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Children with difficult tracheal intubation are at increased risk of severe complications, including hypoxaemia and cardiac arrest. Increasing experience with the simultaneous use of videolaryngoscopy and flexible bronchoscopy (hybrid) in adults led us to hypothesise that this hybrid technique could be used safely and effectively in children under general anaesthesia. We reviewed observational data from the international Pediatric Difficult Intubation Registry from 2017 to 2021 to assess the safety and efficacy of hybrid tracheal intubation approaches in paediatric patients. In total, 140 patients who underwent 180 attempts at tracheal intubation with the hybrid technique were propensity score-matched 4:1 with 560 patients who underwent 800 attempts with a flexible bronchoscope. In the hybrid group, first attempt success was 70% (98/140) compared with 63% (352/560) in the flexible bronchoscope group (odds ratio (95%CI) 1.4 (0.9-2.1), p = 0.1). Eventual success rates in the matched groups were 90% (126/140) for hybrid vs. 89% (499/560) for flexible bronchoscope (1.1 (0.6-2.1), p = 0.8). Complication rates were similar in both groups (15% (28 complications in 182 attempts) hybrid; 13% (102 complications in 800 attempts) flexible bronchoscope, p = 0.3). The hybrid technique was more likely than flexible bronchoscopy to be used as a rescue technique following the failure of another technique (39% (55/140) vs. 25% (138/560), 2.1 (1.4-3.2) p < 0.001). While technically challenging, the hybrid technique has success rates similar to other advanced airway techniques, few complications and may be considered an alternative technique when developing an airway plan for paediatric patients whose tracheas are difficult to intubate under general anaesthesia.
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Laringoscopios , Laringoscopía , Adulto , Niño , Humanos , Laringoscopía/métodos , Broncoscopía/métodos , Intubación Intratraqueal/métodos , Sistema de RegistrosRESUMEN
Right- and left-sided colorectal cancers (RSCRC and LSCRC, respectively) are different developmentally, genetically and prognostically. Clinical data also indicate that they respond differently to anti-EGFR therapies. The role of EGFR protein expression in KRAS wild type colorectal cancer is also controversial. Here we have used a cohort of anti-EGFR antibody treated KRAS-wild type colorectal cancer patients (n = 97) to analyse the prognostic role of EGFR protein expression in relation to sidedness. In our cohort EGFR copy number, determined by FISH, was not associated with the level of EGFR protein, assessed by immunohistochemistry and measured by H-scoring. There was a significantly higher EGFR H-score detected in RSCRC as compared to LSCRC in primary tumors (p = 0.04). Furthermore, in a proportion of cases (n = 31) metastatic tissues were also available and their analysis also found a significantly higher EGFR H-score in metastases of RSCRC compared to LSCRC (p = 0.018). Kaplan Meyer survival analysis demonstrated that anti-EGFR antibody therapies were more effective in case of LSCRC compared to RSCRC. Although in case of progression-free survival data just indicated a trend (p = 0.065), in case of overall survival the difference was significant favouring LSCRC (p = 0.047). These data demonstrated for the first time that the EGFR protein expression is significantly higher in KRAS wild type RSLCL as compared to LSCRC. Meanwhile it is somewhat unexpected that the lower EGFR protein expression was found to be associated with better efficacy of anti-EGFR antibody therapies of colorectal cancer, the finding of which must be further validated.
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Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Adulto , Anciano , Cetuximab/uso terapéutico , Neoplasias Colorrectales/metabolismo , Receptores ErbB/biosíntesis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Panitumumab/uso terapéutico , Proteínas Proto-Oncogénicas p21(ras)/genética , Resultado del TratamientoRESUMEN
It is well known that hyperphenylalaninemia caused by phenylketonuria (PKU) negatively influences cognitive performance. Several tests have been used to study these functions. Until now, no universal, optimal tool has been developed for detecting PKU-caused brain dysfunctions. Using computerized neuropsychological tests during daily routine would be helpful for screening subclinical brain deficits in adult PKU patients. In a monocentric, cross-sectional study, adult patients with PKU (n = 46; median age = 29.5 years; female/male ratio = 21/25) were tested with the computerized Cambridge Cognition (CANTAB) test measuring neurocognitive functions. Patients were divided into two groups: The "on diet" group included patients whose blood Phe-level was under 600 µmol/l (n = 20), and the "loose diet" group included patients whose blood Phe-level was above 600 µmol/l (n = 26) at the examination time. The results of the PKU-affected individuals were compared with a healthy control group (n = 31; median age = 25 years; female/male ratio = 11/20). Compared with the control group, PKU patients had significantly worse test results in memory, problem-solving skills, and strategy. However, there were no significant differences in response speed or initial thinking time. There was no correlation between the blood Phe-level, tyrosine (Tyr)-level or Phe/Tyr ratio and the different cognitive test results. There were no significant differences in test results between the two PKU subgroups. Several cognitive functions measured by CANTAB are negatively influenced by hyperphenylalaninemia in adult PKU patients. However, response speed and initial thinking time were not impaired as seriously as other functions. Patients with lower Phe-levels failed to achieve better test results than patients whose Phe-levels were notably elevated.
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Cognición/fisiología , Memoria a Corto Plazo/fisiología , Fenilalanina/sangre , Fenilcetonurias/sangre , Fenilcetonurias/psicología , Adulto , Estudios Transversales , Función Ejecutiva/fisiología , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Tiempo de Reacción/fisiología , Adulto JovenRESUMEN
BACKGROUND: Lung cancer (LC) is still the most common cause of cancer related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of all LC cases but is not a single entity. It is now accepted that, apart from the characteristic driver mutations, the unique molecular signatures of adeno- (AC) and squamous cell carcinomas (SCC), the two most common NSCLC subtypes should be taken into consideration for their management. Therapeutic interventions, however, frequently lead to chemotherapy resistance highlighting the need for in-depth analysis of regulatory mechanisms of multidrug resistance to increase therapeutic efficiency. METHODS: Non-canonical Wnt5a and canonical Wnt7b and ABC transporter expressions were tested in primary human LC (n = 90) resections of AC and SCC. To investigate drug transporter activity, a three dimensional (3D) human lung aggregate tissue model was set up using differentiated primary human lung cell types. Following modification of the canonical, beta-catenin dependent Wnt pathway or treatment with cisplatin, drug transporter analysis was performed at mRNA, protein and functional level using qRT-PCR, immunohistochemistry, immune-fluorescent staining and transport function analysis. RESULTS: Non-canonical Wnt5a is significantly up-regulated in SCC samples making the microenvironment different from AC, where the beta-catenin dependent Wnt7b is more prominent. In primary cancer tissues ABCB1 and ABCG2 expression levels were different in the two NSCLC subtypes. Non-canonical rhWnt5a induced down-regulation of both ABCB1 and ABCG2 transporters in the primary human lung aggregate tissue model recreating the SCC-like transporter pattern. Inhibition of the beta-catenin or canonical Wnt pathway resulted in similar down-regulation of both ABC transporter expression and function. In contrast, cisplatin, the frequently used adjuvant chemotherapeutic agent, activated beta-catenin dependent signaling that lead to up-regulation of both ABCB1 and ABCG2 transporter expression and activity. CONCLUSIONS: The difference in the Wnt microenvironment in AC and SCC leads to variations in ABC transporter expression. Cisplatin via induction of canonical Wnt signaling up-regulates ABCB1 and ABCG2 drug transporters that are not transporters for cisplatin itself but are transporters for drugs that are frequently used in combination therapy with cisplatin modulating drug response.
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Transportadoras de Casetes de Unión a ATP/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Cisplatino/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Vía de Señalización Wnt/efectos de los fármacos , Células A549 , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Antineoplásicos/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pulmonares/patología , Proteínas de Neoplasias/metabolismo , Resultado del Tratamiento , Células Tumorales CultivadasRESUMEN
Introduction There is evidence for hippocampal dysfunctions in systemic lupus erythematosus (SLE), which may contribute to neuropsychiatric impairments. However, fine structural alterations of the hippocampus have not been investigated in SLE. Methods We measured the volume of hippocampal subfields in 18 SLE patients and 20 healthy control individuals matched for age, gender, and education. The MRI protocol included structural T1 volumes (Philips Achieva 3T scanner, magnetization-prepared rapid acquisition gradient echo (MPRAGE)). For image processing, we used the neuGRID platform and the longitudinal pipeline of FreeSurfer v6.0 with the "hipposubfields" flag. Results Patients with SLE showed reduced volumes of CA1 (Cornu Ammonis 1) and CA4-dentate gyrus subfields relative to the control individuals. Smaller CA1 volumes were associated with worse performance on the Addenbrooke's Cognitive Examination. Conclusions These preliminary results indicate a prominent vulnerability and functional relevance of the CA1 hippocampal subfield in SLE.
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Región CA1 Hipocampal/patología , Giro Dentado/patología , Lupus Eritematoso Sistémico/patología , Imagen por Resonancia Magnética/métodos , Adulto , Disfunción Cognitiva/etiología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Lupus Eritematoso Sistémico/diagnóstico por imagen , Persona de Mediana EdadRESUMEN
Biomarkers for pulmonary manifestations in systemic lupus erythematosus (SLE) are missing. Plasma samples of nine SLE patients with known pulmonary involvement (SLEpulm) and nine SLE patients without pulmonary involvement (SLE) were tested by multiplex microarray analysis for various cyto- and chemokines. Significantly decreased lung function paramters for forced vital capacity (FVC), total lung capacity (TLC), diffusion capacity for carbon monoxide (DLCO) and diffusion of CO corrected on lung volume (KLCO) were observed in SLEpulm as compared to SLE patients. CC chemokine ligand 21 (CCL21) and interferon gamma-induced protein 10 (IP-10) levels were significantly higher in SLEpulm, than in patients without pulmonary manifestations. CCL21 correlated negatively with DLCO ( r = -0.73; p < 0.01) and KLCO ( r = -0.62; p < 0.01), while IP-10 with FVC and forced expiratory volume one second. Receiver Operating Characteristics (ROC) analysis confirmed high sensitivity and specificity for the separation of SLE patients with and without pulmonary involvement for the chemokines CCL21 (Area Under Curve (AUC): 0.85; sensitivity%: 88.90; specificity%: 75.00; p < 0.01) and IP-10 (AUC: 0.82; sensitivity%: 66.67, specificity%: 100; p < 0.01). Pleuropulmonary manifestations in SLE patients associated with lung functional and DLCO/KLCO changes and were associated with significant increase in CCL21 and IP-10. These chemokines might serve as potential biomarkers of lung involvement in SLE patients.
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Biomarcadores/sangre , Quimiocina CCL2/sangre , Quimiocina CXCL10/sangre , Enfermedades Pulmonares/inmunología , Lupus Eritematoso Sistémico/complicaciones , Adulto , Estudios Transversales , Femenino , Volumen Espiratorio Forzado , Humanos , Enfermedades Pulmonares/fisiopatología , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/fisiopatología , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria , Capacidad Pulmonar Total , Regulación hacia ArribaRESUMEN
BACKGROUND: Angiogenesis is important both in normal tissue function and disease and represents a key target in lung cancer (LC) therapy. Unfortunately, the two main subtypes of non-small-cell lung cancers (NSCLC) namely, adenocarcinoma (AC) and squamous cell carcinoma (SCC) respond differently to anti-angiogenic e.g. anti-vascular endothelial growth factor (VEGF)-A treatment with life-threatening side effects, often pulmonary hemorrhage in SCC. The mechanisms behind such adverse reactions are still largely unknown, although peroxisome proliferator activator receptor (PPAR) gamma as well as Wnt-s have been named as molecular regulators of the process. As the Wnt microenvironments in NSCLC subtypes are drastically different, we hypothesized that the particularly high levels of non-canonical Wnt5a in SCC might be responsible for alterations in blood vessel growth and result in serious adverse reactions. METHODS: PPARgamma, VEGF-A, Wnt5a, miR-27b and miR-200b levels were determined in resected adenocarcinoma and squamous cell carcinoma samples by qRT-PCR and TaqMan microRNA assay. The role of PPARgamma in VEGF-A expression, and the role of Wnts in overall regulation was investigated using PPARgamma knock-out mice, cancer cell lines and fully human, in vitro 3 dimensional (3D), distal lung tissue aggregates. PPARgamma mRNA and protein levels were tested by qRT-PCR and immunohistochemistry, respectively. PPARgamma activity was measured by a PPRE reporter system. The tissue engineered lung tissues expressing basal level and lentivirally delivered VEGF-A were treated with recombinant Wnts, chemical Wnt pathway modifiers, and were subjected to PPARgamma agonist and antagonist treatment. RESULTS: PPARgamma down-regulation and VEGF-A up-regulation are characteristic to both AC and SCC. Increased VEGF-A levels are under direct control of PPARgamma. PPARgamma levels and activity, however, are under Wnt control. Imbalance of both canonical (in AC) and non-canonical (in SCC) Wnts leads to PPARgamma down-regulation. While canonical Wnts down-regulate PPARgamma directly, non-canonical Wnt5a increases miR27b that is known regulator of PPARgamma. CONCLUSION: During carcinogenesis the Wnt microenvironment alters, which can downregulate PPARgamma leading to increased VEGF-A expression. Differences in the Wnt microenvironment in AC and SCC of NSCLC lead to PPARgamma decrease via mechanisms that differentially alter endothelial cell motility and branching which in turn can influence therapeutic response.
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Carcinoma de Células Escamosas/patología , Movimiento Celular , Endotelio Vascular/patología , Neoplasias Pulmonares/patología , PPAR gamma/fisiología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteína Wnt-5a/metabolismo , Adenocarcinoma/irrigación sanguínea , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Animales , Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas/irrigación sanguínea , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/irrigación sanguínea , Carcinoma de Células Escamosas/metabolismo , Endotelio Vascular/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/irrigación sanguínea , Neoplasias Pulmonares/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , MicroARNs/genética , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Células Tumorales Cultivadas , Microambiente TumoralRESUMEN
Novel peptide conjugates of two antitubercular drug candidates were synthesised and characterised using new tuftsin peptide derivative (OT14) as carrier moiety. As antitubercular drug candidates two pyridopyrimidine derivatives, TB803 (2-allylamino-4-oxopyrido[1,2-a]pyrimidine-3-carbaldehyde) and TB820 (4-oxo-2-(pyrrolidin-1-yl)-pyrido[1,2-a]pyrimidin-3-carbaldehyde) inhibiting vital enzyme of Mycobacterium tuberculosis were applied. Membrane affinity of the compounds TB803 and TB820 and their peptide conjugates was evaluated using experimental lipid mono- and bilayer models. Penetration ability was assessed tensiometrically from Langmuir monolayer study and applying quartz crystal microbalance for the supported lipid bilayer (SLB) system. Minimal inhibitory concentration (MIC) values remained in a similar micromolar range for both of the conjugates while their cellular uptake rate was improved significantly compared to the drug candidates. A correlation was found between membrane affinity properties and results of in vitro biological investigations. Analysis of physical/structural properties of SLB in contact with bioactive components and visualization of the structural change by atomic-force microscopy (AFM) provided information on the type and route of molecular interaction of drug construction with lipid layers. The possible role of electrostatic interactions between lipid layer and drug candidates was tested in Langmuir-balance experiments using negatively charged lipid mixture (DPPC+DPPG). Especially the peptide conjugates presented increased membrane affinity due to cationic character of the peptide sequence selected for the conjugate formation. That is supposed to be one reason for the enhanced cellular uptake observed in vitro on MonoMac6 cell line. The conjugation of antitubercular agents to a peptidic carrier is a promising approach to enhance membrane affinity, cellular uptake rate and in vitro selectivity.
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Antituberculosos/farmacología , Portadores de Fármacos/química , Membrana Dobles de Lípidos/química , Membranas Artificiales , Modelos Moleculares , Monocitos/citología , Mycobacterium tuberculosis/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Antituberculosos/química , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Portadores de Fármacos/metabolismo , Citometría de Flujo , Humanos , Técnicas In Vitro , Membrana Dobles de Lípidos/metabolismo , Pruebas de Sensibilidad Microbiana , Microscopía de Fuerza Atómica , Monocitos/efectos de los fármacos , Fragmentos de Péptidos/químicaRESUMEN
BACKGROUND: Because depressive illness is recurrent, recurrence prevention should be a mainstay for reducing its burden on society. One way to reach this goal is to identify malleable risk factors. The ability to attenuate sadness/dysphoria (mood repair) and parasympathetic nervous system functioning, indexed as respiratory sinus arrhythmia (RSA), are impaired during depression and after it has remitted. The present study therefore tested the hypothesis that these two constructs also may mirror risk factors for a recurrent major depressive episode (MDE). METHOD: At time 1 (T1), 178 adolescents, whose last MDE had remitted, and their parents, reported on depression and mood repair; youths' RSA at rest and in response to sad mood induction also were assessed. MDE recurrence was monitored until time 2 (T2) up to 2 years later. Mood repair at T1 (modeled as a latent construct), and resting RSA and RSA response to sadness induction (RSA profile), served to predict onset of first recurrent MDE by T2. RESULTS: Consistent with expectations, maladaptive mood repair predicted recurrent MDE, above and beyond T1 depression symptoms. Further, atypical RSA profiles at T1 were associated with high levels of maladaptive mood repair, which, in turn, predicted increased risk of recurrent MDE. Thus, maladaptive mood repair mediated the effects of atypical RSA on risk of MDE recurrence. CONCLUSIONS: This study documented that a combination of behavioral and physiological risk factors predicted MDE recurrence in a previously clinically referred sample of adolescents with depression histories. Because mood repair and RSA are malleable, both could be targeted for modification to reduce the risk of recurrent depression in youths.
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Adaptación Psicológica/fisiología , Síntomas Afectivos/fisiopatología , Trastorno Depresivo Mayor/fisiopatología , Arritmia Sinusal Respiratoria/fisiología , Adolescente , Femenino , Estudios de Seguimiento , Humanos , Masculino , Recurrencia , RiesgoRESUMEN
BACKGROUND: There appears little consensus concerning protein requirements in phenylketonuria (PKU). METHODS: A questionnaire completed by 63 European and Turkish IMD centres from 18 countries collected data on prescribed total protein intake (natural/intact protein and phenylalanine-free protein substitute [PS]) by age, administration frequency and method, monitoring, and type of protein substitute. Data were analysed by European region using descriptive statistics. RESULTS: The amount of total protein (from PS and natural/intact protein) varied according to the European region. Higher median amounts of total protein were prescribed in infants and children in Northern Europe (n=24 centres) (infants <1 year, >2-3g/kg/day; 1-3 years of age, >2-3 g/kg/day; 4-10 years of age, >1.5-2.5 g/kg/day) and Southern Europe (n=10 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, 2 g/kg/day; 4-10 years of age, 1.5-2 g/kg/day), than by Eastern Europe (n=4 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, >2-2.5 g/kg/day; 4-10 years of age, >1.5-2 g/kg/day) and with Western Europe (n=25 centres) giving the least (infants <1 year, >2-2.5 g/kg/day, 1-3 years of age, 1.5-2 g/kg/day; 4-10 years of age, 1-1.5 g/kg/day). Total protein prescription was similar in patients aged >10 years (1-1.5 g/kg/day) and maternal patients (1-1.5 g/kg/day). CONCLUSIONS: The amounts of total protein prescribed varied between European countries and appeared to be influenced by geographical region. In PKU, all gave higher than the recommended 2007 WHO/FAO/UNU safe levels of protein intake for the general population.
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Aminoácidos/administración & dosificación , Caseínas/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Suplementos Dietéticos , Fragmentos de Péptidos/administración & dosificación , Fenilcetonurias/dietoterapia , Adulto , Niño , Preescolar , Europa (Continente) , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Fenilalanina , Encuestas y Cuestionarios , Turquía , Organización Mundial de la SaludRESUMEN
Porous, fluorescent zirconia particles of nearly 380 nm diameter were prepared without template molecules or labeling dyes. The porous structure is the result of aggregation-induced particle formation. The inherent fluorescence is assigned to coordinatively unsaturated Zr4+ ions at the sol-gel derived ZrO2 surface. After physico-chemical characterization of the native zirconia particles carboxyl and/or amine bearing drug molecules (d,l-α-difluoromethylornithine - DFMO, ursolic acid - UA and doxorubicin - DOX) were adsorbed onto their surface, and the products were analyzed with Fourier-transform infrared spectroscopy (FTIR), thermogravimetry (TG), small-angle X-ray scattering (SAXS), fluorimetry and zeta potential vs. pH measurements. We have found that DOX complexes coordinatively unsaturated Zr4+ ions without dislocating them, while carboxyl-bearing drugs interact with basic surface Zr-OH sites eliminating some of the carbonate species. The adsorption of UA at the zirconia surface shifts considerably the isoelectric point of the surface and thus provides kinetic stability to the particles at physiological pH. An in vivo biodistribution study in two healthy dogs performed by SPECT/CT detection after 99mTc labeling of the nanocarriers has shown the possibility of drug delivery application.
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Avascular or aseptic necrosis is a well-defined entity leading to the degradation of cellular elements of the bone. The pathogenesis of osteonecrosis (ON) is still unknown. There are two main types of ON: traumatic or non-traumatic. Several clinical entities could associate with ON, systemic diseases, environmental factors, pregnancy, systemic autoimmune or rheumatic diseases, thrombophilia, corticosteroid therapy, cytotoxic dugs, infections, metabolic and hematologic diseases, etc. Corticosteroids (CS) are still the most frequently used therapeutic options in the early phase and during flares of these diseases. Inflammatory cytokines and antibodies have been described to participate in the pathogenesis of ON. The infiltrative disorders of the bone marrow could also contribute to the development of ON. Hereby, we describe a female patient with NHL followed by SLE in whom ON has developed at least in two localisations. Lupus flare, long-term CS therapy, lymphoma relapse or the presence of antiphospholipid antibodies were excluded. Although the bi-localised ON could be contributed to immunologic factors or trauma, the exact aetiology in this case could not be elucidated.
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Lupus Eritematoso Sistémico/complicaciones , Linfoma de Células B/complicaciones , Osteonecrosis/etiología , Adulto , Femenino , Glucocorticoides/uso terapéutico , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológicoRESUMEN
The clearance of apoptotic cells has an important role in the maintenance of tissue homeostasis and in the protection of tissues from the inflammatory and immunogenic contents of dying cells. A defect in the recognition and phagocytosis of apoptotic cells contributes to the development of chronic inflammation and autoimmune disorders. We have observed that compared with healthy donors, differentiated macrophages from patients with untreated systemic lupus erythematosus (SLE) showed decreased phagocytosis of apoptotic neutrophils. A TaqMan Low Density Array was designed to determine the mRNA expression levels of 95 apopto-phagocytic genes in differentiated non-phagocytosing and phagocytosing macrophages. In the macrophages of clinically and immunoserologically active SLE patients, 39 genes were expressed at lower levels than in the control macrophages. When inactive patients were compared with those with minor immunoserological abnormalities or patients in an immunoserologically active state, a relationship was observed between the altered gene expression profile and the disease state. In the macrophages of patients with engulfing apoptotic cells, an upregulation of genes involved in inflammation, autophagy, and signaling was observed. These results indicate that novel immune-pathological pathways are involved in SLE and suggest targets for potential therapeutic modulation.
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Apoptosis/genética , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/inmunología , Macrófagos/inmunología , Macrófagos/patología , Fagocitosis/genética , Adulto , Antígenos de Superficie/genética , Estudios de Casos y Controles , Diferenciación Celular , Regulación hacia Abajo , Femenino , Humanos , Cadenas beta de Integrinas/genética , Lupus Eritematoso Sistémico/patología , Masculino , Persona de Mediana Edad , Proteínas de la Leche/genética , Monocitos/inmunología , Monocitos/patología , Neutrófilos/inmunología , Neutrófilos/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transcriptoma , Regulación hacia Arriba , Adulto JovenRESUMEN
The aim of this paper was to find possible link between molecular and morphological similarities of 38 Hungarian white grape varieties. Three aspects of morphological and molecular similarity were assessed in the study: comparison of the ordered variety pairs, assessment of molecular and morphological mean similarity differences and separation of varieties into similar groups by divisive cluster analysis to define (DIANA). Molecular similarity was calculated from binary data based on allele sizes obtained in DNA analysis. DNA fingerprints were determined at 9 SSR loci recommended by the European GrapeGen06 project. Morphological similarity was calculated on the basis of quantitative morphological descriptors. Morphological and molecular similarity values were ordered and categorized after pairwise comparison. Overall correlation was found to be weak but case by case assessment of the variety pairs confirmed some coincidence of molecular and morphological similarity. General similarity position of each variety was characterized by Mean Similarity Index (MSI). It was calculated as the mean of n-1 pair similarity values of the variety concerned. Varieties were ordered and compared by the difference of the index. Five varieties had low morphological and high molecular MSI meaning that they share several SSR marker alleles with the others but seems relatively distinct according to the expression of their morphological traits. Divisive cluster analysis was carried out to find similar groups. Eight and twelve cluster solutions proved to be sufficient to distinct varieties. Morphological and molecular similarity groups partly coincided according to the results. Several clusters reflected parent offspring relations but molecular clustering gave more realistic results concerning pedigree.
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Alelos , ADN de Plantas/genética , Sitios Genéticos/fisiología , Repeticiones de Microsatélite/fisiología , Filogenia , Vitis/genética , HungríaRESUMEN
AIMS: This survey was conducted to assess psychosocial problems and functional status among patients on maintenance dialysis in Hungary. METHODS: All adult patients (n = 4,321) receiving maintenance dialysis in the 56 dialysis centers in Hungary in 2006 were approached to participate in a national, cross-sectional survey. Patients completed a brief self-reported questionnaire. Socio-demographic parameters, disease-related information and data about functional status were collected. Self-rated health and depressive symptoms were also assessed. RESULTS: Mean age was 62 ± 14 y; 52% were males. The prevalence of diabetes was 30%. 46% of participants reported having depressive symptoms. Significant functional limitation was frequent. In multivariable regression models, female gender, poor self-reported finances, less education, history of acute myocardial infarction (AMI) or cerebrovascular disease, the presence of visual or hearing impairment and difficulties with basic activities of daily living were independently associated with the presence of depressive symptoms. In a separate model, age, dialysis vintage, history of AMI or cerebrovascular disease, the presence of visual or hearing impairments, difficulties with basic activities of daily living and also having depressive symptoms were independently associated with self-rated health score. CONCLUSIONS: Chronic dialysis patients in Hungary have disadvantaged socioeconomic status, frequent depressive symptoms and many functional limitations. Professional psychosocial help would be particularly important for this underprivileged patient population in addition to high quality dialysis to optimize outcomes.
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Estado de Salud , Diálisis Renal/psicología , Anciano , Estudios Transversales , Depresión/epidemiología , Depresión/etiología , Femenino , Humanos , Hungría , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Análisis Multivariante , Calidad de Vida , Clase Social , Listas de EsperaRESUMEN
Biodegradable polyesters such as poly(lactic-co-glycolic acid) copolymers (PLGA) are preferred materials for drug carrier systems although their surface hydrophobicity greatly limits their use in controlled drug delivery. PLGA thin films on a solid support blended with PEG-containing compound (Pluronic) were used as model systems to study the interfacial interactions with aqueous media. Degree of surface hydrophilization was assessed by wettability, and X-ray photoelectron spectroscopy (XPS) measurements. Protein adsorption behavior was investigated by in situ spectroscopic ellipsometry. The degree of protein adsorption showed a good correlation with the hydrophilicity, and surface composition. Unexpectedly, the layer thickness was found to have a great impact on the interfacial characteristics of the polymer films in the investigated regime (20-200 nm). Thick layers presented higher hydrophilicity and great resistance to protein adsorption. That special behavior was explained as the result of the swelling of the polymer film combined with the partial dissolution of Pluronic from the layer. This finding might promote the rational design of surface modified biocompatible nanoparticles.
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Portadores de Fármacos/química , Ácido Láctico/química , Ácido Poliglicólico/química , Humectabilidad , Adsorción , Materiales Biocompatibles/química , Nanopartículas/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Proteínas/químicaRESUMEN
OBJECTIVES: Disproportionate vitamin D levels may play an important role in the development of certain systemic autoimmune and rheumatic diseases. The aim of the present study was to investigate the prevalence of vitamin D insufficiency in patients with systemic lupus erythematosus (SLE) and to compare serological and clinical parameters in patients with different vitamin D levels from a single centre registry in Central-Eastern Europe. METHODS: A total of 177 patients with SLE were enrolled in the study. 25-Hydroxyvitamin D [25(OH)D] levels were measured by chemiluminescent immunoassay (CLIA). Autoantibody profiles, complement 3 (C3) and C4, clinical symptoms, and disease activity (using the SLE disease activity index, SLEDAI) of the patients were assessed. RESULTS: Vitamin D concentration in the total SLE group investigated was 26.88 ± 13.25 ng/mL. Vitamin D levels were normal (≥ 30 ng/mL) in 18.1% of patients, insufficient (15-30 ng/mL) in 44.6%, and deficient (< 15 ng/mL) in 37.3%. The vitamin levels were significantly reduced in postmenopausal compared to premenopausal patients (p = 0.02). Patients with pericarditis (p = 0.013), neuropsychiatric diseases (p = 0.01), and deep vein thrombosis (p = 0.014) had reduced vitamin D levels. SLEDAI score was significantly increased in patients with reduced vitamin D levels (p = 0.038). Anti-double-stranded (ds)DNA autoantibody concentrations increased from normal to insufficient and further increased from insufficient to deficient patient subsets (p = 0.021). Anti-Smith antigen (anti-Sm) concentrations increased (p < 0.001), C4 levels decreased (p = 0.027), and immunoglobulin (Ig)G concentration increased (p = 0.034) in patients with reduced vitamin D levels. CONCLUSIONS: Our data suggest that vitamin D deficiency in SLE may play a role in perpetuation of the disease.
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Progresión de la Enfermedad , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/fisiopatología , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/fisiopatología , Vitamina D/fisiología , Adolescente , Adulto , Anciano , Autoanticuerpos/sangre , Complemento C4/metabolismo , ADN/inmunología , Suplementos Dietéticos , Femenino , Humanos , Hungría/epidemiología , Inmunoglobulina G/sangre , Lupus Eritematoso Sistémico/sangre , Masculino , Persona de Mediana Edad , Sistema de Registros , Índice de Severidad de la Enfermedad , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/prevención & control , Adulto JovenRESUMEN
Antiphospholipid syndrome (APS) is a distinct clinical entity characterized by arterial and venous thromboembolic events, recurrent fetal loss and the presence of antiphospholipid antibodies in the patients' sera. In primary APS, there is no detectable underlying disease, while overlap APS is associated with clinical syndromes including systemic autoimmune diseases, infections, or malignancies. We carried out a retrospective analysis of serological and clinical manifestations as well as assessed outcome-measures in 165 patients with primary APS. Thrombotic manifestations and possible signs of autoimmune diseases were determined at the time of the diagnosis, followed by the analysis of recurrent thrombotic events and effects of therapy during the follow-up period. Among the 165 patients with primary APS at onset, 105 patients (63%) remained primary APS after a mean 5.2 years of follow-up. In 14% of the patients, subsequently APS became associated with various characteristics of undifferentiated connective tissue disease. Finally 23% of patients evolved into a definitive systemic autoimmune disease during a mean 9.75 years of follow-up. Recurrent thrombotic events were registered in 24% of patients. Our results suggest that primary APS may be considered as a potential early phase of a dynamic transition towards a well-defined systemic autoimmune disease.
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Síndrome Antifosfolípido/fisiopatología , Enfermedades del Tejido Conjuntivo/epidemiología , Trombosis/epidemiología , Adolescente , Adulto , Anciano , Síndrome Antifosfolípido/inmunología , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/etiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Trombosis/etiología , Adulto JovenRESUMEN
The chromosome 1p36 region was previously indicated as a locus for susceptibility to recurrent major depressive disorder based on a linkage study in a sample of 497 sib pairs. We investigated the gamma-aminobutyric acid A (GABA(A)) delta receptor subunit gene, GABRD, as a susceptibility gene to childhood-onset mood disorders (COMD) because of substantial evidence implicating GABAergic dysfunction in mood disorders and the position of this gene near the 1p36 linkage region. Using a sample consisting of 645 Hungarian families with a child/adolescent proband diagnosed with a mood disorder with the onset of the first episode before age 15, we found some evidence for the association of two polymorphisms located within the gene, rs2376805 and rs2376803, as well as significant evidence for biased transmission of the haplotypes of these two markers (global chi(2) test for haplotypes = 12.746, 3 df, P = 0.0052). Furthermore, significant evidence of association was only observed in male subjects (n = 438) when the results were analyzed by sex (chi(2) = 9.000 1 df, P = 0.003 for rs2376805). This was in contrast with the previous linkage findings, as LOD scores exceeding 3 were only in female-female pairs in that study. These findings point to the GABRD gene as a susceptibility gene for COMD; however, this gene may not explain the previous linkage finding.
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Desequilibrio de Ligamiento/genética , Trastornos del Humor/genética , Receptores de GABA-A/genética , Adolescente , Edad de Inicio , Femenino , Genotipo , Haplotipos/genética , Humanos , Hungría/epidemiología , Masculino , Trastornos del Humor/epidemiología , Núcleo Familiar , Polimorfismo de Nucleótido Simple , Factores Sexuales , Ácido gamma-Aminobutírico/metabolismoRESUMEN
BACKGROUND: Low serum vitamin D concentrations have been reported in several autoimmune disorders. OBJECTIVE: To assess whether low serum vitamin D concentrations are related to disease activity of patients with systemic lupus erythematosus (SLE). METHODS: 378 patients from several European and Israeli cohorts were pooled and their disease activity was measured by two different methods: 278 patients had SLE disease activity-2000 (SLEDAI-2K) scores and 100 patients had European Consensus Lupus Activity Measurement (ECLAM) scores. In order to combine the two systems the scores were converted into standardised values (z-scores), enabling univariate summary statistics for the two variables (SLEDAI-2K and ECLAM). The commercial kit, LIAISON 25-OH vitamin D assay (310900-Diasorin) was used to measure serum concentration of 25-OH vitamin D in 378 patients with SLE. RESULTS: A significant negative correlation was demonstrated between the serum concentration of vitamin D and the standardised values (z-scores) of disease activity scores as measured by the SLEDAI-2K and ECLAM scales (Pearson's correlation coefficient r=-0.12, p=0.018). CONCLUSIONS: In a cohort of patients with SLE originating from Israel and Europe vitamin D serum concentrations were found to be inversely related to disease activity.