Analysis of Sturge-Weber syndrome: A retrospective study of multiple associated variables. / Análisis del síndrome de Sturge-Weber: estudio retrospectivo de múltiples variables asociadas.

INTRODUCTION: Sturge-Weber syndrome is a congenital vascular disorder characterised by facial capillary malformation (port-wine stain) associated with venous and capillary malformations in the brain and eye. Neurological symptoms and alterations in other locations may also be observed. OBJECTIVES: This study describes the clinical and epidemiological characteristics and different treatments in a cohort of patients diagnosed with Sturge-Weber syndrome in a tertiary hospital. MATERIAL AND METHODS: This comparative, retrospective and cross-sectional study was conducted by reviewing the medical records of patients diagnosed with Sturge-Weber syndrome between 1998 and 2013. RESULTS: The study included 13 patients (54% male, 46% female) diagnosed with Sturge-Weber syndrome. The mean age at diagnosis was 15 months. Leptomeningeal angiomatosis was present in 100% of cases: right hemisphere (46%), left hemisphere (38%), and bilateral (15%). Facial angioma was present in 61% of the cases: right (23%), left (38%) and bilateral (7%). Other skin disorders were found in 23% of the cases, including 2 with hemilateral involvement on the side where facial and leptomeningeal angiomatosis was present and one case of generalised cutis marmorata. Ocular disease was found in 77% of patients; the most common conditions were glaucoma (46%), strabismus (23%) and choroidal angioma (23%). Epilepsy was present in 100% of the cases, with partial seizures (simple or complex) being the most frequent (62%). Seizure control was highly variable; 31% of the patients had needed to try more than 3 drugs, 15% 3 drugs, and 31% 2 drugs, while 23% experienced good seizure control with monotherapy. One patient required surgery for epilepsy (left hemispherectomy) and has been seizure-free since then. The most frequent observations in electroencephalograms were spikes, polyspikes, and wave spikes in the lobes affected by leptomeningeal angiomatosis (46%). Other neurological symptoms were hemiparesis (39%), recurrent headaches (39%), stroke-like episodes (23%), psychomotor retardation (46%), and mental retardation (46%). Leptomeningeal calcifications could be seen in 85% of patient MRIs, as well as increased calcification in 70%; 54% of the patients had been treated with aspirin. CONCLUSIONS: There are multiple clinical manifestations of Sturge-Weber syndrome. Being familiar with all of them is vitally important for diagnosing and for monitoring and treating the condition correctly, which will improve the quality of life of these patients.

Biological characterization of a new silicon based coating developed for dental implants.

Taking into account the influence of Si in osteoblast cell proliferation, a series of sol-gel derived silicon based coating was prepared by controlling the process parameters and varying the different Si-alkoxide precursors molar rate in order to obtain materials able to release Si compounds. For this purpose, methyltrimethoxysilane (MTMOS) and tetraethyl orthosilicate (TEOS) were hydrolysed together and the sol obtained was used to dip-coat the different substrates. The silicon release ability of the coatings was tested finding that it was dependent on the TEOS precursor content, reaching a Si amount value around ninefolds higher for coatings with TEOS than for the pure MTMOS material. To test the effect of this released Si, the in vitro performance of developed coatings was tested with human adipose mesenchymal stem cells finding a significantly higher proliferation and mineralization on the coating with the higher TEOS content. For in vivo evaluation of the biocompatibility, coated implants were placed in the tibia of the rabbit and a histological analysis was performed. The evaluation of parameters such as the bone marrow state, the presence of giant cells and the fibrous capsule proved the biocompatibility of the developed coatings. Furthermore, coated implants seemed to produce a qualitatively higher osteoblastic activity and a higher number of bone spicules than the control (uncoated commercial SLA titanium dental implant).

Epidemiology of severe trauma in Spain. Registry of trauma in the ICU (RETRAUCI). Pilot phase. / Epidemiología del trauma grave en España. REgistro de TRAuma en UCI (RETRAUCI). Fase piloto.

OBJECTIVE: To describe the characteristics and management of severe trauma disease in Spanish Intensive Care Units (ICUs). Registry of trauma in the ICU (RETRAUCI). Pilot phase. DESIGN: A prospective, multicenter registry. SETTING: Thirteen Spanish ICUs. PATIENTS: Patients with trauma disease admitted to the ICU. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Epidemiology, out-of-hospital attention, registry of injuries, resources utilization, complications and outcome were evaluated. RESULTS: Patients, n=2242. Mean age 47.1±19.02 years. Males 79%. Blunt trauma 93.9%. Injury Severity Score 22.2±12.1, Revised Trauma Score 6.7±1.6. Non-intentional in 84.4% of the cases. The most common causes of trauma were traffic accidents followed by pedestrian and high-energy falls. Up to 12.4% were taking antiplatelet medication or anticoagulants. Almost 28% had a suspected or confirmed toxic influence in trauma. Up to 31.5% required an out-of-hospital artificial airway. The time from trauma to ICU admission was 4.7±5.3hours. At ICU admission, 68.5% were hemodynamically stable. Brain and chest injuries predominated. A large number of complications were documented. Mechanical ventilation was used in 69.5% of the patients (mean 8.2±9.9 days), of which 24.9% finally required a tracheostomy. The median duration of stay in the ICU and in hospital was 5 (range 3-13) and 9 (5-19) days, respectively. The ICU mortality rate was 12.3%, while the in-hospital mortality rate was 16.0%. CONCLUSIONS: The pilot phase of the RETRAUCI offers a first impression of the epidemiology and management of trauma disease in Spanish ICUs.

Evolution of male patients with detrusor underactivity and conservative treatment. Five-year follow-up. / Evolución de pacientes varones con detrusor hipoactivo y tratamiento conservador. Seguimiento a cinco años.

INTRODUCTION: The objective of the study was to compare the evolution of male patients with neurogenic detrusor underactivity (NDU) versus non-neurogenic DU (NNDU) and to establish risk factors to predict the need for clean intermittent catheterization (CIC) during the follow-up period. MATERIAL AND METHODS: Longitudinal, descriptive study of a cohort of patients diagnosed with DU, and 2,496 urodynamic studies (2008-2018) were reviewed. Patients with DU (ICS 2002 and/or Bladder contraction index (< 100)) without treatment were included. Patients with CIC or interventional treatment were excluded. Follow-up included flowmetry every six months. CIC was indicated in cases of high residual volume (PVR) > 200 mL or voiding efficiency (VE)<50%. The need for CIC during follow-up or the appearance of complications (urinary tract infections (UTI), bladder lithiasis) were compared. RESULTS: DU was found in 172 (6.89%) men. Neurological causes were observed in 106 (61,6%) cases. Finally, 62 patients were included with a mean follow-up of 4.9 years (+/- 2.6). Of these patients, 33 (53%) presented NDU and 29 (47%) NNDU. Six patients with NDU needed CIC versus none with NNDU (p = 0.04). Patients requiring CIC had higher PVR (p = 0.009) and lower VE (p = 0.017)), and there were also differences in terms of time until the need for CIC (log Rank: 0.009), which was 15.1 months [4-38]. In the multivariate analysis, none of the variables showed to be predictive of the need for CIC. CONCLUSIONS: The most common cause of DU is neurologic injury. Patients with NDU remain stable without requiring CIC. We have not detected any risk factors that identify patients at risk of needing CIC.

[Recommendations of the Working Groups from the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) for the management of adult critically ill patients in the coronavirus disease (COVID-19)]. / Recomendaciones de «hacer¼ y «no hacer¼ en el tratamiento de los pacientes críticos ante la pandemia por coronavirus causante de COVID-19 de los Grupos de Trabajo de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC).

On March 11, 2020, the Director-General of the World Health Organization (WHO) declared the disease caused by SARS-CoV-2 (COVID-19) as a pandemic. The spread and evolution of the pandemic is overwhelming the healthcare systems of dozens of countries and has led to a myriad of opinion papers, contingency plans, case series and emerging trials. Covering all this literature is complex. Briefly and synthetically, in line with the previous recommendations of the Working Groups, the Spanish Society of Intensive, Critical Medicine and Coronary Units (SEMICYUC) has prepared this series of basic recommendations for patient care in the context of the pandemic.

Outcomes of very elderly trauma ICU patients. Results from the Spanish trauma ICU registry.

OBJECTIVE: To analyze outcomes and factors related to mortality among very elderly trauma patients admitted to intensive care units (ICUs) participating in the Spanish trauma ICU registry. DESIGN: A multicenter nationwide registry. Retrospective analysis. November 2012-May 2017. SETTING: Participating ICUs. PATIENTS: Trauma patients aged ≥80 years. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: The outcomes and influence of limitation of life sustaining therapy (LLST) were analyzed. Comparisons were established using the Wilcoxon test, Chi-squared test or Fisher's exact test as appropriate. Multiple logistic regression analysis was performed to analyze variables related to mortality. A p-value <0.05 was considered statistically significant. RESULTS: The mean patient age was 83.4±3.3 years; 281 males (60.4%). Low-energy falls were the mechanisms of injury in 256 patients (55.1%). The mean ISS was 20.5±11.1, with a mean ICU stay of 7.45±9.9 days. The probability of survival based on the TRISS methodology was 69.8±29.7%. The ICU mortality rate was 15.5%, with an in-hospital mortality rate of 19.2%. The main cause of mortality was intracranial hypertension (42.7%). The ISS, the need for first- and second-tier measures to control intracranial pressure, and being admitted to the ICU for organ donation were independent mortality predictors. LLST was applied in 128 patients (27.9%). Patients who received LLST were older, with more severe trauma, and with more severe brain injury. CONCLUSIONS: Very elderly trauma ICU patients presented mortality rates lower than predicted on the basis of the severity of injury.

Human kinetochore-associated kinesin CENP-E visualized at 17 A resolution bound to microtubules.

The highly dynamic process of cell division is effected, in part, by molecular motors that generate the forces necessary for its enactment. Several members of the kinesin superfamily of motor proteins are implicated in mitosis, such as CENP-E, which plays essential roles in cell division, including association with the kinetochore to stabilize attachment of chromosomes to microtubules prior to and during their separation. Neither the functional assembly state of CENP-E nor its direction of motion along the polar microtubule are certain. To determine the mode of interaction between CENP-E and microtubules, we have used cryo-electron microscopy to visualize CENP-E motor domains complexed with microtubules and calculated a density map of the complex to 17 A resolution by combining helical and single-particle reconstruction methods. The interface between the motor domain and microtubules was modeled by docking atomic-resolution models of the subunits into the cryoEM density map. Our results support a plus end motion for CENP-E, consistent with features of the crystallographic structure. Despite considerable functional differences from the monomeric transporter kinesin KIF1A and the oppositely directed ncd kinesin, CENP-E appears to share many features of the intermolecular interactions, suggesting that differences in motor function are governed by small variations in the loops at the microtubule interface.

Modulation of inhibitory and excitatory synaptic transmission in rat inferior colliculus after unilateral cochleectomy: an in situ and immunofluorescence study.

We investigated whether inhibitory synaptic transmission mediated through glycinergic receptor, GABAA receptors, glutamic acid decarboxylase, the enzyme synthesizing GABA, and excitatory synaptic transmission through alpha-amino-3-hydroxi-5-methylisoxazole-4-propionic acid receptors and N-methyl-D-aspartate receptors are affected in the inferior colliculus by unilateral surgical cochleectomy. In situ hybridization and immunohistofluorescence studies were performed in normal and lesioned adult rats at various times following the lesion (1-150 days). Unilateral auditory deprivation decreased glycine receptor alpha1 and glutamic acid decarboxylase 67 expression in the contralateral central nucleus of the inferior colliculus. This decrease began one day after cochleectomy, and continued until day 8; thereafter expression was consistently low until day 150. The glycine receptor alpha1 subunit decrease did not occur if a second contralateral cochleectomy was performed either on day 8 or 150 after the first cochleectomy. Bilateral cochleectomy caused also a bilateral inferior colliculus diminution of glutamic acid decarboxylase 67 mRNA at post-lesion day 8 but there were no changes in glycine receptor alpha1 compared with controls. In contrast, the abundance of other alpha2-3, and beta glycine receptor, gephyrin, the anchoring protein of glycine receptor, the alpha1, beta2 and gamma2 subunits of GABAA receptors, GluR2, R3 subunits of alpha-amino-3-hydroxi-5-methylisoxazole-4-propionic acid receptors, and NR1 and NR2A transcripts of N-methyl-D-aspartate receptors was unaffected during the first week following the lesion. Thus, unilateral cochlear removal resulted in a selective and long-term decrease in the amount of the glycine receptor alpha1 subunit and of glutamic acid decarboxylase 67 in the contralateral central nucleus of the inferior colliculus. These changes most probably result from the induced asymmetry of excitatory auditory inputs into the central nucleus of the inferior colliculus and may be one of the mechanisms involved in the tinnitus frequently encountered in patients suffering from a sudden hearing loss.

Molecular structure at 1.8 A of mouse liver class pi glutathione S-transferase complexed with S-(p-nitrobenzyl)glutathione and other inhibitors.

The three-dimensional crystal structure of pi class glutathione S-transferase YfYf from mouse liver complexed with the inhibitor S-(p-nitrobenzyl)glutathione has been determined at 1.8 A resolution by X-ray diffraction. In addition two complexes with glutathione sulphonic acid and S-hexylglutathione have been determined at resolutions of 1.9 and 2.2 A, respectively. The high resolution of the S-(p-nitrobenzyl)glutathione complex allows a detailed analysis of the active site including the hydrophobic (H-) subsite. The nitrobenzyl moiety occupies a hydrophobic pocket with its aromatic ring sandwiched between Phe8 and the hydroxyl group of Tyr108. An insertion of two residues Gly41 and Leu42, with respect to the pig enzyme, splits helix alpha B into an alpha-helix and a 3(10) helix. Water bridges between carbonyl oxygen atoms of the alpha-helix at its C terminus and the amide NH groups of the 3(10) helix at its N terminus provide structural continuity between these two secondary elements. Tyr7 appears to be the only residue close to the sulphur atom of glutathione, while three conserved water molecules lie in the surrounding area in all complexes. The enzyme mechanism is discussed on the basis of the structural analysis.

Three-dimensional structure of FEZ-1, a monomeric subclass B3 metallo-beta-lactamase from Fluoribacter gormanii, in native form and in complex with D-captopril.

The beta-lactamases are involved in bacterial resistance to penicillin and related compounds. Members of the metallo-enzyme class are now found in many pathogenic bacteria and are thus becoming of major clinical importance. The structures of the Zn-beta-lactamase from Fluoribacter gormanii (FEZ-1) in the native and in the complex form are reported here. FEZ-1 is a monomeric enzyme, which possesses two zinc-binding sites. These structures are discussed in comparison with those of the tetrameric L1 enzyme produced by Stenotrophomonas maltophilia. From this analysis, amino acids involved in the oligomerization of L1 are clearly identified. Despite the similarity in fold, the active site of FEZ-1 was found to be significantly different. Two residues, which were previously implicated in function, are not present in L1 or in FEZ-1. The broad-spectrum substrate profile of Zn-beta-lactamases arises from the rather wide active-site cleft, where various beta-lactam compounds can be accommodated.

[Cerebellar cognitive affective syndrome secondary to a cerebellar tumour]. / Síndrome afectivo-cognitivo cerebeloso secundario a tumor cerebeloso.

Cerebellar cognitive affective syndrome is characterized by disturbances of executive function, impaired spatial cognition, linguistic difficulties, and personality change. The case of an 11 year old boy is presented, with behavior problems, learning difficulties and social interaction problems. In the physical examination he had poor visual contact, immature behavior, reduced expressive language and global motor disability with gait dyspraxia, with no defined cerebellar motor signs. In the neuropsychological evaluation he has a full scale overall intellectual quotient of 84, with signs of cerebellar cognitive affective syndrome. A tumour affecting inferior cerebellar vermis was observed in the magnetic resonance imaging, which had not significantly grown during 5 years of follow up. The cerebellum participates in controlling cognitive and affective functions. Cerebellar pathology must be considered in the differential diagnosis of children with cognitive or learning disorder with associated behavioral and emotional components.

Characterisation and preliminary X-ray diffraction analysis of human pancreatic procarboxypeptidase A2.

Human procarboxypeptidase A2 has been expressed in a Pichia pastoris heterologous system and purified by hydrophobic interaction and anion exchange chromatographies. The hydrolytic action of carboxypeptidase A2 on peptide substrates with different lengths and residues at the C-terminus was analysed, and a preference towards long substrates with aromatic amino acids in their C-terminal end, particularly tryptophan, was found; with such substrates its activity is similar or higher than that of bovine carboxypeptidase A1. Procarboxypeptidase A2 has been crystallised using a vapour diffusion approach; the crystals obtained belong to the monoclinic system, spacegroup P2(1), and present one procarboxypeptidase A2 molecule per asymmetric unit. The crystals diffract beyond 1.8 A resolution and are suitable for detailed X-ray analysis.

Autotransplantation of peripheral blood stem cells mobilized by G-CSF in hematological malignancies: evidence for rapid and long-term sustained hematopoietic reconstitution.

We assessed the ability of granulocyte colony-stimulating factor (G-CSF) to mobilize peripheral blood stem cells (PBSC), the efficacy of PBSC infusion in the rescue of hematopoiesis after high-dose chemotherapy in 22 adult patients with hematological malignancies, and the long-term quality of engraftment. Bolus subcutaneous injections of G-CSF (12 micrograms/kg/day) were administered for 6 days. A median of three leukaphereses resulted in the collection of a median of 5.45 X 10(8) mononuclear cells/kg, 4.52 X 10(6) CD34+ cells/kg, and 3.97 X 10(4) CFU-GM/kg. G-CSF (5 micrograms/kg daily) was administered after PBSC infusion until granulocyte recovery. The median time to attain a neutrophil level > 0.5 X 10(9)/L and a platelet count > 20 X 10(9)/ L was 11 days. The median follow-up in 17 survivors was 23.8 months. These patients have maintained a complete and stable graft and some of them with neoplastic recurrence tolerated further chemotherapy. These results confirm that mobilization of PBSC by G-CSF can be performed on an outpatient setting and used in heavily pretreated patients. G-CSF mobilized PBSC transplantation provides early and complete engraftment in most patients.

Improvement of the friction behaviour of NiTi orthodontic archwires by nitrogen diffusion.

The lack of low friction coefficient for the NiTi superelastic archwires makes difficult the optimal use of these materials in orthodontic applications. In this study, the decrease of this friction coefficient has been achieved by means of nitrogen diffusion heat treatments. The titanium nitride coating has been characterised by means of optical and scanning electron microscopy. Transformation temperatures, critical stresses, hardness and friction coefficient have been determined. Besides, the metallic ion release studies showed that the titanium nitride coating prevents biodegradation.

[The usefulness of the bcr/abl rearrangement in the diagnosis and evolution of chronic myeloid leukemia]. / Utilidad del reordenamiento bcr/abl en el diagnóstico y la evolución de la leucemia mieloide crónica.

BACKGROUND: The rearrangement of the bcr/abl gene constitutes the molecular substrate of the Philadelphia chromosome (Ph'). The aim of this study was to analyze the usefulness of bcr/abl rearrangement in the diagnosis and evolution of chronic myeloid leukemia (CML). METHODS: The rearrangement of the bcr/abl gene was studied in 81 cases of which 34 corresponded to patients with CML (29 Ph' positive chromosome, 2 Ph' negative chromosome and 3 without karyotype), 2 patients with Ph' positive acute lymphoblastic leukemia, 15 patients with chronic myeloproliferative syndromes different from CML and 30 controls. Of the patients with CML, 6 were reevaluated when a blastic crisis was developed, 2 after receiving interferon treatment and 1 following allogeneic bone marrow transplantation. The technique used was that of Southern blotting using the restriction enzymes Bgl II and BamHI and the transprobe. RESULTS: Rearrangement of the bcr/abl gene was observed in all the patients with CML except in one with Ph' negative chromosome. In the remaining cases bcr/abl rearrangement was not observed. CONCLUSIONS: The Southern blotting technique for the study of the bcr/abl gene rearrangement is a sensitive and specific method in the diagnosis of chronic myeloid leukemia constituting a valid alternative to chromosomic study when this cannot be carried out or is not conclusive. It may also be used for the control of treatment in chronic myeloid leukemia.

[Identification and validation of prognostic factors in differentiated thyroid carcinoma]. / Identificación y validación de factores pronósticos del cáncer diferenciado de tiroides.

BACKGROUND: The aims of this study are to identify prognostic factors of differentiated thyroid carcinoma and to validate the application of prognostic classifications obtained by others studies to another population. PATIENTS AND METHODS: The survival of 208 patients with differentiated thyroid carcinoma (129 papillary and 79 follicular carcinoma) was calculated by the Kaplan-Meier method. The mean follow-up was 7.5 years (1-17.7). Cox-proportional hazard model was used for variables influencing on survival (Mantel-Cox method). In addition, the EORTC, AGES, AJC, AMES and DeGroot classifications were tested. RESULTS: The independent prognostic factors identified were patient age > 60 years, tumor size > 6 cm and the presence of distant metastases. The absence of poor prognostic factors defined the low risk group (153 patients, survival 97% at 17.7 years of follow-up). The application of the other prognostic classifications differentiated several risk groups not in accordance with those obtained in the initial population. CONCLUSIONS: In this series of patients with thyroid carcinoma the main prognostic factors were age, tumor size and the presence of distant metastases. However, there are pitfalls in applying the prognostic classifications of published studies to another population.