Malformaciones arteriovenosas pulmonares: presentación de un caso clínico pediátrico y revisión de la literatura / Pulmonary arteriovenous malformations: presentation of a pediatric case and review of the literature

Las malformaciones arteriovenosas pulmonares (MAVP) consisten en comunicaciones directas entre el sistema arterial y el sistema venoso pulmonar, sin paso de la sangre por el lecho capilar, produciéndose un cortocircuito de derecha a izquierda extracardíaco, pueden ser congénitas o adquiridas. Algunos casos pueden ser asintomáticos, en cambio en otros pueden ocasionar diversas manifestaciones clínicas y se pueden asociar a complicaciones severas. En niños se observa una baja incidencia y son más frecuentes las formas congénitas. La MAVP se debe sospechar por las manifestaciones clínicas y las imágenes de la radiografía de tórax (RxTx) y su confirmación se realiza mediante una AngioTomografía Computada (TC) de tórax. La embolización endovascular es actualmente el tratamiento de elección, con excelentes resultados, aunque requiere de un seguimiento posterior y de un operador experimentado. Reportamos el caso de una niña que ingresó con clínica muy sugerente, incluyendo: disnea, acropaquia, cianosis periférica, e hipoxemia refractaria. Sin embargo, inicialmente el cuadro clínico fue confundido con una crisis asmática. La Angio-TC de tórax confirmó el diagnóstico y el tratamiento mediante embolización endovascular resultó exitoso.

Pulmonary arteriovenous malformations (PAVM) are communications between the arterial and the pulmonary venous system, without passage of blood through the capillary bed, causing a left to right extracardiac shunt. Some cases may be asymptomatic, while others may cause various clinical manifestations and may be associated with severe complications. In children a low incidence is observed, and congenital forms are more frequent. PAVM should be suspected by clinical manifestations and chest x-ray imaging and confirmed by chest Computed Tomography Angiography (CTA). Endovascular embolization is currently the treatment of choice, with excellent results, although it requires subsequent follow-up. We report a patient who was admitted with a very suggestive clinical history, including: dyspnea, clubbing, peripheral cyanosis, and severe hypoxemia, refractory to oxygen therapy. However, initially the clinical picture was confounded with an asthmatic crisis. CTA confirmed the diagnosis and treatment by endovascular embolization was successful.

Salbutamol tolerability and efficacy in patients with spinal muscular atrophy type II.

Spinal muscular atrophy (SMA) is an autosomal recessive disease caused by homozygous deletions or loss-of-function mutations in SMN1, which result in a degeneration of motor neurons in the spinal cord and brain stem. Even without a randomized placebo-controlled trial, salbutamol has been offered to patients with SMA in the neuromuscular clinics of most of hospitals for many years. We describe the response to salbutamol in 48 patients with SMA type II who were not taking any other medication. We investigate the changes over an eighteen-month period in motor functional scales and we analyze side effects and subjective response to treatment. Our results suggest that oral administration of salbutamol might be helpful in the maintenance of motor function in patients with SMA type II. An apparent beneficial effect was observed in functional scales of children under the age of 6, especially during the first 6 months of therapy. The majority of patients of all ages referred some kind of subjective positive effect associated with therapy intake. Salbutamol seemed safe and was well tolerated without serious side effects.

Simulations and Experiments Delineate Amyloid Fibrilization by Peptides Derived from Glaucoma-Associated Myocilin.

Mutant myocilin aggregation is associated with inherited open angle glaucoma, a prevalent optic neuropathy leading to blindness. Comprehension of mutant myocilin aggregation is of fundamental importance to glaucoma pathogenesis and ties glaucoma to amyloid diseases such as Alzheimer's. Here, we probe the aggregation properties of peptides derived from the myocilin olfactomedin domain. Peptides P1 (residues 326-337) and P3 (residues 426-442) were identified previously to form amyloids. Coarse-grained discontinuous molecular dynamics simulations using the PRIME20 force field (DMD/PRIME20) predict that P1 and P3 are aggregation-prone; P1 consistently forms fibrillar aggregates with parallel in-register ß-sheets, whereas P3 forms ß-sheet-containing aggregates without distinct order. Natural abundance 13C solid-state NMR spectra validate that aggregated P1 exhibits amyloid signatures and is more homogeneous than aggregated P3. DMD/PRIME20 simulations provide a viable method to predict peptide aggregation propensities and aggregate structure/order which cannot be accessed by bioinformatics or readily attained experimentally.

Trifunctional High-Throughput Screen Identifies Promising Scaffold To Inhibit Grp94 and Treat Myocilin-Associated Glaucoma.

Gain-of-function mutations within the olfactomedin (OLF) domain of myocilin result in its toxic intracellular accumulation and hasten the onset of open-angle glaucoma. The absence of myocilin does not cause disease; therefore, strategies aimed at eliminating myocilin could lead to a successful glaucoma treatment. The endoplasmic reticulum Hsp90 paralog Grp94 accelerates OLF aggregation. Knockdown or pharmacological inhibition of Grp94 in cells facilitates clearance of mutant myocilin via a non-proteasomal pathway. Here, we expanded our support for targeting Grp94 over cytosolic paralogs Hsp90α and Hsp90ß. We then developed a high-throughput screening assay to identify new chemical matter capable of disrupting the Grp94/OLF interaction. When applied to a blind, focused library of 17 Hsp90 inhibitors, our miniaturized single-read in vitro thioflavin T -based kinetics aggregation assay exclusively identified compounds that target the chaperone N-terminal nucleotide binding site. In follow up studies, one compound (2) decreased the extent of co-aggregation of Grp94 with OLF in a dose-dependent manner in vitro, and enabled clearance of the aggregation-prone full-length myocilin variant I477N in cells without inducing the heat shock response or causing cytotoxicity. Comparison of the co-crystal structure of compound 2 and another non-selective hit in complex with the N-terminal domain of Grp94 reveals a docking mode tailored to Grp94 and explains its selectivity. A new lead compound has been identified, supporting a targeted chemical biology assay approach to develop a protein degradation-based therapy for myocilin-associated glaucoma by selectively inhibiting Grp94.

Phylogeography of a ground beetle species in La Gomera (Canary Islands): the effects of landscape topology and population history.

Paraeutrichopus pecoudi (Coleoptera, Carabidae) is a species endemic to the mountain laurel forests of La Gomera in the Canary archipelago. La Gomera is an island of volcanic origin (9.4 mya), where a well-preserved laurel forest is partly fragmented by valleys and ridges. Historically restricted gene flow with isolation by distance are deduced at different clade levels for P. pecoudi populations, an expected scenario arising from landscape discontinuity, which has caused local isolation of these flightless insects. Methodological considerations were investigated for nested clade phylogeographic analysis (NCPA), comparing the results obtained using either (a) pairwise distances between collecting sites measured as surface (route) distances or (b) standard geographical distances calculated from latitude-longitude coordinates. Some differences were found in the NCPA statistics and associated inferences at the higher clade levels in relation to the assumed distance criteria. Coalescent simulations and posterior automated NCPAs assuming different geographical distances were performed to test the robustness of the method when considering the distances used. These analyses showed no significant differences in NCPA conclusions, and the scenario of restricted gene flow was recovered using both distance calculators at the same rate, although the parameter statistics were slightly different. We suggest that in landscapes with extreme topography, geographical distances separating populations are certainly underestimated by standard techniques. More complex and explicit descriptions of the potential dispersal of terrestrial organisms should be explored for implementation in statistical phylogeography in such cases.

[Acute-phase reactants and markers of inflammation in venous thromboembolic disease: correlation with clinical and evolution parameters]. / Reactantes de fase aguda y marcadores de inflamación en pacientes con enfermedad tromboembólica venosa: correlación con parámetros clínicos y evolutivos.

OBJECTIVE: To asses the association of acute reactants and interleukin 6 and 8 (IL-6 & IL-8) at diagnosis of venous thromboembolic disease (VTD) and clinical outcome. METHODS: 100 patients were diagnosed of VTD by image tests. Acute reactants (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen), D-dimer and IL-6 and IL-8 we measured at the moment of diagnosis. We made a 12 month follow-up of these patients to notice any clinical evolution outcomes (recurrences, bleeding, post-phlebitic syndrome, death). RESULTS: IL-6 was increased in 9 patients and IL-8 in 3. The risk factors, time to diagnosis and pulmonary embolism rate were similar in both interleukin groups (normal and high levels). Fibrinogen levels were significantly increased in high IL-6 group (585 +/- 179 vs. 485 +/- 154 mgr/dl; p = 0.05). During follow-up there were 5 deaths, 3 recurrences, 11 bleedings and 43 postphlebitic syndromes. Normal ESR level was associated to postphlebitic syndrome (17.8 +/- 14.5 vs. 31.4 +/- 27.4 mm/1st h; p = 0.016). Patients who had high levels of IL-6 had worse survival than these with normal levels (p = 0.015). CONCLUSION: IL-6, ESR, and CPR at diagnosis of VTD could be useful to identified patients with higher risks of death and postphlebitic syndrome during the first year after diagnosis.

[Estimate of a mortality table starting from quinqenial survival relations]. / Estimacion de una tabla de mortalidad a partir de relaciones de sobrevivencias quinquenales

PIP: This paper presents a new alternative to the construction of mortality tables when only using quinquennial survival data. Because of the persistence in many countries of such problems as the accuracy in vital statistics there is a need to find alternatives to construct mortality tables. The methodology proposed is based on the use of an interactive method that needs a microcomputer programmed to graphic statistical tables. The article is divided into the following sections: 1) estimating a mortality tables based on surviving relations; 2) relationships used in the proposed methodology; 3) estimating the probability of dying at birth; 4) applications; 5) conclusions. The 3 tables are: 1) Times Lived and Separation Factors by Sex and Levels; 2) Male Survival Relations, Times Lived and Probability of Dying Calculated on Different levels, West Model, Level 22; 3) Male Survival Relations, Times Lived and Probability of Dying Calculated with Different Levels Among Quinquennial Age Groups. The article has 2 graphs demonstrating the probabilities of quinquennial deaths.^ieng

[[Decomposition of the group with less than 5 years of age by simple ages starting from quinquennial survival relations]].

PIP: The author reports on 5 procedures to disaggregate data for those under age 5 in population-based projections because of the need to understand the data associated with health and pre-school data. Some techniques in interpolation could be useful but changes in fertility levels and in infant mortality are characteristic of those age 0-5 which limits its applicability. The first 3 techniques use relations that are manageable with stable populations, and more limited in the case of real populations. The 4th procedure is based on rejuvenating populations from age 5-9 by simple ages, and by quinquennial age groups after the year considered. The last procedure is used directly in Sprague's game of multipliers. The proposed procedures use projected information and is used to construct mortality tables when wishing to do a population projection. The author cautions against differentiating between closed populations and those affected by migration movements. This paper uses the example of Chilean males ages 0-4 for the year 1990.^ieng

[The decomposition of data on children under five years of age to single years of age based on population projections]. / Descomposicion del grupo de menores de 5 anos en edades simples en base a las proyecciones de poblacion.

PIP: A method to develop estimates of the population under age five by single years of age from data on five-year age groups normally available from population projections is described using Chilean data. (SUMMARY IN ENG)^ieng