Identification of extraocular extension in uveal melanoma by ophthalmological ultrasound.

BACKGROUND AND PURPOSE: Uveal melanoma is the most common primary malignant intraocular tumour in the adult population, with a survival rate of 50% despite advances in treatment and knowledge of this disease. The presence of extraocular extension (EE) worsens the prognosis of these patients, so its proper identification can ensure its management and early intervention. Ophthalmological ultrasound is the technique of choice for the diagnosis and follow-up of these patients, both of the anterior EE using ultrasonic biomicroscopy (UBM), and the posterior EE using A and B ultrasound. The aim of this study is to describe the ultrasound characteristics of the BMU and the A and B ultrasound. MATERIAL AND METHODS: A descriptive and retrospective study is carried out on patients diagnosed with uveal melanoma (UM) and EE from 2003 to 2019. The ultrasound characteristics of the local disease and the follow-up after treatment were recorded completely and at each visit. In the case of anterior EE, photographs of the anterior segment and UBM were taken, while those involving the posterior segment were explored under A and B mode ultrasound. All enucleated eyes were sent for anatomopathological study. RESULTS: Ten patients with an average age of 72.3 years were included. The largest proportion of them were medium-sized tumours, followed by large and small ones. The most frequent morphology of the primary tumour was cupuliform. All the EE presented lower internal reflectivity compared to the primary tumour. No trans-scleral connection bridges were found between the primary tumour and the EE in the ultrasound studies. 50% of patients underwent primary enucleation at the time of diagnosis of intraocular MU due to the presence of the EE, and the remaining 50% presented the EE after initial treatment of the primary tumour with I125 brachytherapy. Sixty percent of the patients presented with posterior EE, and were therefore diagnosed with ultrasound A and B. The most frequent histopathological pattern with 87.5% of patients was the epithelioid pattern. DISCUSSION: Ultrasound scanning in patients with MU is mandatory for diagnosis and follow-up of EE. BMU and A and B ultrasound are the test of choice for anterior and posterior EE, respectively. EE have particular ultrasound characteristics such as low internal reflectivity, regularity of their contour and their location usually adjacent to the base of the primary intraocular tumor.

[Intestinal failure and transplantation in microvillous inclusion disease]. / Fracaso intestinal y trasplante en la enfermedad por inclusiones microvellositarias.

INTRODUCTION: Microvillous inclusion disease is a rare autosomal recessive condition, characterized by severe secretory diarrhea that produces a permanent intestinal failure and dependency on parenteral nutrition. It usually begins in the neonatal period, and the only treatment at present is intestinal transplantation. PATIENTS AND METHODS: A retrospective review was conducted on 6 patients (three males and three females) diagnosed with microvillous inclusion disease between 1998 and 2013. RESULTS: All debuted in the first month of life, with a median age of three days (range, 3-30 days), and had secretory diarrhea dependent on parenteral nutrition, with fasting fecal volume of 150-200ml/kg/day. Light microscopy of duodenal biopsy samples showed varying degrees of villous atrophy without cryptic hyperplasia, accumulation of PAS positive material in the cytoplasm of enterocytes brush border, and anti-CD10 immunostaining was suggestive of intracytoplasmic inclusions. Diagnostic confirmation was performed with electron microscopy. Two of them had a genetic study, and showed mutations in MYO5B gene. Three died and three are alive; two of them with an intestinal transplantation and the third waiting for a multivisceral transplantation.

[Propranolol: Treatment of capillary hemangioma with orbital involvement]. / Propranolol: tratamiento del hemangioma capilar con afectación orbitaria.

CLINICAL CASE: A 2-months-old girl had a fast growth hemangioma in the left side of the face, that involved upper eyelid and superior and external portion of the orbit, covering her visual axis and pushing the eye and lateral rectus muscle. We gave oral propranolol as treatment and we noticed a fast and constant hemangioma reduction and resolution of orbital and palpebral component. DISCUSSION: According to previous researches, propranolol seems to be an effective and safe drug to treat capillary hemangioma. In our case, response to propranolol was satisfactory and with no side effects. This treatment should be considered as a promising alternative.

The submarine volcano eruption at the island of El Hierro: physical-chemical perturbation and biological response.

On October 10 2011 an underwater eruption gave rise to a novel shallow submarine volcano south of the island of El Hierro, Canary Islands, Spain. During the eruption large quantities of mantle-derived gases, solutes and heat were released into the surrounding waters. In order to monitor the impact of the eruption on the marine ecosystem, periodic multidisciplinary cruises were carried out. Here, we present an initial report of the extreme physical-chemical perturbations caused by this event, comprising thermal changes, water acidification, deoxygenation and metal-enrichment, which resulted in significant alterations to the activity and composition of local plankton communities. Our findings highlight the potential role of this eruptive process as a natural ecosystem-scale experiment for the study of extreme effects of global change stressors on marine environments.

Estimation of the uncertainty associated with the results based on the validation of chromatographic analysis procedures: application to the determination of chlorides by high performance liquid chromatography and of fatty acids by high resolution gas chromatography.

This article presents a model to calculate the uncertainty associated with an analytical result based on the validation of the analysis procedure. This calculation model is proposed as an alternative to commonly used bottom-up and top-down methods. This proposal is very advantageous as the validation of the procedures and the estimation of the uncertainty of the measurement are part of the technical requirements needed in order to obtain the ISO 17025:2005 accreditation. This model has been applied to the determination of chloride by liquid chromatography in lixiviates and in the determination of palmitic acid and stearic acid by gas chromatography in magnesium stearate samples.

Novel splice donor site mutation in MERTK gene associated with retinitis pigmentosa.

BACKGROUND/AIM: Mutations in MERTK, a member of the MER/AXL/TYRO3 receptor kinase family, have been associated with disruption of the Retinal Pigment Epithelium (RPE) phagocytosis pathway and settling of autosomal recessive RP (arRP) in humans. This study reports a novel MERTK mutation (IVS16+1G>T) in a Spanish consanguineous family presenting arRP. METHODS: 21 genes were screened by high-throughput SNP multiplexing assay. Subsequent direct sequencing was performed in exons and intronic boundaries of the cosegregating gene. The effect of the mutation in mRNA splicing was confirmed by cDNA analysis. RESULTS: Haplotypic data revealed MERTK cosegregation with RP in affected individuals. MERTK sequencing showed a G-to-T substitution at the first nucleotide of intron 16. Finally, cDNA analysis confirmed the lack of exon 16 in the mRNA splicing process. CONCLUSIONS: IVS16+1G>T disrupts the splice donor site causing exon 16 skipping. Absence of exon 16 causes a frameshift and, subsequently, the introduction of a premature termination codon into exon 17 creating an altered mRNA transcript with a seriously affected tyrosine kinase domain.

[Vogt Koyanagi Harada syndrome]. / Síndrome de Vogt Koyanagi Harada.

CASE REPORTS: Case 1. A female patient with visual loss and migraine who was found to have an exudative, bilateral retinal detachment. Steroid therapy was commenced initially and then cyclosporin-A added. Nine months later, her vision was 10/10 in the right eye and 9/10 in the left eye. Case 2. A female patient with unclear vision who was found to have an exudative, bilateral retinal detachment. Systemic steroid therapy was given and ultimately her vision was 9/10 in the right eye and 8/10 in the left eye. DISCUSSION: Vogt Koyanagi Harada syndrome is a bilateral granulomatous panuveitis associated with neurologic and dermatologic disorders. When a patient has exudative multifocal and bilateral retinal detachment and systemic symptomatology, the possibility of this disease needs to be suspected. Good visual prognosis is possible if early treatment is given.

Expression of TGF-betas in the embryonic nervous system: analysis of interbalance between isoforms.

Transforming growth factor-beta (TGF-beta) is a family of growth factors with essential and multiple roles during embryonic development. In mammals, three isoforms (TGF-beta1, TGF-beta2, TGF-beta3) have been described. In the nervous system, the presence of TGF-beta1 has remained undetectable in other structures than meninges and choroids plexus, while TGF-beta2 and TGF-beta3 were considered as the neural members of the family. In the present study, we have analysed the expression pattern of the three isoforms in the neural tube, brain, and spinal cord during development in both mouse and chicken. The data reveal specific patterns for each isoform. This work also shows that both TGF-beta1 and TGF-beta3 are expressed in neural crest cells. In addition, we demonstrate the existence of interbalance between TGF-beta1 and TGF-beta3 with possible functional implications, which, together with the expression of TGF-beta1 in the CNS, represents one of the most important contributions of this work.

Role of inhibitors of isoprenylation in proliferation, phenotype and apoptosis of human retinal pigment epithelium.

BACKGROUND: Isoprenoid biosynthesis is known to be essential for diverse cellular functions, including cell proliferation. The aim of this work was to study the effects caused by the addition of different inhibitors of isoprenylation (lovastatin, manumycin A, farnesyltransferase inhibitor III and N-acetyl-S-farnesyl-L-cysteine) to human retinal pigment epithelium (RPE) in culture, as potential coadjunctive-to-surgery treatments applicable to proliferative vitreoretinopathy. METHODS: Human RPE cell cultures were established from adult corneal donors. Proliferation levels were evaluated using the incorporation of 5-bromo-2'-deoxyuridine into the DNA. Cell viability was measured by tetrazolium bromide transformation. Apoptosis was determined by DNA fragmentation assay, TdT-mediated d-UTP-X nick-end labeling (TUNEL) and phosphatidylserine exposure assessment. Changes in cell morphology and actin cytoskeleton were evaluated using a phase-contrast microscope and by fluorescent staining of actin cables with TRITC-phalloidin. RESULTS: We found that lovastatin showed an important antiproliferative effect on human RPE cells in culture. This effect was clearly dose-dependent, and adding mevalonate could reverse it. We also found that lovastatin induced changes in the distribution of actin cytoskeleton and, finally, that it also induced RPE apoptosis. Manumycin A, farnesyltransferase inhibitor III and N-acetyl-S-farnesyl-L-cysteine also showed antiproliferative effects in RPE. However, they do not have any effect on cell morphology or induction of apoptosis. DISCUSSION: We identified various effects of lovastatin on human RPE cultures: inhibition of cell proliferation, modifications of the phenotype and induction of apoptosis. Interestingly, the addition of different inhibitors of protein isoprenylation only affected the proliferation of the cells. There was no evidence that isoprenylated proteins inhibition is related to lovastatin-induced RPE apoptosis.

Expression of the G protein-coupled receptor kinase 2 during early mouse embryogenesis.

Whilst several G protein-coupled receptors (GPCRs) have been shown to play important roles during development, little study has been carried out on the G protein-coupled receptor kinases (GRKs) that modulate their activity in embryos. Here, we have analyzed the expression of GRK2, the predominant GRK expressed during embryogenesis. We show that at early stages, the expression of GRK2 is restricted to populations of cells that are undifferentiated, multipotent and in many cases, migratory. As such, GRK2 transcripts were found in the early mesoderm and neural crest as they migrate from the primitive streak and the neural tube, respectively. In the limb bud, GRK2 transcripts were observed in cells of the progress zone and in the interdigital areas. At later stages, the expression in the heart is compatible with the phenotype observed in the GRK2 deficient mice.

The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression.

The Snail family of transcription factors has previously been implicated in the differentiation of epithelial cells into mesenchymal cells (epithelial-mesenchymal transitions) during embryonic development. Epithelial-mesenchymal transitions are also determinants of the progression of carcinomas, occurring concomitantly with the cellular acquisition of migratory properties following downregulation of expression of the adhesion protein E-cadherin. Here we show that mouse Snail is a strong repressor of transcription of the E-cadherin gene. Epithelial cells that ectopically express Snail adopt a fibroblastoid phenotype and acquire tumorigenic and invasive properties. Endogenous Snail protein is present in invasive mouse and human carcinoma cell lines and tumours in which E-cadherin expression has been lost. Therefore, the same molecules are used to trigger epithelial-mesenchymal transitions during embryonic development and in tumour progression. Snail may thus be considered as a marker for malignancy, opening up new avenues for the design of specific anti-invasive drugs.

[The influence of tobacco consumption on the prevalence of symptoms related to asthma]. / Influencia del consumo de tabaco en la prevalencia de síntomas relacionados con el asma.

OBJECTIVE: To determine whether tobacco consumption affects the prevalence of asthmatic symptoms. The European Asthma Study Questionnaire was used. DESIGN: Cross-sectional descriptive study. SETTING: Guadalajara Health Area. PATIENTS: Sample of 3000 people between 20 and 44 living in Guadalajara. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measuring instrument was the European Asthma Study Questionnaire, to which two items on tobacco dependency were added. All the symptoms except asthma attack changed in function of the amount of tobacco consumed. Sibilant noises varied from 8.3% in non-smokers (NS), to 17.5% in light smokers (LS), 28.7% in moderate smokers (MS) and 42.6% in heavy smokers (HS). Night cough also increased in parallel with consumption: 14.1% in NS, 23.2% in LS, 41.2% in HS. Nocturnal thoracic pressure (14.7%), attacks of breathlessness (12.3%) and being considered to have asthma symptoms (14.2%) were more common in heavy smokers. Non-smokers had greater prevalence of sibilant noise with breathlessness (NS 57.7%, LS 39.2%, MS 30.4%, HS 34.5%) and without an associated cold (NS 45.2%, LS 20.3%, MS 23.4%, HS 29.9%), and used asthma treatments more often (NS 3.5%, LS 1.7%, MS 1.5%, HS 1%). CONCLUSIONS: The studies using this questionnaire should include additional questions on the tobacco history of the participants, since it seems that tobacco smoking and its amount may affect findings.

[Prevalence of symptoms related to asthma in Guadalajara]. / Prevalencia de síntomas relacionados con el asma en Guadalajara.

The objective of this study was to determine the prevalence of asthma-related symptoms in the Guadalajara Health Area, using the methods prescribed by the first phase of the European Asthma Study (EAS). A transversal descriptive study by self-administered questionnaire in a population of 2,968 subjects aged 20 to 44 years old assigned to the Guadalajara Health Area was performed. The study took place between September 1995 and February 1996. We received 2,435 responses (81.2% of the sample). Each symptom was studied in relation to sex, age, domicile and smoking and the results were compared to data from other Spanish health areas participating in the EAS. Significant differences were found between our results and those of other Spanish health areas. Subjects reporting asthma symptoms accounted for 8.6% (C.I. 7.5% to 9.8%) of the sample. Presence of asthma was related to place of residence but not to age or sex.

Anafilaxia transoperatoria en cirugía de enfermedad hidatidica: Reporte de caso / Transoperative anaphylaxis in the surgery of Hydatidic disease

La enfermedad hidatidica (Equinococosis) existe en todo el mundo: Su frecuencia en el ser humano depende de la incidencia de la enfermedad en huéspedes intermediarios. El quiste hidatidico más frecuente es el causado por el Echinococcus Granulosus, estos pueden alojarse en cualquier órgano o tejido pero la mayoría de las veces se aloja en el hígado y pulmones. El goteo del líquido del quiste produce sensibilización y origina eosinofilia; si el goteo es importante, ya sea espontáneo, traumático o por intervención quirúrgica, puede presentar una reacción anafilactica grave o hasta mortal. Presentamos un caso de reacción anafilactica en un paciente con quiste hidatidico el cual fue tratado quirúrgicamente. Se presenta la revisión de la literatura y se sugiere un manejo transoperatorio