RESUMEN
In the field of encapsulation, microcapsules containing perfume have emerged as effective vehicles for delivering active ingredients across various applications. The present study employed a multivariate analysis framework to examine polyacrylate microcapsules for household products synthesized using different acrylate monomers. The advanced multivariate approach allowed us to quantify critical properties such as the Molecular Weight between Cross-links (MWc), mechanical attributes, Encapsulation Efficiency (EE), and On-Fabric delivery. It is worth noting that the mechanical properties were gauged using a novel nanoindentation technique, which measures the Rupture Force per unit diameter (RFD). Both Encapsulation Efficiency and On-Fabric delivery were assessed using GC-MS. Our findings identified the optimal microcapsule system as one synthesized with 100% aromatic hexafunctional urethane acrylate, showcasing a 94.3% Encapsulation Efficiency and an optimal RFD of 85 N/mm. This system achieved an exemplary On-Fabric delivery rate of 307.5 nmol/L. In summary, this research provides crucial insights for customizing microcapsule design to achieve peak delivery efficiency. Furthermore, by designing acrylic monomers appropriately, there is potential to reduce the amount of active ingredients used, owing to enhanced delivery efficiency and the optimization of other microcapsule properties. Such advancements pave the way for more environmentally friendly and sustainable production processes in the fast-moving consumer goods industry.
RESUMEN
Measurement of the surface free energy (SFE) of a material allows the prediction of its adhesion properties. Materials can have microscale or sub-microscale surface inhomogeneities, engineered or random, which affect the surface macroscopic behaviour. However, quantitative characterization of the SFE at such length scales remains challenging in view of the variety of instruments and techniques available, the poor knowledge of critical variables and parameters during measurements and the need for appropriate contact models to derive the SFE from the measurements. Failure to characterize adhesion correctly may result in defective components or lengthy process optimization costing billions to industry. Conversely, for planar and homogeneous surfaces, contact angle (CA) measurements are standardized and allow for calculating the SFE using for example the Owen-Wendt model, relying only on the properties of the probing liquids. As such, we assessed and report here a method to correlate quantitative measurements of force-distance curves made with an atomic force microscope (AFM) and with silica and polystyrene (PS) colloidal probe pairs, with quantitative CA measurements and CA-derived SFE values. We measured five surfaces (mica, highly oriented pyrolytic graphite, thermally grown silica on silicon, silicon, and silicon with a super-hydrophobic coating), ranging from hydrophilic to super-hydrophobic, and found an excellent classification of the AFM measurements when these are represented by a set of principal components (PCs), and when both silica and PS colloidal probes are considered together. A regression of the PCs onto the CA measurements allows recovery of the SFE at the length scale of the colloidal probes, which is here ca. 1 micron. We found that once the PC-regression model is built, test sets of only ten AFM force-distance curves are sufficient to predict the local SFE with the calibrated silica and PS colloidal probes.
RESUMEN
The increasing demand on the performance of existing structures, together with their degradation, is among the main drivers towards the development of innovative strengthening solutions. While such solutions are generally aimed at increasing the load-bearing capacity of structural elements, serviceability limit states also play an important role in ensuring the performance and durability of the structure. An experimental campaign was performed to assess the cracking behaviour of reinforced concrete beams strengthened with different typologies of Textile-Reinforced Concrete. The specimens were monitored using Digital Image Correlation (DIC) technology in order to obtain a quantitative evaluation of the evolution of the crack pattern throughout the whole test. Results show the beneficial effects of this retrofitting strategy both at ultimate limit states and serviceability limit states, provide detailed insights on the progression of damage in the specimens and highlight how different parameters impact the cracking behaviour of the tested elements.
RESUMEN
In this chapter we describe: (1) the procedure for the synthesis of four single chain bolaamphiphiles, displaying chains of 12, 16, 20 and 30 methylene units and triphenylphosphonium moieties as headgroups (TPP1-TPP4); (2) the methods used to characterize TPP1-TPP4 spontaneous aggregation in aqueous solution. We illustrate the determination of Krafft point and cac by conductivity measurements and the procedures used to investigate dimensions, morphology, and stability by dynamic and dielectrophoretic laser light scattering, dialysis, transmission electron microscopy, and Raman spectroscopy measurements.
Asunto(s)
Furanos/química , Mitocondrias/efectos de los fármacos , Compuestos Organofosforados/síntesis química , Piridonas/química , Dispersión Dinámica de Luz , Microscopía Electrónica de Transmisión , Estructura Molecular , Compuestos Organofosforados/química , Compuestos Organofosforados/farmacología , Espectrometría Raman , Agua/químicaRESUMEN
Surface free energy (SFE) of titanium surfaces plays a significant role in tissue engineering, as it affects the effectiveness and long-term stability of both active coatings and functionalization and the establishment of strong bonds to the newly growing bone. A new contact-mechanics methodology based on high-resolution non-destructive elastic contacting nanoindentation is applied here to study SFE of micro- and nano-structured titanium surfaces, right after their preparation and as a function of exposure to air. The effectiveness of different surface treatments in enhancing SFE is assessed. A time-dependent decay of SFE within a few hours is observed, with kinetics related to the sample preparation. The fast, non-destructive method adopted allowed for SFE measurements in very hydrophilic conditions, establishing a reliable comparison between surfaces with different properties.
RESUMEN
Silver-based low-emissivity (low-E) coatings are applied on architectural glazing to cost-effectively reduce heat losses, as they generally consist of dielectric/Ag/dielectric multilayer stacks, where the thin Ag layer reflects long wavelength infrared (IR), while the dielectric layers both protect the Ag and act as an anti-reflective barrier. The architecture of the multilayer stack influences its mechanical properties and it is strongly dependent on the residual stress distribution in the stack. Residual stress evaluation by combining focused ion beam (FIB) milling and digital image correlation (DIC), using the micro-ring core configuration (FIB-DIC), offers micron-scale lateral resolution and provides information about the residual stress variation with depth, i.e., it allows depth profiling for both equibiaxial and non-equibiaxial stress distributions and hence can be effectively used to characterize low-E coatings. In this work, we propose an innovative approach to improve the depth resolution and surface sensitivity for residual stress depth profiling in the case of ultra-thin as-deposited and post-deposition annealed Si3N4/Ag/ZnO low-E coatings, by considering different fractions of area for DIC strain analysis and accordingly developing a unique influence function to maintain the sensitivity of the technique at is maximum during the calculation. Residual stress measurements performed using this novel FIB-DIC approach revealed that the individual Si3N4/ZnO layers in the multilayer stack are under different amounts of compressive stresses. The magnitude and orientation of these stresses changes significantly after heat treatment and provides a clear explanation for the observed differences in terms of scratch critical load. The results show that the proposed FIB-DIC combined-areas approach is a unique method for accurately probing non-equibiaxial residual stresses with nano-scale resolution in thin films, including multilayers.
RESUMEN
OBJECTIVE: Autoimmune diseases are associated with psychological distress, resulting in greatly impaired quality of life. Tandem-Psychotherapy comprises trauma-focused psychotherapy with hypnosis and eye movement desensitization and reprocessing (EMDR), followed by supportive-expressive group therapy. The objective was to evaluate whether Tandem-Psychotherapy could reduce psychological distress and improve quality of life. METHODS: In a case-control study, 45 patients were divided into two groups: 24 patients in the therapy group (TG) and 21 in the control group (CG). The autoimmune diagnoses were undifferentiated connective tissue disease (9 patients in TG and 12 in CG), Behçet's syndrome (4/TG, 5/CG), mixed connective tissue disease (3/TG, 1/CG), and other diagnoses (8/TG and 3/CG). At start of treatment point, the patients were evaluated with SCL-90-R for distress and psychological symptoms, Life Stressor Checklist-Revised for relevant trauma, and SF-36 for quality of life. SF36 and SCL-90 were repeated at the end of treatment and at 6-month follow-up. RESULTS: Relevant trauma was found in 24/24 TG patients and in 17/21 CG. Eighteen out of twenty-four TG patients exhibited psychiatric comorbidity with 18/21 in the CG. At start of treatment, all patients exhibited high level of distress (GSI > 0.5) and high Depression and Anxiety scores in SCL-90-R. At end of therapy, the TG exhibited greatly improved GSI (p < 0.001), Depression (p < 0.001), and Anxiety (p < 0.001) compared with the GC; SF-36 scores were also much better in the TG, with significant differences ranging from p = 0.002 to p = 0.0004 at end of therapy. These results persisted at the 6-month follow-up. CONCLUSIONS: Tandem-Psychotherapy is effective for improving psychological symptoms and quality of life in autoimmune patients with high levels of distress and relevant psychiatric comorbidity.Key Points⢠Psychological distress is very high in autoimmune patients, often for previous traumatic experiences.⢠Psychological support must be both trauma-focused and aimed to improve social functioning.⢠Quality of life is very much improved by reducing psychological distress.⢠Tandem-Psychotherapy is feasible because it is contained within a relatively limited time, also for patients with history of trauma.
Asunto(s)
Enfermedades Autoinmunes/psicología , Desensibilización y Reprocesamiento del Movimiento Ocular/métodos , Hipnosis/métodos , Psicoterapia/métodos , Estrés Psicológico/terapia , Adulto , Anciano , Ansiedad/terapia , Estudios de Casos y Controles , Depresión/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Distrés Psicológico , Psicoterapia de Grupo , Calidad de Vida , Estrés Psicológico/psicología , Adulto JovenRESUMEN
HYPOTHESIS: Bolaamphiphiles are characterized by wide polymorphism of their aggregates, due to the connection of the headgroups that renders their investigation very intriguing in several technological applications. Some bolaamphiphiles displaying the triphenylphosphonium motif (TPP-bolaamphiphiles) were previously explored for their ability in crossing the mitochondrial membranes but their colloidal features, which are crucial for the potential development of an effective drug delivery system, were never investigated. EXPERIMENTS: Single chain TPP-bolaamphiphiles, featuring chains of 12, 16, 20 and 30 methylene units, were synthesized and their aggregation features (Krafft point, cac, dimensions, morphology, stability) were investigated by conductivity, dialysis, transmission electron microscopy, Raman spectroscopy, dynamic and dielectrophoretic laser light scattering measurements. FINDINGS: All the TPP-bolaamphiphiles spontaneously self-assemble into vesicles, independently of the chain length. The bolaamphipile with the longest chain forms monodispersed vesicles whereas for the other bolaamphiphiles two distinct populations of vesicles are observed. All vesicles are not equilibrium systems, in particular vesicles formed by the bolaamphiphiles featuring 20 and 30 methylene units result notably stable to dilution thanks to both the tightening of molecular packing at increasing chain length and the progressive reduction of the monomer percentage in U-shaped conformation. These features make these TPP-bolaamphiphiles very attractive as minor components for the development of novel mitochondriotropic liposomes.
Asunto(s)
Furanos/química , Compuestos Organofosforados/química , Piridonas/química , Dimerización , Dispersión Dinámica de Luz , Liposomas/química , Tamaño de la Partícula , Espectrometría Raman , Electricidad Estática , Tensoactivos/química , TermodinámicaAsunto(s)
Anafilaxia/complicaciones , Tratamiento de Urgencia/métodos , Cuerpos Extraños/diagnóstico por imagen , Enfisema Mediastínico/diagnóstico por imagen , Enfisema Subcutáneo/diagnóstico por imagen , Anciano de 80 o más Años , Anafilaxia/tratamiento farmacológico , Diagnóstico Diferencial , Dopamina/administración & dosificación , Esófago/diagnóstico por imagen , Esófago/lesiones , Femenino , Cuerpos Extraños/cirugía , Humanos , Hipotensión/tratamiento farmacológico , Hipotensión/etiología , Infusiones Intravenosas , Enfisema Mediastínico/complicaciones , Enfisema Mediastínico/terapia , Punciones , Enfisema Subcutáneo/etiología , Enfisema Subcutáneo/terapia , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Systemic lupus erythematosus (SLE) is characterized by the production of a wide array of autoantibodies and dysregulation of B cell function. The leukocyte associated Immunoglobulin (Ig)-like receptor (LAIR)1 is a transmembrane molecule belonging to Ig superfamily which binds to different types of collagen. Herein, we have determined the expression and function of LAIR1 on B lymphocyte from SLE patients. LAIR1 expression in peripheral blood B lymphocytes from 54 SLE, 24 mixed connective tissue disease (MCTD), 20 systemic sclerosis (SSc) patients, 14 rheumatoid arthritis (RA) and 40 sex and age matched healthy donors (HD) have been analyzed by immunofluorescence. The effect of LAIR1 ligation by specific monoclonal antibodies, collagen or collagen producing mesenchymal stromal cells from reactive lymph nodes or bone marrow on Ig production by pokeweed mitogen and B cell receptor (BCR)-mediated NF-kB activation was assessed by ELISA and TransAM assay. The percentage of CD20(+) B lymphocytes lacking or showing reduced expression of LAIR1 was markedly increased in SLE and MCTD but not in SSc or RA patients compared to HD. The downregulation of LAIR1 expression was not dependent on corticosteroid therapy. Interestingly, LAIR1 engagement by collagen or collagen-producing mesenchymal stromal cells in SLE patients with low LAIR1 expression on B cells delivered a lower inhibiting signal on Ig production. In addition, NF-kB p65 subunit activation upon BCR and LAIR1 co-engagement was less inhibited in SLE patients than in HD. Our findings indicate defective LAIR1 expression and function in SLE B lymphocytes, possible contributing to an altered control of B lymphocytes behavior.
Asunto(s)
Linfocitos B/metabolismo , Lupus Eritematoso Sistémico/metabolismo , Enfermedad Mixta del Tejido Conjuntivo/metabolismo , Receptores Inmunológicos/metabolismo , Esclerodermia Sistémica/metabolismo , Adulto , Anciano , Linfocitos B/inmunología , Calcio/metabolismo , Estudios de Casos y Controles , Células Cultivadas , Colágeno/metabolismo , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Inmunoglobulina G/metabolismo , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/patología , Activación de Linfocitos , Masculino , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Persona de Mediana Edad , Enfermedad Mixta del Tejido Conjuntivo/inmunología , Enfermedad Mixta del Tejido Conjuntivo/patología , FN-kappa B/metabolismo , Transporte de Proteínas , Esclerodermia Sistémica/inmunología , Esclerodermia Sistémica/patología , Transcripción Genética , Adulto JovenRESUMEN
OBJECTIVE: This prospective pilot study assesses the recurrence rate and severity of abnormal pregnancy outcome (APO), excluding early pregnancy complications, in pregnant patients, without acquired thrombophilia, treated by prophylactic doses of low-molecular-weight heparin (LMWH), independently from their congenital thrombophilic condition. METHODS: We recruited a cohort of 128 pregnant patients with previous APO; 100 of whom with APO and intrauterine growth restriction (IUGR) and 28 with maternal APO only. LMWH treatment was started at recruitment. Composite cross-over recurrence rate IUGR, gestational hypertension, preeclampsia, help syndrome, abruptio placenta were analyzed. The main outcome measure was severe APOs with iatrogenic delivery ≤ 32 weeks of gestation. RESULTS: Median gestational age at LMWH treatment was 20 weeks. Severe APO decreased in treated pregnancies from 45% to 4% (relative risk = 0.3, confidence interval 95% = 0.2-0.8). This value was not significantly different in thrombophilic and nonthrombophilic patients. When severe and minor complications were analyzed altogether, the recurrence rate was 28%. In patients with APO and fetal growth restriction (FGR) in the index pregnancy, newborn weights were significantly better in the treated pregnancy: 1090 g (1035-1145) vs. 850 g (535-1200), p < 0.01. CONCLUSIONS: Prophylactic regimen of LMWH significantly reduced the recurrence rate of severe composite APO in pregnancies affected in the index pregnancy by APO and FGR or small for gestational age newborns. This result was independent from the patients' inherited thrombophilic conditions.
Asunto(s)
Heparina de Bajo-Peso-Molecular/uso terapéutico , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/prevención & control , Resultado del Embarazo/epidemiología , Adulto , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Femenino , Heparina de Bajo-Peso-Molecular/efectos adversos , Humanos , Recién Nacido , Enfermedades del Recién Nacido/epidemiología , Proyectos Piloto , Embarazo , Estudios Prospectivos , Recurrencia , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: Large acute ST-elevation myocardial infarction (STEMI) sometimes leaves extensive ischemic damage despite timely and successful primary angioplasty. This clinical picture of good recanalization with incomplete reperfusion represents a good model to assess the reparative potential of locally administered cell therapy. Thus, we conducted a randomized controlled trial aimed at evaluating the effect of intracoronary administration of CD133 stem cells on myocardial blood flow and function in this setting. METHODS: Fifteen patients with large anterior STEMI, myocardial blush grade 0-1 and more than 50% ST-elevation recovery after optimal coronary recanalization (TIMI 3 flow) with stenting were randomly assigned to receive CD133 cells from either bone marrow (group A) or peripheral blood (group B), or to stay on drug therapy alone (group C). The cells were intracoronary injected within 10-14 days of STEMI. Infarct-related myocardial blood flow (MBF) was evaluated by NH positron emission tomography 2-5 days before cell administration and after 1 year. RESULTS: MBF increased in the infarct area from 0.419 (0.390-0.623) to 0.544 (0.371-0.729) ml/min per g in group A, decreased from 0.547 (0.505-0.683) to 0.295 (0.237-0.472) ml/min per g in group B and only slightly changed from 0.554 (0.413-0.662) to 0.491 (0.453-0.717) ml/min per g in group C (A vs. C: P = 0.023; B vs. C: P = 0.066). Left ventricular volume tended to increase more in groups B and C than in group A, ejection fraction and wall motion score index remained stable in the three groups. CONCLUSION: These findings support the hypothesis that intracoronary administration of bone marrow-derived, but not peripheral blood-derived CD133 cells 10-14 days after STEMI may improve long-term perfusion.
Asunto(s)
Angioplastia Coronaria con Balón , Infarto de la Pared Anterior del Miocardio/terapia , Antígenos CD/análisis , Trasplante de Médula Ósea , Circulación Coronaria , Glicoproteínas/análisis , Miocardio/patología , Péptidos/análisis , Trasplante de Células Madre de Sangre Periférica , Células Madre/inmunología , Antígeno AC133 , Adulto , Análisis de Varianza , Angioplastia Coronaria con Balón/instrumentación , Infarto de la Pared Anterior del Miocardio/diagnóstico , Infarto de la Pared Anterior del Miocardio/fisiopatología , Infarto de la Pared Anterior del Miocardio/cirugía , Ecocardiografía , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Recuperación de la Función , Stents , Volumen Sistólico , Factores de Tiempo , Resultado del Tratamiento , Función Ventricular IzquierdaRESUMEN
Treatment of Hodgkin's lymphoma (HL) is perceived to be relatively straightforward. Consequently, patients are not usually referred to hemato-oncologically specialized centres and are treated locally instead. Comprehensive findings beyond prospective controlled trials are therefore lacking. Clinical data of 209 patients who had received a HL diagnosis were collected. A total of 7 patients received radiotherapy (RT) alone (3%), 75 (35%) were treated with a combination of chemotherapy (CT) and RT and 127 patients received CT alone [mainly doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD)]. Complete response (CR) following first-line treatment was achieved in 178 patients (85%) and in 195 (93%) after salvage treatment. Favorable disease (p=0.000359), limited-stage disease (p=0.0003), involvement of lymph nodes above the diaphragm (p=0.05) and absence of mediastinal bulky tumor involvement positively affected the CR rate following first-line treatment. Out of the 195 patients that achieved CR, 31 relapsed. Male gender (p=0.043) and age over 45 years (p=0.047) were significantly associated with an increased incidence of relapse. Age at diagnosis was the key factor affecting long-term outcome. The event-free survival (EFS) projected at 120 months was 80 and 57% for patients younger and older than 45 years, respectively (p=0.022). The overall survival (OS) projected at 120 months was 92 and 38% for patients younger and older than 45 years, respectively (p=0.00561). A second neoplasia was diagnosed in 8 patients. The development of a tumor in 4 cases (breast, lung and thyroid cancer) was likely RT-related. Only 1 patient not receiving RT developed acute myeloid leukemia. The EFS and OS of the 141 early-stage patients treated with CT + RT (n=62) or with CT alone (n=79) were not statistically different.
RESUMEN
From February 2006 to March 2008, 42 pregnant women homozygous for the 677CT-methylenetetrahydrofolate reductase (MTHFR) allele were recruited in our obstetrics service for pregnancy at risk. All had antithrombotic prophylaxis with low-dose aspirin and/or low-molecular-weight heparin, supplemented with folic acid. In all, 2 women lost the fetus and 4 were lost to follow-up before delivery. A total of 36 women delivered term infants who all underwent transfontanellar ultrasonography within 24 hours of birth. Six (16.6%) had ischemic or hemorrhagic cerebral lesions. No differences were observed in gestational age, birth weight, or umbilical cord pH between the 30 healthy infants and the 6 with cerebral lesions. Neonatal outcomes were negative in spite of maternal folic acid supplementation and antithrombotic prophylaxis during pregnancy. This suggests a relationship between maternal homozygous mutation in the 677CT-MTHFR allele and neonatal cerebral lesions.
Asunto(s)
Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Complicaciones Hematológicas del Embarazo/genética , Trombofilia/genética , Alelos , Peso al Nacer/genética , Ecoencefalografía , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Homocigoto , Humanos , Recién Nacido , Masculino , Embarazo , Resultado del Embarazo , Estudios Prospectivos , Riesgo , Estadísticas no ParamétricasRESUMEN
OBJECTIVE: To identify predictive risk factors for conversion to open splenectomy and postoperative complications in patients undergoing elective laparoscopic splenectomy. BACKGROUND: The laparoscopic approach represents the "gold standard" for splenectomy, but its use in the treatment of splenomegaly and malignant disease is controversial. Factors that influence immediate outcome are clinical, anatomic, and pathologic. METHODS: Univariate and multivariate analyses of data from the Italian Registry of Laparoscopic Surgery of the Spleen, a multicenter database supported by 25 referral centers. Analysis of data (1993-2007) was performed on a series of patients (n = 676) undergoing elective laparoscopic splenectomy. Demographic data, the operative indications, the surgical technique applied, and any intra- and/or postoperative complications with respect to the patients were assessed. Records were analyzed retrospectively using the Student t test, the chi test, and logistic regression. RESULTS: Conversion to open splenectomy was necessary in 39 cases (5.8%). Perioperative deaths occurred in 3 cases (0.4%). There were no complications in 560 patients (82.8%), with a mean hospital stay of 5 days (range, 2-54). Overall, morbidity occurred in 116 patients (17.2%). Multivariate analysis found that the body mass index (P = 0.01) and the presence of hematologic malignancy (P < 0.001) were independent predictors for intraoperative complications and surgical conversion. Spleen longitudinal diameter (P = 0.001) and surgical conversion (P = 0.001) were independent predictors for the occurrence of postoperative complications. CONCLUSIONS: This large multicenter study provides evidence for the significance of predictive risk factors for intra- and postoperative complications in laparoscopic splenic surgery. Besides splenic dimensions, other factors like the patient's habitus and the specific underlying hematologic pathology should be recognized by the surgeon to reduce complications and initiate adequate treatment.
Asunto(s)
Laparoscopía , Esplenectomía/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Complicaciones Posoperatorias/epidemiología , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Esplenectomía/efectos adversos , Resultado del TratamientoRESUMEN
IGHV mutational status and ZAP-70 or CD38 expression correlate with clinical course in B-cell chronic lymphocytic leukaemia (CLL). The three markers may be discordant in the single case and there is no consensus on their combined use in clinical practise. This multicenter study investigated this issue. Two-hundred and sixty-two Binet stage A patients were studied for the three markers. Sixty patients were profiled with HG-U133A gene expression chips. Disease progression was determined by time from diagnosis to treatment (TTT). The probability of being treatment-free at 3 years was significantly shorter in patients with unmutated IGHV genes (IGHVunmut 66% vs. 93%, chi square of log-rank = 30, P < 0.0001), ZAP-70 positive (ZAP-70pos 73% vs. 96%, chi square of log-rank = 8.2, P = 0.004) or CD38-positive cells (CD38pos 68% vs. 91%, chi square of log-rank = 21, P < 0.0001). Cox multivariate regression analysis showed that the three markers had an independent predictive value for TTT of similar power. A prognostic system based on presence of none (low-risk), one (intermediate-risk) or two or three (high-risk) markers was generated. Based on such criteria, 56%, 23% and 21% of cases were clustered in low (HR = 1), intermediate [HR = 2.8, 95% confidence interval (CI) 2.4-5.8] and high-risk group (HR = 8.0, 95% CI 3.9-16.2). Specific transcriptional patterns were significantly associated with risk groups.
Asunto(s)
Genes de las Cadenas Pesadas de las Inmunoglobulinas , Leucemia Linfocítica Crónica de Células B/genética , Mutación , ADP-Ribosil Ciclasa 1/análisis , Anciano , Biomarcadores de Tumor/análisis , Progresión de la Enfermedad , Femenino , Perfilación de la Expresión Génica/métodos , Marcadores Genéticos , Humanos , Región Variable de Inmunoglobulina/genética , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/metabolismo , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Medición de Riesgo/métodos , Proteína Tirosina Quinasa ZAP-70/análisisRESUMEN
We retrospectively reviewed 139 stage I-II HL patients who were diagnosed and followed up in an Italian northern region (Liguria) from 1995 to 2007, and who received either chemotherapy (CT) alone (mainly doxorubicin, bleomycin, vinblastine, and dacarbazine; ABVD) or a combined modality treatment (chemotherapy + radiotherapy, CT + RT). The two therapeutic groups were comparable for clinical and histologic features. Complete remission rate after CT + RT was higher than what was achieved with CT alone (96% vs. 84%, respectively, p = 0.03). Relapse rate (12%) was the same in both groups and disease-free survival curves were comparable (82% and 83%, p = 0.47). The overall survival of the two therapeutic groups is comparable. No second tumors have been reported among patients receiving chemotherapy alone, whereas a second neoplasia has been diagnosed in four patients (in two cases possibly radiotherapy related) in the CT + RT group (5%, p = 0.09) In conclusion, our retrospective study shows that CT + limited RT is an effective and well-tolerated option for early stage Hodgkin's lymphoma, even if the use of RT is associated with a certain risk of developing a second tumor. However, four to six courses of ABVD can lead to similar, optimal, long-term disease control without exposing patients to the risk of a second neoplasia.
Asunto(s)
Antineoplásicos/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/radioterapia , Adolescente , Adulto , Anciano , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/prevención & control , Humanos , Italia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/patología , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: The human leukocyte antigen (HLA) system includes genes involved in graft-vs-host rejection and in immune response. The discovery that HLAs are associated with several diseases led to appealing developments both in basic biomedical research and in clinical medicine, and offered the opportunity to improve the understanding of pathogenesis and classification of diseases, as well as to provide diagnostic and prognostic indicators. The aim of this article is to review the association between HLA alleles and autoimmune digestive disease and its current relationship with modern HLA nomenclature and clinical practice. METHODS: Articles dealing with the association between HLAs and autoimmune digestive disease (including celiac disease, inflammatory bowel disease, autoimmune hepatitis, sclerosing cholangitis and primary biliary cirrhosis) were searched for using Pubmed and SCOPUS databases from earliest records to January 2008. RESULTS: The review has provided two sections. In the first, we explain the basic principles of HLA structure, function, and nomenclature, as an introduction to the second section, which describes current associations between HLA alleles and digestive diseases. The clinical implications of each HLA association are critically discussed. Actually, a clinical role for HLA typing is suggested for only a few conditions, e.g., celiac disease. CONCLUSIONS: The knowledge of current HLA nomenclature and of its association with some digestive diseases such as celiac disease can be useful in clinical practice for diagnostic and prognostic purposes. This can avoid improper HLA typing as well as stressing the need for further studies on other possible clinical applications.
Asunto(s)
Enfermedades Autoinmunes/inmunología , Enfermedades del Sistema Digestivo/inmunología , Antígenos HLA , Enfermedades Autoinmunes/genética , Enfermedad Celíaca/genética , Enfermedad Celíaca/inmunología , Colangitis Esclerosante/genética , Colangitis Esclerosante/inmunología , Enfermedades del Sistema Digestivo/genética , Predisposición Genética a la Enfermedad , Antígenos HLA/genética , Antígenos HLA/inmunología , Hepatitis Autoinmune/genética , Hepatitis Autoinmune/inmunología , Humanos , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/inmunología , Cirrosis Hepática Biliar/genética , Cirrosis Hepática Biliar/inmunologíaRESUMEN
OBJECTIVE: To evaluate the role of vascular endothelial growth factor (VEGF) in accelerated atherosclerosis in patients with Systemic Lupus Erythematosus (SLE). METHODS: We have enrolled 80 SLE female patients and 80 age-matched healthy control females who underwent a structured interview, physical examination, routine laboratory tests, VEGF plasma level determination and B-mode ultrasonography of carotid arteries to determine carotid intima media thickness (IMT). Framingham risk factors for cardiovascular events were also calculated and VEGF plasma levels were correlated with traditional and nontraditional cardiovascular risk factors. RESULTS: SLE was significantly associated with higher mean IMT values (0.74+/-0.15 mm versus 0.59+/-0.12 mm in controls, p<0.001) and higher mean plasma VEGF levels (307.9+/-292.2 pg/mL versus 120.7+/-118.4 pg/mL in controls, p<0.001) independently from age, smoking habits, and Framingham risk factors. A significant correlation was also found between IMT and VEGF values (r=0.25; p<0.001). CONCLUSION: We show that SLE patients have increased mean IMT and VEGF values as compared with healthy age-matched controls and that IMT and VEGF values are independently and directly associated with SLE disease.