Constitutional mosaicism in RASA1-related capillary malformation-arteriovenous malformation.

Capillary malformation-arteriovenous malformation (CM-AVM) is caused by germline RASA1 and EPHB4 alterations. RASA1 intralesional second hits have also been reported. Here we report RASA1 constitutional mosaicism, defined here as the presence of a mosaic variant in all cell types of an individual, in two patients with CM-AVM. High-throughput sequencing was used to search for RASA1 pathogenic variants in blood samples from two unrelated patients with CM-AVM. An affected tissue sample from one of the patients was also analyzed. Both patients showed different nonsense RASA1 variants in mosaic, ranging from 7% to 21.5%, in blood samples and in the corresponding affected tissue sample from one of the patients. In conclusion, we report for the first time the presence of RASA1 constitutional mosaicism in CM-AVM. Constitutional mosaicism has implications for accurate molecular diagnosis and recurrence risk and helps to explain the great phenotypic variability in CM-AVM.

[Economic evaluation of a program of coordination between levels for complex chronic patients' management]. / Evaluación económica de un programa de coordinación entre niveles para el manejo de pacientes crónicos complejos.

OBJECTIVE: The complex chronic patient program (CCP) of the Alt Penedès aims to improve the coordination of care. The objective was to evaluate the relationship between the costs associated with the program, and its results in the form of avoided admissions. DESIGN: Dost-effectiveness analysis from the perspective of the health System based on a before-after study. LOCATION: Alt Penedès. MAIN MEASUREMENTS: Health services utilisation (hospital [admissions, emergency visits, day-care hospital] and primary care visits). CCP Program results were compared with those prior to its implementation. The cost assigned to each resource corresponded to the hospital CatSalut's concert and ICS fees for primary care. A sensitivity analysis using boot strapping was performed. The intervention was considered cost-effective if the incremental cost-effectiveness ratio (ICER) did not exceed the cost of admission (€ 1,742.01). RESULTS: 149 patients were included. Admissions dropped from 212 to 145. The ICER was €1,416.3 (94,892.9€/67). Sensitivity analysis showed that in 95% of cases the cost might vary between €70,847.3 and €121,882.5 and avoided admissions between 30 and 102. In 72.4% of the simulations the program was cost-effective. CONCLUSIONS: Sensitivity analysis showed that in most situations the PCC Program would be cost-effective, although in a percentage of cases the program could raise overall cost of care, despite always reducing the number of admissions.

[Empowerment and power: their relationship in the proces of caring for the chronically ill in primary care]. / Empoderamiento y poder: su vinculación en el proceso de cuidar al enfermo crónico en atención primaria.

The concepts of "power" and "empowerment" are used in various disciplines, both political and social. Now are these terms frequently in the field of health. Our goal is to know its meaning as a synonym of expressions: "energy", "force", "domain", "vigour", "power", "capacity", "authority" and "control", which have been always within our practice nurse's own lexicon. Semantically analyzing them will help us in the understanding of its nuance. The literature review facilitates their understanding and allows us to link these words within the management of care. In this way we can propose diagnoses, interventions and outcomes specifically related to these concepts, which will help us optimize the efficiency in the management of care plans. The purpose of various collective nurses from different institutions is that the person is able to not generate dependencies and have the option of choosing your own lifestyle according to their culture and environment, independently or with the help. Generate knowledge is to generate power. The person should be educated and informed, to be expert and active and taking action to help control and minimize the progression of your health problem chronic and its possible complications. We are in the process of reformulation of the health system, whether it is private or public, and is necessary to know the power of the various actors involved in the management of the care to us. Each of these main actors--person ill, family/caregiver or nurse--has to know what is his role in this process.

[Association of FTO gene polymorphisms and morbid obesity in the population of Extremadura (Spain)]. / Asociación de polimorfismos en el gen FTO con la obesidad mórbida en la población extremeña.

OBJECTIVE: To select individuals whose morbid obesity can be attributed mainly to their individual genetic profile. After excluding patients with potential monogenic syndromes or diseases associated with obesity, we evaluated the association of the single nucleotide polymorphisms (SNPs) rs1861868 and rs9939609 of the fat-mass and obesity-associated FTO gene with an inherited predisposition to morbid obesity. PATIENTS AND METHODS: We evaluated 270 patients with morbid obesity and onset before the age of 14 years and selected 194 due to their phenotypes and family history; 289 control individuals were included. The rs1861868 and rs9939609 variants, located in the FTO gene, were genotyped. Genotype and haplotype frequencies were compared between cases and controls. RESULTS: The A allele of rs9939609 was associated with severe obesity starting in childhood among the Spanish population. The rs1861868 G/rs9939609 A haplotype of the FTO gene was also significantly associated with severe obesity in our population, with an odds ratio of 3.03 (95% confidence interval, 1.74-5.27). CONCLUSION: Analysis of the genetic basis of obesity requires rigorous selection of cases. In this study, the association of the rs9939609 SNP with obesity widely described in distinct populations was confirmed among overweight Spanish children. Genotyping rs1861868 allowed us to identify the first risk haplotype in the FTO gene, which is located in the adjacent haplotype block containing rs9939609. In-depth study of the variability of the FTO gene is essential to define its deleterious capacity.

Antibacterial Activity of Hen Egg White Lysozyme Denatured by Thermal and Chemical Treatments.

The aim of this study was to increase the antibacterial spectrum of modified hen egg white lysozyme (HEWL) with thermal and chemical treatments against Gram-negative bacteria. The antibacterial activity of heat-denatured HEWL and chemical denatured HEWL against Gram-negative and Gram-positive bacteria was evaluated in 15 h of incubation tests. HEWL was denatured by heating at pH 6.0 and pH 7.0 and chemical denaturing was carried out for 1.0, 1.5, 2.0, and 4.0 h with DL-Dithiothreitol (DTT). HEWL modified by thermal and chemical treatments was characterized using the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) electrophoresis method. Heat-denatured HEWL lytic activity against Micrococcus lysodeikticus lessened with increasing temperature and time of incubation with the chemical agent (DTT). The loss of lytic activity in modified HEWL suggests that the mechanism of action of the antibacterial activity is not dependent on the lytic activity. Thermal and chemical treatments of HEWL enabled the production of oligoforms and increased antibacterial activity over a wider spectrum. Heat-denatured HEWL at pH 6.0 and chemically-denatured HEWL increased the HEWL antibacterial spectrum against Gram-negative bacteria (Escherichia coli ATCC 25922). HEWL at 120 °C and pH 6.0 (1.0 mg/mL) inhibited 78.20% of the growth of E. coli. HEWL/DTT treatment for 4.0 h (1.0 mg/mL) inhibited 68.75% of the growth E. coli. Heat-denatured HEWL at pH 6.0 and pH 7.0 and chemically-denatured HEWL (1.0, 1.5, 2.0, and 4.0 h with DTT) were active against Gram-positive bacteria (Staphylococcus carnosus CECT 4491T). Heat-denatured and chemical-denatured HEWL caused the death of the bacteria with the destruction of the cell wall. LIVE/DEAD assays of fluorescent dye stain of the membrane cell showed membrane perturbation of bacteria after incubation with modified HEWL. The cell wall destruction was viewed using electron microscopy. The results obtained in this study suggest that heat-denatured HEWL at pH 6.0 and chemical-denatured HEWL treatments increase the HEWL antibacterial activity against Gram-negative bacteria.

Whole exome sequencing using Ion Proton system enables reliable genetic diagnosis of inherited retinal dystrophies.

Inherited retinal dystrophies (IRD) comprise a wide group of clinically and genetically complex diseases that progressively affect the retina. Over recent years, the development of next-generation sequencing (NGS) methods has transformed our ability to diagnose heterogeneous diseases. In this work, we have evaluated the implementation of whole exome sequencing (WES) for the molecular diagnosis of IRD. Using Ion ProtonTM system, we simultaneously analyzed 212 genes that are responsible for more than 25 syndromic and non-syndromic IRD. This approach was used to evaluate 59 unrelated families, with the pathogenic variant(s) successfully identified in 71.18% of cases. Interestingly, the mutation detection rate varied substantially depending on the IRD subtype. Overall, we found 63 different mutations (21 novel) in 29 distinct genes, and performed in vivo functional studies to determine the deleterious impact of variants identified in MERTK, CDH23, and RPGRIP1. In addition, we provide evidences that support CDHR1 as a gene responsible for autosomal recessive retinitis pigmentosa with early macular affectation, and present data regarding the disease mechanism of this gene. Altogether, these results demonstrate that targeted WES of all IRD genes is a reliable, hypothesis-free approach, and a cost- and time-effective strategy for the routine genetic diagnosis of retinal dystrophies.

Comprehensive SNP-chip for retinitis pigmentosa-Leber congenital amaurosis diagnosis: new mutations and detection of mutational founder effects.

Fast and efficient high-throughput techniques are essential for the molecular diagnosis of highly heterogeneous hereditary diseases, such as retinitis pigmentosa (RP). We had previously approached RP genetic testing by devising a chip based on co-segregation analysis for the autosomal recessive forms. In this study, we aimed to design a diagnostic tool for all the known genes (40 up to now) responsible for the autosomal dominant and recessive RP and Leber congenital amaurosis (LCA). This new chip analyzes 240 single nucleotide polymorphisms (SNPs) (6 per gene) on a high-throughput genotyping platform (SNPlex, Applied Biosystems), and genetic diagnosis is based on the co-segregation analysis of SNP haplotypes in independent families. In a single genotyping step, the number of RP candidates to be screened for mutations is considerably reduced, and in the most informative families, all the candidates are ruled out at once. In a panel of RP Spanish pedigrees, the disease chip became a crucial tool for selecting those suitable for genome-wide RP gene search, and saved the burdensome direct mutational screening of every known RP gene. In a large adRP family, the chip allowed ruling out of all but the causative gene, and identification of an unreported null mutation (E181X) in PRPF31. Finally, on the basis of the conservation of the SNP haplotype linked to this pathogenic variant, we propose that the E181X mutation spread through a cohort of geographically isolated families by a founder effect.

Semiótica del vértigo postural paroxístico benigno / Semiotic of benign paroxysmal postural vertigo

El presente trabajo tiene como objetivo, el estudio de la semiótica observada por el compromiso canicular en el cuadro del VPPB, su correlación anatómica y etiopatogénica, permitiendo entender la lógica de cada etapa postulada en el manejo kinésico de este cuadro. Para concretar este objetivo, fue creado el policlínico de vértigo en el Servicio de Otorrinolaringología del Hospital Clínico de la Universidad de Chile Dr José Joaquín Aguirre, con 3 horas semanales, destinado a absorver la demanda espontánea y derivada por patología vertiginosa, seleccionando para nuestro estudio sólo los de origen postural periférico, aplicándoles un protocolo diseñado por los autores del trabajo, que incluyen anamnesis del episodio actual, antecedentes y examen físico otorrinolaringológico, maniobras de provocación para canales semicirculares verticales y horizontales hipótesis diagnóstica y tratamiento propuesto con maniobras kinésicas según canal identificado

Apnea obstructiva en el niño: caso clínico y revisión bibliográfica / Obstructive sleep apnea in children: clinical case and bibliographic review

Se presenta un caso clínico de una niña de 8 años, obesa mórbida, portadora de una hiperplasia adenoamigdaliana obstructiva severa y síndrome de apnea obstructiva del sueño de carácter grave. Además se muestra metodología de estudio disgnóstico, tratamiento y manejo en equipo multidisciplinario propuesto en la actualidad

Cirugía craneofacial con compromiso de fosa craneana anterior / Craniofacial surgery with cranial fossas compromise

El perfeccionamiento de las técnicas de diagnóstico y tratamiento, ha permitido el desarrollo de nuevos procedimientos quirúrgicos, entre ellos la cirugía craneofacial. Esta ha permitido un aumento tanto de la tasa de sobrevida como de calidad de vida de pacientes con tumores de la supraestructura comprometiendo fosa craneana anterior, (15 por ciento sobrevida precirugía craneofacial versus 50 por ciento poscirugía craneofacial). El objetivo del presente trabajo es evaluar nuestra experiencia respecto a histología de los tumores operados por cirugía craneofacial, morbimortalidad quirúrgica, sobrevida y factores pronósticos. Se revisa retrospectivamente las fichas de los pacientes sometidos a cirugía craneofacial entre 1990-1999, de acuerdo a una pauta especialmente diseñada. Se encuentra un total de 17 pacientes: 6 con tumores benignos y 11 con tumores malignos. De los tumores malignos, el 54 por ciento correspondió a estesioneuroblastoma; todos recibieron radioterapia. La sobrevida de los pacientes con cáncer fue de 72 por ciento, y de 100 por ciento para los tumores benignos. Los tres pacientes fallecidos sufrieron exenteración orbitaria y tenían cánceres muy indiferenciados. Nuestra sobrevida para los tumores benignos es comparable con otras series, pero para los cánceres es mejor que la relatada en la literatura; lo anterior podría deberse a la presencia de pacientes sin tratamiento previo, con cierre primario y sin compromiso del lóbulo frontal

Sarcoidosis laríngea: caso clínico / Laryngeal sarcoidosis: clinical case

Se presenta un caso de paciente se sexo masculino de 17 años, portador de Sarcoidosis localizada en laringe (supraglotis), con la metodología de estudio, diagnóstico y tratamiento empleado, mostrando una remisión lenta, pero estable. Además se hace una revisión de dicha patología en cuanto a sus características generales, diagnóstico, histopatología y alternativas terapéuticas

Tumores malignos de nariz y cavidades perinasales / Nose and paranasal cavities malignant tumors

Se analizan 83 pacientes portadores de tumores de nariz y cavidades perinasales, recopilados entre los años 1990 y 1999. Se realizó un análisis descriptivo retrospectivo en cuanto a su histología, clínica, estadío, origen, estudio preoperatorio, vía de toma de biopsia, vía de abordaje, tratamiento, complicaciones y resultados. Estos se comparan con los obtenidos en el período 1976-1986. El tratamiento siempre ha sido el mismo: cirugía radical complementada con radioterapia postoperatoria. A partir de 1990 se comenzó a realizar de rutina la cirugía craneofacial para los tumores que comprometían la base de cráneo (fosa anterior) o se sospechara tal compromiso. Se comparan ambos decenios respecto a la sobrevida a dos años de pacientes con tratamiento curativo y paliativo, pacientes con compromiso de supraestructura e infraestructura y pacientes con tumores de seno maxilar en estadio T3 y T4. Se discute las indicaciones de exanteración orbitaria y su evolución en el tiempo, las distintas modalidades de reconstrucción de la órbita y la indicación de cirugía endoscópica para estos tumores