INTRODUCTION: metatarsophalangeal resection arthroplasty is considered a salvage surgical procedure able to improve the quality of life of patients with major forefoot deformities. MATERIAL AND METHODS: a retrospective observational study of 31 patients (36 feet) with major forefoot deformities operated at our institution was performed. Thirty two feet required additional surgery involving the first ray, most of them (72.2%) through MTP joint fusion. The mean follow-up period was 10.3 ± 4.6 years. Most patients were women (87.1%), the mean age was 74.2 ± 11.5 years. RESULTS: at the final follow-up, mean AOFAS score was 77.9 ± 10.2 points and mean MOxFQ score was 18.3 ± 8.3 points. Visual analog scale (VAS) for pain improved significantly from 7.5 ± 1.2 points to 3.4 ± 2.1 points on average. Good clinical results were also reported on ability to put on shoes comfortably. The mean resection arthroplasty spaces at the end of the study were 1.3, 1.8, 2.5 and 4.4 mm, for second to fifth rays, respectively. The mean sizes of remodeling osteophytes at the end of the study were 1.6, 1.4, 1.1 and 0.7 mm, respectively. Significant improvement was also achieved in the hallux valgus angle (HVA) and intermetatarsal angle (IMA) at the end of the study. CONCLUSION: in our experience, metatarsophalangeal resection arthroplasty continues to be a valid choice in patients with major forefoot deformities, with satisfactory long-term clinical and radiographic results.
INTRODUCCIÓN: la artroplastía de resección metatarsofalángica se considera un procedimiento quirúrgico de salvamento capaz de mejorar la calidad de vida de pacientes con deformidades importantes en el antepié. MATERIAL Y MÉTODOS: se realizó un estudio observacional retrospectivo de 31 pacientes (36 pies) con deformidades importantes en el antepié operados en nuestra institución. Treinta y dos pies requirieron cirugía adicional que involucró el primer metatarsiano, la mayoría de ellos (72.2%) a través de la fusión de la articulación metatarsofalángica. El período de seguimiento promedio fue 10.3 ± 4.6 años. La mayoría de los pacientes fueron mujeres (87.1%), con una edad promedio de 74.2 ± 11.5 años. RESULTADOS: en la última visita de seguimiento, la puntuación AOFAS promedio fue de 77.9 ± 10.2 puntos y la puntuación MOxFQ promedio fue de 18.3 ± 8.3 puntos. La escala visual analógica (EVA) para el dolor mejoró significativamente, pasando de 7.5 ± 1.2 puntos a 3.4 ± 2.1 puntos de media. También se constataron buenos resultados clínicos en cuanto a la capacidad de calzarse con comodidad. Los espacios de resección promedio al final del estudio fueron 1.3, 1.8, 2.5 y 4.4 mm para el segundo al quinto radio, respectivamente. Los tamaños promedio de los osteofitos por remodelación al final del estudio fueron de 1.6, 1.4, 1.1 y 0.7 mm, respectivamente. También se logró una mejora significativa en el ángulo de hallux valgus (AHV) y en el ángulo intermetatarsiano (IMA) al final del estudio. CONCLUSIÓN: en nuestra experiencia, la artroplastía de resección metatarsofalángica sigue siendo una opción válida en pacientes con deformidades graves del antepié, con resultados clínicos y radiográficos satisfactorios a largo plazo.
Arthroplasty , Humans , Female , Retrospective Studies , Male , Aged , Middle Aged , Arthroplasty/methods , Aged, 80 and over , Time Factors , Metatarsophalangeal Joint/surgery , Metatarsophalangeal Joint/diagnostic imaging , Follow-Up Studies , Radiography , Treatment Outcome , Foot Deformities/surgery , Foot Deformities/diagnostic imaging
To slow the spread of the COVID-19 virus, some U.S. State governments restricted public activity by implementing lockdowns. The possibility remains that lockdowns may need to be implemented in the future, whether to combat novel strains of COVID-19 or entirely different viruses. The present experiment tested whether thinking about a future lockdown affects people's attitudes toward institutions. We found that conservative participants who thought about a future lockdown reported less intention to adhere to the Centers for Disease Control and Prevention (CDC) guidelines and less trust in the government compared to conservative participants in a control condition. We also found that liberal participants who thought about a future lockdown reported more trust in the government and the CDC, compared to liberal participants in a control condition. These findings suggest that merely considering a future lockdown affects people's intended adherence and institutional trust. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-04208-2.
INTRODUCTION: The deforming condition of the navicular bone known as Müller-Weiss disease (MWD) is a rare disease. Patients present with chronic pain in the talonavicular joint and a paradoxical flat foot with a varo hindfoot. OBJECTIVE: To analyze the clinical results of a lateral osteotomy of calcaneus applied to patients with MWD. MATERIAL AND METHODS: Retrospective observational study carried out in two hospitals. The series consists of nine cases in eight patients, all of them with symptomatic Müller-Weiss disease, treated by lateral osteotomy of the calcaneus between 2012 and 2017, obtaining an average follow-up of 4 years (2-6). The mean age was 62 years (50-75). In all patients, Costa-Bartani angles (CB), Kite angle and Calcaneal Inclination (CI) were measured. In addition, the Manchester Oxford Scale (MO) to measure the post-surgical satisfaction of patients. RESULTS: All patients report having improved their pain by obtaining a postoperative score on the mean Manchester Oxford scale of 32.54 points (15.62-53.75). In 66% of patients the CB angle improves, the Kite angle in 89% and the CI in 33%. CONCLUSION: The improvement in the pain of the patients in our series is not accompanied by radiological changes in the same proportion, it is a simple and uncomplicated technique in our follow-up.
INTRODUCCIÓN: La afección deformante del hueso navicular conocida como enfermedad de Müller-Weiss (EMW) es una enfermedad rara. Los pacientes presentan dolor crónico en la articulación talonavicular y un pie plano paradójico con retropié varo. OBJETIVO: Analizar los resultados clínicos de la osteotomía valguizante de calcáneo aplicada a pacientes con EMW. MATERIAL Y MÉTODOS: Estudio observacional, retrospectivo, realizado en dos centros hospitalarios. La serie consta de nueve casos en ocho pacientes, todos ellos con enfermedad de Müller-Weiss sintomática, fueron tratados mediante osteotomía valguizante de calcáneo entre 2012 y 2017, con un seguimiento medio de cuatro años (dos a seis). La edad media fue de 62 años (50-75). En todos los pacientes se midieron los ángulos de Costa-Bartani (CB), el ángulo de Kite y la inclinación calcánea (IC). Además, se utilizó la escala Manchester Oxford (MO) para medir la satisfacción postquirúrgica de los pacientes. RESULTADOS: Todos los pacientes refieren haber mejorado en su dolor, obteniendo una puntuación postoperatoria media de 32.54 puntos (15.62-53.75) en la escala Manchester Oxford. En 66% de los pacientes el ángulo CB mejoró, al igual que en el ángulo de Kite en 89% y la IC en 33%. CONCLUSIÓN: La mejoría en el dolor de los pacientes de nuestra serie no está acompañada por cambios radiológicos en la misma proporción, es una técnica sencilla y sin complicaciones en nuestro seguimiento.
Calcaneus , Cartilage Diseases , Flatfoot , Tarsal Bones , Calcaneus/surgery , Humans , Middle Aged , Osteotomy/methods , Pain
BACKGROUND: The search for treatments to improve cancer survival has led to the emergence of immunotherapy and the study of the tumour microenvironment existing in neoplasms. This preliminary study aims to understand the clinical and pathological relationship of clec9a expression in oral cancer and to explore survival models for future studies. MATERIAL AND METHODS: Immunohistochemical study that included 26 patients with a diagnosis of oral squamous cell carcinoma (OSCC) in mobile tongue and floor of the mouth. Clinical and histopathological variables were recorded, and the biomarkers clec9a for dendritic cells and CD8 and CD4 for lymphocytes were used. RESULTS: Clec9a was expressed in 58% of the sample. It was more common in cases with low lymphoplasmacytic infiltration and in type 2 invasion patterns. It was significantly related to CD8 expression (p=0.055 and p=0.007). No prognostic risks were evident in the survival models studied (overall survival, disease-specific survival, disease-free survival). CONCLUSIONS: CLEC9A expression is present in the OSCC microenvironment and is mainly related to the presence of CD8 lymphocytes. The relationship of its expression with survival prognosis in OSCC could not be confirmed; however, this needs to be confirmed through future studies with larger sample size.
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Lectins, C-Type , Pilot Projects , Prognosis , Receptors, Mitogen , Tumor Microenvironment
BACKGROUND: Oral mucositis (OM) is a painful lesion that takes place in the mucosa of the oral cavity, usually its etiology is associated with drug therapies in cancer patients. It is presented as well-defined ulcers whose painful symptomatology sometimes implies the suspension of oncological treatment or parenteral feeding, being therefore an important adverse effect, marking the evolution of these types of therapies against cancer. The present work aim is to know the prevalence of oral mucositis in oral cancer immunotherapy compared to its prevalence in standard therapy. MATERIAL AND METHODS: A protocol was developed for a systematic review following PRISMA® guidelines and a focused question (PICO) was constructed. A comprehensive literature search was conducted on electronic databases including PubMed, the SCOPUS database, the Cochrane library and the Web of Science (WOS). RESULTS: Six clinical trials were included that met the different inclusion criteria. In these articles, a discrepancy between the prevalence of OM in patients treated with chemotherapy and patients treated with immunotherapy related to the immune checkpoint PD-1/PD-L1 (Nivolumab and Pembrolizumab) was observed. CONCLUSIONS: The prevalence of oral mucositis is lower in new immunotherapy with monoclonal antibodies against oral cancer than drugs used so far (chemotherapy drugs [methotrexate, cisplatin] as well as cetuximab). However, more studies should be carried out to confirm these data.
Mouth Neoplasms , Stomatitis , B7-H1 Antigen , Humans , Immunotherapy/adverse effects , Mouth Neoplasms/therapy , Nivolumab , Stomatitis/chemically induced
INTRODUCTION: There are multiple methods and implants used for the metatarsophalangeal arthrodesis of hallux without evidence in favor of one or the other in the bibliography. The goal was to compare the clinical and radiological results of 2 methods and implants used in our center. MATERIAL AND METHODS: Retrospective review of 37 feet between 2013 and 2017 (22 feet by plate and 15 by cannulated screws). Clinical and radiological variables were collected and the AOFAS and Manchester-Oxford scales were applied. Variables were studied descriptively and analytically through the SPSSv15 program. RESULTS: The group intervened by plate was composed of 77% of women, with an average age of 65 years and a distribution by diagnosis of severe hallux valgus (HV) (36%), hallux valgus relapse (HVR) (36%) and hallux rigidus (HR) (28%), compared to 80% of women, 68 years old and HV (34%), HVR (46%) HR (20%) in the group of cannulated screws. No significant differences were found in the correction of angles for HV or HVR. The rate of painful pseudoarthrosis was 13% in both and the re-intervention was 18% in the plate group and 26% in the screw group. Both the AOFAS and M-O scales were better in the plate group 63.8 vs 52.6 (p = 0.07); 30.1 vs 41.0 (p = 0.10); as well as patient satisfaction 86% vs 66% (p 0.05) and postoperative pain 3.68 vs 5.58 (p 0.05). CONCLUSION: Small study groups, not implant randomization, both options are functional without being able to find a preferred one.
INTRODUCCIÓN: Existen múltiples métodos e implantes utilizados para la artrodesis metatarsofalángica del hallux sin evidencia a favor de uno u otro en la bibliografía. El objetivo fue comparar los resultados clínicos y radiológicos de dos métodos e implantes utilizados en nuestro centro. MATERIAL Y MÉTODOS: Revisión retrospectiva de 37 pies entre 2013 y 2017 (22 pies mediante placa y 15 mediante tornillos canulados). Se recogieron variables clínicas y radiológicas y se aplicaron las escalas AOFAS y Manchester-Oxford. Se estudiaron las variables descriptivas y analíticamente mediante el programa SPSS v15. RESULTADOS: El grupo intervenido mediante placa lo compuso 77% de mujeres, con una edad media de 65 años y una distribución por diagnósticos de hallux valgus (HV) severo (36%), recidiva de hallux valgus (RHV) (36%) y hallux rigidus (HR) (28%), frente a 80% de mujeres, con media de 68 años y HVS (34%), RHV (46%) y HR (20%) en el grupo de tornillos canulados. No se encontró diferencias significativas en la corrección de los ángulos para HVS o RHV. La tasa de seudoartrosis dolorosa fue de 13% en ambos y la reintervención fue de 18% en el grupo de placas y 26% en el grupo de tornillos. Tanto la escala AOFAS como la M-O fueron mejores en el grupo de placa 63.8 versus 52.6 (p = 0.07); 30.1 versus 41.0 (p = 0.10); así como la satisfacción del paciente 86 versus 66% (p 0.05) y el dolor postoperatorio 3.68 versus 5.58 (p 0.05). CONCLUSIÓN: Son grupos pequeños de estudio, sin aleatorización de implantes, ambas opciones son funcionales sin poder encontrar una preferente.
Hallux Rigidus , Hallux Valgus , Hallux , Metatarsophalangeal Joint , Aged , Arthrodesis , Bone Screws , Female , Humans , Retrospective Studies , Treatment Outcome
BACKGROUND AND PURPOSE: Cytomegalovirus (CMV) infection has recently been associated with a lower multiple sclerosis (MS) susceptibility, although it remains controversial whether it has a protective role or is merely an epiphenomenon related to westernization and early-life viral infections. We aimed to evaluate whether CMV serostatus may differ in patients with early MS as compared with patients with non-early MS, analyzing the putative association of this virus with MS clinical course and humoral immune responses against other herpesviruses. METHODS: Multicentric analysis was undertaken of 310 patients with MS (early MS, disease duration ≤5 years, n = 127) and controls (n = 155), evaluating specific humoral responses to CMV, Epstein-Barr virus and human herpesvirus-6, as well as T-cell and natural killer (NK)-cell immunophenotypes. RESULTS: Cytomegalovirus seroprevalence in early MS was lower than in non-early MS or controls (P < 0.01), being independently associated with disease duration (odds ratio, 1.04; 95% confidence interval, 1.01-1.08, P < 0.05). CMV+ patients with MS displayed increased proportions of differentiated T-cells (CD27-CD28-, CD57+, LILRB1+) and NKG2C+ NK-cells, which were associated with a lower disability in early MS (P < 0.05). CMV+ patients with early MS had an age-related decline in serum anti-EBNA-1 antibodies (P < 0.01), but no CMV-related differences in anti-human herpesvirus-6 humoral responses. CONCLUSIONS: Low CMV seroprevalence was observed in patients with early MS. Modification of MS risk attributed to CMV might be related to the induction of differentiated T-cell and NK-cell subsets and/or modulation of Epstein-Barr virus-specific immune responses at early stages of the disease.
Cytomegalovirus Infections/complications , Cytomegalovirus/isolation & purification , Hygiene Hypothesis , Multiple Sclerosis/virology , Adult , Antibodies, Viral/blood , Female , Humans , Male , Middle Aged , Multiple Sclerosis/blood , Seroepidemiologic Studies , Young Adult
Diabetes and hypertension have been associated with cardiovascular diseases and stroke. Some reports have related the coexistence of hypertension and diabetes with increase in the risk of developing vascular complications. Recently some studies have shown results suggesting that in the early stages of diabetes and hypertension exist a reduced functional response to vasopressor agents like angiotensin II (Ang II), which plays an important role in blood pressure regulation mechanism through the activation of its AT1 and AT2 receptors. For that reason, the aim of this work was to study the gene and protein expression of AT1 and AT2 receptors in aorta of diabetic SHR and WKY rats. Diabetes was induced by the administration of streptozotocin (60 mg/kg i.p.). After 4 weeks of the onset of diabetes, the protein expression was obtained by western blot and the mRNA expression by RT-PCR. Our results showed that the hypertensive rats have a higher mRNA and protein expression of AT1 receptors than normotensive rats while the AT2 expression remained unchanged. On the other hand, the combination of diabetes and hypertension increased the mRNA and protein expression of AT1 and AT2 receptors significantly. In conclusion, our results suggest that diabetes with hypertension modifies the mRNA and protein expression of AT1 and AT2 receptors. However, the overexpression of AT2 could be associated with the reduction in the response to Ang II in the early stage of diabetes.
Angiotensin II/metabolism , Aorta/metabolism , Diabetes Mellitus, Experimental/metabolism , Hypertension/metabolism , Receptor, Angiotensin, Type 1 , Receptor, Angiotensin, Type 2 , Animals , Aorta/physiopathology , Blood Pressure/physiology , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/physiopathology , Gene Expression Profiling , Hypertension/complications , Hypertension/physiopathology , Male , RNA, Messenger/metabolism , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Receptor, Angiotensin, Type 1/genetics , Receptor, Angiotensin, Type 1/metabolism , Receptor, Angiotensin, Type 2/genetics , Receptor, Angiotensin, Type 2/metabolism
Introducción: Las enfermeras con frecuencia son responsables de la clasificación inmediata y la evaluación inicial de los pacientes con traumatismo craneoencefálico. El reconocimiento precoz de los signos del daño cerebral es fundamental para permitir la prestación de tratamientos oportunos. Objetivo: Identificarla utilidad clínica de la escala de coma de Glasgow (GCS, por sus siglas en inglés, Glasgow Coma Scale) y determinar el uso apropiado por el personal de Enfermería. Métodos: Para la búsqueda de información se seleccionaron 3 de las principales bases de datos en el área de la salud: Medline, CINHAL y BVS. Los descriptores empleados fueron: Glasgow coma scale, brain injuries, coma, trauma severity, nursing assessment, neurologic assessment, la búsqueda se limitó a 10 años, sólo en población adulta. Resultados: La GCS es un instrumento con alta sensibilidad para la valoración en pacientes con daño cerebral. Se han observado diversas fallas e inconsistencias al momento de su uso e interpretación como suponer condiciones clínicas más graves de lo que en verdad se presentan, o por el contrario, pasar por alto datos de deterioro neurológico; sin embargo, se ha demostrado que al haber un entrenamiento continuo acerca del uso de esta escala se genera una mejora significativa en las evaluaciones y el reporte de resultados entre evaluadores. Conclusiones: La valoración de Glasgow se compone de 3 subescalas que califican de manera individual 3 aspectos de la consciencia: la apertura ocular, la respuesta verbal y la respuesta motora; el puntaje se da con base en la mejor respuesta obtenida de cada uno de estos rubros. Su propósito es alertar al personal médico y de Enfermería ante alguna alteración neurológica del paciente. Proporciona un lenguaje común y objetivo para mejorar la comunicación en el reporte de los resultados conseguidos. Actualmente, es el parámetro más usado tanto en el ámbito hospitalario como en el campo prehospitalario.
Introduction: nurses are frequently responsible of immediate classification and initial as-sessment of patients suffering from a cranium encephalic traumatism. Early acknowledgement of brain damage signs is fundamental to offer timely treatments. Objective: To identify the usefulness of the Glasgow Coma Scale, and determine its appropriate use by the nursing staff. Methods: information search was performed through 3 main health databases: Medline, CINHAL and BVS. The search words used were Glasgow coma scale, brain injuries, coma, trauma severity, nursing assessment, and neurologic assessment. The search was limited to 10 years, and considering only in the adult population. Results: the Glasgow coma scale is a highly sensible instrument to assess patients with some de-gree of brain injuries. Some failures and inconsistencies in its use and interpretation have been observed, such as supposing worse clinical conditions than the real ones, or on the other hand, underestimate the neurological impairment; however, it has been demonstrated that a continuous training on the use of this scale significantlyimproves the assessments and the results outcomes. Conclusions: the Glasgow coma scale has 3 sub-scales which individually estimate 3 aspects of consciousness: ocular aperture, verbal response, and motor response. The fnal score is made up with the best responses in the 3 sub-scales. the objective is to alert the medical and nursing staff regarding any neurologic alteration in the patient. the scale has a common and objective language in order to improve the communication from the results, and at present, it is the most widely used parameter both in the hospital and pre-hospital scenarios.
Humans , Adult
The identity and emission rates of volatile organic compounds (VOCs) in headspace vapors over electronic components were determined at temperatures from 75 to 200°C using gas chromatography/mass spectrometry. The emission of VOCs may provide a basis to detect the onset of the overheating of electronic components in confined atmospheres near electronic bays on airplanes and submarines before smoldering or ignition. VOCs found in headspace vapors over components, including resistors, capacitors, diodes, transistors, and insulation from wires of a transformer, were composed of simple mixtures of substances with 6 to 10 carbon number from chemical families including ketones, aldehydes, substituted benzenes, alcohols, and phenols. Composition of the vapors was characteristic but not exclusive of a particular electrical component, except for phenols and methylstyrene, which were found only in a single component. Emission rates were expressed as nanogram of chemical per gram of component per minute, and increased from a low of 0.001 ng/g-min for nonanal from transformer wire at 100°C to a maximum of 2.5 ng/g-min at 150°C for isophorone from a resistor. Patterns of persistence with repeated sampling of headspace for components at 200°C over 5 hr suggested that VOCs arose from impurities in plastics rather than from thermal decomposition of the polymer.
Electrical Equipment and Supplies , Occupational Exposure/analysis , Volatile Organic Compounds/analysis , Environmental Monitoring , Gas Chromatography-Mass Spectrometry , Temperature , Transistors, Electronic , Volatile Organic Compounds/chemistry
BACKGROUND: According to the reverse epidemiology hypothesis, high cholesterol levels might be protective and associated with greater survival rates under certain conditions. In stroke patients, a clear correlation between lipid levels and mortality after ischaemic and hemorrhagic strokes has been demonstrated. The aim of this study was to analyze the impact of lipid levels on 3-month mortality in patients with ischaemic stroke (IS) homogeneously treated with intravenous rtPA and admitted to a monitored acute stroke unit. METHODS: Retrospective analysis of a prospective cohort of 220 patients with an IS treated with rtPA within the first 4.5 h in a single tertiary hospital from January 2005 to August 2010. RESULTS: Mortality at 3 months was 15.0%. Univariate analysis showed that age, NIHSS at admission, heart failure, and atrial fibrillation were directly related to 3-month mortality; cholesterol, triglycerides, and low density lipoprotein were inversely associated. The death rate by cholesterol level was 5.5% for the highest tertile (>192 mg/dl), 13.7% for the middle (192-155 mg/dl), and 25.7% for the lowest (<155 mg/dl), P = 0.003. Multivariate analysis showed that amongst the lipid determinations, only cholesterol [OR: 0.985 (95% CI: 0.972-0.998), P = 0.021] was inversely associated with 3-month mortality. The 'protective' effect of cholesterol was independent of stroke severity and remained significant in non-lacunar strokes. CONCLUSIONS: Survival of stroke patients receiving current, most effective medical treatment is related to blood cholesterol levels, with an inverse relationship between cholesterol and mortality. The mechanism of this apparently paradoxical situation remains unexplained but merits further research.
Cholesterol/blood , Fibrinolytic Agents/therapeutic use , Stroke , Tissue Plasminogen Activator/therapeutic use , Aged , Aged, 80 and over , Blood Glucose/metabolism , Cerebral Hemorrhage/blood , Cerebral Hemorrhage/etiology , Cohort Studies , Factor Analysis, Statistical , Female , Humans , Logistic Models , Male , Middle Aged , Retrospective Studies , Stroke/blood , Stroke/drug therapy , Stroke/mortality , Time Factors
CD56(bright) NK cells, which may play a role in immunoregulation, are expanded in multiple sclerosis (MS) patients treated with immunomodulatory therapies such as daclizumab and interferon-beta (IFNß). Yet, whether this NK cell subset is directly involved in the therapeutic effect is unknown. As NK receptor (NKR) expression by subsets of NK cells and CD8+ T lymphocytes is related to MS clinical course, we addressed whether CD56(bright) NK cells and NKR in IFNß-treated MS patients differ according to the clinical response. IFNß was associated to lower LILRB1+ and KIR+NK cells, and higher NKG2A+NK cell proportions, an immunophenotypic pattern mainly found in responders. After IFNß treatment, a CD56(bright) NK cell expansion was significantly related to a positive clinical response. Our results reveal that IFNß may promote in responders changes in the NK cell immunophenotype, corresponding to the profile found at early maturation stages of this lymphocyte lineage.
Immunologic Factors/therapeutic use , Interferon-beta/therapeutic use , Killer Cells, Natural/immunology , Multiple Sclerosis/drug therapy , Adult , CD56 Antigen/immunology , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , Case-Control Studies , Female , Humans , Immunologic Factors/immunology , Interferon-beta/immunology , Male , Middle Aged , Multiple Sclerosis/immunology , Receptors, Natural Killer Cell/immunology
NK cell receptors (NKR) are expressed in subsets of NK and CD8+ T cells, lymphocytes involved in multiple sclerosis (MS) pathogenesis. Clinical implications of NKR expression in MS are unknown. Here, we show that the proportions of CD8+ T cells displaying LILRB1, an inhibitory NKR expressed at late stages of T cell differentiation, were directly related with age and MS duration, and inversely with the immunomodulatory therapy-dependent increase of CD56(bright) NK cells. Similar associations were found for KIR+ and CD56+ CD8+ T cells, whereas no age-related NKR distribution was perceived in controls. Moreover, active MS had lower LILRB1+ NK cells, and IFN-ß-treated patients exhibited a phenotypic profile related to shorter disease evolution. Progressive accumulation of terminally differentiated T lymphocytes and experienced NK cells in MS, presumably stimulated in response to a persistent challenge and modulated by IFN-ß therapy, may support the analysis of NKR distribution as new biomarkers.
Antigens, CD/metabolism , Interferon-beta/therapeutic use , Lymphocytes/metabolism , Multiple Sclerosis/drug therapy , Multiple Sclerosis/immunology , Receptors, Immunologic/metabolism , Receptors, Natural Killer Cell/metabolism , Adult , Aging/metabolism , Antibodies/blood , Antibodies/immunology , Biomarkers/metabolism , CD56 Antigen/metabolism , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/metabolism , Cell Count , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/immunology , Female , Humans , Killer Cells, Natural/cytology , Killer Cells, Natural/metabolism , Leukocyte Immunoglobulin-like Receptor B1 , Leukocytes, Mononuclear/cytology , Lymphocytes/cytology , Lymphocytes/drug effects , Male , Middle Aged , Multiple Sclerosis/diagnosis , Multiple Sclerosis/metabolism , Multiple Sclerosis, Chronic Progressive/diagnosis , Multiple Sclerosis, Chronic Progressive/drug therapy , Multiple Sclerosis, Chronic Progressive/immunology , Multiple Sclerosis, Chronic Progressive/metabolism , Multiple Sclerosis, Relapsing-Remitting/diagnosis , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/immunology , Multiple Sclerosis, Relapsing-Remitting/metabolism , NK Cell Lectin-Like Receptor Subfamily C/metabolism , Receptors, KIR/metabolism , Recurrence , Time Factors
The genetic susceptibility to multiple sclerosis (MS) is only partially explained, and it shows geographic variations. We analyse here two series of Spanish patients and healthy controls and show that relapsing MS (R-MS) is associated with a gene deletion affecting the hypothetically soluble leukocyte immunoglobulin (Ig)-like receptor A3 (LILRA3, 19q13.4), in agreement with an earlier finding in German patients. Our study points to a gene-dose-dependent, protective role for LILRA3, the deletion of which synergizes with HLA-DRB1(*)1501 to increase the risk of R-MS. We also investigated whether the risk of suffering R-MS might be influenced by the genotypic diversity of killer-cell Ig-like receptors (KIRs), located only approximately 400 kb telomeric to LILRA3, and implicated in autoimmunity and defence against viruses. The relationship of LILRA3 deletion with R-MS is not secondary to linkage disequilibrium with a KIR gene, but we cannot exclude some contributions of KIR to the genetic susceptibility to R-MS.
Gene Deletion , HLA-DR Antigens/genetics , Multiple Sclerosis/genetics , Receptors, Immunologic/genetics , Adolescent , Adult , Aged , Case-Control Studies , Child , Female , Genetic Variation , Genotype , HLA-DRB1 Chains , Humans , Linkage Disequilibrium , Male , Middle Aged , Multiple Sclerosis/epidemiology , Receptors, KIR/genetics , Spain/epidemiology , Young Adult
OBJECTIVE: to evaluate the influence of clustering of vascular risk factors (VRF) on in-hospital mortality in patients with acute ischemic stroke (AIS) developing a risk score for mortality prediction. METHODS: clinical data from 1527 patients admitted to hospital with a first-ever AIS were prospectively evaluated from 1997 to 2005 assessing the presence of six VRF: diabetes, hypertension, hyperlipidemia, ischemic heart disease, atrial fibrillation and peripheral arterial disease. A composite vascular risk score (VRS) was created using five risk factors. Hyperlipidemia was excluded from the score due to its protective impact on mortality. Two modified VRS models were created and assessed for their accuracy as predictors for in-hospital mortality based on the odds ratio for each VRF obtained in the univariate analysis. RESULTS: 197 patients (12.9 %) died during the acute hospitalization period. Stroke severity increased with each additional VRF (p = 0.002). Cox proportional hazards model adjusted for confounders showed an association between the composite VRS and in-hospital mortality (p = 0.045). According to the clustering of VRS, the risk for in-hospital death increased from 1.951 (95 % CI 1.041-3.665) for patients having one VRS to 2.343 (95% CI 1.081-5.076) for those having a VRS > or = 4. ROC curves showed that the modified VRS model based on a given value of one for each accumulated VRF, including the absence of hyperlipidemia, had the highest predictive capability for in-hospital mortality (p < 0.0001). CONCLUSIONS: the presence of multiple VRF in patients with acute ischemic stroke increases the stroke severity and the risk of in-hospital death.
Hospital Mortality , Stroke/etiology , Stroke/mortality , Aged , Aged, 80 and over , Atrial Fibrillation/complications , Brain Ischemia/complications , Cluster Analysis , Diabetes Mellitus , Disease Progression , Female , Humans , Hypertension/complications , Male , Middle Aged , Predictive Value of Tests , Proportional Hazards Models , Prospective Studies , ROC Curve , Retrospective Studies , Risk Factors
A mobility spectrometer was used to characterize gas-phase ions produced from laser ablation of solids in air at 100 degrees C and at ambient pressure with a beam focused to a diameter of
