El futuro de la elaboración de medicamentos: comentarios al proyecto de modificación del RD175/2001 / The future of drug compounding: comments on the Real Decreto 175/2001 modification project

Objetivo: El 22 de marzo de 2022 la Agencia Española de Medicamentos y Productos Sanitarios y el Ministerio de Sanidad sacaron a consulta pública el proyecto de Real Decreto para modificar el RD175/2001 que regula la elaboración y control de calidad de fórmulas magistrales y preparados oficinales. Este trabajo sugiere lo que la nueva norma debería tener en cuenta para potenciar la elaboración de medicamentos bajo un estándar de calidad más elevado.Método: Se ha realizado un estudio de la situación, legislativa y práctica, de la actividad elaboradora en España, así como técnicas y conceptos de calidad empleados en la industria farmacéutica a nivel internacional.Resultados: La elaboración debe considerarse una actividad más de entre todas las que llevan a cabo los Servicios de Farmacia y por esto debe estar enmarcada dentro de todo su contexto normativo. Es conveniente ampliar los esfuerzos en la garantía de calidad para poder elaborar medicamentos con clasificaciones más abiertas, permitiendo emplear los recursos de forma más eficiente y ajustada al compromiso de cada Servicio con la actividad elaboradora.Conclusión: Por tanto, el nuevo Real Decreto debe considerar la calidad de los medicamentos que llegan al paciente como el objetivo principal de esta actividad. (AU)

Aim: In March 2022, the Spanish Agency of Medicines and Medical Devices and the Ministry of Health presented for public consultation the project of Real Decreto to modify the RD175/2001, which regulates the compounding of magistral formulas and formulations typified in the National Formulary. This work intends to signify what the new regulation should consider boosting compounding under a higher quality standard. Method: Current state of art of compounding in Spain has been studied, just as quality techniques and concepts developed in pharmaceutical industry at an international level.Results: Compounding needs to be considered as one between all the activities developed by Pharmacy Services and, hence, it must be framed inside all its regulatory context. It would be desirable to increase the efforts in quality assurance to permit a wider classification for the presentations, using resources in a more efficient way and commensurate to the commitment of each Service with compounding.Conclusion: Accordingly, the new Real Decreto should acknowledge that the quality of the medicines which reach patients should be the primal objective of this activity. (AU)

Valor pronóstico de la TcPO2 en la cicatrización de lesiones en pie diabético tras revascularización / TcPO 2 prognostic value of healing in diabetic foot after revascularization

INTRODUCCIÓN: La medición de la presión transcutánea de oxígeno (TcPO2) es una herramienta útil en el diagnóstico vascular no invasivo, además de ser una prueba con valor pronóstico de cicatrización de úlceras vasculares antes y después de la revascularización. OBJETIVO: Nuestro estudio tiene como objetivo hallar el valor umbral de TcPO2 más fiable para predecir la cicatrización, así como valorar si el ascenso de la TcPO2 tras una revascularización es un buen predictor de buena evolución tras la misma en pacientes diabéticos isquémicos con úlceras isquémicas. MATERIAL Y MÉTODOS: Realizamos un estudio retrospectivo de la base de datos de la Unidad de Pie Diabético del Hospital Universitario Fundación de Alcorcón, mantenida prospectivamente. Se reclutaron pacientes diabéticos con ulceración y criterios de isquemia crítica, sobre los que se realizó TcPO2 pre y posrevascularización. Se registró el tipo de lesión (clasificación de TEXAS), tipo de revascularización, éxito de cicatrización y tiempo hasta la misma. RESULTADOS: Se encontraron 18 pacientes, el 72% eran varones y el 28% mujeres. La edad media fue de 68 años, el 94,7% eran hipertensos, el 73,7% tenían dislipidemia y el 63,2% presentaban retinopatía. Se realizaron en total 19 revascularizaciones, de las cuales 13 fueron endovasculares, 4 bypass y 2 procedimientos híbridos. El ITB no fue valorable en el 68%. Se obtuvo una tasa de cicatrización del 53% y una mediana de tiempo hasta la misma de 103 días. La media de los valores preoperatorios de TcPO2 en cicatrizados y no cicatrizados fue de 14,6 ± 9,40 y 18,6 ± 12,93 mm Hg respectivamente (p = 0,4404). Los niveles postoperatorios fueron de 40,8 ± 10,85 mm Hg en cicatrizados y de 23,5 ± 13,27 mm Hg en no cicatrizados (p = 0,0063). Mediante el análisis de las curva ROC determinamos que cifras de TcPO2 superiores o iguales a 35 mm Hg eran cifras superiores o indicadores de buen pronóstico para la cicatrización. El incremento de la TcPO2 por encima de 15 mm Hg es un factor de buen pronóstico tras la revascularización en el pie diabético. CONCLUSIONES: La TcPO2 es una herramienta útil para determinar el valor pronóstico en la cicatrización del paciente diabético con isquemia crítica, especialmente en pacientes con presiones parciales no valorables. El valor umbral de buen pronóstico de cicatrización se sitúa, según nuestro estudio, en una cifra ≥ 35 mm Hg. También es factor de buen pronóstico el incremento de la TcPO2 por encima de 15 mm Hg respecto del valor basal tras la revascularización

INTRODUCTION: The measurement of transcutaneous oxygen pressure (TcPO2) is a useful tool in non-invasive vascular diagnosis, as well as being a valuable prognostic test of vascular ulcer healing before and after revascularization. OBJECTIVE: The aim of this study was to determine the most reliable TtPO2 cut-off value for predicting healing, as well as to find out if the increase in the TcPO2 after revascularization can be predictor of a good outcome after this intervention in diabetic patients with ischemic ulcers. MATERIAL AND METHODS: A retrospective study was performed using the prospectively maintained data base of the Diabetic Foot Unit of the Hospital Universitario Fundación de Alcorcón. Diabetic patients with ulceration and critical ischemia criteria were included, particularly those that had TcPO2 performed before and after revascularization, successful wound healing and time to healing. RESULTS: A total of 18 patients were found, of whom 72% were males and 28% females. The mean age was 68 years, with 94.7% hypertension, 73.7% dyslipidemia, and 63.2% retinopathy. A total of 19 revascularizations were performed, of which 13 were endovascular, 4 bypass, and 2 hybrid procedures. The ankle-brachial index was not assessable in 68%. A healing rate of 53% and a median time to healing of 103 days were obtained. The mean preoperative TcPO2 values in healed and non-healed was 14.6 ± 9.40 and 18.6 ± 12.93 mm Hg, respectively (P = .4404). The mean postoperative levels of TcPO2 were 40.8 ± 10.85 mm Hg in healed and 23.5 ± 13.27 mmHg in non-healed (P = .0063). Using ROC curve analysis, it was determined that TcPO2 levels equal to or greater than 35 mmHg were indicators of a good prognosis for wound healing. An increase in the TcPO2 above 15 mm Hg is a factor of a good prognosis after revascularization of diabetic foot. CONCLUSIONS: TcPO2 is a useful tool for determining the prognostic value in wound healing in the diabetic patient with critical ischemia, particularly in patients with non-assessable partial pressures. The cut-off for a good prognosis of wound healing, according to this study, is equal to or greater than 35 mm Hg. An increase in the TcPO2 above 15 mm Hg from the baseline value is also a factor of a good prognosis after revascularization

[Glaucoma: pharmacological implications]. / Glaucoma: implicaciones farmacológicas.

Glaucoma is the first cause of irreversible blindness worldwide. Its prevalence in our country is 2%; half of patients remain undiagnosed. Certain drugs can trigger and/or exacerbate glaucoma; hence the importance of having knowledge of these drugs by Primary Care physician. In addition, the drugs used in the treatment of glaucoma, even topically, can have systemic side effects that should be also know to the Primary Care physician. An adequate knowledge of all the drug groups and the prescribing of the appropriate drug in patients with risk factors and underlying pathology, will enable the Primary Care physician to optimise the risk/benefit ratio in the therapeutic management of these patients. An update is presented on this ophthalmological disease, with special attention to its implications for pharmacological treatments.

Glaucoma: implicaciones farmacológicas / Glaucoma: pharmacological implications

El adecuado conocimiento de todos estos grupos farmacológicos y su correcta prescripción en pacientes con factores de riesgo y enfermedad de base, permitirá al médico de atención primaria una optimización de la relación riesgo/beneficio en el manejo terapéutico de este tipo de pacientes. Se efectúa una actualización de esta enfermedad oftalmológica, con especial atención a sus implicaciones con los tratamientos farmacológicos. El glaucoma es la primera causa mundial de ceguera irreversible. Su prevalencia en nuestro medio es del 2%; la mitad de los pacientes permanecen sin diagnóstico. Determinados fármacos pueden desencadenar o exacerbar el glaucoma, de ahí la importancia del conocimiento de estos fármacos por parte del médico de atención primaria. Además, los fármacos empleados en el tratamiento del glaucoma, incluso por vía tópica, pueden tener efectos secundarios sistémicos que también debe conocer el médico de atención primaria (AU)

An adequate knowledge of all the drug groups and the prescribing of the appropriate drug in patients with risk factors and underlying pathology, will enable the Primary Care physician to optimise the risk/benefit ratio in the therapeutic management of these patients. An update is presented on this ophthalmological disease, with special attention to its implications for pharmacological treatments. Glaucoma is the first cause of irreversible blindness worldwide. Its prevalence in our country is 2%; half of patients remain undiagnosed. Certain drugs can trigger and/or exacerbate glaucoma; hence the importance of having knowledge of these drugs by Primary Care physician. In addition, the drugs used in the treatment of glaucoma, even topically, can have systemic side effects that should be also know to the Primary Care physician (AU)

Revisión de las recomendaciones actuales y protocolos de actuación en prevención del pie diabético / No disponible

No disponible

Asynchronous non-invasive brain-actuated control of an intelligent wheelchair.

In this paper we present further results of our asynchronous and non-invasive BMI for the continuous control of an intelligent wheelchair. Three subjects participated in two experiments where they steered the wheelchair spontaneously, without any external cue. To do so the users learn to voluntary modulate EEG oscillatory rhythms by executing three mental tasks (i.e., mental imagery) that are associated to different steering commands. Importantly, we implement shared control techniques between the BMI and the intelligent wheelchair to assist the subject in the driving task. The results show that the three subjects could achieve a significant level of mental control, even if far from optimal, to drive an intelligent wheelchair.

[Management of Descemet's membrane rupture by intracameral injection of SF6 in acute hydrops]. / Tratamiento de la rotura de la membrana de Descemet mediante SF6 intracamerular en hydrops agudo.

CASE REPORT: Hydrops occurring in the eye secondary to keratoconus, grade 4. It was managed by sulfur hexafluoride (SF6) gas injected into the anterior chamber, with an early resolution of corneal edema obtained. DISCUSSION: Intervention with intracameral SF6 injection has proven to be a safe and effective therapy for early reduction of corneal edema in an eye with Descemet's membrane detachment and acute hydrops (Arch Soc Esp Oftalmol 2009; 84: 533-536).

Tratamiento de la rotura de la membrana de Descemet mediante SF6 intracamerular en hydrops agudo / Management of Descemet's membrane rupture by intracameral injection of SF6 in acute hydrops

Caso clínico: Hydrops corneal secundario a queratocono,grado 4. Se trató con inyección intracamerularde hexafluoruro de azufre (SF6) obteniéndoseuna resolución temprana del edema corneal.Discusión: La inyección de SF6 intracamerularfue efectiva para reducir el edema de córnea y nomostró complicaciones en un ojo que presentabauna rotura de la membrana de Descemet e hydrops agudo(AU)

Case report: Hydrops occurring in the eye secondaryto keratoconus, grade 4. It was managed bysulfur hexafluoride (SF6) gas injected into the anteriorchamber, with an early resolution of cornealedema obtained.Discussion: Intervention with intracameral SF6injection has proven to be a safe and effective therapyfor early reduction of corneal edema in an eyewith Descemet’s membrane detachment and acutehydrops(AU)

Estudio de prevalencia de la enfermedad arterial periférica y diabetes en España / A study of the prevalence of peripheral arterial disease and diabetes in Spain

Objetivo. Evaluar la prevalencia de la enfermedad arterial periférica (EAP) en pacientes diabéticos y la prevalenciade diabetes en pacientes con enfermedad arterial periférica en España mediante un estudio observacional y decorte transversal. Pacientes y métodos. Medición del índice tobillo-brazo en pacientes diabéticos que acuden a consultasde endocrinología y medición de la glucosa en pacientes que acuden a consultas de cirugía vascular. Los criterios de inclusiónhan sido pacientes de cualquier edad y género que hayan firmado el consentimiento. Se han incluido 2.293 pacientes,477 (20,8%) en consultas de endocrinología y 1.816 (79,2%) en consultas de cirugía vascular. Edad media de 59años en consultas de endocrinología y 68 años en consultas de cirugía vascular. El 53,2 y el 81,5% de varones en consultasde endocrinología y cirugía vascular, respectivamente. El 11,8 y el 15,8% presentaban antecedentes cerebrovasculares,el 19,5 y el 27,9% antecedentes de coronariopatía y el 25,0 y 97,8%, antecedentes de enfermedad arterial periféricaconocida en consultas de endocrinología y cirugía vascular, respectivamente. Resultados. La prevalencia de EAP en consultasde endocrinología fue del 37,3%, el 34,6% leve-moderada y 2,6%, grave. La prevalencia de EAP se incrementabacon la edad, en hombres, presencia de síndrome metabólico y años de evolución de la diabetes. La prevalencia de diabetesen consultas de cirugía vascular fue el 67,6%. La prevalencia de diabetes aumentaba con el índice de masa corporal,en mujeres, y con la presencia del síndrome metabólico. Conclusión. Este estudio confirma la alta prevalencia de EAP ydiabetes en España y marca tendencias para una optimización terapéutica

Aim. To evaluate the prevalence of peripheral arterial disease (PAD) in diabetic patients and the prevalenceof diabetes in patients with PAD in Spain by means of an observation-based cross-sectional study. Patients and methods.The method chosen for this analysis was to measure the ankle-brachial index in diabetic patients who visited endocrinologydepartments and also the measurement of glucose levels in patients who visited vascular surgery. Eligibility criteriawere patients of any age and gender who signed the consent documents. In all, 2293 patients were included, 477(20.8%) in visits to the endocrinology department and 1816 (79.2%) in visits to vascular surgery. The mean age ofpatients was 59 years old in endocrinology and 68 years old in visits to vascular surgery. Males accounted for 53.2%and 81.5% of the visits to endocrinology and vascular surgery, respectively. A history of cerebrovascular events waspresent in 11.8 and 15.8%, 19.5 and 27.9% had a history of heart disease and 25.0 and 97.8% had a history of knownperipheral arterial disease, in endocrinology and vascular surgery, respectively. Results. The prevalence of PAD amongthose who visited endocrinology was 37.3%, 34.6% of which were mild-moderate and 2.6% were severe. The prevalenceof PAD increased with age, in males, in the presence of metabolic syndrome and with the number of years since the onsetof diabetes. The prevalence of diabetes in vascular surgery patients was 67.6%. The prevalence of diabetes increasedwith body mass index, in females, and in the presence of metabolic syndrome. Conclusions. This study confirms the highprevalence of PAD and diabetes in Spain and establishes guidelines to be followed for the optimisation of therapy

A brain-actuated wheelchair: asynchronous and non-invasive Brain-computer interfaces for continuous control of robots.

OBJECTIVE: To assess the feasibility and robustness of an asynchronous and non-invasive EEG-based Brain-Computer Interface (BCI) for continuous mental control of a wheelchair. METHODS: In experiment 1 two subjects were asked to mentally drive both a real and a simulated wheelchair from a starting point to a goal along a pre-specified path. Here we only report experiments with the simulated wheelchair for which we have extensive data in a complex environment that allows a sound analysis. Each subject participated in five experimental sessions, each consisting of 10 trials. The time elapsed between two consecutive experimental sessions was variable (from 1h to 2months) to assess the system robustness over time. The pre-specified path was divided into seven stretches to assess the system robustness in different contexts. To further assess the performance of the brain-actuated wheelchair, subject 1 participated in a second experiment consisting of 10 trials where he was asked to drive the simulated wheelchair following 10 different complex and random paths never tried before. RESULTS: In experiment 1 the two subjects were able to reach 100% (subject 1) and 80% (subject 2) of the final goals along the pre-specified trajectory in their best sessions. Different performances were obtained over time and path stretches, what indicates that performance is time and context dependent. In experiment 2, subject 1 was able to reach the final goal in 80% of the trials. CONCLUSIONS: The results show that subjects can rapidly master our asynchronous EEG-based BCI to control a wheelchair. Also, they can autonomously operate the BCI over long periods of time without the need for adaptive algorithms externally tuned by a human operator to minimize the impact of EEG non-stationarities. This is possible because of two key components: first, the inclusion of a shared control system between the BCI system and the intelligent simulated wheelchair; second, the selection of stable user-specific EEG features that maximize the separability between the mental tasks. SIGNIFICANCE: These results show the feasibility of continuously controlling complex robotics devices using an asynchronous and non-invasive BCI.

Quantifying soluble HLA-G in supernatants of cultured embryos as a marker of implantation potential in an assisted reproduction program

HLA-G desempeña un papel tolerogénico en la interfase maternofetal.En programas de reproducción asistida, en los que se cultivan embrionesin vitro, ha cobrado interés la detección de las isoformas solubles deesta molécula (sHLA-G) en el medio en el que se han crecido los embriones.Aunque la determinación es compleja, tiene interés por su aparenterelación con la idoneidad de dichos embriones. En el presente trabajo,se ha puesto a punto un ensayo ELISA amplificado para medir sHLA-Ga las concentraciones esperables en dichos sobrenadantes. Como modelocomparativo se ha utilizado el cultivo a dilución límite de la línea de coriocarcinomaJEG-3. Con el ELISA desarrollado se han analizado retrospectivamente111 sobrenadantes recogidos a las 44-48 horas de efectuadafecundación mediante inyección intracitoplasmática del espermatozoide,y los datos se han correlacionado con los resultados reproductivos dedichos embriones. En 22 de los sobrenadantes (19.8%) se ha detectadosHLA-G. No se ha encontrado relación entre los niveles de sHLA-G y elgrado morfológico de los embriones. Los resultados reproductivos de losembriones de morfología normal que fueron transferidos al útero de laspacientes (2-3 por caso) fueron los siguientes: en el grupo de mujeres querecibió únicamente embriones sHLA-G negativos, las tasas de embarazoe implantación fueron, respectivamente, 29% (4 embarazos/14 mujeres)y 14% (5 sacos gestacionales/35 embriones transferidos). Por contra,en el grupo que recibió al menos un embrión sHLA-G positivo, las tasasde embarazo e implantación subieron al 60% (3 / 5) y 29% (4/14) respectivamente.En conclusión, es posible cuantificar niveles de sHLA-G ensobrenadantes de embriones y los resultados obtenidos sugieren asociacióncon la probabilidad de embarazo. La detección de sHLA-G, por tanto,podría ser un buen complemento de la selección morfológica de embrionesútil para incrementar la tasa de implantación y reducir la de embarazosmúltiples

HLA-G plays a tolerogenic function at the maternal-fetal interface.Detection of the soluble isoforms of HLA-G (sHLA-G) in culture mediumderived from embryos grown in vitro, although technically complex,has gained interest in assisted reproduction programs because of an apparentrelationship with embryo competence. Here, an amplified ELISA wasdesigned to measure sHLA-G at the concentrations expected in embryosupernatants using a limiting-dilution assay of the choriocarcinoma JEG-3 cell line as a surrogate model. With this ELISA approach, 111 singleembryo culture supernatants, collected 44-48 hours after intracytoplasmicsperm injection, were retrospectively analysed and levels correlatedwith pregnancy results. The presence of sHLA-G was demonstrated in 22(19.8%) of the embryo cultures. There was no relationship between sHLAGlevels and grading of embryo morphology. The reproductive outcomeof the morphologically normal embryos that were transferred to thewomen uterus (2-3 per patient) was as follows: in the group of women inwhich all transferred embryos were sHLA-G negative, the pregnancy andimplantation rates were 29% (4 pregnancies/14 women) and 14% (5 gestationalsacs/35 embryos transferred), respectively. In contrast, in thegroup in which the embryo transfers included at least one sHLA-G positivethe pregnancy and implantation rates increased to 60% (3/5) and29% (4/14) respectively. In conclusion, sHLA-G levels in preimplantationembryo supernatants can be quantified and results suggest positive associationwith pregnancy likelihood. sHLA-G detection seems to be usefulto complement morphology in selecting good quality embryos for increasingimplantation rates and reducing multiple gestations

Detección de problemas en pacientes geriátricos con fractura de cadera. Importancia de la colaboración entre traumatólogo y geriatra / Detection of health conditions in elderly patients with a hip fracture. Importance of collaboration between orthopedic and geriatric specialists

Objetivo. Evaluar el beneficio que proporciona un Equipo Consultor Geriátrico (ECG) a los pacientes geriátricos que ingresan con fractura de cadera en cuanto a la detección de problemas clínicos. Material y método. Estudio prospectivo y controlado que compara dos grupos: los pacientes manejados por el ECG y los que no conoció dicho equipo. Resultados. Fueron estudiados 449 pacientes, con una edad media de 83 años y el 80% mujeres. El ECG detectó más antecedentes personales (5,4 frente a 3,3) y más síndromes geriátricos previos (2 frente 0,4). A lo largo del ingreso el ECG detectó más complicaciones (3,8 frente a 0,4), más nuevos diagnósticos (2,1 frente a 0,4) y más síndromes geriátricos (3,6 frente a 0,5). Las diferencias resultaron significativas en los siguientes problemas: anemia, desnutrición, estreñimiento, delirium, osteoporosis, úlceras por presión, demencia, déficit sensoriales e incontinencia. Algunos de los datos recogidos nos sugieren que pudo haber diagnósticos no detectados en el grupo control. Conclusiones. La revisión diaria por parte del ECG de los pacientes ofrece una evaluación más completa y reduce la probabilidad de infradiagnóstico de problemas clínicos importantes. La colaboración entre traumatólogo y geriatra da como resultado un manejo del paciente más efectivo

Purpose. To assess the benefits of a Geriatric Consultant Team (GCT) to detect health conditions in elderly patients hospitalized for a hip fracture. Materials and methods. This was a prospective controlled study that compared two groups: patients under the care of a GCT and those not under the care of a GCT. Results. A total of 449 patients were studied; mean age 83 years; 80% women. The GCT detected more incidents in clinical records (5.4 compared to 3.3), and more previous geriatric syndromes (2 compared to 0.4). During hospitalization the GCT detected a higher rate of complications (2.1 compared to 0.4) and more geriatric syndromes (3.6 compared to 0.5). Significant differences were seen in the following conditions: anemia, malnutrition, constipation, delirium, osteoporosis, bedsores, dementia, sensory deficits and incontinence. Some of the data collected suggested that there might have been non-detected health conditions in the control group. Conclusions. The GCT reviewed patients daily, which resulted in a more complete assessment and a reduction in the probability of under-diagnosing significant clinical conditions. More effective patient care is achieved when Geriatric and Orthopedic Specialists work together (AU)

Lipolysis, proteolysis, physicochemical and sensory characteristics of different types of Spanish ostrich salchichon.

The objective of this study was to compare three different types of salchichon: made of ostrich meat, made of ostrich meat and lean pork, and made of ostrich meat and pork belly, from physicochemical and sensory viewpoints. To evaluate the intensity of lipolysis and proteolysis produced during the ripening process, the profile and content of free fatty acids, the degree of rancidity, the non-protein, water-soluble and aminoacidic nitrogen content were determined. In addition, the composition of the fermented sausages (pH, a(w), moisture, fat, protein, ash, sodium chloride and sodium nitrite content) was analysed. From a sensory viewpoint, the organoleptic characteristics of the different types of salchichon were studied using free choice profiling. The fermented sausages had varying characteristics depending on their formulation (ostrich meat or ostrich meat plus pork) and all of them were well accepted by the panelists. This study helps characterise the different types of ostrich salchichon made in Spain.

Molecular and clinical characterisation of three Spanish families with maternally inherited non-syndromic hearing loss caused by the 1494C->T mutation in the mitochondrial 12S rRNA gene.

Mutations in the 12S rRNA gene of the mitochondrial genome are responsible for maternally inherited non-syndromic hearing loss (NSHL), and for increased susceptibility to the ototoxicity of aminoglycoside antibiotics. Among these mutations, 1555A-->G is the most prevalent in all populations tested so far. Recently, the 1494C-->T mutation was reported in two large Chinese pedigrees with maternally inherited NSHL. In this study, sequencing of the 12S rRNA gene in a Spanish family with maternally inherited NSHL showed the presence of the 1494C-->T mutation. An additional screening of 1339 unrelated Spanish patients with NSHL allowed the authors to find two other families with the mutation. Audiological data were obtained from 17 confirmed 1494C-->T carriers, which showed that the hearing loss was sensorineural, bilateral and symmetrical, with a remarkable variability in age of onset and severity. Three carriers were asymptomatic. Three affected carriers had a history of treatment with aminoglycoside antibiotics. The mitochondrial genome of one affected person from each of these three families was entirely sequenced, and it was established that they belong to different mitochondrial haplogroups (H, U5b, U6a). The study results further support the pathogenic role of 1494C-->T on hearing, and show that this mutation can be found in different Caucasian mitochondrial DNA backgrounds.

Contenido de metales pesados en hígado y plumas de aves marinas afectadas por el accidente del "Prestige" en la costa de Galicia / Heavy metal content in liver and feathers of seabirds affected by the "Prestige" accident on the Galician coast

Las aves marinas son organismos situados en la cumbre de las cadenas alimentarias oceánicas, lo que permite su empleo en programas de biomonitorización para evaluar el efecto de los más diversos contaminantes sobre estos sensibles eco-sistemas. En el presente trabajo se han analizado las concentraciones de distintos metales pesados (Pb, Zn, Cd y Cu) en hígado y plumas de tres especies de aves marinas (arao, frailecillo y alca) directamente afectadas por el vertido de crudo del “Prestige” en noviembre de 2002, empleando para ello animales que murieron a lo largo de la costa de Galicia. Las concentraciones cuantificadas de los cuatro elementos fueron en general bajas para los dos tipos de muestras analizadas (hígado y plumas), situándose en niveles comparables a los cuantificados en estas mismas especies marinas en otras zonas geográficas, no excediendo los niveles que pudieran indicar un incremento en la exposición medioambiental a estos contaminantes inorgánicos (AU)

Heavy metal content in liver and feathers of seabirds affected by the “Prestige” accident on the Galician coast. Seabirds are organisms considered to be top consumers in marine foodchains and therefore can be used in biomonitoring programs in order to assess the effect of a broad spectrum of contaminants on those highly sensitive ecosystems. In this work, heavy metal (Pb, Zn, Cd and Cu) content in liver and feathers of three different seabird species (common guillemot, Atlantic puf-fin and razorbill) directly affected by the “Prestige” oil spill in November 2002 have been analyzed. The samples were obtained from animals which died along the Galician coast. In general, the levels of these four analyzed elements were low in both analyzed samples (liver and feathers), representing levels comparable to those quantified for the same seabird species in other geographical areas; the levels were not indicative of increased environmental exposure to such inorganic pollutants (AU)

Detection of hepatitis E virus in patients sera in southern Spain.

The aim of the present study was to detect acute Hepatitis E virus (HEV) infection in patients with abnormal alanine transaminase (ALT) in which other viral hepatitis infections had been excluded in southern Spain, an area adjacent to regions where this disease is endemic. Of 336 sera tested 30 (8.92%) were positive for IgM antibodies against HEV (anti-HEV IgM) and 7 (2.08%) were negative in a repeated assay. Immunoblot analysis (IBA) was applied to the 37 positive sera in the first assay; its results were positivity for 26 (7.73%), ambiguous for 5 and negative for 6 sera. Amplification of ORF1 and ORF2 of HEV by means of nested RT-PCR was carried out with the 37 sera that were either positive or ambiguous by ELISA; a positive result was obtained only with one serum for the ORF2 protein. IgM antibodies against the HEV ORF2 protein could be a useful marker in the diagnosis of acute infection and a substitute for the determination of viral RNA in serum; this is of both diagnostic and epidemiological importance as it would allow the patients transmitting the infection to be recognized by means of a simple determination of antibodies. The sequence of the ORF2 fragment of HEV occurring in samples taken from both humans and animals amplified in this study has considerable homology with the sequences of HEV strains/isolates of European origin. These results demonstrate that an autochthonous HEV circulates in Spain.

Mutation screening of USH3 gene (clarin-1) in Spanish patients with Usher syndrome: low prevalence and phenotypic variability.

Usher syndrome type III is an autosomal recessive disorder clinically characterized by the association of retinitis pigmentosa (RP), variable presence of vestibular dysfunction and progressive hearing loss, being the progression of the hearing impairment the critical parameter classically used to distinguish this form from Usher syndrome type I and Usher syndrome type II. Usher syndrome type III clinical subtype is the rarest form of Usher syndrome in Spain, accounting only for 6% of all Usher syndrome Spanish cases. The gene responsible for Usher syndrome type III is named clarin-1 and it is thought to be involved in hair cell and photoreceptor cell synapses. Here, we report a screening for mutations in clarin-1 gene among our series of Usher syndrome Spanish patients. Clarin-1 has been found to be responsible for the disease in only two families: the first one is a previously reported family homozygous for Y63X mutation and the second one, described here, is homozygous for C40G. This accounts for 1.7% of Usher syndrome Spanish families. It is noticeable that, whereas C40G family is clinically compatible with Usher syndrome type III due to the progression of the hearing loss, Y63X family could be diagnosed as Usher syndrome type I because the hearing impairment is profound and stable. Thus, we consider that the progression of hearing loss is not the definitive key parameter to distinguish Usher syndrome type III from Usher syndrome type I and Usher syndrome type II.

Progresión de la poliquistosis renal autosómica dominante. Influencia de polimorfismos de genes de sintasa endotelial del óxido nítrico (ecNOS) y del sistema renina-angiotensina / Progression of autosomic dominant polycystic kidney disease. Influence of endothelial NO synthase (ecNOS) and renin angiotensin system gene polymorphisms

Glomerular filtration rate decline (GFRd) is variable in autosomic dominant polycystic kidney disease (ADPKD). In 88 ADPKD patients, GFRd was assessed by 1/S(Cr) and compared with the association to AT1A1166C (AT1R), AGTM235T (angiotensinogen) and ecNOSGlu298Asp (NO endothelial synthase) polymorphisms. Age at S(Cr) values of 2 and 6 mg/dl were assumed as beginning of progressive phase (A2) and end-stage-renal disease (A6), respectively. Polymorphisms were studied by PCR-RFLP. The group as a whole showed GFRd (ml/min/year) of 6.9+/-0.5; A2 and A6 of 48.9+/-1.3 and 55.0+/-1.4 years and mean arterial pressure of 111.2+/-1.2 mmHg. When A6 was considered, two populations were defined (< or = and > 55 years). In < or = 55 (assumed as PKD1 phenotype) (n=42), A2 and A6 of the AT1 1166CC genotype were 36.0+/-1.2 and 41.4+/-0.9 years vs AA-AC (42.8+/-1.0 and 47.5+/-0.8, p<0.001). A2 and A6 of the ecNOS298Asp/Asp genotype were 34.8+/-1.5 and 41.1+/-0.6 years vs. Glu/Glu-Glu/Asp (42.4+/-0.9 and 47.1+/-0.8, p<0.02). In AGT235TT genotype, GFRd was 12.4+/-2.2 ml/min/year vs MM-MT (7.9+/-0.7, p<0.03). This difference was also observed when all ADPKD patients were considered (TT: 11.02+/-1.5 vs. MM-MT: 6.44+/-0.5 ml/ min/year, p<0.003). AT1 1166CC and ecNOS 298Asp/Asp are associated with earlier A2 and A6 whereas AGT 235TT induce twofold increase in GFRd, suggesting that RAS and ecNOS are involved in ADPKD progression.(AU)

La velocidad de progresión (VdP) de la poliquistosis renal autosómica dominante (PQRAD) es variable.Estudiamos la asociación de los polimorfismos AGTM235T (angiotensinógeno), AT1A1166C(ATR1) y ecNOSGlu298Asp (NO sintasa endotelial) con la VdP en 88 pacientes. VdP fue estimada por 1/Crplvs edad. Consideramos edades de Crpl 2 y 6 mg/dl como comienzo de progresión (E2) y arribo a insuficienciarenal crónica terminal (E6), respectivamente. Los polimorfismos se estudiaron por PCR-RFLP. El grupo en sutotalidad presentó VdP (ml/min/año) de 6.9±0.5, E2 y E6 de 48.9±1.3 y 55.0±1.4 años y tensión arterial media(TAM) de 111.2±1.2 mmHg. Según E6 observamos dos grupos (≤ y > a 55 años). En ≤ 55 (fenotipo PKD1,n=42), E2 y E6 del genotipo CC de AT1A1166C fueron 36.0±1.2 y 41.4±0.9 años vs. AA-AC (42.8±1.0 y 47.5±0.8, p < 0.001). E2 y E6 del genotipo ecNOS298Asp/Asp fueron 34.8±1.5 y 41.1±0.6 años vs. Glu/Glu-Glu/Asp (42.4±0.9 y 47.1±0.8, p < 0.02). En el genotipo AGT235TT, la VdP fue 12.4±2.2 ml/min/año vs. MM-MT (7.9±0.7, p < 0.03). Esta diferencia también se observó cuando analizamos todos los pacientes PQRAD (TT: 11.02±1.5 vs. MM-MT: 6.44±0.5 ml/min/año, p < 0.003). Los genotipos AT1 1166CC y ecNOS 298Asp/Asp anticipan E2 y E6 mientras que AGT235TT duplica VdP, sugiriendo la participación del sistema renina angiotensina y NO sintasaendotelial en la progresión de la PQRAD.(AU)

Progresión de la poliquistosis renal autosómica dominante. Influencia de polimorfismos de genes de sintasa endotelial del óxido nítrico (ecNOS) y del sistema renina-angiotensina / Progression of autosomic dominant polycystic kidney disease. Influence of endothelial NO synthase (ecNOS) and renin angiotensin system gene polymorphisms

Glomerular filtration rate decline (GFRd) is variable in autosomic dominant polycystic kidney disease (ADPKD). In 88 ADPKD patients, GFRd was assessed by 1/S(Cr) and compared with the association to AT1A1166C (AT1R), AGTM235T (angiotensinogen) and ecNOSGlu298Asp (NO endothelial synthase) polymorphisms. Age at S(Cr) values of 2 and 6 mg/dl were assumed as beginning of progressive phase (A2) and end-stage-renal disease (A6), respectively. Polymorphisms were studied by PCR-RFLP. The group as a whole showed GFRd (ml/min/year) of 6.9+/-0.5; A2 and A6 of 48.9+/-1.3 and 55.0+/-1.4 years and mean arterial pressure of 111.2+/-1.2 mmHg. When A6 was considered, two populations were defined (< or = and > 55 years). In < or = 55 (assumed as PKD1 phenotype) (n=42), A2 and A6 of the AT1 1166CC genotype were 36.0+/-1.2 and 41.4+/-0.9 years vs AA-AC (42.8+/-1.0 and 47.5+/-0.8, p<0.001). A2 and A6 of the ecNOS298Asp/Asp genotype were 34.8+/-1.5 and 41.1+/-0.6 years vs. Glu/Glu-Glu/Asp (42.4+/-0.9 and 47.1+/-0.8, p<0.02). In AGT235TT genotype, GFRd was 12.4+/-2.2 ml/min/year vs MM-MT (7.9+/-0.7, p<0.03). This difference was also observed when all ADPKD patients were considered (TT: 11.02+/-1.5 vs. MM-MT: 6.44+/-0.5 ml/ min/year, p<0.003). AT1 1166CC and ecNOS 298Asp/Asp are associated with earlier A2 and A6 whereas AGT 235TT induce twofold increase in GFRd, suggesting that RAS and ecNOS are involved in ADPKD progression.

La velocidad de progresión (VdP) de la poliquistosis renal autosómica dominante (PQRAD) es variable.Estudiamos la asociación de los polimorfismos AGTM235T (angiotensinógeno), AT1A1166C(ATR1) y ecNOSGlu298Asp (NO sintasa endotelial) con la VdP en 88 pacientes. VdP fue estimada por 1/Crplvs edad. Consideramos edades de Crpl 2 y 6 mg/dl como comienzo de progresión (E2) y arribo a insuficienciarenal crónica terminal (E6), respectivamente. Los polimorfismos se estudiaron por PCR-RFLP. El grupo en sutotalidad presentó VdP (ml/min/año) de 6.9±0.5, E2 y E6 de 48.9±1.3 y 55.0±1.4 años y tensión arterial media(TAM) de 111.2±1.2 mmHg. Según E6 observamos dos grupos (≤ y > a 55 años). En ≤ 55 (fenotipo PKD1,n=42), E2 y E6 del genotipo CC de AT1A1166C fueron 36.0±1.2 y 41.4±0.9 años vs. AA-AC (42.8±1.0 y 47.5±0.8, p < 0.001). E2 y E6 del genotipo ecNOS298Asp/Asp fueron 34.8±1.5 y 41.1±0.6 años vs. Glu/Glu-Glu/Asp (42.4±0.9 y 47.1±0.8, p < 0.02). En el genotipo AGT235TT, la VdP fue 12.4±2.2 ml/min/año vs. MM-MT (7.9±0.7, p < 0.03). Esta diferencia también se observó cuando analizamos todos los pacientes PQRAD (TT: 11.02±1.5 vs. MM-MT: 6.44±0.5 ml/min/año, p < 0.003). Los genotipos AT1 1166CC y ecNOS 298Asp/Asp anticipan E2 y E6 mientras que AGT235TT duplica VdP, sugiriendo la participación del sistema renina angiotensina y NO sintasaendotelial en la progresión de la PQRAD.