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Asma , Dermatitis Atópica , Compuestos Heterocíclicos con 3 Anillos , Rinitis Alérgica , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Asma/tratamiento farmacológico , Asma/complicaciones , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/complicaciones , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Estudios Retrospectivos , Rinitis Alérgica/tratamiento farmacológico , Rinitis Alérgica/complicaciones , Índice de Severidad de la EnfermedadAsunto(s)
COVID-19 , Dermatología , Humanos , Italia/epidemiología , Pandemias , SARS-CoV-2 , Factores de TiempoRESUMEN
INTRODUCTION: This is an Italian single-center retrospective study evaluating safety and efficacy of biologic agents in psoriatic patients with a previous diagnosis of malignant cancer. AIM: Management of moderate and severe psoriasis patients with a past medical history of malignancies could be difficult because biologic agents are historically associated with a presumptive increased risk of neoplastic reactivation or of a new incoming cancer. The aim of this study is to assess the safety of biologics in patients with a previous cancer diagnosis. MATERIAL AND METHODS: The study analyzed 16 moderate to severe psoriasis patients with a diagnosis of malignant cancer in the previous 10 years treated with biologic agents for up to at least 96 weeks. In five of these patients, cancer was diagnosed in the previous 5 years. RESULTS: We observed a rapid decrease in PASI (psoriasis area severity index) reaching a 90% improvement in 100% of patients. Oncologic follow up did not show any worsening or reactivation of cancer during the entire observation period. No new malignancies were observed in the analyzed sample. CONCLUSIONS: Biologic agents in our experience have demonstrated to be safe and effective in psoriatic patients with a past medical history of malignant cancer.
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Terapia Biológica , Neoplasias , Psoriasis , Anticuerpos Monoclonales/uso terapéutico , Humanos , Neoplasias/inducido químicamente , Neoplasias/complicaciones , Psoriasis/patología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Paroxysmal nocturnal haemoglobinuria (PNH) is a haematopoietic disorder characterized by expansion of phosphatidylinositol glycan-A-defective progenitor(s). Immune-dependent mechanisms, likely involving a deranged T cell-dependent autoimmune response, have been consistently associated with the selection/dominance of PNH precursors. Natural killer (NK) lymphocytes might participate in PNH pathogenesis, but their role is still controversial. NK activity is dependent on the balance between activating and inhibiting signals. Key component in such regulatory network is represented by killer immunoglobulin-like receptors (KIR). KIR are also involved in the regulation of adaptive cytotoxic T cell response and associated with autoimmunity. This study investigated on the frequency of KIR genes and their known human leukocyte antigen (HLA) ligands in 53 PNH Italian patients. We observed increased frequency of genotypes characterized by ≤2 activating KIR as well as by the presence of an inhibitory/activating gene ratio ≥3.5. In addition, an increased matching between KIR-3DL1 and its ligand HLA-Bw4 was found. These genotypes might be associated with lower NK-dependent recognition of stress-related self molecules; this is conceivable with the hypothesis that an increased availability of specific T cell targets, not cleared by NK cells, could be involved in PNH pathogenesis. These data may provide new insights into autoimmune PNH pathogenesis.
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Antígenos HLA-B/genética , Hemoglobinuria Paroxística/genética , Células Asesinas Naturales/inmunología , Receptores KIR3DL1/genética , Linfocitos T/inmunología , Adulto , Alelos , Estudios de Casos y Controles , Femenino , Expresión Génica , Frecuencia de los Genes , Antígenos HLA-B/inmunología , Haplotipos , Hemoglobinuria Paroxística/inmunología , Hemoglobinuria Paroxística/patología , Humanos , Italia , Células Asesinas Naturales/metabolismo , Células Asesinas Naturales/patología , Ligandos , Masculino , Persona de Mediana Edad , Tipificación Molecular , Receptores KIR3DL1/inmunología , Transducción de Señal , Linfocitos T/metabolismo , Linfocitos T/patologíaRESUMEN
Patients have a privileged perspective on health care quality, thus it is important to obtain from them judgments about offered services. Currently, there are no well developed quality monitoring systems related to the patient's perspective, though Istat data sources would b helpful on this issues. We performed a descriptive analysis relating to the satisfaction degree of Italian population for hospital admissions between 1997and 2009. Data were taken from the Istat Multipurpose analysis on some aspect of daylife. Our results show a positive appraisal for medical and nursing assistance; however the rating for the quality of food is lower Our analysis would give a contribution to the appraisal of an outstanding dimension of patients' appraisal of quality of care among the Regions, by considering the implementation of devolution in healthcare since 2001.
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Atención a la Salud/normas , Satisfacción del Paciente/estadística & datos numéricos , Hospitalización , Humanos , Italia , Factores de TiempoRESUMEN
The transit in vivo dosimetry performed by the Electronic Portal Imaging Device (EPID), avoids the problem of solid-state detector positioning on the patient. Moreover, the dosimetric characterization of the recent Elekta aSi EPIDs in terms of signal stability and linearity enables these detectors adaptable for the transit in vivo dosimetry with 6, 10 and 15 MV photon beams. However, the implementation of the EPID transit dosimetry requires several measurements. Recently, the present authors have developed an in vivo dosimetry method for the 3D CRT based on correlation functions defined by the ratios between the transit signal, s(t) (w,L), by the EPID and the phantom mid-plane dose, D(m)(w,L), at the Source to Axis Distance (SAD) as a function of the phantom thickness, w, and the square field dimensions, L. When the phantom mid-plane was positioned at distance d from the SAD, the ratios st(w,L)/s't(d,w,L), were used to take into account the variation of the scattered photon contributions on the EPID as a function of, d and L. The aim of this paper was the implementation of a procedure that uses generalized correlation functions obtained by nine Elekta Precise linac beams. The procedure can be used by other Elekta Precise linacs equipped with the same aSi EPIDs assuring the stabilities of the beam output factors and the EPID signals. The calibration procedure of the aSi EPID here reported avoids measurements in solid water equivalent phantoms needed to implement the in vivo dosimetry method in the radiotherapy center. A tolerance level ranging between ±5% and ±6% (depending on the type of tumor) was estimated for the comparison between the reconstructed isocenter dose, D(iso) and the computed dose D(iso,TPS) by the treatment planning system (TPS).
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Radiometría , Dosificación Radioterapéutica , Radioterapia Conformacional/métodos , Calibración , Humanos , Neoplasias/radioterapia , Fantasmas de Imagen , Radiometría/instrumentación , Radiometría/métodos , Planificación de la Radioterapia Asistida por Computador/instrumentación , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Conformacional/instrumentación , AguaRESUMEN
The lymphatic system has an early development in the embryo. Usually, its development is complete by the 40th postconceptional day. If this connection fails to develop, lymphatic stasis and dilatation of the lymphatic channels may occur, causing a number of pathologies such as: lymphangiomas, lymphangiectasis and cystic hygromas. Prenatal diagnosis can be made during the first trimester of pregnancy by ultrasonographic examination. A case of a twin pregnancy associated with cystic hygroma and bilateral hypoplasia of lower and upper limbs of both foetuses without chromosomal abnormalities is reported.
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Enfermedades en Gemelos , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Linfangioma Quístico/diagnóstico por imagen , Adulto , Femenino , Feto , Humanos , Deformidades Congénitas de las Extremidades Inferiores/diagnóstico por imagen , Embarazo , Ultrasonografía Prenatal , Deformidades Congénitas de las Extremidades Superiores/diagnóstico por imagenRESUMEN
INTRODUCTION: Alzheimer's disease is characterized by a general and progressive dementia and by the presence of beta-amiloide deposits. OBJECTIVE: The levels of neuronal nitric oxide synthase (NOS) and protein kinase C (PKC), and the relationship between these proteins, the free-radical theory and the high level of beta-amiloide in Alzheimer's disease, have been studied. MATERIAL AND METHODS: The study has been performed in samples of Alzheimer's disease (superior, medial and inferior regions of temporalis gyrus) from control individuals and patients. The tissue was homogenized and the proteins were analyzed using monoclonal antibodies for NOS and PKC. RESULTS: Lower levels of neuronal constitutive NOS (37% +/- 2.5 and 52% +/- 3.0) in Alzheimer's disease derived superior and inferior temporalis gyrus, respectively, were observed. No changes were found in superior temporalis gyrus in PKC isoforms levels, involved in the processing for the beta-amiloide precursor protein. In the medial and inferior regions the PKC level was 5% +/- 0.5 to 22% +/- 3.0. CONCLUSIONS: These results could be related with an imbalance in the superoxide/nitric oxide ratio as a consequence of the non-inhibition of lipoxygenase, and with a neurotransmission dysfunction due, all this, to the decrease of nitric oxide levels. On the other hand, a relationship could be proposed between the high concentrations of beta-amiloide and the decrease in PKC levels in Alzheimer's disease.
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Enfermedad de Alzheimer/enzimología , Óxido Nítrico Sintasa/análisis , Óxido Nítrico Sintasa/metabolismo , Proteína Quinasa C/análisis , Proteína Quinasa C/metabolismo , Lóbulo Temporal/química , Lóbulo Temporal/metabolismo , Anciano , Enfermedad de Alzheimer/patología , Precursor de Proteína beta-Amiloide/metabolismo , Anticuerpos Monoclonales , Atrofia/patología , Femenino , Humanos , Mediciones Luminiscentes , Masculino , Neuronas/química , Neuronas/enzimología , Lóbulo Temporal/patologíaRESUMEN
This study examined the temporal relationships of endothelin-1-stimulated rabbit platelets tyrosine phosphorylated proteins. The effect of endothelin-1 on tyrosine phosphorylation was dose- and time-dependent and caused a rapid tyrosine phosphorylation of three groups of proteins in the molecular mass range 70-100 kDa, 100-150 kDa and 150-200 kDa. Significant protein tyrosine phosphatase activity and amount were found to be associated with the cytoskeleton of endothelin-1-stimulated rabbit platelets. Under our experimental conditions, translocation from the cytosolic fraction to the cytoskeleton reached its highest levels within 10-20 sec of endothelin-1 stimulation. Endothelin-1-induced translocation of protein tyrosine phosphatase, associated with the increase in its activity was demonstrated by immunoblotting and immunoelectron microscopy.
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Plaquetas/fisiología , Endotelina-1/farmacología , Proteínas Tirosina Fosfatasas/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Transporte Biológico/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Fosforilación , Activación Plaquetaria/efectos de los fármacos , Conejos , Factores de Tiempo , Tirosina/metabolismoRESUMEN
Protein tyrosine phosphorylation, modulated by the rate of both protein tyrosine kinase and protein tyrosine phosphatase activities, is critical for cellular signal transduction cascades. We report that endothelin-1 stimulation of rabbit platelets resulted in a dose- and time-dependent tyrosine phosphorylation of four groups of proteins in the molecular mass ranges of 50, 60, 70-100 and 100-200 kDa and that one of these corresponds to focal adhesion kinase. This effect is also related to the approximately 60% decrease in protein tyrosine phosphatase activity. Moreover, this inhibited activity was less sensitive to orthovanadate. In the presence of forskolin that increases the cAMP level a dose-dependent inhibition of the endothelin-stimulated tyrosine phosphorylation of different protein substrates and a correlation with an increase in the protein tyrosine phosphatase activity (11.6-fold compared to control) have been found. Further studies by immunoblotting of immunoprecipitated soluble fraction with anti-protein tyrosine phosphatase-1C from endothelin-stimulated platelets have demonstrated that the tyrosine phosphorylation of platelet protein tyrosine phosphatase-1C is correlated with the decrease in its phosphatase activity. As a consequence, modulation and regulation by endothelin-1 in rabbit platelets can be proposed through a cAMP-dependent pathway and a tyrosine phosphorylation process that may affect some relevant proteins such as focal adhesion kinase.
Asunto(s)
Plaquetas/enzimología , Endotelina-1/farmacología , Proteínas Tirosina Fosfatasas/metabolismo , Animales , Plaquetas/efectos de los fármacos , Moléculas de Adhesión Celular/sangre , Colforsina/farmacología , AMP Cíclico/sangre , Proteína-Tirosina Quinasas de Adhesión Focal , Péptidos y Proteínas de Señalización Intracelular , Fosforilación , Fosfotirosina/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Proteína Tirosina Fosfatasa no Receptora Tipo 6 , Proteínas Tirosina Fosfatasas/sangre , Proteínas Tirosina Quinasas/sangre , Conejos , Transducción de Señal , Vanadatos/farmacologíaRESUMEN
Activation of platelets by different agents results in the increased tyrosine phosphorylation of several substrate proteins. Thus, the effect of endothelin-1 on the stimulation of tyrosine phosphorylation in rabbit platelets can be inhibited by preincubation with forskolin, which increase the cAMP level. However, incubations of platelets with 8-Bromo-cGMP showed lower inhibitory effect. Forskolin produced a dose-dependent inhibition on three different protein substrates, with an IC50 of approximately 12.8, 4.0 and 8.0 microM in the three molecular mass ranges of 50, 60 and 100-200 kDa, respectively. These results show that the endothelin-stimulated tyrosine phosphorylation in rabbit platelets can be regulated by a novel pathway of platelet signal transduction in which the cAMP level could be more relevantly involved than cGMP in some molecular mass ranges of tyrosine phosphorylated proteins.
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Plaquetas/metabolismo , AMP Cíclico/farmacología , GMP Cíclico/farmacología , Endotelinas/farmacología , Fosfotirosina/sangre , Animales , Plaquetas/efectos de los fármacos , Colforsina/administración & dosificación , Colforsina/farmacología , GMP Cíclico/administración & dosificación , GMP Cíclico/análogos & derivados , Relación Dosis-Respuesta a Droga , Peso Molecular , Fosforilación , Conejos , Transducción de SeñalRESUMEN
Arterial blood pressure was recorded in 15 hypertensive patients with ischemic cerebrovascular disease in the post-acute stage and under treatment with nicardipine, a drug with tropism for the muscular cells of cerebral vessels. Blood pressure was measured at rest and during rehabilitation sessions. Patients were periodically assessed by Doppler examination of the cerebral vessels in order to evaluate the effect of the drug on vascular resistance. A significant reduction of blood pressure was observed without changes in pulse rate and without significant side effects. Hemodynamic parameters showed reduced resistance of cerebral vessels. These findings confirm the need for accurate control of arterial blood pressure during neurologic rehabilitation; they also bear out the efficacy and safety of nicardipine in this clinical situation.