessary based on a single-center validation of 1109 NGS variants in 825 clinical exomes.

Despite the improved accuracy of next-generation sequencing (NGS), it is widely accepted that variants need to be validated using Sanger sequencing before reporting. Validation of all NGS variants considerably increases the turnaround time and costs of clinical diagnosis. We comprehensively assessed this need in 1109 variants from 825 clinical exomes, the largest sample set to date assessed using Illumina chemistry reported. With a concordance of 100%, we conclude that Sanger sequencing can be very useful as an internal quality control, but not so much as a verification method for high-quality single-nucleotide and small insertion/deletions variants. Laboratories might validate and establish their own thresholds before discontinuing Sanger confirmation studies. We also expand and validate 23 copy number variations detected by exome sequencing in 20 samples, observing a concordance of 95.65% (22/23).

Riesgo de catarata en fumadores: metaanálisis de estudios observacionales / Risk of cataract in smokers: A meta-analysis of observational studies

Objetivo: El propósito del estudio fue comparar el riesgo de catarata en fumadores y exfumadores. Métodos: La búsqueda sistemática de estudios observacionales se realizó en las bases de datos Medline, Embase y Lilacs. Se seleccionaron estudios que hubieran evaluado la asociación entre fumar cigarrillos y cualquier tipo de catarata diagnosticada clínicamente. Se extrajeron los estimadores de asociación ajustados al menos por edad y se combinaron mediante modelos de efectos aleatorios, por tipo de estudio observacional (cohorte, casos y controles y transversal), por tipo de catarata (nuclear, cortical o subcapsular posterior) y de exposición (fumador actual o exfumador). Se evaluaron heterogeneidad estadística, análisis de meta-regresión y sesgo de publicación. Resultados: Fueron seleccionados 13 estudios de cohortes, 12 de casos y controles y 18 de corte transversal. Se encontró riesgo de catarata en fumadores actuales: cohortes (OR: 1,41; IC 95%: 1,24-1,60), casos y controles (OR: 1,45; IC 95%: 1,08-1,96) y transversales (OR: 1,21; IC 95%: 1,09-1,34) y riesgo de catarata nuclear: cohortes (OR: 1,71; IC 95%: 1,47-1,98), casos y controles (OR: 1,79; IC 95%: 1,43-2,25) y corte transversal (OR: 1,45; IC 95%: 1,27-1,65). No se observó riesgo de catarata cortical ni subcapsular posterior en exfumadores. Conclusiones: En fumadores existe riesgo de catarata, especialmente de tipo nuclear. Con estudios transversales se obtienen resultados similares a los obtenidos con cohortes y casos y controles

Objective: The aim of the study was to compare the risk of cataract in smokers and ex-smokers. Methods: A systematic search of observational studies was carried out in Medline, Embase, and Lilacs databases. Studies that have evaluated the association between cigarette smoking and any type of clinically diagnosed cataract were selected. The association estimators were extracted, adjusted at least by age, and were combined using random-effects models, by subtype of study (cohort, case control and cross sectional), subtype of cataract (nuclear, cortical, and posterior subcapsular), and exposure (current smoker or ex-smoker). Statistical heterogeneity, meta-regression analysis and publication bias were assessed. Results: A total of 13 cohort studies, 12 case-control studies, and 18 cross-sectional studies were selected. A risk of cataract was found in current smokers: cohort (OR: 1.41; 95% CI: 1.24-1.60), cases and controls (OR: 1.45; 95% CI: 1.08-1.96), and cross-sectional studies (OR: 1.21; 95% CI: 1.09-1.34); risk of nuclear cataract: cohort (OR: 1.71; 95% CI: 1.47-1.98), case-control (OR: 1.79; 95% CI: 1.43-2.25), and cross sectional studies (OR: 1.45; 95% CI: 1.27-1.65). There was no risk of cortical or posterior subcapsular cataract in ex-smokers. Conclusions: There is a risk of cataract in smokers, particularly nuclear type. With cross-sectional studies, similar results are obtained with cohorts and cases and controls

Risk of cataract in smokers: A meta-analysis of observational studies. / Riesgo de catarata en fumadores: metaanálisis de estudios observacionales.

OBJECTIVE: The aim of the study was to compare the risk of cataract in smokers and ex-smokers. METHODS: A systematic search of observational studies was carried out in Medline, Embase, and Lilacs databases. Studies that have evaluated the association between cigarette smoking and any type of clinically diagnosed cataract were selected. The association estimators were extracted, adjusted at least by age, and were combined using random-effects models, by subtype of study (cohort, case control and cross sectional), subtype of cataract (nuclear, cortical, and posterior subcapsular), and exposure (current smoker or ex-smoker). Statistical heterogeneity, meta-regression analysis and publication bias were assessed. RESULTS: A total of 13 cohort studies, 12 case-control studies, and 18 cross-sectional studies were selected. A risk of cataract was found in current smokers: cohort (OR: 1.41; 95%CI: 1.24-1.60), cases and controls (OR: 1.45; 95%CI: 1.08-1.96), and cross-sectional studies (OR: 1.21; 95%CI: 1.09-1.34); risk of nuclear cataract: cohort (OR: 1.71; 95%CI: 1.47-1.98), case-control (OR: 1.79; 95%CI: 1.43-2.25), and cross sectional studies (OR: 1.45; 95%CI: 1.27-1.65). There was no risk of cortical or posterior subcapsular cataract in ex-smokers. CONCLUSIONS: There is a risk of cataract in smokers, particularly nuclear type. With cross-sectional studies, similar results are obtained with cohorts and cases and controls.

Evaluación radiológica de muñeca para visualizar la superficie articular del radio / Wrist X ray for analysis of the articular surface of distal radius

Resumen: En la fractura del radio distal se requieren proyecciones radiológicas que permitan ver adecuadamente la superficie articular sin interposición de estructuras. El objetivo fue determinar si las proyecciones radiológicas laterales a 7 y 22o mejoran el análisis de esta superficie. Método: Serie de casos con radiografías de pacientes sanos y operados para identificar las facetas del semilunar y escafoides en las proyecciones lateral y anteroposterior, igualmente se evaluó con tornillos. Se analizaron cualitativamente los hallazgos obtenidos en las radiografías de 7 y 22o para la proyección lateral y de 11o en la anteroposterior. Resultados: 14 radiografías de voluntarios sanos, 10 pacientes con fractura de radio que recibieron osteosíntesis y dos piezas anatómicas. En los 14 sanos y los 10 pacientes se encontró que en las proyecciones a 7 y 22o pueden apreciarse mejor las carillas radio-semilunar y radio-escafoides respectivamente, observando imágenes con menor superposición de estructuras en la radiografía de 22o tanto en los sanos como en los pacientes con fracturas. Discusión: Las proyecciones radiológicas son importantes para poder determinar los resultados inmediatos de una osteosíntesis realizada en una fractura de radio distal. En este estudio se observa que la proyección lateral a 7o identifica mejor la posición de los tornillos ubicados en la carilla semilunar del radio. La proyección lateral a 22o muestra mejor la carilla con el escafoides. Por último en la proyección anteroposterior a 11o nos permite ver la articulación radiocarpiana con menor superposición de imágenes.

Abstract: In the distal radius fracture requires radiographic views that allow you to see the articular surface without interposition. The objective was to determine whether lateral radiographic projections 7 and 22o improve the analysis of this surface. Method: Case series study with radiographs of healthy and operated patients, in order to identify the lunate and scaphoid facets in lateral and anteroposterior projections. Qualitative analysis was made on the radiographs of the distal radius with wedges of 7 and 22o in the lateral views and 11o in the anteroposterior view. Results: There were evaluated 14 radiographs of the distal radius of healthy volunteers and 10 patients with distal radius fractures who recieved surgery with internal fixation, and also two anatomical models. In 14 healthy and 10 patients, it was found that the views at 7 and 22o can be better appreciated radio lunate and radio scaphoid surface respectively, observing images with less overlapping in the radiograph of 22o in both groups. Discussion: Radiographic views are important to determine the immediate results of fixation on a distal radius fracture. We observe that the lateral view at 7o is better to show the screws on the lunate facet of the radius. The lateral view at 22o is better to show the facet of the radius with the scaphoid. Finally, the anteroposterior projection at 11o allows us to see the radio carpal joint with lower image overlay.

[Wrist X ray for analysis of the articular surface of distal radius]. / Evaluación radiológica de muñeca para visualizar la superficie articular del radio.

In the distal radius fracture requires radiographic views that allow you to see the articular surface without interposition. The objective was to determine whether lateral radiographic projections 7 and 22° improve the analysis of this surface. METHOD: Case series study with radiographs of healthy and operated patients, in order to identify the lunate and scaphoid facets in lateral and anteroposterior projections. Qualitative analysis was made on the radiographs of the distal radius with wedges of 7 and 22° in the lateral views and 11° in the anteroposterior view. RESULTS: There were evaluated 14 radiographs of the distal radius of healthy volunteers and 10 patients with distal radius fractures who recieved surgery with internal fixation, and also two anatomical models. In 14 healthy and 10 patients, it was found that the views at 7 and 22° can be better appreciated radio lunate and radio scaphoid surface respectively, observing images with less overlapping in the radiograph of 22° in both groups. DISCUSSION: Radiographic views are important to determine the immediate results of fixation on a distal radius fracture. We observe that the lateral view at 7° is better to show the screws on the lunate facet of the radius. The lateral view at 22° is better to show the facet of the radius with the scaphoid. Finally, the anteroposterior projection at 11° allows us to see the radio carpal joint with lower image overlay.

En la fractura del radio distal se requieren proyecciones radiológicas que permitan ver adecuadamente la superficie articular sin interposición de estructuras. El objetivo fue determinar si las proyecciones radiológicas laterales a 7 y 22° mejoran el análisis de esta superficie. Método: Serie de casos con radiografías de pacientes sanos y operados para identificar las facetas del semilunar y escafoides en las proyecciones lateral y anteroposterior, igualmente se evaluó con tornillos. Se analizaron cualitativamente los hallazgos obtenidos en las radiografías de 7 y 22° para la proyección lateral y de 11° en la anteroposterior. Resultados: 14 radiografías de voluntarios sanos, 10 pacientes con fractura de radio que recibieron osteosíntesis y dos piezas anatómicas. En los 14 sanos y los 10 pacientes se encontró que en las proyecciones a 7 y 22° pueden apreciarse mejor las carillas radio-semilunar y radio-escafoides respectivamente, observando imágenes con menor superposición de estructuras en la radiografía de 22° tanto en los sanos como en los pacientes con fracturas. Discusión: Las proyecciones radiológicas son importantes para poder determinar los resultados inmediatos de una osteosíntesis realizada en una fractura de radio distal. En este estudio se observa que la proyección lateral a 7° identifica mejor la posición de los tornillos ubicados en la carilla semilunar del radio. La proyección lateral a 22° muestra mejor la carilla con el escafoides. Por último en la proyección anteroposterior a 11° nos permite ver la articulación radiocarpiana con menor superposición de imágenes.

Dopamine D2 and angiotensin II type 1 receptors form functional heteromers in rat striatum.

Identification of G protein-coupled receptors and their specific function in a given neuron becomes essential to better understand the variety of signal transduction mechanisms associated with neurotransmission. We hypothesized that angiotensin II type 1 (AT1) and dopamine D2 receptors form heteromers in the central nervous system, specifically in striatum. Using bioluminescence resonance energy transfer, a direct interaction was demonstrated in cells transfected with the cDNA for the human version of the receptors. Heteromerization did not affect cAMP signaling via D2 receptors but attenuated the coupling of AT1 receptors to Gq. A common feature of heteromers, namely cross-antagonism, i.e. the blockade of the signaling of one receptor by the blockade of the partner receptor, was tested in co-transfected cells. Candesartan, the selective AT1 receptor antagonist, was able to block D2-receptor mediated effects on cAMP levels, MAP kinase activation and ß-arrestin recruitment. This effect of candesartan, which constitutes a property for the dopamine-angiotensin receptor heteromer, was similarly occurring in primary cultures of neurons and rat striatal slices. The expression of heteromers in striatum was confirmed by robust labeling using in situ proximity ligation assays. The results indicate that AT1 receptors are expressed in striatum and form heteromers with dopamine D2 receptors that enable drugs selective for the AT1 receptor to alter the functional response of D2 receptors.

Heteromerization of GPR55 and cannabinoid CB2 receptors modulates signalling.

BACKGROUND AND PURPOSE: Heteromerization of GPCRs is key to the integration of extracellular signals and the subsequent cell response via several mechanisms including heteromer-selective ligand binding, trafficking and/or downstream signalling. As the lysophosphatidylinositol GPCR 55 (GPR55) has been shown to affect the function of the cannabinoid receptor subtype 2 (CB2 receptor) in human neutrophils, we investigated the possible heteromerization of CB2 receptors with GPR55. EXPERIMENTAL APPROACH: The direct interaction of human GPR55 and CB2 receptors heterologously expressed in HEK293 cells was assessed by co-immunoprecipitation and bioluminescence resonance energy transfer assays. The effect of cross-talk on signalling was investigated at downstream levels by label-free real-time methods (Epic dynamic mass redistribution and CellKey impedance assays), ERK1/2-MAPK activation and gene reporter assays. KEY RESULTS: GPR55 and CB2 receptors co-localized on the surface of HEK293 cells, co-precipitated in membrane extracts and formed heteromers in living HEK293 cells. Whereas heteromerization led to a reduction in GPR55-mediated activation of transcription factors (nuclear factor of activated T-cells, NF-κB and cAMP response element), ERK1/2-MAPK activation was potentiated in the presence of CB2 receptors. CB2 receptor-mediated signalling was also affected by co-expression with GPR55. Label-free assays confirmed cross-talk between the two receptors. CONCLUSIONS AND IMPLICATIONS: Heteromers, unique signalling units, form in HEK293 cells expressing GPR55 and CB2 receptors. The signalling by agonists of either receptor was governed (i) by the presence or absence of the partner receptors (with the consequent formation of heteromers) and (ii) by the activation state of the partner receptor.

CB1 and GPR55 receptors are co-expressed and form heteromers in rat and monkey striatum.

Heteromerization of G-protein-coupled receptors is an important event as they integrate the actions of extracellular signals to give heteromer-selective ligand binding and signaling, opening new avenues in the development of potential drug targets in pharmacotherapy. The aim of the present paper was to check for cannabinoid CB1-GPR55 receptor heteromers in the central nervous system (CNS), specifically in striatum. First, a direct interaction was demonstrated in cells transfected with the cDNA for the human version of the receptors, using bioluminescence resonance energy transfer and in situ proximity ligation assays (PLA). In the heterologous system, a biochemical fingerprint consisting on cross-antagonism in ERK1/2 phosphorylation was detected. The cross-antagonism was also observed on GPR55-mediated NFAT activation. Direct identification of GPR55 receptors in striatum is here demonstrated in rat brain slices using a specific agonist. Moreover, the heteromer fingerprint was identified in these rat slices by ERK1/2 phosphorylation assays whereas PLA assays showed results consistent with receptor-receptor interactions in both caudate and putamen nuclei of a non-human primate. The results indicate not only that GPR55 is expressed in striatum but also that CB1 and GPR55 receptors form heteromers in this specific CNS region.

Relación entre acúfenos y dolor orofacial: el acúfeno somatosensorial / Relationship between tinnitus and orofacial pain: Somatosensory tinnitus

El objetivo de este trabajo es realizar una puesta al día de la relación entre acúfeno somatosensorial y dolor orofacial. Para ello se analiza la literatura publicada sobre este síntoma, exponiendo las hipótesis sobre los mecanismos fisiopatológicos descritos que intentan explicar como el Núcleo Coclear Dorsal desempeña un papel clave en la generación del acúfeno. También se abordan las características clínicas más importantes a las que el odontólogo debe prestar más atención, desarrollando el protocolo descrito por Levine para su correcto diagnóstico, y por último se exponen las distintas opciones terapéuticas propuestas en la literatura para su manejo y tratamiento desde un enfoque multidisciplinar (AU)

The purpose of this study is to achieve an update of the relationship between somatic tinnitus and orofacial pain. For that aim we analyze the papers published of this symptom, explaining the proposed pathophysiological hypothesis that try to explain how the Dorsal Cochlear Nucleus plays a key role in the tinnitus development. We also make an approach to the most important clinicalcharacteristics for the dentist wich allows us the development of the protocol described by Levine for its correct diagnosis and atlast expose the different therapeutic options proposed in scientific researches for its management and treatment from a multidisciplinaryapproach (AU)

Odontalgía atípica, conocimientos actuales / Atypical odontalgia, current knowledge

En este trabajo se presenta el conocimiento actual acerca de una enfermedad que permanece sin explicación médica, la odontalgia atípica (OA), patología que por su naturaleza es difícil de diagnosticar. OA es una forma crónica de dolor dental sin signos de patología odontológica. Clínicamente se presenta con dolor persistente refractario a los tratamientos dentales convencionales. La mayoría de las veces esta patología se diagnostica erróneamente, lo que puede conducir a tratamientos innecesarios, y producir tanto al paciente como al profesional graves problemas. Vamos a revisar los conocimientos actuales sobre la epidemiología, etiología, fisiopatología, manifestaciones clínicas, diagnóstico, diagnóstico diferencial, pronóstico y tratamiento para tratar de obtener el conocimiento suficiente para tratar con ella si tenemos la oportunidad. En este momento, la mejor hipótesis sobre la fisiopatología de la OA es una condición de dolor neuropático. Diferentes enfermedades tales como dolor odontogénico, la sinusitis o la neuralgia del trigémino entre otros deben ser consideradas en el diagnóstico diferencial. El tratamiento actual se basa en un tratamiento similar al dolor neuropático periférico, se trata con medicamentos tópicos y sistémicos tales como anestésicos locales, antidepresivos y anticonvulsivantes. Siendo conscientes, sin embargo, que todavía hay más preguntas que responder sobre el asunto que las respuestas que aparecen en este artículo (AU)

This paper presents the current knowledge about a disease that still remains medically unexplained, atypical odontalgia (AO), a pathology that by its nature is difficult to diagnose. AO is a chronic form of dental pain without signs of dental pathology. Clinically it is presented with persistent pain refractory to conventional dental treatment, most of the time this condition is misdiagnosed, can lead to unnecessary treatments, and produce serious problems to both the patient and the practitioner. We will review the current knowledge on the epidemiology, etiology, pathophysiology, clinical manifestations, diagnosis, differential diagnosis, prognosis and treatment to try to get enough knowledge to deal with it if is given the chance. At this point, the best hypothesis about the pathophysiology of the AO is that of a neuropathic pain condition. Different diseases such as odontogenic pain, sinusitis or trigeminal neuralgia among others should be considered in the differential diagnosis. Current treatment is based on a similar treatment to peripheral neuropathic pain treated with topical and systemic drugs such as local anesthetics, antidepressants and anticonvulsants. Being aware, however, that there are still more questions to answer on the matter than answers in this article (AU)

Pautas de prevención de defectos congénitos con especial referencia a los niveles primario y secundario. Guías de actuación preventiva desde la atención primaria / Guidelines for the prevention of congenital defects, particularly at primary and secondary level. Prevention guidelines from Primary Care

La prevención de defectos congénitos (DC) no difiere en esencia de la que se sigue para cualquier otra enfermedad. En el primer nivel, el de la prevención primaria, se trata de impedir que se produzca el trastorno. El segundo nivel se aplica cuando el DC ya se ha producido, y consiste en curar la enfermedad o, cuando ello no es posible, como en la mayoría de los DC, evitar que se agrave. Este nivel se basa en el diagnóstico precoz y correcto de la enfermedad, y en instaurar inmediatamente el tratamiento adecuado y las medidas correctoras o paliativas. El tercer nivel se instaura una vez que han fracasado los 2 anteriores y se centra en medidas que mejoren la autonomía y la calidad de vida del paciente (integración social y laboral de los afectados, supresión de barreras arquitectónicas, etc.). Por último, existe un «cuarto nivel de prevención» que consiste en evitar toda sobreactuación médica, en la que se someta al paciente a pruebas innecesarias que no sólo no le ayudan sino que, además, pueden generarle efectos adversos añadidos incluyendo problemas psíquicos. En este artículo se resumen las medidas más relevantes que se deberían implantar desde el colectivo de médicos de atención primaria, para conseguir todos los niveles de prevención de DC y, especialmente, de prevención primaria (AU)

There is essentially no difference in the prevention of congenital defects (CD) from that of any other disease. Primary prevention consists of preventing the causes that produce the disease. Secondary prevention is applied when the CD has already occurred, and consists of curing the disease, or when this is not possible, as in the majority of CD, to prevent it getting worse. This level is based on the early and correct diagnosis of the disease, and initiating immediate and appropriate treatment and corrective or palliative measures. The third level is started when the previous ones fail, and is focussed on measures that improve independence and quality of life (social and occupational integration of those affected, removal of architectural obstacles, etc.). Lastly, there is a “fourth level of prevention”, which consists of avoiding over-medication, in which the patient is subjected to unnecessary tests, which not only do not help the patient, but can also produce added adverse effects, including psychiatric problems. This article summarises the most important measures that Primary Care doctors should introduce to achieve all levels of CD prevention, and particularly primary prevention (AU)

Valproate reduces CHOP levels and preserves oligodendrocytes and axons after spinal cord injury.

Spinal cord injury (SCI) is a major cause of disability to which there are not yet effective treatments. We previously reported that degeneration of oligodendrocytes and neurons that occurs after SCI is associated with the development of endoplasmic reticulum (ER) stress and the progressive accumulation of the pro-apoptotic factor CHOP. Since following ER stress, the balance between the pro-survival chaperone BiP and CHOP drives the cell destiny, we aimed to find drugs that modulate this ratio in favour of the former. We found that valproate (VPA) induced a significant reduction of CHOP levels after ER stress in an organotypic-based culture of spinal cord in vitro. We then administered different doses of VPA to rats following spinal cord contusion, and found that the treatment caused a marked reduction of CHOP levels early after the lesion. In addition, VPA administration partially prevented cord tissue, myelin and axonal loss, and significantly increased the relative number of surviving oligodendrocytes in the damaged spinal cord. Besides, VPA-treated rats showed better recovery of the locomotor activity than vehicle-treated rats after SCI. Since VPA is a drug already in clinical use, these results open the avenue for its therapeutical use in SCI as well as in demyelinating disorders.

Tratamiento farmacológico de la mujer embarazada: fármacos contraindicados durante la gestación / Pharmacological treatment in the pregnant woman: drugs contraindicated during pregnancy

Los médicos de atención primaria atienden a las mujeres embarazadas y en edad reproductiva, por lo que han de decidir sobre el tratamiento que deben seguir. Para ello, han de enfrentarse a la difícil situación de evaluar el riesgo que las diferentes alternativas terapéuticas pueden suponer para el desarrollo embrionario/fetal. Una evaluación que no es sencilla porque no se pueden establecer normas de aplicación general. De hecho, un mismo medicamento puede ser utilizado en algunas mujeres embarazadas y no ser adecuado en otras. Esto implica que la decisión sobre el tratamiento que se debe aplicar durante el embarazo requiera una evaluación individualizada en cada mujer. Por otra parte, la identificación del efecto de los diferentes medicamentos sobre el desarrollo embrionario y fetal humano es muy difícil y, además, está generalmente basada en estudios epidemiológicos observacionales. Esto supone una dificultad añadida porque en muchos casos este tipo de publicaciones no resultan fáciles de entender, lo que dificulta su traslación a la práctica clínica. Esto dio lugar en muchos países a la organización de servicios de información telefónica sobre teratógenos, atendidos por expertos tanto en evaluación de los riesgos para el embrión y feto, como sobre los procesos del desarrollo prenatal. No obstante, sabemos que hay fármacos que no parecen alterar el desarrollo y que pueden utilizarse durante el embarazo si se necesitan, otros que sí conllevan riesgo pero tienen que utilizarse para controlar la enfermedad materna y, por último se conocen otros cuya utilización en mujeres embarazadas o que planean estarlo está contraindicada. Estos últimos en mujeres en edad reproductiva han de utilizarse siguiendo unas estrictas normas para prevención de embarazos. En este artículo se ofrece una visión general sobre los tratamientos en mujeres embarazadas o que pueden estarlo, junto con sus potenciales efectos y se ofrece la lista de aquellos fármacos que se consideran seguros de utilizar durante la gestación y los que están contraindicados (AU)

As primary care doctors treat pregnant women and those of fertile age, they must decide which treatments they should follow. Therefore, they have to confront the difficult situation of assessing the risks that different alternative treatments may have on embryo/foetal development. An assessment that is not straightforward as established general guidelines may not be applicable. For example, one drug may be used in some pregnant women but may not be appropriate in others. This implies that the decision on treatments given during pregnancy requires an individualised assessment in each woman. On the other hand, identifying the effects of different drugs on human embryo and foetal development is very difficult, and is also mainly based on observational epidemiological studies. This makes it even more difficult as in many cases these publications are not easy to understand, making it difficult to apply in clinical practice. This has led to introducing Telephone Information Services on Teratogenics in many countries, which are answered by experts in the assessment of risks for the embryo and foetus, as well as on the processes of prenatal development. However, we know that there are drugs that do not seem to affect this development and can be used during pregnancy if required. Similarly, others are also known to be used in pregnant women or those planning a pregnancy are totally contraindicated. For this reason, women who take these have to follow strict guidelines to prevent becoming pregnant. This article provides a general view on treatments for pregnant women or those planning a pregnancy, together with their potential effects, as well as a list of those drugs that may be considered safe to use during pregnancy, and those that are contraindicated (AU)

Desórdenes temporomandibulares y acúfenos / Temporomandibular joint disorders and tinnitus

Ensayos clínicos recientes han demostrado la mayor prevalencia de acúfenos en pacientes diagnosticados de desórdenes temporomandibulares. A día de hoy el mecanismo fisiopatológico del acúfeno aún no se ha confirmado y las distintas teorías planteadas para relacionar ambas entidades tampoco se han podido demostrar en su totalidad. El objetivo de este trabajo es realizar una revisión bibliográfica del tema, exponiendo aquellas hipótesis que se consideran más relevantes en la actualidad (AU)

Recent clinical trials have demonstrated the greater prevalence of tinnitus in patients diagnosed with temporomandibular disorders. To date the physiopathological mechanism of the tinnitus has not yet been confirmed and it has not been possible to demonstrate completely the different theories proposed to relate the two entities. The objective of this work is to perform a bibliographical review of the subject, setting out the hypotheses that are considered more relevant at present (AU)

[HIV retinal vasculitis]. / Vasculitis retiniana por VIH.

CASE REPORT: We present a case of a 47 year-old woman, infected with human immunodeficiency virus (HIV) diagnosed 5 years ago without receiving any treatment, who had floaters in her left eye. A peripheral retinal vasculitis was discovered and confirmed by an angiography. No source of infection was found, antiretroviral and corticosteroid treatment was given, with a complete resolution of the vasculitis. DISCUSSION: From 70-80% of positive untreated HIV patients develop ocular complications, with intraocular inflammation in more than half of them. Intraocular inflammation can be associated with opportunistic infections, tumours and as in our case, secondary to the HIV. Antiretroviral therapy is the proper treatment in these patients.

Vasculitis retiniana por VIH / HIV retinal vasculitis

Caso clínico: Mujer de 47 años con infección por el virus de la inmunodeficiencia humana(VIH) de 5 años de evolución sin tratamiento que acude por miodesopsias. Se le halla unfoco de vasculitis retiniana periférica en el ojo izquierdo (OI) confirmado angiográficamente.Se descarta otra patología infecciosa por parte de Medicina Interna y se inicia tratamientoantirretroviral y corticoideo sistémico, con resolución del foco de vasculitis.Discusión: Entre un 70 y un 80% de los pacientes positivos para VIH sin tratamiento desarrollancomplicaciones oculares, con inflamación intraocular en más de la mitad de ellos.La inflamación intraocular puede ser debida a infecciones oportunistas, neoplasias y, comoen nuestro caso, secundarias al propio virus. En estos pacientes el tratamiento antirretroviralconsigue la resolución del cuadro(AU)

Case report: We present a case of a 47 year-old woman, infected with humanimmunodeficiency virus (HIV) diagnosed 5 years ago without receiving any treatment, whohad floaters in her left eye. A peripheral retinal vasculitis was discovered and confirmed byan angiography. No source of infection was found, antiretroviral and corticosteroidtreatment was given, with a complete resolution of the vasculitis.Discussion: From 70-80% of positive untreated HIV patients develop ocular complications,with intraocular inflammation in more than half of them. Intraocular inflammation can beassociated with opportunistic infections, tumours and as in our case, secondary to the HIV.Antiretroviral therapy is the proper treatment in these patients(AU)

[Unilateral exophthalmos as the debut of a non-secretory multiple myeloma]. / Exoftalmos unilateral como debut de mieloma múltiple no secretor.

CASE REPORT: A 56 year-old male presented blurred vision and diplopia for 2 months, left unilateral exophthalmos, restricted ocular motility and papilledema. The imaging proofs showed osteolytic lesions in the left sphenoid bone, fourth rib and fourth dorsal vertebral body with associated masses of soft tissues. Biopsy was performed and the diagnosis of plasma cell neoplasm was established. The diagnosis of non-secretory multiple myeloma was made by analytical criteria and bone marrow biopsy. Local radiotherapy and polychemotherapy was prescribed. CONCLUSIONS: The ophthalmologist can play an important role in the diagnosis of systemic neoplasms that require the intervention of a multidisciplinary team.

[Characteristics of neonates with and without a single umbilical artery. Analysis of two consecutive series of neonates with and without congenital defects]. / Características de los neonatos con y sin arteria umbilical única. Análisis de dos series consecutivas de recién nacidos con y sin defectos congénitos.

BACKGROUND AND OBJECTIVE: The implications of the presence of a single umbilical artery (SUA) are unknown. Although most articles are based on selected samples, they suggest a relationship between SUA and malformations. Consequently, prenatal detection of SUA causes concern, since there are no definitive guidelines that can be followed after identification of this abnormality. The objective of this study was to comparatively analyze SUA in two series of consecutive births, with and without congenital defects. PATIENTS AND METHODS: A total of 19,909 cases and 19,148 controls from the Registry of the Spanish Collaborative Study on Congenital Malformations were studied. The variables analyzed were sex, birth weight, length, occipito-frontal circumference, gestational age, prematurity, delivery by caesarean section, umbilical cord length, placental weight, survival at 72 hours, primiparity, oligohydramnios, and polyhydramnios. Calculations included relative frequency, odds ratios (OR) and 95 % confidence intervals, the chi-square test, Fisher's p-value, and Student's t-test. RESULTS: SUA was found in 2.29 % of cases and in 1.03 % of controls (p = 0.0000001). These figures showed secular variation due to improvements in prenatal diagnosis and interruption of some pregnancies. When cases with and without SUA were compared, those with SUA had lower values of somatometry at birth, umbilical cord length and gestational age and had a higher risk for oligohydramnios, polyhydramnios, caesarean section, and death in the first 72 hours. Among controls, the only differences were a shorter umbilical cord and a higher frequency of oligohydramnios among infants with SUA. CONCLUSIONS: The results suggest that certain malformations associated with SUA could cause some of the differences among cases. Shortening of the umbilical cord and oligohydramnios could be related to SUA, as these abnormalities were found in both cases and controls. Comparison of cases and controls suggests that the etiopathogenesis of SUA could differ in the two groups.

Características de los neonatos con y sin arteria umbilical única. Análisis de dos series consecutivas de recién nacidos con y sin defectos congénitos / Characteristics of neonates with and without a single umbilical artery. Analysis of two consecutive series of neonates with and without congenital defects

Antecedentes y objetivo Se desconocen las implicaciones de la presencia de arteria umbilical única (AUU). Aunque la mayoría de los trabajos utilizan muestras seleccionadas, sugieren una relación entre la AUU y malformaciones. Esto supone una gran preocupación cuando se detecta una AUU prenatalmente, ya que no hay pautas de actuación tras su identificación. El objetivo de este trabajo es analizar comparativamente la AUU en dos series consecutivas de nacimientos, con y sin defectos congénitos. Pacientes y métodos Se utilizaron 19.909 casos y 19.148 controles del Registro del Estudio Colaborativo Español de Malformaciones Congénitas, y se analizaron: sexo, peso, talla, perímetro cefálico, edad gestacional, prematuridad, parto por cesárea, longitud del cordón umbilical, peso de la placenta, supervivencia a las 72 h, primiparidad, oligoamnios y polihidramnios. Se calculó la frecuencia relativa, el odds ratio (OR) e intervalos de confianza del 95 %, chi cuadrado, valor p de Fisher, y la t de Student. Resultados El 2,29 % de los casos y el 1,03 % de controles tenían AUU (p = 0,0000001), mostrando variación secular por la mejora del diagnóstico prenatal, e interrupciones del embarazo. Comparando casos con y sin AUU, los que tenían AUU presentaban menores valores de somatometría al nacimiento, longitud del cordón y edad gestacional, y mayor riesgo de oligohidramnios, polihidramnios, cesárea y muerte antes de las 72 h. Entre los controles, sólo diferían en que los que tenían AUU, presentaban cordón más corto y mayor frecuencia de oligoamnios. Conclusiones Los resultados sugieren que ciertas malformaciones asociadas a la AUU, podrían ser responsables de las diferencias entre los casos. El acortamiento del cordón y oligohidramnios podrían relacionarse con la AUU, porque se asocia tanto entre casos como entre controles. Comparando los casos con los controles se sugiere que la AUU podría tener diferente etiopatogenia en ambos grupos

Background and objective The implications of the presence of a single umbilical artery (SUA) are unknown. Although most articles are based on selected samples, they suggest a relationship between SUA and malformations. Consequently, prenatal detection of SUA causes concern, since there are no definitive guidelines that can be followed after identification of this abnormality. The objective of this study was to comparatively analyze SUA in two series of consecutive births, with and without congenital defects. Patients and methods A total of 19,909 cases and 19,148 controls from the Registry of the Spanish Collaborative Study on Congenital Malformations were studied. The variables analyzed were sex, birth weight, length, occipito-frontal circumference, gestational age, prematurity, delivery by caesarean section, umbilical cord length, placental weight, survival at 72 hours, primiparity, oligohydramnios, and polyhydramnios. Calculations included relative frequency, odds ratios (OR) and 95 % confidence intervals, the chi-square test, Fisher's p-value, and Student's t-test. Results SUA was found in 2.29 % of cases and in 1.03 % of controls (p = 0.0000001). These figures showed secular variation due to improvements in prenatal diagnosis and interruption of some pregnancies. When cases with and without SUA were compared, those with SUA had lower values of somatometry at birth, umbilical cord length and gestational age and had a higher risk for oligohydramnios, polyhydramnios, caesarean section, and death in the first 72 hours. Among controls, the only differences were a shorter umbilical cord and a higher frequency of oligohydramnios among infants with SUA. Conclusions The results suggest that certain malformations associated with SUA could cause some of the differences among cases. Shortening of the umbilical cord and oligohydramnios could be related to SUA, as these abnormalities were found in both cases and controls. Comparison of cases and controls suggests that the etiopathogenesis of SUA could differ in the two groups

Pre-gestational maternal body mass index predicts an increased risk of congenital malformations in infants of mothers with gestational diabetes.

AIMS: The aim of the present study was to identify characteristics in women diagnosed with gestational diabetes mellitus (GDM) that could be predictive of congenital malformations in their infants. METHODS: Using data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), a hospital-based case-control study and surveillance system, we assessed the relationship between a number of maternal variables, including pre-gestational body mass index (BMI), and specific congenital malformations in their infants. RESULTS: The overall risk for a selected group of congenital malformations in an infant of an obese mother with GDM compared with an obese mother with normal glucose tolerance (NGT) was 2.78 (1.38-5.55, P < 0.001). Within the group of mothers with GDM, obesity (BMI > or = 30 kg/m2) was associated with a significantly increased risk of cardiovascular defects compared with non-obese women [OR = 2.82 (1.31-7.04), P < 0.01]. In mothers with NGT, pre-gestational BMI was not associated with congenital malformations. CONCLUSION: Pre-gestational obesity is a predictive variable for congenital malformations in infants of mothers with GDM. The greater their BMI, the higher the risk for congenital malformations in their offspring. Given the blastogenic origin of the congenital defects identified, and the relationship between obesity and Type 2 diabetes, it is probable that this increased risk is as a result of previously unidentified pre-gestational diabetes mellitus (PGD). It is important that overweight and obese women planning a pregnancy be evaluated for the presence of diabetes.