Biogeographical origin and timing of the founder ichthyosis TGM1 c.1187G > A mutation in an isolated Ecuadorian population.

An unusually high frequency of the lamellar ichthyosis TGM1 mutation, c.1187G > A, has been observed in the Ecuadorian province of Manabí. Recently, the same mutation has been detected in a Galician patient (Northwest of Spain). By analyzing patterns of genetic variation around this mutation in Ecuadorian patients and population matched controls, we were able to estimate the age of c.1187G > A and the time to their most recent common ancestor (TMRCA) of c.1187G > A Ecuadorian carriers. While the estimated mutation age is 41 generations ago (~1,025 years ago [ya]), the TMRCA of Ecuadorian c.1187G > A carrier haplotypes dates to just 17 generations (~425 ya). Probabilistic-based inferences of local ancestry allowed us to infer a most likely European origin of a few (16% to 30%) Ecuadorian haplotypes carrying this mutation. In addition, inferences on demographic historical changes based on c.1187G > A Ecuadorian carrier haplotypes estimated an exponential population growth starting ~20 generations, compatible with a recent founder effect occurring in Manabí. Two main hypotheses can be considered for the origin of c.1187G > A: (i) the mutation could have arisen in Spain >1,000 ya (being Galicia the possible homeland) and then carried to Ecuador by Spaniards in colonial times ~400 ya, and (ii) two independent mutational events originated this mutation in Ecuador and Galicia. The geographic and cultural characteristics of Manabí could have favored a founder effect that explains the high prevalence of TGM1 c.1187G > A in this region.

The geographic mosaic of Ecuadorian Y-chromosome ancestry.

Ecuadorians originated from a complex mixture of Native American indigenous people with Europeans and Africans. We analyzed Y-chromosome STRs (Y-STRs) in a sample of 415 Ecuadorians (145 using the AmpFlSTR® Yfiler™ system [Life Technologies, USA] and 270 using the PowerPlex®Y23 system [Promega Corp., USA]; hereafter Yfiler and PPY23, respectively) representing three main ecological continental regions of the country, namely Amazon rainforest, Andes, and Pacific coast. Diversity values are high in the three regions, and the PPY23 exhibits higher discrimination power than the Yfiler set. While summary statistics, AMOVA, and RST distances show low to moderate levels of population stratification, inferred ancestry derived from Y-STRs reveal clear patterns of geographic variation. The major ancestry in Ecuadorian males is European (61%), followed by an important Native American component (34%); whereas the African ancestry (5%) is mainly concentrated in the Northwest corner of the country. We conclude that classical procedures for measuring population stratification do not have the desirable sensitivity. Statistical inference of ancestry from Y-STRS is a satisfactory alternative for revealing patterns of spatial variation that would pass unnoticed when using popular statistical summary indices.

PLA2G6 mutations associated with a continuous clinical spectrum from neuroaxonal dystrophy to hereditary spastic paraplegia.

PLA2G6-associated neurodegeneration (PLAN) and hereditary spastic paraplegia (HSP) are 2 groups of heterogeneous neurodegenerative diseases. In this study, we report PLA2G6 gene mutations in 3 families from Turkey, Morocco, and Romania. Two affected Turkish siblings presenting HSP adds the disease to PLAN phenotypes. They were homozygous for the PLA2G6 missense c.2239C>T, p.Arg747Trp variant and the ages of onset were 9 and 21. Parkinsonism, dystonia or cognitive decline were not the clinical elements in these patients contrary to the cases that has been previously reported with the same variant, however, iron accumulation was evident in their cranial magnetic resonance imaging. The Moroccan patient was homozygous for a novel missense c.1786C>T, p.Leu596Phe variant and the Romanian patient had 2 novel mutations; c.1898C>T, p.Ala633Val and c.1765_1768del, p.Ser589ThrfsTer76. Both of these patients conformed better to childhood onset PLAN with the age of onset at 4 and 7 years, respectively. Interestingly, all identified mutations were affecting the highly conserved patatin-like phospholipase domain of the PLA2G6 protein.

Evaluating the Calling Performance of a Rare Disease NGS Panel for Single Nucleotide and Copy Number Variants.

INTRODUCTION: Variant detection protocols for clinical next-generation sequencing (NGS) need application-specific optimization. Our aim was to analyze the performance of single nucleotide variant (SNV) and copy number (CNV) detection programs on an NGS panel for a rare disease. METHODS: Thirty genes were sequenced in 83 patients with hereditary spastic paraplegia. The variant calls obtained with LifeScope, GATK UnifiedGenotyper and GATK HaplotypeCaller were compared with Sanger sequencing. The calling efficiency was evaluated for 187 (56 unique) SNVs and indels. Five multiexon deletions detected by multiple ligation probe assay were assessed from the NGS panel data with ExomeDepth, panelcn.MOPS and CNVPanelizer software. RESULTS: There were 48/51 (94%) SNVs and 1/5 (20%) indels consistently detected by all the calling algorithms. Two SNVs were not detected by any of the callers because of a rare reference allele, and one SNV in a low coverage region was only detected by two algorithms. Regarding CNVs, ExomeDepth detected 5/5 multi-exon deletions, panelcn.MOPs 4/5 and only 3/5 deletions were accurately detected by CNVPanelizer. CONCLUSIONS: The calling efficiency of NGS algorithms for SNVs is influenced by variant type and coverage. NGS protocols need to account for the presence of rare variants in the reference sequence as well as for ambiguities in indel calling. CNV detection algorithms can be used to identify large deletions from NGS panel data for diagnostic applications; however, sensitivity depends on coverage, selection of the reference set and deletion size. We recommend the incorporation of several variant callers in the NGS pipeline to maximize variant detection efficiency.

Carborane-stilbene dyads: the influence of substituents and cluster isomers on photoluminescence properties.

Two novel styrene-containing meta-carborane derivatives substituted at the second carbon cluster atom (Cc) with either a methyl (Me) or a phenyl (Ph) group are introduced herein along with a new set of stilbene-containing ortho- (o-) and meta- (m-) carborane dyads. The latter set of compounds have been prepared from styrene-containing carborane derivatives via a Heck coupling reaction. High regioselectivity has been achieved for these compounds by using a combination of palladium complexes [Pd2(dba)3]/[Pd(t-Bu3P)2] as a catalytic system, yielding exclusively E isomers. All compounds have been fully characterised and the crystal structures of seven of them were analysed by X-ray diffraction. The absorption spectra of these compounds are similar to those of their respective fluorophore groups (styrene or stilbene), showing a very small influence of the substituent (Me or Ph) linked to the second Cc atom or the cluster isomer (o- or m-). On the other hand, fluorescence spectroscopy revealed high emission intensities for Me-o-carborane derivatives, whereas their Ph-o-carborane analogues evidenced an almost total lack of fluorescence, confirming the significant role of the substituent bound to the adjacent Cc in o-carboranes. In contrast, all the m-carborane derivatives display similar photoluminescence (PL) behavior regardless of the substituent attached to the second Cc, demonstrating its small influence on emission properties. Additionally, m-carborane derivatives are significantly more fluorescent than their o-counterparts, reaching quantum yield values as high as 30.2%. Regarding solid state emission, only stilbene-containing Ph-o-carborane derivatives, which showed very low fluorescence in solution, exhibited notable PL emission in films attributed to aggregation-induced emission. DFT calculations were performed to successfully complement the photoluminescence studies, supporting the experimentally observed photophysical behavior of the styrene and stilbene-containing carborane derivatives. In conclusion, in this work it is proved that it is possible to tailor the PL properties of carborane-stilbene dyads by changing the Cc substituent and the carborane isomer.

Medical genomics: The intricate path from genetic variant identification to clinical interpretation.

The field of medical genomics involves translating high throughput genetic methods to the clinic, in order to improve diagnostic efficiency and treatment decision making. Technical questions related to sample enrichment, sequencing methodologies and variant identification and calling algorithms, still need careful investigation in order to validate the analytical step of next generation sequencing techniques for clinical applications. However, the main foreseeable challenge will be interpreting the clinical significance of the variants observed in a given patient, as well as their significance for family members and for other patients. Every step in the variant interpretation process has limitations and difficulties, and its quote of contribution to false positive and false negative results. There is no single piece of evidence enough on its own to make firm conclusions on the pathogenicity and disease causality of a given variant. A plethora of automated analysis software tools is being developed that will enhance efficiency and accuracy. However a risk of misinterpretation could derive from biased biorepository content, facilitated by annotation of variant functional consequences using previous datasets stored in the same or linked repositories. In order to improve variant interpretation and avoid an exponential accumulation of confounding noise in the medical literature, the use of terms in a standard way should be sought and requested when reporting genetic variants and their consequences. Generally, stepwise and linear interpretation processes are likely to overrate some pieces of evidence while underscoring others. Algorithms are needed that allow a multidimensional, parallel analysis of diverse lines of evidence to be carried out by expert teams for specific genes, cellular pathways or disorders.

Endocarditis micótica en pacientes sin cardiopatías previas / Infective fungal endocarditis in patients with no previous cardiac disease

La endocarditis infecciosa es una grave y poco frecuente afección del endocardio. La etiología micótica representa menos del 10% de dichos casos. Cada vez son más frecuentes, como grupos de riesgo, los niños con tratamiento antibiótico endovenoso, alimentación parenteral y catéteres venosos centrales por tiempo prolongado, aún sin cardiopatías previas. Se revisaron retrospectivamente las historias clínicas de 6 niños con endocarditis por Cándida y se describen los factores predisponentes, la evolución clínica y la terapéutica empleada. Los antimicóticos empleados fueron anfotericin B, 5-fluorocitocina y fluconazol. Se realizó exéresis quirúrgica de las vegetaciones, 5 plastias valvulares tricuspídeas y una sustitución valvular mitral. Sobrevivieron todos los pacientes y uno necesitó nueva plastia valvular tricuspídea después de un año de operado. Con un seguimiento medio de 5 años, todos mantienen buena función valvular sin recidivas infecciosas. Se recomienda una combinación de tratamiento antimicótico sinérgico y prolongado con la intervención quirúrgica precoz(AU)

Infective endocarditis is a serious and uncommon condition affecting the endocardium. Less than 10% of these cases are of fungal origin. A growing number of individuals are at high risk, due to insertion of central venous catheters, total parenteral nutrition and prolonged exposure to broad-spectrum antibiotics, even without previous heart diseases. We retrospectively analysed the records of six children with Candida endocarditis, reviewing the comorbidities, clinical outcome, and treatment. The antifungal agents used were amphotericin B, 5-fluorocytosine and fluconazole. Patients underwent surgical excision of vegetation, five tricuspid valve repairs and one mitral valve replacement. There were no hospital deaths, and one child needed a new valvuloplasty one year later. The mean follow up was five years, and all have good valvular function without recurrent endocarditis. A combination of synergistic long-term antifungal treatment and early surgical intervention is recommended(AU)

[Infective fungal endocarditis in patients with no previous cardiac disease]. / Endocarditis micótica en pacientes sin cardiopatías previas.

Infective endocarditis is a serious and uncommon condition affecting the endocardium. Less than 10% of these cases are of fungal origin. A growing number of individuals are at high risk, due to insertion of central venous catheters, total parenteral nutrition and prolonged exposure to broad-spectrum antibiotics, even without previous heart diseases. We retrospectively analysed the records of six children with Candida endocarditis, reviewing the comorbidities, clinical outcome, and treatment. The antifungal agents used were amphotericin B, 5-fluorocytosine and fluconazole. Patients underwent surgical excision of vegetation, five tricuspid valve repairs and one mitral valve replacement. There were no hospital deaths, and one child needed a new valvuloplasty one year later. The mean follow up was five years, and all have good valvular function without recurrent endocarditis. A combination of synergistic long-term antifungal treatment and early surgical intervention is recommended.

Seguir o no seguir las recomendaciones farmacológicas de los prescriptores: «this is the question» / To follow or not to follow the advice of health professionals, this is the question

No disponible

[Papillary renal cell carcinoma spectrum]. / El espectro del carcinoma renal papilar.

OBJECTIVES: Significant conceptual expansion of renal cancer continues to increase. The key point to this phenomenon is based on the combination of morphology and molecular data. The result is the new 2004 WHO classification of renal tumors in adults. The apparently never ending advance in molecular genetics is constantly pushing to update recently proposed listings. MATERIAL AND METHODS: Papillary renal cell carcinoma, considered the term in the broader sense, is the subject of this study. This histological phenotype in renal cancer, with an accelerated growth in the last times, is a good example of the never ending evolution of pathology as a clinical discipline. RESULTS: The genetic background and the phenotype of all renal neoplasms with papillary or tubulo-papillary phenotype, or with its genetic background, some of them being very recently described entities even now under discussion is wide and heterogenous: conventional sporadic papillary carcinoma, papillary carcinomas linked to genetic syndromes (hereditary papillary carcinoma, papillary carcinoma associated to hereditary leiomyomatosis, papillary carcinoma associated to hereditary papillary thyroid carcinoma, Birt-Hogg-Dubé syndrome) or to specific genetic disorders (Xp11.2 associated papillary carcinoma), papillary carcinoma with distinct morphology (micropapillary carcinoma, inverted papillary carcinoma, papillary carcinoma with spindle cells and angulated tubules) and new renal carcinomas included within the group of papillary carcinoma (tubulo-cystic carcinoma and tubular, mucinous and spindle cell carcinoma). CONCLUSION: Aside from the classically known histological variants, several new entities, some of them still badly delineated, are progressively enlarging the group of renal carcinomas with papillary phenotype. This growth will continue in the next times on the light of the new findings and pathologists will be main actors in this fact.

[Plasmacytoid urothelial carcinoma of the urinary bladder. A study of 7 cases]. / Carcinoma urotelial plasmocitoide de vejiga urinaria. Estudio de 7 casos.

OBJECTIVE: Plasmacytoid urothelial carcinoma is a rare and aggressive variant of bladder cancer that mimics plasmacytoma histologically and that can be confused with hemolymphoid neoplasms secondarily affecting the urinary bladder. Only single cases and short series have been described so far. PATIENTS AND METHODS: Seven cases of plasmacytoid urothelial carcinoma have been found among 720 high grade urothelial carcinomas of the urinary bladder. RESULTS: In our series, 0.97% of high grade urothelial carcinomas of the urinary bladder show plasmacytoid phenotype. All the cases were smoking males between 58 and 75 years old. Histologically, two cases showed pure plasmacytoid features, while in the other five cases the plasmacytoid phenotype was mixed with conventional transitional cell or glandular histologies. By immunohistochemistry, all the plasmacytoid areas showed fair epithelial differentiation. The clinical behaviour was aggressive in all the cases, with distant metastases at diagnosis in three cases and early tumor recurrence after chemotherapy in four of them. CONCLUSIONS: In our experience, the plasmacytoid urothelial carcinoma of the urinary bladder is a rare tumor that can also be detected in association with areas of conventional urothelial carcinoma. It is mandatory to recognize this histological subtype due to the clinical and prognostic implications of this diagnosis.

[Premedication with intraoperative clonidine and low-dose ketamine in outpatient laparoscopic cholecystectomy]. / Premedicación con clonidina y ketamina intraoperatoria a bajas dosis en la colecistectomía laparoscópica ambulatoria.

OBJECTIVE: To determine the efficacy of premedication with intraoperative clonidine in association with low-dose ketamine to reduce the need for postoperative opiate analgesia in outpatient laparoscopic cholecystectomy. PATIENTS AND METHODS: We performed a prospective study of patients undergoing outpatient laparoscopic cholecystectomy between November 2005 and November 2006. The patients were distributed randomly in 2 groups: patients in the clonidine-ketamine group received clonidine (0.15 mg orally 60 minutes before surgery) and ketamine (20-mg intravenous bolus followed by intraoperative perfusion of 20 mg h(-1)); patients in the control group did not receive this medication. Pain assessed on a verbal numerical scale, number of times rescue analgesia was required to achieve a value below 3, and adverse effects of the medication were recorded in the postoperative period. RESULTS: Thirty-one patients (16 in the clonidine-ketamine group and 15 in the control group) were enrolled. Rescue analgesia was required on 2 occasions by 25% of patients in the clonidine-ketamine group and on 2 or 3 occasions by 533% of patients in the control group. Adverse effects were reported by 87.5% of patients in the clonidine-ketamine group (mainly visual disturbances, sedation, and nausea) and by 46.7% in the control group. This difference was significant during the patients' stay in the postanesthesia recovery unit. CONCLUSIONS: Patients receiving clonidine and ketamine required less additional opiate analgesia to achieve mild pain values (<3 on the numerical verbal scale) but suffered more adverse effects during their stay in the postanesthesia recovery unit. Discharge was not delayed, however.

Utilidad de los diferentes métodos no invasivos de predicción de fibrosis hepática en pacientes del País Vasco con hemocromatosis fenotípica / No disponible

Objetivo: determinar si el producto de la edad por la concentraciónde hierro hepático (índice de fibrosis) y los valores de plaquetas,ferritina y transaminasas están relacionados con el riesgode padecer fibrosis avanzada (F >= 3) en hemocromatosis.Métodos: estudio retrospectivo de 32 pacientes con hemocromatosishereditaria con expresión fenotípica. Todos los pacientesfueron biopsiados obteniéndose la concentración de hierrohepático.Resultados: en 7 pacientes se realizó RM (1,5T) con obtenciónde concentración de hierro hepático (protocolo de Alustiza).Biopsia hepática: en 23 pacientes fibrosis 0-2; en 9 fibrosis 3-4.El índice de fibrosis mostró una especificidad del 68%, sensibilidaddel 85,7%, VPP del 42,8% y VPN del 94,4% para fibrosis avanzada.La cifra de plaquetas (< 200.000) reveló un VPN 94,4%,ferritina (> 1.000) VPN 75% y el índice de fibrosis por RMN (puntocorte 480.000) VPN 80%. La combinación de los mismos, elíndice de fibrosis (por biopsia o por RM) con las transaminasas ylas plaquetas con las transaminasas, reveló un VPN del 100%.Conclusiones: el índice de fibrosis (> 480.000) y las plaquetas(< 200.000) tienen la mayor sensibilidad para predecir fibrosisde alto grado. Un resultado negativo en ambos permite descartarfibrosis significativa en el 94% de los casos. La RM permite unabuena predicción de fibrosis

Objective: to determine whether the product of multiplyingage by liver iron concentration (LIC) (fibrosis index; cut-off,480,000), platelets, transaminases, and ferritin values are relatedto the risk of high grade fibrosis.Methods: a retrospective study of 32 patients with hereditaryhemochromatosis (HH) with phenotypic expression. All patientshad a liver biopsy with LIC.Results: in 7 patients a magnetic resonance imaging (MRI)scan (1.5 T) was obtained with LIC following Alustiza’s protocol.Liver biopsy: fibrosis grade (F) 0-2 in 23 patients; F 3-4 in 9. Fibrosisindex (FI) showed a specificity of 68%, sensitivity of 85.7%,positive predictive value (PPV) of 42.8%, and negative predictivevalue (NPV) of 94.4% for high-grade fibrosis. Platelet count(< 200,000) revealed a NPV of 94.7% for F3-4. Aspartatetransaminase (AST) levels above the upper limit of normal showeda NPV of 94.4%; ferritin levels (> 1,000) a NPV of 75%, andMRI-derived LIC x age (> 480,000) a NPV of 80%. The combinationof FI (either by biopsy or MRI) with transaminases, and ofplatelets with transaminases revealed a NPV of 100%.Conclusions: FI > 480,000 and platelets < 200,000 havethe highest sensitivity for high-degree fibrosis prediction. A negativeresult allows to discard significant fibrosis in 94% of cases.MRI allows a good fibrosis prediction

El espectro del carcinoma renal papilar / Papillary renal cell carcinoma spectrum

Objetivos: Los últimos años están asistiendo a la gran expansión conceptual del cáncer renal. La conjunción entre los hallazgos histológicos y los datos moleculares ha sido un punto clave en este fenómeno, y resultado de ello ha sido la clasificación de los tumores renales del adulto de la OMS de 2004. En ella se han unido viejos y nuevos tumores renales. Lejos de estar cerrada, esta clasificación se actualiza gracias a nuevos puntos de vista surgidos a la luz de los nuevos hallazgos que se obtienen fundamentalmente en el campo de la genética. Material y Métodos: El carcinoma papilar renal en el sentido más amplio del término es el objeto de revisión en este trabajo. Este fenotipo histológico en el cáncer renal es un buen ejemplo de evolución incesante de la anatomía patológica como disciplina clínica, con un crecimiento importante en los últimos tiempos. Resultados: El conjunto de neoplasias renales que muestran una histología papilar o túbulo-papilar, o que tienen su sustrato genético, algunas de las cuales son entidades muy recientes y están aún hoy en día en discusión, es amplio y variado: carcinoma papilar esporádico convencional, carcinomas papilares ligados a síndromes genéticos (carcinoma papilar hereditario, carcinoma papilar asociado a leiomiomatosis hereditaria, carcinoma papilar asociado a carcinoma papilar hereditario de tiroides, síndrome de Birt-Hogg-Dubé) o a alteraciones genéticas específicas (carcinomas papilares con translocación Xp11.2), carcinomas papilares con morfología peculiar (carcinoma micropapilar, carcinoma papilar invertido, carcinoma papilar con células fusiformes y túbulos angulados) y carcinomas renales de nuevo cuño englobados dentro del grupo del carcinoma papilar (carcinoma tubulo-quístico y carcinoma mucinoso, tubular y fusocelular).Conclusión: Además de las variedades clásicamente reconocidas, nuevas entidades, algunas no bien definidas aún, están engrosando de forma progresiva el grupo de carcinomas renales con morfología papilar. Lejos de agotarse, este crecimiento continuará en los próximos años a la luz de los nuevos hallazgos, y en éstos los patólogos tendrán mucho que decir (AU)

Objectives: Significant conceptual expansion of renal cancer continues to increase. The key point to this phenomenon is based on the combination of morphology and molecular data. The result is the new 2004 WHO classification of renal tumors in adults. The apparently never ending advance in molecular genetics is constantly pushing to update recently proposed listings. Material and Methods: Papillary renal cell carcinoma, considered the term in the broader sense, is the subject of this study. This histological phenotype in renal cancer, with an accelerated growth in the last times, is a good example of the never ending evolution of pathology as a clinical discipline. Results: The genetic background and the phenotype of all renal neoplasms with papillary or tubulo-papillary phenotype, or with its genetic background, some of them being very recently described entities even now under discussion is wide and heterogenous: conventional sporadic papillary carcinoma, papillary carcinomas linked to genetic syndromes (hereditary papillary carcinoma, papillary carcinoma associated to hereditary leiomyomatosis, papillary carcinoma associated to hereditary papillary thyroid carcinoma, Birt-Hogg-Dubé syndrome) or to specific genetic disorders (Xp11.2 associated papillary carcinoma), papillary carcinoma with distinct morphology (micropapillary carcinoma, inverted papillary carcinoma, papillary carcinoma with spindle cells and angulated tubules) and new renal carcinomas included within the group of papillary carcinoma (tubulo-cystic carcinoma and tubular, mucinous and spindle cell carcinoma).Conclusion: Aside from the classically known histological variants, several new entities, some of them still badly delineated, are progressively enlarging the group of renal carcinomas with papillary phenotype. This growth will continue in the next times on the light of the new findings and pathologists will be main actors in this fact (AU)

Carcinoma urotelial plasmocitoide de vejiga urinaria. Estudio de 7 casos / Plasmacytoid urothelial carcinoma of the urinary bladder. A study of 7 cases

Objetivo: El carcinoma urotelial plasmocitoide es una variedad rara y agresiva de carcinoma vesical que histológicamente simula un plasmocitoma y que puede ser confundido con una neoplasia hemolinfoide que afecte secundariamente a la vejiga urinaria. Hasta la fecha solo se han descrito casos aislados y series cortas de esta variante neoplásica. Pacientes y Método: Se han encontrado un total de 7 casos de carcinoma urotelial con fenotipo plasmocitoide total o parcial entre un total de 720 casos consecutivos de carcinoma urotelial de alto grado. Resultados: El 0,97% de los carcinomas vesicales uroteliales de alto grado analizados muestra morfología plasmocitoide. Todos los casos correspondieron a varones con edades comprendidas entre 58 y 75 años. Histológicamente, dos casos presentaban morfología plasmocitoide pura, mientras que en cinco de ellos el fenotipo plasmocitoide estaba combinado con áreas transicionales y/o glandulares convencionales. La inmunohistoquímica demostró en todos los casos el carácter epitelial de las áreas plasmocitoides. El comportamiento clínico fue agresivo en todos los casos, con metástasis a distancia en tres de ellos en el momento del diagnóstico y recurrencia precoz tras el tratamiento quimioterápico en cuatro. Conclusiones: En nuestra experiencia, el carcinoma urotelial plasmocitoide de vejiga urinaria es muy poco frecuente, y puede presentarse de manera pura o asociado a áreas de carcinoma vesical convencional. Es conveniente reconocer esta variedad histológica debido a las implicaciones que conlleva en el pronóstico de los pacientes (AU)

Objective: Plasmacytoid urothelial carcinoma is a rare and aggressive variant of bladder cancer that mimics plasmacytoma histologically and that can be confused with hemolymphoid neoplasms secondarily affecting the urinary bladder. Only single cases and short series have been described so far. Patients and Methods: Seven cases of plasmacytoid urothelial carcinoma have been found among 720 high grade urothelial carcinomas of the urinary bladder. Results: In our series, 0.97% of high grade urothelial carcinomas of the urinary bladder show plasmacytoid phenotype. All the cases were smoking males between 58 and 75 years old. Histologically, two cases showed pure plasmacytoid features, while in the other five cases the plasmacytoid phenotype was mixed with conventional transitional cell or glandular histologies. By immunohistochemistry, all the plasmacytoid areas showed fair epithelial differentiation. The clinical behaviour was aggressive in all the cases, with distant metastases at diagnosis in three cases and early tumor recurrence after chemotherapy in four of them. Conclusions: In our experience, the plasmacytoid urothelial carcinoma of the urinary bladder is a rare tumor that can also be detected in association with areas of conventional urothelial carcinoma. It is mandatory to recognize this histological subtype due to the clinical and prognostic implications of this diagnosis (AU)

Premedicación con clonidina y ketamina intraoperatoria a bajasdosis en la colecistectomía laparoscópica ambulatoria / Premedication with intraoperative clonidine and low-dose ketamine in outpatient laparoscopic cholecystectomy

OBJETIVO: Comprobar la eficacia de la premedicacióncon clonidina, asociada a ketamina intraoperatoria abajas dosis, para disminuir la necesidad de analgésicosopioides postoperatorios en la colecistectomía laparoscópicaambulatoriaPACIENTES Y MÉTODOS: Se realizó un estudio prospectivoen pacientes sometidos a colecistectomía laparoscópicaambulatoria desde noviembre de 2005 anoviembre de 2006. Se distribuyeron de forma aleatoriaen 2 grupos, grupo CK a los que se administró clonidina(0,15 mg vía oral 60 minutos antes de la cirugía)y ketamina (bolo de 20 mg intravenoso seguido deperfusión intraoperatoria de 20 mg h-1), y grupo O alos que no se suministró esa medicación. Se determinóla Escala Verbal Numérica (EVN) durante el postoperatorio,número de rescates analgésicos necesariospara obtener un valor inferior a 3 y efectos adversos ala medicación.RESULTADOS: Se incluyeron 31 pacientes (16 en el grupoCK y 15 en el grupo O). 25% de los pacientes necesitaron2 rescates en el grupo A, mientras que en el grupoB 53,3% necesitaron 2 ó 3 rescates. Presentaron efectosadversos un 87,5% en el grupo CK (principalmente alteracionesvisuales, sedación y nauseas), y un 46,7% en elgrupo O. Esta diferencia fue significativa durante supermanencia en la Unidad de Recuperación Postanestésica(URPA).CONCLUSIONES: Los pacientes con clonidina y ketaminaprecisan menos analgesia adicional con opioides paraalcanzar valores de dolor leve (EVN menor de 3) perotuvieron más efectos adversos durante su permanenciaen URPA, aunque no retrasó el alta hospitalaria (AU)

OBJECTIVE: To determine the efficacy of premedicationwith intraoperative clonidine in association with low-doseketamine to reduce the need for postoperative opiateanalgesia in outpatient laparoscopic cholecystectomy.PATIENTS AND METHODS: We performed a prospectivestudy of patients undergoing outpatient laparoscopiccholecystectomy between November 2005 and November2006. The patients were distributed randomly in 2groups: patients in the clonidine-ketamine groupreceived clonidine (0.15 mg orally 60 minutes beforesurgery) and ketamine (20-mg intravenous bolusfollowed by intraoperative perfusion of 20 mg·h-1);patients in the control group did not receive thismedication. Pain assessed on a verbal numerical scale,number of times rescue analgesia was required toachieve a value below 3, and adverse effects of themedication were recorded in the postoperative period.RESULTS: Thirty-one patients (16 in the clonidineketaminegroup and 15 in the control group) wereenrolled. Rescue analgesia was required on 2 occasionsby 25% of patients in the clonidine-ketamine group andon 2 or 3 occasions by 53.3% of patients in the controlgroup. Adverse effects were reported by 87.5% ofpatients in the clonidine-ketamine group (mainly visualdisturbances, sedation, and nausea) and by 46.7% in thecontrol group. This difference was significant during thepatients’ stay in the postanesthesia recovery unit.CONCLUSIONS: Patients receiving clonidine and ketaminerequired less additional opiate analgesia to achieve mildpain values (<3 on the numerical verbal scale) but sufferedmore adverse effects during their stay in the postanesthesiarecovery unit. Discharge was not delayed, however (AU)

[Utility of various non-invasive methods for fibrosis prediction among Basque Country patients with phenotypic hemochromatosis]. / Utilidad de los diferentes métodos no invasivos de predicción de fibrosis hepática en pacientes del País Vasco con hemocromatosis fenotípica.

OBJECTIVE: To determine whether the product of multiplying age by liver iron concentration (LIC) (fibrosis index; cut-off, 480,000), platelets, transaminases, and ferritin values are related to the risk of high grade fibrosis. METHODS: A retrospective study of 32 patients with hereditary hemochromatosis (HH) with phenotypic expression. All patients had a liver biopsy with LIC. RESULTS: In 7 patients a magnetic resonance imaging (MRI) scan (1.5 T) was obtained with LIC following Alustiza's protocol. Liver biopsy: fibrosis grade (F) 0-2 in 23 patients; F 3-4 in 9. Fibrosis index (FI) showed a specificity of 68%, sensitivity of 85.7%, positive predictive value (PPV) of 42.8%, and negative predictive value (NPV) of 94.4% for high-grade fibrosis. Platelet count ( < 200,000) revealed a NPV of 94.7% for F3-4. Aspartate transaminase (AST) levels above the upper limit of normal showed a NPV of 94.4%; ferritin levels (> 1,000) a NPV of 75%, and MRI-derived LIC x age (> 480,000) a NPV of 80%. The combination of FI (either by biopsy or MRI) with transaminases, and of platelets with transaminases revealed a NPV of 100%. CONCLUSIONS: FI > 480,000 and platelets < 200,000 have the highest sensitivity for high-degree fibrosis prediction. A negative result allows to discard significant fibrosis in 94% of cases. MRI allows a good fibrosis prediction.

[Accidental dural puncture during epidural injection of corticosteroids: a different approach?]. / Punción dural accidental en la infiltración epidural con corticoide. Un abordaje diferente?

We report 6 cases diagnosed with accidental dural puncture after epidural injection of corticosteroids for low back pain. All the patients reported postdural puncture headache during their stay in the postanesthetic recovery unit. For 3 patients, pain resolved with treatment given in the recovery unit. Two other patients also required mild analgesics for 1 week. In the last patient, a blood patch was used to treat incapacitating headache 22 days after the epidural procedure and mild analgesics were needed for 4 more weeks. It is important to establish a protocol for treating postdural puncture headache in pain clinics to facilitate decision making. Good physician-patient communication is necessary to avoid refusals for permission for other epidural techniques and to facilitate management of symptoms.

Punción dural accidental en la infiltración epidural con corticoide. ¿Un abordaje diferente? / Accidental dural puncture during epidural injection of corticosteroids: a different approach?

Presentamos los 6 casos de pacientes en los que sediagnosticó una punción dural accidental tras infiltraciónepidural con corticoide por lumbociatalgia. Todos refirieroncefalea postpunción dural durante su permanenciaen la Unidad de Recuperación Postanestésica. En 3 deellos la cefalea remitió con los tratamientos recibidos enesta unidad, dos pacientes necesitaron además tratamientocon analgésicos menores durante 1 semana y en el últimopaciente se realizó un parche hemático por cefaleainvalidante a los 22 días de la infiltración y tratamientocon analgésicos menores durante 4 semanas más.Es importante disponer de un protocolo de tratamientode Cefalea Postpunción Dural en los pacientes entratamiento en las Unidades de Dolor para facilitar latoma de decisiones, y es fundamental un buen entendimientomédico-paciente para evitar negativas ante nuevastécnicas epidurales y facilitar el abordaje del cuadro

We report 6 cases diagnosed with accidental duralpuncture after epidural injection of corticosteroids forlow back pain. All the patients reported postdural punctureheadache during their stay in the postanestheticrecovery unit. For 3 patients, pain resolved with treatmentgiven in the recovery unit. Two other patients alsorequired mild analgesics for 1 week. In the last patient,a blood patch was used to treat incapacitating headache22 days after the epidural procedure and mild analgesicswere needed for 4 more weeks.It is important to establish a protocol for treating postduralpuncture headache in pain clinics to facilitate decisionmaking. Good physician-patient communication isnecessary to avoid refusals for permission for other epiduraltechniques and to facilitate management of symptoms

Efectos del ultrasonido externo sobre el adipocito en la liposucción / Effects of external ultrasound on fat tissue in liposuction

Se ha desarrollado un método de liposucción asistida con ultrasonido externo, aplicado directamente sobre la piel, sin embargo no existe en la literatura un estudio formal que describa los cambios provocados en las diferentes estructuras y tejidos con la aplicación de diferentes intensidades de ultrasonido externo por períodos variables. Ante la inexistencia de una guía científica para el uso del ultrasonido externo en la lipoescultura, este estudio se desarrollo para conocer sus efectos, así como los parámetros capaces de producir la destrucción selectiva de las células de grasa, facilitando su extracción por aspiración y que sean seguros para no lesionar los tejidos adyacentes. Se utilizaron diez cerdos machos de raza criolla, en los cuales se aplicó el ultrasonido externo y se observaron los cambios macroscópicos del tejido graso bajo visión directa a través de una fibra óptica; simultáneamente se tomaron biopsias a diferentes intensidades y a diferentes periodos de tiempo, quefueron analizadas histológicamente, con lo que se demostró que el ultrasonido externo no produce los fenómenos de licuefacción grasa y microcavitación. Las quemaduras producidas en la piel se presentan solo cuando el transductor se mantiene en un halo igual a su diámetro durante un minuto o más; mientras se realice un movimiento continúo del transductor que sobrepase el diámetro de éste, la aplicación del ultrasonido externo es segura hasta periodos de 20 minutos (AU)

Liposuction method assisted with external ultrasound has been developed, applied directly on the skin, however it doesn’t exist in the literature a formal report that describes the provoked changes to the different structures and tissues and the application in different intensities of external ultrasound, per variables periods. There is not any scientific guide for the use of the external ultrasound in the liposculpturing. This study tries to know the effects of this energy, as well as the parameters that are able to produce the selective destruction of the cells of fat to facilitate its extraction by aspiration and all that in a so safe way that we don’t injure the adjacent tissues. Ten creole race male pigs were used, in which the external ultrasound was applied and the macroscopic changes of the fatty low direct vision were observed through an optic fiber; we took simultaneously biopsies to different intensities and periods of time. It was demonstrated that the external ultrasound does not produce the phenomenons of fatty liquefaction and acoustic cavitation. The burns on skin are presented when the transducer stays in a halo similar to its diameter for one minute or more; while the transducer is moving on a diameter bigger than its surface, the external ultrasound application is safe until for 20 minutes (AU)