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.

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.

Chronic antigenic stimuli as a possible explanation for the immunodepression caused by liver cirrhosis.

The objectives of this work were the analysis of the functional characteristics of circulating monocytes and T lymphocytes in patients with liver cirrhosis, and evaluation of the relationship with an increased exposure to antigens due to bacterial translocation. Forty patients with liver cirrhosis (20 with compensated cirrhosis and 20 with ascitic decompensation) and 20 healthy control subjects were studied. Bacterial translocation was evaluated by serum levels of lipopolysaccharide binding protein (LBP). Macrophage activation was studied by CD40 antigen expression. T lymphocytes were analysed for activation (CD25(+), CD122(+)), effector function (CD8(+)CD45RO(+)CD57(+)), apoptosis (CD95(+)) and regulatory abilities, either by analysis of the membrane expression of co-stimulatory molecules CD80, CD86 and CD28, or by quantification of regulatory T cells CD4(+)CD25(high)forkhead box P3 (FoxP3). The percentage of activated monocytes and T lymphocytes in patients was increased significantly. The proportions of effector senescent cells and of those near to apoptosis were also significantly higher. With respect to these proportions, there were no significant differences between patients in function of the presence or absence of decompensation or in function of the increased or normal values of LBP. Conversely, those patients with elevated levels of LBP presented a significantly higher frequency of regulatory T cells than those with normal levels. In conclusion, patients with liver cirrhosis showed an intensive activation state with a higher percentage of cells committed to activation-induced death, even in non-advanced stages. It is possible that bacterial permeability and endotoxaemia contribute to the expansion of those lymphocyte populations implicated in the prevention of a more severe antigen-induced immunopathology.

[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.

Subcellular effects of drought stress in Rosmarinus officinalis.

The use of Rosmarinus officinalis, and other wild plant species, in the Mediterranean area is an interesting solution in order to avoid the desertification and rapid soil erosion, because of their good resistance to environmental conditions. Previous articles have described experiments designed to determine the impact of water stress at the plant level in this species, but more knowledge is required at the subcellular and ultrastructural levels. An anatomic and ultrastructural study of the leaves was conducted on Rosmarinus officinalis plants growing under different water treatments. In the leaves of water-stressed plants, the leaf water potential and turgor decreased, and leaf osmotic potential became more negative with respect to control plants. The anatomic investigations showed that both the mesophyll intercellular spaces and the epidermal cell size were reduced significantly under the more intense drought stress conditions. At the subcellular level, chloroplasts accumulated plastoglobuli and lipid bodies, and cuticle thickness was increased under water stress. In our experiment, the anatomic and ultrastructural modifications of Rosmarinus officinalis could be considered an additional adaptation to drought stress together with physiological and biochemical modifications as antioxidant accumulation.

[Treatment of angioid streaks with phothodynamic therapy]. / Tratamiento con terapia fotodinámica en las estrías angioides.

CLINICAL CASE: A patient had bilateral angioid streaks complicated by cicatricial degeneration in the left eye and subfoveal choroidal neovascularization in the right eye. Photodynamic therapy resulted in a favorable response with normalization of the visual acuity and angiographic resolution of the lesions. DISCUSSION: The most serious complication of angioid streaks is choroidal neovascularization. Today photodynamic therapy is an effective treatment of subfoveal choroidal neovascularization. It also appears useful in the treatment of choroidal neovascularization in angioid streaks.

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.

Evolutionary patterns in ontogenetic transformation: from laws to regularities.

The concept of heterochrony derives from classical approaches to the study of ontogeny and phylogeny. Under the influence of landmark books by deBeer (1930) and Gould (1977), the traditional theories have been revised to fit into the conceptual framework of modern genetics and evolutionary theory. The current scheme, however, suffers from a problem of lack of precise definitions. The term heterochrony is now used to refer to a developmental process as well as to an evolutionary pattern. That is, it refers to a microevolutionary process of adaptation, operating in local populations under selection and to a macroevolutionary pattern based on undefined internal laws of form. Such conceptually contradictory frameworks are a source of confusion and of empirical misuse of concepts. We propose to reduce the dependence of current thinking about heterochrony on the concept of "timing" and instead focus on the organization of sequences of developmental events in ontogeny. Although Haeckelian views have been rejected, most experts would agree that some subtle parallelism between ontogeny and phylogeny does occur. This relationship deserves renewed attention and urodeles are particularly suited to study it due to their variable patterns of ontogeny and complex life cycles. Current reductionist attempts to apply the morphological terminology and postulates of classical heterochrony concepts to cellular and molecular (genetic) aspects of morphogenesis are problematic. Molecular heterochrony requires a linear or strictly hierarchical structure of gene regulation of development. In addition, isomorphism between genetic mutations and morphological changes would be required for the existing terminology to apply. Finally, we caution against a broad interpretation of heterochronic processes at the molecular level, since the approach may end up permitting the meaningless interpretation of any developmental change as heterochrony.

[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.

Distribution of neurons in the main cuneate nucleus projecting to the inferior olive in the cat. Evidence that they differ from those directly projecting to the cerebellum.

The distribution in the main cuneate nucleus of cells projecting to the inferior olive and the intermediate zone of the cerebellar anterior lobe were compared by means of double retrograde labeling methods in the cat. The tracer combinations were either Fast Blue and Diamidino Yellow Dihydrochloride; or horseradish peroxidase conjugated to wheat germ agglutinin and Diamidino Yellow Dihydrochloride. Neurons in the caudal, middle and rostral subdivisions of the main cuneate nucleus project to the inferior olive. Differences exist, however, in its number and location along the rostrocaudal extent of the nucleus. Cells projecting to the inferior olive predominate in the caudal and middle subdivisions, where they concentrate ventrally. No cells in the "clusters region" project to the inferior olive. Main cuneate nucleus neurons projecting to the cerebellum concentrate rostral to the obex, bordering the external cuneate nucleus and partially intermixing with the rostrally located cells projecting to the inferior olive. However, no double-labeled cells were found. The results indicate that the main cuneate nucleus projections to the inferior olive and cerebellar anterior lobe originate from different populations of neurons with high specific locations within the nucleus. This finding is in agreement with previous studies suggesting that each of the main cuneate nucleus targets receives its input from a distinct population of neurons within the nucleus.

Stability of coagulation proteins in frozen plasma.

This study reports on the frozen stability of all commonly measured coagulation proteins in normal citrated plasma: activated partial thromboplastin time, prothrombin time (%), thrombin time and fibrinogen (Clauss); clotting assays for factors II, V, VII, VIII, IX, X, XI and XII; functional assays for protein C (clotting), protein S (clotting), antithrombin (chromogenic) and plasminogen (chromogenic); and immunological assays for von Willebrand factor and D-dimer. All these factors listed are stable for up to 3 months if frozen at -24 degrees C or lower. At -74 degrees C, all these factors (allowing for 10% variation) were stable for at least 18 months, most were stable for 24 months. The number of proteins showing > 5% variation over baseline after 6 months storage indicates that some decay does occur even at -74 degrees C. There was no clear advantage in snap freezing at -74 degrees C and then storing at -24 degrees C over both freezing and storing at -24 degrees C; therefore, the freezing process itself is not responsible for the loss of stability. The best stability, especially at -24 degrees C, was obtained when small samples (1 ml) were stored in screw-cap tubes with a minimum dead space. The decrease in stability of the coagulation proteins directly correlates with the effect of temperature and time.

Evolutionary mechanisms of rib loss in anurans: a comparative developmental approach.

ABSTRACT The presence of free ribs is presumed to be a primitive morphological character observed only in a few families of Recent anurans, whereas the absence of ribs has been considered to be a derived condition that is widespread within this order. A comparative study of rib development based on representatives of several anuran lineages (Alytes, Bombina, Bufo, Discoglossus, Hyla, Pelobates, Pelodytes, Rana, and Xenopus) reveals a previously undetected diversity of developmental features in the formation and interaction between neural arches and ribs. The absence of free ribs at premetamorphic or later stages is verified in some groups, but we present for the first time evidence of the existence of larval rib rudiments in others, both in the anterior (Rana, Hyla) and posterior (Bufo, Discoglossus, Pelobates) presacral regions. Heterochrony seems to have played a major role in the processes underlying rib reduction. The intracolumnar differences between anterior (V(2)-V(4)) and posterior (V(5)-V(8)) regions are based on perturbations in the timing of early differentiation. Furthermore, a clear shift in the relative timing of ossification among evolutionary lineages was detected. In this respect Xenopus has a highly derived condition. The use of the morphological character of "rib loss" in phylogenetic analyses must be reconsidered due to the different convergent developmental paths described here. The phylogenetic analysis of a "sequence units" matrix of rib development is compared with current anuran phylogenies. Some evolutionary information appears to be clearly present in the ontogenetic data of this "missing morphology," but its value for evolutionary inferences is rather limited.

Nuclear magnetic resonance investigations of the inclusion complexation of gliclazide with beta-cyclodextrin.

The formation of the gliclazide-beta-cyclodextrin (GL-beta-CD) inclusion compound has been studied in the liquid state by phase solubility techniques and by 1H and 13C NMR spectroscopy. From the initial straight portion of the solubility curve (Bs type), the value of the apparent stability constant (Kc) was calculated as 1094 M(-1). The nuclear magnetic resonance studies confirm that GL yields a complex with beta-CD in aqueous medium, which is mainly due to the penetration of the azabicyclooctyl group of GL into the cavity of beta-CD. The study of the monodimensional nuclear Overhauser effect (NOE) of the H3 proton of CD has shown that the tolyl group also interacts with CD, but to a lesser extent than the azabicyclooctyl moiety. Finally, the application of the continous variation technique confirmed the 1:2 drug:CD stoichiometry of the complex.

Complexation of ursodeoxycholic acid with beta-cyclodextrin-choline dichloride coprecipitate.

The inclusion complexes of ursodeoxycholic acid (UDCA) with beta-cyclodextrin (betaCD) coprecipitated with choline dichloride (CDC) or beta-cyclodextrin were investigated to evaluate the effect of the presence of choline for UDCA inclusion in betaCD. The inclusion complexes were investigated in solution by phase solubility diagrams and 1H NMR spectrometry and in solid state (kneading, freeze-drying, sealed heating and spray-drying) by DSC, SEM, HSM, XRD and IR spectroscopy. Stability constants were determined at pH 5.5 and 7.0 to simulate the environmental pH of the first intestinal tract and at different temperatures (25, 30 and 37 degrees C) to obtain the thermodynamic parameters of inclusion. Both betaCD-CDC and betaCD increased the water solubility of UDCA particularly betaCD-CDC. All complexes showed a high dissolution rate particularly the spray-dried complexes obtained in the presence of betaCD-CDC.

Contrasting physiological responses of dwarf sea-lavender and marguerite to simulated sea aerosol deposition.

Plants of two wild native species from littoral areas, marguerite [Argyranthemum coronopifolium (Willd.) C.J. Humphries] and dwarf sea-lavender [Limonium pectinatum (Aiton) O. Kuntze], grown in an unheated plastic greenhouse, were sprayed 2 to 3 min per day over a 7-d period with different aqueous solutions containing (i) an anionic surfactant (S1); (ii) a solution simulating the composition of sea aerosol (S2); (iii) a solution simulating sea aerosol with anionic surfactant (S3), and (iv) deionized water alone (control). The plant resistance to sea aerosol and the ability to recover from treatments were studied. By the end of the spraying period, marguerite showed a significant reduction in growth compared with control. However, most of the growth parameters were significantly unaffected in dwarf sea-lavender when plants were treated with sea aerosol containing surfactant. Measurements of water relations variables in marguerite showed a slight decrease in leaf turgor potential after spraying with sea aerosol containing surfactant. The surfactant enhanced the foliar absorption of salt in marguerite plants, inducing reductions in leaf stomatal conductance and causing such damage in the photosynthetic apparatus that the level of net photosynthesis decreased and had not recovered by the end of the experiment. The treatments had no effect on leaf stomatal conductance and photosynthesis rate in dwarf sea-lavender plants. The response of the species studied to sea aerosol was related to the degree of salinity tolerance. Although both species are wild native plants from littoral areas, marguerite is not salt tolerant and was the most sensitive to the sea aerosol treatments, while dwarf sea-lavender, a halophyte species, was more efficient at decreasing the toxic salt content of the tissues as its growth and ornamental characteristics were not affected.

Differences in the effects of simulated sea aerosol on water relations, salt content, and leaf ultrastructure of rock-rose plants.

White-leaf rock-rose (Cistus albidus L.) and Montpellier rock-rose (C. monspeliensis L.) plants were sprayed 2 to 3 min per day over a 7-d period, in an unheated plastic greenhouse, with different aqueous solutions containing deionized water alone (control); an anionic surfactant (sodium dodecylbenzenesulfonate 82.5%, 50 mg L(-1)) (S1); a solution simulating the composition of sea aerosol (S2); and a solution simulating sea aerosol with anionic surfactant (S3). White-leaf rock-rose was more sensitive to sea aerosol, showing greater leaf damage and markedly decreased growth, and the presence of surfactant enhanced the phytotoxic effect leading to greater increases in mortality. Montpellier rock-rose did not appear to be more adversely affected when surfactant was used in combination with sea aerosol, and manifested slight or less severe symptoms than white-leaf rock-rose. There was a significant increase in leaf turgor potential in the plants treated with both sea aerosol treatments by osmotic adjustment effect. The decrease in photosynthesis level seems to be due to both stomatal and nonstomatal factors. The results of microscopical analysis of Montpellier rock-rose plants show that sea aerosol treatment caused alterations in the chloroplast structure, reducing the starch grain and swelling the thylakoid membranes. The results of this study indicated that Montpellier rock-rose was more tolerant to sea aerosol than white-leaf rock-rose, showing a lower reduction in plant growth and less leaf damage, probably because of its ability to compartmentalize the toxic ions at the intracellular level.

[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.

Spanish norms for the Harvard Group Scale of Hypnotic Susceptibility, Form A.

The results of administering the Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS:A) of Shor and E. Orne (1962) to a Spanish sample are on the whole consistent with those results obtained in other normative studies, especially Bongartz's work with a German sample, and they confirm HGSHS:A's usefulness in non-Anglophone countries. The Spanish HGSHS:A's reliability and validity remain within the limits reported for other locales, but there are certain discrepancies with respect to the difficulty of two HGSHS:A items.

[Hyperimmunoglobulinemia D and periodic fever syndrome. A phenotypical analysis of a Spanish family]. / Hiperinmunoglobulinemia D y fiebre periódica. Análisis fenotípico de una familia española.

BACKGROUND: Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) is a disorder diagnosed with low frequency, that produces a very prolonged and recurrent fever with other symptoms and analytical markers of inflammation. Its origin seems to be hereditary with a recessive autosomic pattern, but its pathogenic mechanisms are unclear. The aim of this study is to analyse the clinical characteristics and serum levels of immunoglobulins a Spanish family with HIDS. METHODS: We describe a young woman diagnosed with HIDS and investigate the other memberships of her family (parents and 5 brothers) by clinical interview, physical examination, hematological and biochemical analyses and measurements of IgG, IgA, IgM, IgE, IgD and the kappa/lambda ratio of light chains. Moreover, we also determine the IgD in a control group of 35 healthy blood donors. RESULTS: One male brother of the index case also showed a clinical picture of HIDS. The serum IgD levels were increased (above 100 U/ml) in both and in other two sisters without symptoms and were normal in the rest of the family. With only one exception, all individuals of the control group showed a normal IgD level and this was not associated with sex or age. The other immunoglobulins were normal in the family. In spite of the different treatments tested in the index case, only glucocorticoids aborted her fever attacks. CONCLUSIONS: In HIDS the clinical picture and the high IgD levels are both transmitted with a recessive autosomic pattern, but these are not necessarily associated in the same memberships of the family. Its diagnosis is difficult and there is not effective and long-term safe treatment.