Pharmacogenetic studies in Alzheimer disease.

INTRODUCTION: Alzheimer disease (AD) is the most common cause of dementia and is considered one of the main causes of disability and dependence affecting quality of life in elderly people and their families. Current pharmacological treatment includes acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine; however, only one-third of patients respond to treatment. Genetic factors have been shown to play a role in this inter-individual variability in drug response. DEVELOPMENT: We review pharmacogenetic reports of AD-modifying drugs, the pharmacogenetic biomarkers included, and the phenotypes evaluated. We also discuss relevant methodological considerations for the design of pharmacogenetic studies into AD. A total of 33 pharmacogenetic reports were found; the majority of these focused on the variability in response to and metabolism of donepezil. Most of the patients included were from Caucasian populations, although some studies also include Korean, Indian, and Brazilian patients. CYP2D6 and APOE are the most frequently studied biomarkers. The associations proposed are controversial. CONCLUSIONS: Potential pharmacogenetic biomarkers for AD have been identified; however, it is still necessary to conduct further research into other populations and to identify new biomarkers. This information could assist in predicting patient response to these drugs and contribute to better treatment decision-making in a context as complex as ageing.

Antiviral drugs targeting endosomal membrane proteins inhibit distant animal and human pathogenic viruses.

The endocytic pathway is a common strategy that several highly pathogenic viruses use to enter into the cell. To demonstrate the usefulness of this pathway as a common target for the development of broad-spectrum antivirals, the inhibitory effect of drug compounds targeting endosomal membrane proteins were investigated. This study entailed direct comparison of drug effectiveness against animal and human pathogenic viruses, namely Ebola (EBOV), African swine fever virus (ASFV), and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A panel of experimental and FDA-approved compounds targeting calcium channels and PIKfyve at the endosomal membrane caused potent reductions of entry up to 90% in SARS-CoV-2 S-protein pseudotyped retrovirus. Similar inhibition was observed against transduced EBOV glycoprotein pseudovirus and ASFV. SARS-CoV-2 infection was potently inhibited by selective estrogen receptor modulators in cells transduced with pseudovirus, among them Raloxifen inhibited ASFV with very low 50% inhibitory concentration. Finally, the mechanism of the inhibition caused by the latter in ASFV infection was analyzed. Overall, this work shows that cellular proteins related to the endocytic pathway can constitute suitable cellular targets for broad range antiviral compounds.

Etiología del acúfeno pulsátil. Caso clínico / Etiology of pulsatile tinnitus. Case report

Resumen El acúfeno es un síntoma relativamente frecuente en una consulta de otorrinolaringología. Se han descrito interacciones en las células ciliadas externas o internas, desequilibrios en el balance de las fibras aferentes y fenómenos de reorganización cortical tras lesiones periféricas que están involucrados en un 90%-95% de las causas del acúfeno. El restante 5%-10% está constituido por un tipo de acúfenos llamados objetivos, que no comparten estos mecanismos fisiopatológicos, sino que se originan en alguna estructura del organismo generalmente ajena a la vía auditiva y estimulan el aparato auditivo igual que lo haría un sonido del exterior. Presentamos el caso de un varón de 52 años remitido al Servicio de Otorrinolaringología de nuestro hospital por acúfeno pulsátil de meses de evolución, sin asociar hipoacusia, ni vértigo, ni otra sintomatología.

Abstract Tinnitus is a relatively frequent symptom in an otolaryngology consultation. Interactions in external or internal hair cells, imbalances in the afferent fiber balance and cortical reorganization phenomena after peripheral injuries have been described in 90%-95% of the causes of tinnitus. The remaining 5%-10% is comprised of a type of tinnitus called objective, which do not share these pathophysiological mechanisms, but originate from some structure of the body generally external to the auditory pathway and stimulate the auditory apparatus just as a sound from the exterior. We present the case of a 52-year-old man referred to the Otolaryngology service at our hospital for pulsatile tinnitus of months of evolution, with no hearing loss, vertigo, or other symptoms associated.

Interchromosomal effect in carriers of translocations and inversions assessed by preimplantation genetic testing for structural rearrangements (PGT-SR).

PURPOSE: Balanced carriers of structural rearrangements have an increased risk of unbalanced embryos mainly due to the production of unbalanced gametes during meiosis. Aneuploidy for other chromosomes not involved in the rearrangements has also been described. The purpose of this work is to know if the incidence of unbalanced embryos, interchromosomal effect (ICE) and clinical outcomes differ in carriers of different structural rearrangements. METHODS: Cohort retrospective study including 359 preimplantation genetic testing cycles for structural rearrangements from 304 couples was performed. Comparative genomic hybridisation arrays were used for chromosomal analysis. The results were stratified and compared according to female age and carrier sex. The impact of different cytogenetic features of chromosomal rearrangements was evaluated. RESULTS: In carriers of translocations, we observed a higher percentage of abnormal embryos from day 3 biopsies compared with day 5/6 biopsies and for reciprocal translocations compared with other rearrangements. We observed a high percentage of embryos with aneuploidies for chromosomes not involved in the rearrangement that could be attributed to total ICE (aneuploid balanced and unbalanced embryos). No significant differences were observed in these percentages between types of rearrangements. Pure ICE (aneuploid balanced embyos) was independent of female age only for Robertsonian translocations, and significantly increased in day 3 biopsies for all types of abnormalities. Furthermore, total ICE for carriers of Robertsonian translocations and biopsy on day 3 was independent of female age too. High ongoing pregnancy rates were observed for all studied groups, with higher pregnancy rate for male carriers. CONCLUSION: We observed a higher percentage of abnormal embryos for reciprocal translocations. No significant differences for total ICE was found among the different types of rearrangements, with higher pure ICE only for Robertsonian translocations. There was a sex effect for clinical outcome for carriers of translocations, with higher pregnancy rate for male carriers. The higher incidence of unbalanced and aneuploid embryos should be considered for reproductive counselling in carriers of structural rearrangements.

Pharmacogenetic studies in Alzheimer disease. / Estudios farmacogenéticos en la enfermedad de Alzheimer.

INTRODUCTION: Alzheimer disease (AD) is the most common cause of dementia and is considered one of the main causes of disability and dependence affecting quality of life in elderly people and their families. Current pharmacological treatment includes acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine; however, only one-third of patients respond to treatment. Genetic factors have been shown to play a role in this inter-individual variability in drug response. DEVELOPMENT: We review pharmacogenetic reports of AD-modifying drugs, the pharmacogenetic biomarkers included, and the phenotypes evaluated. We also discuss relevant methodological considerations for the design of pharmacogenetic studies into AD. A total of 33 pharmacogenetic reports were found; the majority of these focused on the variability in response to and metabolism of donepezil. Most of the patients included were from Caucasian populations, although some studies also include Korean, Indian, and Brazilian patients. CYP2D6 and APOE are the most frequently studied biomarkers. The associations proposed are controversial. CONCLUSIONS: Potential pharmacogenetic biomarkers for AD have been identified; however, it is still necessary to conduct further research into other populations and to identify new biomarkers. This information could assist in predicting patient response to these drugs and contribute to better treatment decision-making in a context as complex as aging.

Farmacogenética de reacciones adversas a fármacos antiepilépticos / Pharmacogenetics of adverse reactions to antiepileptic drugs

INTRODUCCIÓN: Las reacciones adversas a medicamentos (RAM) son un problema de salud pública y una importante causa de morbimortalidad a nivel mundial. En el caso de los fármacos antiepilépticos (FAE), la presencia de RAM puede ser un impedimento para lograr el éxito terapéutico al dificultar la adherencia al tratamiento e impactar la calidad de vida del paciente. La farmacogenética busca la identificación de variantes genéticas asociadas a la seguridad de los fármacos. En este artículo se revisan los genes que codifican para enzimas metabolizadoras y transportadores de fármacos, así como en el sistema HLA asociados a RAM inducidas por FAE. DESARROLLO: A la fecha, se ha reportado la asociación de los alelos CYP2C9*2 y *3, que codifican para enzimas de actividad reducida, con efectos neurotóxicos por fenitoína (PHT); alelos nulos de GSTM1 asociados con hepatotoxicidad inducida por carbamazepina (CBZ) y ácido valproico (VPA); polimorfismos genéticos de EPHX1 en la teratogénesis inducida por PHT; variantes genéticas de ABCC2 asociadas con RAM neurológicas por CBZ y VPA, y también diversos alelos de HLA (p. ej., HLA-B*15:02, -A*31:01, -B*15:11, -C*08:01) asociados con RAM de tipo cutáneas. CONCLUSIONES: Los hallazgos publicados muestran que existen RAM con base farmacogenética con una alta variabilidad interétnica, lo que refleja la necesidad de que se realicen estudios en distintas poblaciones para poder obtener resultados que sean de utilidad a un número mayor de pacientes. La búsqueda de biomarcadores que permitan la predicción de RAM a FAE podría mejorar la farmacoterapia en la epilepsia

INTRODUCTION: Adverse drug reactions (ADRs) are a major public health concern and a leading cause of morbidity and mortality in the world. In the case of antiepileptic drugs (AEDs), ADRs constitute a barrier to successful treatment since they decrease treatment adherence and impact patients' quality of life of patients. Pharmacogenetics aims to identify genetic polymorphisms associated with drug safety. This article presents a review of genes coding for drug metabolising enzymes and drug transporters, and HLA system genes that have been linked to AED-induced ADRs. DEVELOPMENT: To date, several genetic variations associated with drug safety have been reported: CYP2C9*2 and *3 alleles, which code for enzymes with decreased activity, have been linked to phenytoin (PHT)-induced neurotoxicity; GSTM1 null alleles with hepatotoxicity induced by carbamazepine (CBZ) and valproic acid (VPA); EPHX1 polymorphisms with teratogenesis; ABCC2 genetic variations with CBZ- and VPA-induced neurological ADRs; and HLA alleles (e.g. HLA-B*15:02, -A*31:01, -B*15:11, -C*08:01) with cutaneous ADRs. CONCLUSIONS: Published findings show that there are ADRs with a pharmacogenetic basis and a high interethnic variability, which indicates a need for future studies in different populations to gather more useful results for larger number of patients. The search for biomarkers that would allow predicting ADRs to AEDs could improve pharmacotherapy for epilepsy

Pharmacogenetics of adverse reactions to antiepileptic drugs. / Farmacogenética de reacciones adversas a fármacos antiepilépticos.

INTRODUCTION: Adverse drug reactions (ADRs) are a major public health concern and a leading cause of morbidity and mortality in the world. In the case of antiepileptic drugs (AEDs), ADRs constitute a barrier to successful treatment since they decrease treatment adherence and impact patients' quality of life of patients. Pharmacogenetics aims to identify genetic polymorphisms associated with drug safety. This article presents a review of genes coding for drug metabolising enzymes and drug transporters, and HLA system genes that have been linked to AED-induced ADRs. DEVELOPMENT: To date, several genetic variations associated with drug safety have been reported: CYP2C9*2 and *3 alleles, which code for enzymes with decreased activity, have been linked to phenytoin (PHT)-induced neurotoxicity; GSTM1 null alleles with hepatotoxicity induced by carbamazepine (CBZ) and valproic acid (VPA); EPHX1 polymorphisms with teratogenesis; ABCC2 genetic variations with CBZ- and VPA-induced neurological ADRs; and HLA alleles (e.g. HLA-B*15:02, -A*31:01, -B*15:11, -C*08:01) with cutaneous ADRs. CONCLUSIONS: Published findings show that there are ADRs with a pharmacogenetic basis and a high interethnic variability, which indicates a need for future studies in different populations to gather more useful results for larger number of patients. The search for biomarkers that would allow predicting ADRs to AEDs could improve pharmacotherapy for epilepsy.

Quantitative volcanic susceptibility analysis of Lanzarote and Chinijo Islands based on kernel density estimation via a linear diffusion process.

Risk management stakeholders in high-populated volcanic islands should be provided with the latest high-quality volcanic information. We present here the first volcanic susceptibility map of Lanzarote and Chinijo Islands and their submarine flanks based on updated chronostratigraphical and volcano structural data, as well as on the geomorphological analysis of the bathymetric data of the submarine flanks. The role of the structural elements in the volcanic susceptibility analysis has been reviewed: vents have been considered since they indicate where previous eruptions took place; eruptive fissures provide information about the stress field as they are the superficial expression of the dyke conduit; eroded dykes have been discarded since they are single non-feeder dykes intruded in deep parts of Miocene-Pliocene volcanic edifices; main faults have been taken into account only in those cases where they could modified the superficial movement of magma. The application of kernel density estimation via a linear diffusion process for the volcanic susceptibility assessment has been applied successfully to Lanzarote and could be applied to other fissure volcanic fields worldwide since the results provide information about the probable area where an eruption could take place but also about the main direction of the probable volcanic fissures.

Confirmation rates of array-CGH in day-3 embryo and blastocyst biopsies for preimplantation genetic screening.

PURPOSE: The purpose of this study was to compare the confirmation rate of day-3 embryo biopsy (blastomere) and trophectoderm biopsy using array-comparative genomic hybridization (array-CGH) technology. METHODS: A blinded study was conducted to re-analyse 109 embryos previously diagnosed as chromosomally abnormal by array-CGH. Preimplantation genetic screening (PGS) was performed using array-CGH on day 3 (n = 50) or day 5 (n = 59). Partial chromosome gains or losses were excluded (n=6), and only whole chromosome aneuploidies were considered. Re-analysis of whole blastocysts was carried out following the same array-CGH protocol used for PGS. RESULTS: The PGS result was confirmed in the whole blastocyst in (a) 49/50 (98 %) abnormal embryos after day-3 biopsy and (b) 57/59 (96.6 %) abnormal embryos after trophectoderm biopsy. One embryo (1/50; 2 %) was diagnosed as abnormal, with monosomy 18, on day 3, and software analysis of the whole blastocyst gave a euploid result; however, a mosaic pattern was observed for monosomy 18 in the whole blastocyst. Two trophectoderm biopsy cases (3.4 %) did not have the abnormalities (trisomy 7, and trisomy 1 and 4, respectively) verified in the whole embryo. Concordance rates for both biopsy strategies and for individual chromosomes were evaluated by Fisher's exact test and showed no significant differences. CONCLUSIONS: Both types of biopsies showed similar high concordance rates with whole blastocyst results. Therefore, regarding the confirmation rates shown in this work, day-3 embryo biopsies can be representative of the whole embryo and both types of biopsy can be used for clinical analysis in PGS following the described array-CGH protocol.

Interethnic variation of CYP2C19 alleles, 'predicted' phenotypes and 'measured' metabolic phenotypes across world populations.

The present study evaluates the worldwide frequency distribution of CYP2C19 alleles and CYP2C19 metabolic phenotypes ('predicted' from genotypes and 'measured' with a probe drug) among healthy volunteers from different ethnic groups and geographic regions, as well as the relationship between the 'predicted' and 'measured' CYP2C19 metabolic phenotypes. A total of 52 181 healthy volunteers were studied within 138 selected original research papers. CYP2C19*17 was 42- and 24-fold more frequent in Mediterranean-South Europeans and Middle Easterns than in East Asians (P<0.001, in both cases). Contrarily, CYP2C19*2 and CYP2C19*3 alleles were more frequent in East Asians (30.26% and 6.89%, respectively), and even a twofold higher frequency of these alleles was found in Native populations from Oceania (61.30% and 14.42%, respectively; P<0.001, in all cases), which may be a consequence of genetic drift process in the Pacific Islands. Regarding CYP2C19 metabolic phenotype, poor metabolizers (PMs) were more frequent among Asians than in Europeans, contrarily to the phenomenon reported for CYP2D6. A correlation has been found between the frequencies of CYP2C19 poor metabolism 'predicted' from CYP2C19 genotypes (gPMs) and the poor metabolic phenotype 'measured' with a probe drug (mPMs) when subjects are either classified by ethnicity (r=0.94, P<0.001) or geographic region (r=0.99, P=0.002). Nevertheless, further research is needed in African and Asian populations, which are under-represented, and additional CYP2C19 variants and the 'measured' phenotype should be studied.

CYP2C9, CYP2C19, ABCB1 genetic polymorphisms and phenytoin plasma concentrations in Mexican-Mestizo patients with epilepsy.

We aimed to explore the possible influence of CYP2C9 (*2, *3 and IVS8-109 A>T), CYP2C19 (*2, *3 and *17) and ABCB1 (1236C>T, 2677G>A/T and 3435C>T) on phenytoin (PHT) plasma concentrations in 64 Mexican Mestizo (MM) patients with epilepsy currently treated with PHT in mono- (n=25) and polytherapy (n=39). Genotype and allele frequencies of these variants were also estimated in 300 MM healthy volunteers. Linear regression models were used to assess associations between the dependent variables (PHT plasma concentration and dose-corrected PHT concentration) with independent variables (CYP2C9, CYP2C19 and ABCB1 genotypes, ABCB1 haplotypes, age, sex, weight, and polytherapy). In multivariate models, CYP2C9 IVS8-109 T was significantly associated with higher PHT plasma concentrations (t(64)=2.27; P=0.03). Moreover, this allele was more frequent in the supratherapeutic group as compared with the subtherapeutic group (0.13 versus 0.03, respectively; P=0.05, Fisher's exact test). Results suggest that CYP2C9 IVS8-109 T allele may decrease CYP2C9 enzymatic activity on PHT. More research is needed to confirm findings.

Carlos Richard de Beauregard y el tratamiento de la estenosis uretral blenorrágica en el Madrid del siglo XVIII: publicidad, secreto e impostura / Charles Richard de Beauregard and the treatment of blennorrhagic urethral stenosis in Madrid in the 18th century: Advertising, secrecy and deception

Objetivos: Describir la introducción del tratamiento de la estenosis uretral blenorrágica en la ciudad de Madrid en el siglo XVIII por el cirujano francés Charles de Beauregard, las formulaciones empleadas en la elaboración de sus personales ®candelillas», la publicidad en prensa, su comercialización y distribución. Material y métodos: Revisión no sistemática de la prensa madrileña Gaceta de Madrid y Diario curioso, erudito, económico y comercial, entre 1759 y 1790. Revisión de la bibliografía médica del siglo XVIII conservada en el Fondo Antiguo de la Biblioteca Histórica de la Universidad Complutense (Madrid). Búsqueda en portal Google ®Carlos Richard de Beauregard». Resultados: Charles de Beauregard dedicó preferentemente su actividad profesional al tratamiento de las secuelas uretrales de la blenorragia, fimosis y parafimosis, introduciendo en la sociedad española del siglo XVIII, con pretendida originalidad y manifiesto interés comercial, métodos terapéuticos basados en el acetato de plomo, que ya habían sido desarrollados en Francia por Thomas Goulard. Conclusiones: Las secuelas uretrales de enfermedades como la uretritis blenorrágica, la fimosis estenótica o la parafimosis eran muy prevalentes, y de compleja solución para la urología de la época en el Madrid del siglo XVIII. Charles de Beauregard introdujo novedosos tratamientos (pero no originales), invasivos pero no cruentos, alcanzando fama y prestigio social, recurriendo a publicitar su actividad profesional y comercializar los productos terapéuticos que elaboraba mediante anuncios remitidos a la prensa periódica(Gaceta de Madrid)

Objectives: Describe the introduction of the treatment for blennorrhagic urethral stenosis in the city of Madrid in the 18th century by the French surgeon Charles de Beauregard, the formulations employed in the preparation of his personal ®bougies», the advertising in the press, their marketing and distribution. Material and methods: Nonsystematic review of the Madrid newspaper Gaceta de Madrid y Diario curioso, erudito, económico y comercial (Madrid Gazette, curious, erudite, financial and commercial) between 1759 and 1790. Review of the medical literature of the 18th century preserved in the Fondo Antiguo of the Biblioteca Histórica ofUniversidad Complutense de Madrid (Historical Resource of the Historical Library of the Complutense University of Madrid). A Google search of ®Charles Richard de Beauregard». Results: Charles de Beauregard focused his professional work mainly on the treatment of the urethral sequela of blennorrhagia, phimosis and paraphimosis. He introduced to 18th century Spanish society (with purported originality and clear commercial interests) therapeutic methods based on lead acetate that had already been developed in France by Thomas Goulard. Conclusions: The urethral sequela of diseases such as blennorrhagic urethritis, stenotic phimosis and paraphimosis were highly prevalent in 18th century Madrid and required complex solutions for the practice of urology of that era. Charles de Beauregard introduced innovative but not original treatments that were invasive but not bloody and that provided him with fame and social prestige. He advertised his professional activity and marketed his therapeutic products through advertisements submitted to the daily press (Madrid Gazette, Gaceta de Madrid)

Charles Richard de Beauregard and the treatment of blennorrhagic urethral stenosis in Madrid in the 18th century: Advertising, secrecy and deception.

OBJECTIVES: Describe the introduction of the treatment for blennorrhagic urethral stenosis in the city of Madrid in the 18th century by the French surgeon Charles de Beauregard, the formulations employed in the preparation of his personal «bougies¼, the advertising in the press, their marketing and distribution. MATERIAL AND METHODS: Nonsystematic review of the Madrid newspaper Gaceta de Madrid y Diario curioso, erudito, económico y comercial (Madrid Gazette, curious, erudite, financial and commercial) between 1759 and 1790. Review of the medical literature of the 18th century preserved in the Fondo Antiguo of the Biblioteca Histórica of Universidad Complutense de Madrid (Historical Resource of the Historical Library of the Complutense University of Madrid). A Google search of «Charles Richard de Beauregard¼. RESULTS: Charles de Beauregard focused his professional work mainly on the treatment of the urethral sequela of blennorrhagia, phimosis and paraphimosis. He introduced to 18th century Spanish society (with purported originality and clear commercial interests) therapeutic methods based on lead acetate that had already been developed in France by Thomas Goulard. CONCLUSIONS: The urethral sequela of diseases such as blennorrhagic urethritis, stenotic phimosis and paraphimosis were highly prevalent in 18th century Madrid and required complex solutions for the practice of urology of that era. Charles de Beauregard introduced innovative but not original treatments that were invasive but not bloody and that provided him with fame and social prestige. He advertised his professional activity and marketed his therapeutic products through advertisements submitted to the daily press (Madrid Gazette, Gaceta de Madrid).

Perforación vaginal iatrogénica tras colonoscopia virtual / Latrogenic vaginal perforation after computed tomographic colonography

La colonoscopia virtual o colonografía por tomografía computarizada (TC) es una alternativa potencial a la colonoscopia convencional para la detección de pólipos y cáncer colorrectal. Presentamos un caso inusual de perforación iatrogénica vaginal durante una colonoscopia virtual. El paciente fue tratado con medidas conservadoras sin complicaciones. El presente caso es el primero en la literatura de perforación vaginal iatrogénica debido a la introducción del catéter de Foley a través de la vagina durante la realización de una colonografía por TC. La perforación vaginal es una complicación rara, fácilmente evitable con una correcta exploración clínica

Computed tomographic colonography is a potential alternative to conventional colonoscopy for the detection of colorectal polyps and cancers. We present an unusual case of iatrogenic vaginal perforation during a computed tomographic colonography. The patient was managed with conservative treatment without complications. The present case is the first in the literature of iatrogenic vaginal perforation due to the introduction of the Foley's catheter through vagina during the accomplishment of a computed tomographic colonography. Vaginal perforation is a rare complication, easily avoidable with a correct clinical exploration

Hernia paraduodenal izqueirda gigante / Giant left paraduodenal hernia

Introducción: las hernias internas causan el 0,9% de las obstrucciones intestinales y de estas entre 50-55% son hernias paraduodenales. La edad media de diagnóstico es 38.5 años y son tres veces más comunes en el varón. El riesgo de desarrollar una obstrucción intestinal es del 50% en estos pacientes y puede alcanzar una mortalidad del 20 al 50%. Caso clínico: varón de 36 años con dolor abdominal tipo cólico y mal definido con vómitos de 24 horas de evolución. En la radiografía simple de abdomen presentaba dilatación de asas de intestino delgado. Una tomografía computada abdominal evidenció: encapsulación de las asas intestinales con dilatación desde unión duodeno-yeyunal hasta íleon terminal, con signos de sufrimiento intestinal. Por laparotomía exploradora urgente se observó una hernia mesocólica izquierda gigante, donde el intestino delgadose encuentra compartimentalizado en un saco peritoneal y los vasos mesentéricos desplazados a la derecha y la vena mesentérica inferior se encuentra malposicionada formando un ojal a través del que pasa íleon terminal. El saco peritoneal fue resecado, liberando la vena mesentérica inferior hasta su origen, pasando por el ojal el paquete intestinal, quedando este y el ciego a la derecha de la vena mesentérica inferior. El paciente evolucionó satisfactoriamente, siendo dado de alta al 4º día postoperatorio. Conclusión: la hernia paraduodenal gigante es una patología infrecuente, con elevado riesgo de obstrucción. Donde la tomografía computada se convierte en la prueba de imagen por excelencia que aporta datos concluyentes que ayudan al diagnóstico

Introduction: Internal hernias cause 0.9% of intestinal obstructions and of these 50-55% are paraduodenal hernias. The average age at diagnosis is 38.5 years and are three times more common in men. Paraduodenal risk of developing intestinal obstruction is 50% in these patients and may reach 20 mortality at 50%. Clinical case: A 36 year old male with poorly defined abdominal and vomiting of 24 hours history. Abdominal radiography showed dilated small bowel loops. A computed tomography scan revealed; encapsulation dilated bowel loops from duodenal-jejunal junction to terminal ileum with signs of intestinal distres. For urgent laparotomy showed a giant left mesocolic hernia, where the small intestine was compartmentalized in a peritoneal sac and mesenteric vessels and displaced right inferior mesenteric vein was poorly positioned forming an eyelet through which passes terminal ileum. Peritoneal sac was resected, releasing the inferior mesenteric vein to its origin, through the intestinal buttonhole, leaving the blind and the inferior mesenteric vein to the right. The patient progressed satisfactorily, being discharged on postoperative day 4. Conclusion: The giant paraduodenal hernia is an uncommon condition with high risk of blockage. Where the computed tomography becomes the quintessential image test that provides conclusive data that help the diagnosis

Sacral nerve stimulation in the treatment of severe faecal incontinence: long-term clinical, manometric and quality of life results.

BACKGROUND: Faecal incontinence (FI) is a complex and multifactorial health problem. Treatment has to be individualised, analysing the aetiology and gravity in every case. Sacral nerve stimulation (SNS) has been shown to effectively improve treatment of FI. METHODS: Fifty patients with severe FI treated with SNS between March 2002 and December 2010 were analysed. Preoperative assessment included physical examination, anorectal manometry and anal endosonography. Anal continence was evaluated using the Wexner continence grading system. Quality of life was evaluated using the Fecal Incontinence Quality of life Scale (FIQLS). Follow-up appointments were scheduled at 1, 6 and 12 months and annually thereafter. Wexner score, FIQLS and the ability to defer defecation were assessed at each visit. RESULTS: Fifty patients underwent a permanent implant. The overall mean follow-up period was 55.52 ± 31.84 months. After 6 months, SNS significantly improved FI and positively impacted quality of life, as evidence by significant improvements in all 4 scales of the FIQLS. Anorectal manometry showed a trend towards an increase in maximum resting pressure and maximum pressure. After the first assessment at 6 months, Wexner score and FIQLS remained stable. Ability to defer defecation was also maintained. During follow-up, 3 patients (6 %) experienced implant site pain and episodes of extremity pain and paresthesias that were refractory to medical management and required device explantation. The implant site infection rate was 2 %. CONCLUSIONS: Analysis of our long-term results confirms the safety and effectiveness of SNS in the management of patients with FI.

Neumoperitoneo secundario al lavado quirúrgico de absceso isquiorrectal con agua oxigenada / Pneumoperitoneum secondary to ischiorectal abscess surgical scrub with hydrogen peroxide

El agua oxigenada es una sustancia usada frecuentemente como un agente seguro e inocuo; sin embargo, se han descrito diversas complicaciones que establecen la voz de alarma sobre su uso. Presentamos un caso de neumoperitoneo secundario al lavado quirúrgico con agua oxigenada en un paciente con diagnóstico de absceso isquiorrectal. Ante las complicaciones observadas del uso de una sustancia tan ampliamente extendida en cirugía, debería replantearse su uso o al menos darle un empleo más restringido, en cavidades o espacios semicerrados y usar en su lugar sustancias más seguras que hasta ahora no hayan mostrado efectos tan nocivos (AU)

Hydrogen peroxide is a substance often used as a safe and harmless agent, various complications have been described that set the alarm on their use. We present a case of pneumoperitoneum secondary to surgical scrub with hydrogen peroxide in a patient with ischiorectal abscess. Given the complications of the use of a substance as widespread in surgery, we should rethink their use or at least give it more restricted use, in cavities or semi-enclosed spaces and instead use other safer chemicals (AU)

Ingesta de cuerpos extraños / Ingest of foreign bodies

La ingesta de cuerpos extraños supone una consulta habitual en los servicios de urgencias. En la mayoría de los casos, eltratamiento médico es suficiente, pero existe una pequeña proporción de casos en los que es necesario recurrir a la cirugía. Presentamos dos casos de ingesta de cuerpo extraño (AU)

The ingestion of foreign bodies supposes a habitual consultation in the services of urgencies. In most cases, the medical treatment is sufficient, but there exists a small proportion of cases in which it is necessary to resort to the surgery. We present two cases of ingestion of foreign body (AU)

A179L, a new viral Bcl2 homolog targeting Beclin 1 autophagy related protein.

Autophagy is a relevant cellular defense mechanism that directly eliminates intracellular pathogens and has a crucial role for innate and adaptive immune responses. Some viruses have developed tools to counteract this cellular response. A179L, the viral Bcl2 homolog of African swine fever virus, interacts with proapoptotic Bcl2 family proteins to inhibit apoptosis. Here we report that this gene manipulates autophagy by interacting with Beclin 1 through its BH3 homology domain. At subcellular level, A179L colocalized with Beclin 1 at mitochondria and the endoplasmic reticulum. Virus infection inhibited autophagosome formation in cells; however, when autophagy was induced prior to or at the time of infection the number of infected cells was severely decreased.