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PURPOSE: The aim of our retrospective study is to analyze how spinopelvic dissociations (SPDs) were treated in a single center trying to better understand how to improve surgical and non-surgical options. METHODS: Twenty patients of a single center surgically treated for SPDs between 2013 and 2021 were retrospectively included in this study. Three surgical techniques have been used: modified triangular stabilization, triangular stabilization and double iliac screws stabilization. Follow-up was assessed for up to 11.6 ± 9.9 months through ODI, MRS, NRS, IIEF or FSFI, a CT scan and whole spine X-ray examination. RESULTS: Twenty patients were admitted to our ER for traumatic spinopelvic dissociation. Surgical treatment for spinopelvic dissociation has been performed on average 11.5 ± 6.7 days after the trauma event. Eighteen fractures were C3 type and two C2 types. Neurological examination showed nerve root injury (N2) in 5 patients, incomplete spinal cord injury (N3) in 4 patients and cauda equina syndrome in two patients (N4). In case of neurologic deficits, routinary nerve decompression was performed. Three different surgical techniques have been used: 8 triangular fixations (Group 1), 6 modified triangular stabilization (Group 2) and 6 double iliac screws triangular fixation (Group 3). CONCLUSION: In patients with post-traumatic neurological deficit, decompression surgery and fracture reduction seem to be associated with clinical improvement; however, sexual disorders seem to be less responsive to the treatment. Some open stabilization techniques, such as the double iliac screw, could help in restoring the sagittal balance in case of severe deformities.
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Fracturas Óseas , Fracturas de la Columna Vertebral , Humanos , Estudios Retrospectivos , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/cirugía , Fracturas de la Columna Vertebral/complicaciones , Fijación Interna de Fracturas/métodos , Sacro/cirugía , Fracturas Óseas/complicaciones , Resultado del TratamientoRESUMEN
A limit analysis numerical approach oriented to predict the peak/collapse load of human proximal femur, under two different loading conditions, is presented. A yield criterion of Tsai-Hu-type, expressed in principal stress space, is used to model the orthotropic bone tissues. A simplified human femur 3D model is envisaged to carry on numerical simulation of in-vitro tests borrowed from the relevant literature and to reproduce their findings. A critical discussion, together with possible future developments, is presented.
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Huesos , Fémur , Simulación por Computador , Análisis de Elementos Finitos , Humanos , Técnicas In Vitro , Modelos Biológicos , Estrés MecánicoRESUMEN
Phenotypic intermediacy is an indicator of putative hybrid origin and has provided the main clues to discovering hybrid plants in nature. Mandevilla pentlandiana and M. laxa (Apocynaceae) are sister species with clear differences in floral phenotype and associated pollinator guilds: diurnal Hymenoptera and nocturnal hawkmoths, respectively. The presence of individuals with intermediate phenotypes in a wild population raises questions about the roles of visual and olfactory signals (i.e. corolla morphology and floral fragrances) as barriers to interbreeding, and how the breakdown of floral isolation occurs. We examined phenotypic variation in a mixed Mandevilla population, analysing the chemical composition of floral fragrances, characterising floral shape through geometric morphometrics and assessing individual grouping through taxonomically relevant traits and an unsupervised learning algorithm. We quantified the visitation frequencies of floral visitors and tracked their foraging movements using pollen analogues. The presence of morphologically intermediate individuals and pollen analogue movement suggested extensive hybridisation between M. laxa and M. pentlandiana, along with asymmetrical rates of backcrossing between these putative hybrids and M. laxa. Floral volatiles from putative hybrid individuals showed a transgressive phenotype, with additional compounds not emitted by either parental species. Our results suggest the presence of a hybrid swarm between sympatric M. pentlandiana and M. laxa and indicate that initial hybridisation events between these parental species are rare, but once they occur, visits between putative hybrids and M. laxa are common and facilitate continued introgression.
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Apocynaceae/anatomía & histología , Flores/anatomía & histología , Polinización , Aislamiento Reproductivo , Animales , Hibridación Genética , Himenópteros , Mariposas Nocturnas , Odorantes , Fenotipo , Polen/fisiología , Especificidad de la EspecieRESUMEN
BACKGROUND AND PURPOSE: Mitochondrial neurogastrointestinal encephalopathy is a rare disorder due to recessive mutations in the thymidine phosphorylase gene, encoding thymidine phosphorylase protein required for mitochondrial DNA replication. Clinical manifestations include gastrointestinal dysmotility and diffuse asymptomatic leukoencephalopathy. This study aimed to elucidate the mechanisms underlying brain leukoencephalopathy in patients with mitochondrial neurogastrointestinal encephalopathy by correlating multimodal neuroradiologic features to postmortem pathology. MATERIALS AND METHODS: Seven patients underwent brain MR imaging, including single-voxel proton MR spectroscopy and diffusion imaging. Absolute concentrations of metabolites calculated by acquiring unsuppressed water spectra at multiple TEs, along with diffusion metrics based on the tensor model, were compared with those of healthy controls using unpaired t tests in multiple white matters regions. Brain postmortem histologic, immunohistochemical, and molecular analyses were performed in 1 patient. RESULTS: All patients showed bilateral and nearly symmetric cerebral white matter hyperintensities on T2-weighted images, extending to the cerebellar white matter and brain stem in 4. White matter, N-acetylaspartate, creatine, and choline concentrations were significantly reduced compared with those in controls, with a prominent increase in the radial water diffusivity component. At postmortem examination, severe fibrosis of brain vessel smooth muscle was evident, along with mitochondrial DNA replication depletion in brain and vascular smooth-muscle and endothelial cells, without neuronal loss, myelin damage, or gliosis. Prominent periependymal cytochrome C oxidase deficiency was also observed. CONCLUSIONS: Vascular functional and histologic alterations account for leukoencephalopathy in mitochondrial neurogastrointestinal encephalopathy. Thymidine toxicity and mitochondrial DNA replication depletion may induce microangiopathy and blood-brain-barrier dysfunction, leading to increased water content in the white matter. Periependymal cytochrome C oxidase deficiency could explain prominent periventricular impairment.
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Enfermedades de los Pequeños Vasos Cerebrales/patología , Leucoencefalopatías/patología , Mitocondrias/patología , Encefalomiopatías Mitocondriales/patología , Adulto , Encéfalo/metabolismo , Encéfalo/patología , Enfermedades de los Pequeños Vasos Cerebrales/etiología , Enfermedades de los Pequeños Vasos Cerebrales/metabolismo , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Leucoencefalopatías/etiología , Leucoencefalopatías/metabolismo , Masculino , Mitocondrias/metabolismo , Encefalomiopatías Mitocondriales/complicaciones , Encefalomiopatías Mitocondriales/metabolismoRESUMEN
BACKGROUND: Hemiplegic Celebral Palsy (CP) children commonly use AFO orthoses as walking aids. It is known that AFOs may have a detrimental effect on gait. To enhance mechanical properties of AFOs we developed an innovative, custom-made, carbon, ankle-foot orthosis (Ca.M.O) which offers the opportunity to tune its response to the patient's gait characteristics and/or functional maturity. OBJECTIVE: To assess the efficacy of Ca.M.O. in improving gait in a group of hemiplegic CP children and to compare its performances with those of commonly prescribed AFO. METHODS: A clinical and instrumental gait analysis was performed on a group of 15 spastic hemiplegic children (WINTERS-GAGE type I-II) walking barefoot, with commonly prescribed AFOs and with Ca.M.O.Temporal, kinematic and kinetic data were collected with an 8 cameras optoelectronic system and 2 force plates. RESULTS: Studied variables were comparable walking with Ca.M.O. and with the commonly prescribed AFO and are significantly different (pâ<â0.01) with respect to barefoot condition. CONCLUSIONS: Both types of orthoses normalize the kinematics of the first and second ankle rocker. The main advantage of Ca.M.O. is its modularity that allows to tune its effect on gait in relationship with the progress or involution of the child's functional development.
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Carbono , Parálisis Cerebral/rehabilitación , Ortesis del Pié/tendencias , Hemiplejía/rehabilitación , Invenciones/tendencias , Parálisis Cerebral/fisiopatología , Niño , Preescolar , Femenino , Pie/fisiopatología , Marcha/fisiología , Hemiplejía/fisiopatología , Humanos , Masculino , Caminata/fisiologíaRESUMEN
Renin-angiotensin system (RAS) inhibitors are currently advocated as the first line approach for diabetic patients with high blood pressure, particularly if early signs of renal damage are manifest. This mostly relies on the supposed benefits of these drugs, either achieved indirectly by blood pressure lowering or directly by pleiotropic effects, on cardiovascular and renal outcomes. Yet, data from large randomized controlled trials and independent meta-analyses seem to raise some concerns on the compelling use of RAS-inhibitors in the whole diabetic population as improvements in cardiovascular and renal endpoints may not be as definite as generally believed. Furthermore, the risk of adverse events, such as hyperkalemia, deserves more attention in diabetic patients.In this brief review we aimed at summarizing the most relevant available evidence on "negative" or "null" effects of RAS-inhibitors on clinical outcomes in diabetic patients, providing reasons for a "personalized" rather than generalized use of these drugs according to individual characteristics.
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Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Nefropatías Diabéticas/tratamiento farmacológico , Receptores de Superficie Celular/antagonistas & inhibidores , Sistema Renina-Angiotensina/efectos de los fármacos , ATPasas de Translocación de Protón Vacuolares/antagonistas & inhibidores , HumanosRESUMEN
We report the rational design, based on docking simulations, and synthesis of the first fluorescent and selective probe of GPER for bioimaging purposes and functional dissecting studies. It has been conceived as a Bodipy derivative and obtained by accessible and direct synthesis. Its optical properties have been measured in different solvents, showing insensitivity to their polarity. Its binding to GPER was achieved by competition assays with [3H]E2 and [5,6-3H] nicotinic acid in ER-negative and GPER-positive SkBr3 breast cancer cells. SkBr3 cells, transfected with a GPER expression vector containing a FLAG tag, were used to confirm that the fluorophore binds to GPER in a specific manner.
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Compuestos de Boro/química , Técnicas de Química Analítica/métodos , Colorantes Fluorescentes/química , Receptores Acoplados a Proteínas G/análisis , Sitios de Unión , Células Cultivadas , Técnicas de Química Analítica/instrumentación , Colorantes Fluorescentes/síntesis química , Humanos , Modelos Moleculares , Estructura MolecularRESUMEN
INTRODUCTION: This study aimed to determine whether a controlled portal blood arterialization by a liver extracorporeal device (L.E.O2 NARDO) is effective in treating acute hepatic failure (AHF) induced in swine by carbon tetrachloride (CCl4) administration. MATERIALS AND METHODS: Sixteen swine with AHF induced by intraperitoneal injection of CCl4 in oil solution were randomly divided into 2 groups: animals that received L.E.O2 NARDO treatment 48 hours after the intoxication (study group; n = 8); and animals that were sham operated 48 hours after the intoxication (control group; n = 8). Blood was withdrawn from the iliac artery and reversed in the portal venous system by an interposed extracorporeal device. Each treatment lasted 6 hours. The survival was assessed at 5 days after L.E.O2 NARDO treatment or sham operation. In both groups blood samples were collected for biochemical analysis at different study time and liver biopsies were performed 48 hours after intoxication and at humane killing. RESULTS: In the study group decreased transaminases levels and a more rapid international normalized ratio (INR) recover were detected as compared with the control group. Six animals of the study group (75%) versus 1 animal (12.5%) of the control group survived at 5 days after surgery with a statistically significant difference (P < .05). Liver biopsies performed at humane killing showed damaged areas of the livers reduced in the study group compared with biopsies of the control group. CONCLUSIONS: Arterial blood supply in the portal system through the L.E.O2 NARDO device is easily applicable, efficacious, and safe in a swine model of AHF induced by CCl4 intoxication.
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Circulación Extracorporea/métodos , Fallo Hepático Agudo/cirugía , Regeneración Hepática , Hígado/crecimiento & desarrollo , Vena Porta/cirugía , Animales , Biopsia , Intoxicación por Tetracloruro de Carbono/fisiopatología , Modelos Animales de Enfermedad , Oxigenación por Membrana Extracorpórea/métodos , Femenino , Relación Normalizada Internacional , Hígado/irrigación sanguínea , Hígado/patología , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/enzimología , Pruebas de Función Hepática , Distribución Aleatoria , Porcinos , Transaminasas/metabolismoRESUMEN
BACKGROUND & AIMS: We have recently reported that a polymorphism (rs734553) in a major urate transporter gene (GLUT9) is a strong predictor of incident renal events in stage 2-5 CKD patients implying that life-time exposure to high uric acid levels may be causally implicated in CKD progression. Since disturbed NO bioavailability is a major pathway whereby high uric may cause renal damage, we tested the interaction between the major endogenous inhibitor of NO synthase, asymmetric-dimethylargine (ADMA), and the rs734553 polymorphism for CKD progression in the same cohort. METHODS & RESULTS: Over a 29 ± 11 months follow-up the risk for incident renal events was higher in patients harboring the risk allele of the polymorphism (T) as compared to those without the risk allele (HR: 2.35, 95% CI: 1.25-4.42, P = 0.008) (p = 0.01). Similarly, patients with ADMA > median value had an increased risk for the same outcome (HR: 1.37, 95% CI: 1.06-1.76, P = 0.016). Interaction analysis showed a strong amplification by ADMA of the risk for renal events associated to the T allele because in adjusted (P = 0.016) and bootstrapping validated (P = 0.020) analyses the risk excess associated to this allele was progressively higher across increasing ADMA levels. CONCLUSIONS: The rs734553 polymorphism, the strongest genetic marker of uric acid levels discovered so far, interacts with ADMA in determining the risk for CKD progression in CKD patients. This synergic interaction conforms to biological knowledge indicating that disturbed NO bio-availability is a critical pathway whereby life time exposure to high uric acid may engender renal damage.
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Arginina/análogos & derivados , Marcadores Genéticos , Proteínas Facilitadoras del Transporte de la Glucosa/genética , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/genética , Ácido Úrico/sangre , Anciano , Alelos , Arginina/sangre , Proteína C-Reactiva/metabolismo , Calcio/sangre , Estudios de Casos y Controles , Estudios de Cohortes , Creatinina/sangre , Progresión de la Enfermedad , Determinación de Punto Final , Femenino , Estudios de Seguimiento , Proteínas Facilitadoras del Transporte de la Glucosa/metabolismo , Hemoglobinas/metabolismo , Humanos , Hiperuricemia/sangre , Hiperuricemia/genética , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Polimorfismo de Nucleótido Simple , Modelos de Riesgos Proporcionales , Albúmina Sérica/metabolismoRESUMEN
INTRODUCTION: Several near-infrared spectroscopy oximeters are commercially available for clinical use, with lack of standardization among them. Accordingly, cerebral oxygen saturation thresholds for hypoxia/ischemia identified in studies conducted with INVOS(TM) models do not necessarily apply to other devices. In this study, the measurements made with both INVOS(TM) and EQUANOX(TM) oximeters on the forehead of 10 patients during conventional cardiac surgery are directly compared, in order to evaluate the interchangeability of these two devices in clinical practice. METHODS: Cerebral oxygen saturation measurements were collected from both INVOS(TM) 5100C and EQUANOX(TM) 7600 before anesthetic induction (baseline), two minutes after tracheal intubation, at cardiopulmonary bypass onset/offset, at aortic cross-clamping/unclamping, at the end of surgery and whenever at least one of the two devices measured a reduction in cerebral oxygen saturation equal to or greater than 20% of the baseline value. Bland-Altman analysis was used to compare the bias and limits of agreement between the two devices. RESULTS: A total of 140 paired measurements were recorded. The mean bias between INVOS(TM) and EQUANOX(TM) was -5.1%, and limits of agreement were ±16.37%. Considering the values as percent of baseline, the mean bias was -1.43% and limits of agreement were ±16.47. A proportional bias was observed for both absolute values and changes from baseline. CONCLUSIONS: INVOS(TM) and EQUANOX(TM) do not seem to be interchangeable in measuring both absolute values and dynamic changes of cerebral oxygen saturation during cardiac surgery. Large investigations, with appropriate design, are needed in order to identify any device-specific threshold.
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BACKGROUND AND AIMS: Pro-inflammatory molecules produced by adipose tissue have been implicated in the risk of cardiovascular (CV) disease in obesity. We investigated the expression profile of 19 pro-inflammatory and seven anti-inflammatory genes in subcutaneous adipose tissue (SAT) and in visceral adipose tissue (VAT) in 44 severely obese individuals who underwent bariatric surgery. METHODS AND RESULTS: SAT and VAT expressed an identical series of pro-inflammatory genes. Among these genes, 12 were significantly more expressed in SAT than in VAT while just one (IL18) was more expressed in VAT. The remaining genes were equally expressed. Among pro-inflammatory cytokines, both IL6 and IL8 were about 20 times more intensively expressed in SAT than in VAT. The expression of nine genes was highly associated in SAT and VAT. Only for three pro-inflammatory cytokines (IL8, IL18, SAA1) in SAT the gene expression in adipose tissue associated with the circulating levels of the corresponding gene products while no such an association was found as for VAT. CONCLUSIONS: The expression of critical pro-inflammatory genes is substantially higher in SAT than in VAT in individuals with morbid obesity. The variability in circulating levels of pro-inflammatory cytokines is, in small part and just for three pro-inflammatory cytokines, explained by underlying gene expression in SAT but not in VAT. These results point to a compartment-specific adipose tissue contribution to inflammation in obesity and indicate that abdominal SAT contributes more than VAT to the pro-inflammatory milieu associated with severe obesity.
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Citocinas/genética , Inflamación/genética , Grasa Intraabdominal/metabolismo , Obesidad Mórbida/genética , Grasa Subcutánea/metabolismo , Adulto , Cirugía Bariátrica , Índice de Masa Corporal , Citocinas/metabolismo , Femenino , Expresión Génica , Humanos , Inflamación/metabolismo , Interleucina-16/genética , Interleucina-16/metabolismo , Interleucina-18/genética , Interleucina-18/metabolismo , Masculino , Persona de Mediana Edad , Obesidad Mórbida/cirugía , Proteína Amiloide A Sérica/genética , Proteína Amiloide A Sérica/metabolismoAsunto(s)
Atropina , Medicación Preanestésica , Androstanoles/antagonistas & inhibidores , Androstanoles/farmacología , Atropina/administración & dosificación , Atropina/efectos adversos , Atropina/farmacología , Bradicardia/prevención & control , Contraindicaciones , Interacciones Farmacológicas , Humanos , Trastornos de la Memoria/inducido químicamente , Isquemia Miocárdica/inducido químicamente , Isquemia Miocárdica/fisiopatología , Medicación Preanestésica/tendencias , Rocuronio , Salivación/efectos de los fármacos , Taquicardia/inducido químicamenteRESUMEN
INTRODUCTION: Systemic sclerosis (SSc) is a rare conjunctive tissue disorder characterized by fibrosis of the skin and internal organs, and vascular obliteration phenomena. Patients with SSc often experience elevated symptoms of psychological distress, determined by the disfiguration, the pain, the fatigue sensation, and the difficult in daily life occupations. The characteristics of the disease may influence the perceived quality of life (QoL) in people with SSc. METHODS: This is a narrative review aiming to define the amount of impairment of Quality of Life in patients with Systemic Sclerosis and the component of this impairment due to depressive or other psychiatric symptoms. The search of the significant articles was carried out in PubMed for the key words "Psychiatric symptoms and Systemic Sclerosis"; "Quality of life and Systemic Sclerosis"; "Depressive Disorders and Systemic Sclerosis". RESULTS: Psychiatric symptoms are frequents in patients with SSc, but pain, fatigue, disability, body changes don't appear to explain the high prevalence of psychiatric comorbidity in SSc. Many studies founded a significant impairment in SSc patients' QoL, and despite the undeniable correlation between physical symptoms and SSc patients' QoL, mental health was found significantly impaired. DISCUSSION: The high rate of depression seems to strictly correlate with poor quality of life, and this finding needs more research to establish the cause of such a correlation. Patients' point of view regarding their health-related QoL could help physicians to enlarge the knowledge about physical and mental correlates of the disease, and to fit therapies as patient required. Particular attention must be given to provide the patient with correct information, in order to mitigate the anxious state on disease course, and to enhance coping skills of the patients.
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We analyze the deformability of individual red blood cells (RBCs) using SiCMA technology. Our approach is adequate to quickly measure large numbers of individual cells in heterogeneous populations. Individual cells are trapped in a large-scale array of micro-wells, and dielectrophoretic (DEP) force is applied to deform the cells. The simple structures of micro-wells and DEP electrodes facilitate the analysis of thousands of RBCs in parallel. This unique method allows the correlation of red cell deformation with cell surface and cytosolic characteristics to define the distribution of individual cellular characteristics in heterogeneous populations.
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BACKGROUND AND AIM: Systemic inflammation is a hallmark of chronic kidney disease (CKD) and obesity represents a major risk factor for CKD. We investigated the relationship between plasma interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) and the glomerular filtration rate (GFR) in 75 stage 2-5 CKD patients. METHODS AND RESULTS: We studied the steady-state relationship between plasma and subcutaneous adipose tissue (SAT) gene expression of the same cytokines in 19 patients and in 17 well-matched healthy subjects (HS) and compared SAT gene expression of these cytokines and of two additional cytokines (IL-1ß and IL-8) in CKD patients and in HS. Plasma IL-6 and TNF-α were higher in CKD patients than in HS (P < 0.001). IL-6 was similarly increased in patients with mild, moderate and severe CKD and largely independent of the GFR (r = -0.03, P = NS). TNF-α was inversely related to GFR, which was the first factor in rank (ß = -0.37, P = 0.001) explaining the variability in TNF-α in CKD. SAT messenger RNA (mRNA) levels of IL-6, TNF-α, IL- ß and IL-8 were similar in CKD patients and in HS. Plasma and SAT mRNA levels of IL-6 and TNF-α levels were largely unrelated. CONCLUSIONS: Plasma IL-6 rises early in CKD and does not show any further increase at more severe stages of CKD, whereas TNF-α is inversely associated with the GFR indicating a substantial difference in the dynamics of the relationship between these cytokines and renal function. Cytokines are not overexpressed in SAT in these patients, and circulating IL-6 and TNF-α are dissociated from the corresponding mRNA levels in SAT, both in CKD patients and in HS.
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Tejido Adiposo/metabolismo , Interleucina-1beta/sangre , Interleucina-6/sangre , Interleucina-8/sangre , Insuficiencia Renal Crónica/sangre , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Expresión Génica , Tasa de Filtración Glomerular , Humanos , Interleucina-1beta/genética , Interleucina-6/genética , Interleucina-8/genética , Modelos Lineales , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Insuficiencia Renal Crónica/fisiopatología , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Hormonal therapy is the preferred systemic treatment for recurrent or metastatic, post-menopausal hormone-receptor-positive breast cancer. Previous studies have shown that there is no cross-resistance between exemestane and reversible aromatase inhibitors. Exposure to hormonal therapy does not hamper later response to chemotherapy. Patients with locally advanced or metastatic, hormonal receptor positive or unknown, breast cancer were treated with oral anastrozole, until disease progression, followed by oral exemestane until new evidence of disease progression. The primary end point of the study was clinical benefit, defined as the sum of complete responses (CR), partial responses (PR) and > 24 weeks stable disease (SD). In all, 100 patients were enrolled in the study. Anastrozole produced eight CR and 19 PR for an overall response rate of 27% (95% CI: 18.6-36.8%). An additional 46 patients had long-term (> 24 weeks) SD for an overall clinical benefit of 73% (95% CI: 63.2-81.4). Median time to progression (TTP) was 11 months (95% CI: 10-12). A total of 50 patients were evaluated for the second-line treatment: exemestane produced one CR and three PR; 25 patients had SD which lasted > or = 6 months in 18 patients. Median TTP was 5 months. Toxicity of treatment was low. Our study confirms that treatment with sequential hormonal agents can extend the period of time during which endocrine therapy can be used, thereby deferring the decision to use chemotherapy.
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Androstadienos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Nitrilos/uso terapéutico , Triazoles/uso terapéutico , Administración Oral , Adulto , Anciano , Anastrozol , Androstadienos/administración & dosificación , Antineoplásicos Hormonales/administración & dosificación , Quimioterapia Adyuvante , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Nitrilos/administración & dosificación , Triazoles/administración & dosificaciónRESUMEN
Disponer de un sistema de información de utilidad para la gestión clínica de la atención ambulatoria especializada, y en concreto de la de consultas externas, es una necesidad urgente en nuestros hospitales. Su implantación debe realizarse sobre un modelo que recoja la filosofía de los conjuntos mínimos de datos básicos, y que evite los altos costes de transacción que conlleva un sistema de información sobre un área de tanta actividad como es la ambulatoria. Una vez que disponemos de datos informatizados sobre la cita previa, y que pueden ser utilizados para la captura de los datos del paciente y de la visita, nos encontramos con otros problemas que afectan a la viabilidad última del sistema y que aparecen ligados a la necesaria colaboración del médico que realiza la visita para la captura del dato clínico, y de las unidades de codificación clínica de los Servicios de Admisión y Documentación Clínica para el tratamiento de estos datos. Para ello, el empleo de formularios predefinidos ha supuesto en nuestro caso una herramienta útil, aunque probablemente insuficiente para el ámbito de la totalidad del hospital, por lo que debería ser complementada con desarrollos informáticos que minimicen la participación del médico en la captura de ciertos procedimientos y del codificador en el tratamiento de todos ellos. Aparece también un aspecto crucial en el modelo de análisis a emplear. Si bien el análisis en base a la visita médica aislada es útil y ofrece información de interés para el clínico y para el gestor, es conveniente avanzar hacia modelos más integrados utilizando para ello el concepto de episodio de consultas. En este artículo describimos las soluciones que hemos implantado en nuestro Hospital para resolver estas cuestiones, así como las propuestas que hacemos para avanzar en el modelo de análisis de la información (AU)
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Humanos , Sistemas de Información en Hospital , Atención Ambulatoria , Atención Secundaria de Salud , 34003 , Visita a Consultorio MédicoRESUMEN
Based on the role of cytokines in the pathogenesis of cancer-related anorexia-cachexia and the ability of progestins, such as medroxyprogesterone acetate, to reduce cytokine production and relieve cancer-related anorexia-cachexia symptoms, the authors designed an open, dose-finding phase I study of a combined chemotherapy regimen (cisplatin [CDDP], epidoxorubicin [EPI]), including recombinant interleukin-2 (IL-2) and medroxyprogesterone acetate for patients with stage IIIB to IV inoperable primary lung cancer. The end points were clinical response and toxicity with definition of dose-limiting toxicity and maximal tolerable dose; relief of cancer-related anorexia-cachexia symptoms; the assessment of patient serum levels of IL-1beta, IL-6, tumor-necrosing factor-alpha (TNF-alpha), and soluble IL-2 receptor (sIL-2R). From March to October 1997, 16 patients (M:F ratio, 14:2; mean age, 60.5 years; age range, 41 to 74 years) were enrolled. All patients were evaluable for toxicity and 14 of them for response. The patients were assigned to increasing dose levels of drugs according to a dose-escalation schedule. The weekly schedule consisted of a combination of CDDP given intravenously on day 1, EPI given intravenously on day 1, 1 g/day medroxyprogesterone acetate given orally on days 1 to 7, and recombinant IL-2 1.8 MIU administered subcutaneously on days 2 to 7 plus 300 microg granulocyte-colony stimulating factor support given subcutaneously on days 2 to 5. Administration of medroxyprogesterone acetate began 1 week before the first cycle. Dose escalation of the drugs was as follows: 30 mg x m2 x week(-1) CDDP and 25 mg x m2 x week(-1) EPI (first level, two patients); 30 mg x m2 x week(-1) CDDP and 33 mg x m2 x week(-1) EPI (second level, 2 patients); 40 mg x m2 x week(-1) CDDP and 33 mg x m2 x week(-1) EPI (third level, 6 patients); and 40 mg x m2 x week(-1) CDDP and 40 mg x m2 x week(-1) EPI (fourth level, 6 patients). Six cycles were planned for each patient. The actual dose intensity delivered was more than 80% of the projected dose intensity of all drugs. After six cycles, clinical response (according to World Health Organization criteria), toxicity (according to World Health Organization criteria), Eastern Cooperative Oncology Group (ECOG) performance status, body weight, appetite, and serum levels of cytokines were evaluated. After six cycles, 9 of 14 patients (64.3%) had partial response, 3 of 14 (21.4%) had stable disease, and 2 of 14 (14.3%) had progressive disease, and the objective response rate was 64.3%. ECOG performance status and body weight did not change significantly after treatment, whereas appetite showed an increase that was of borderline statistical significance. Toxicity was acceptable and only hematologic. Dose-limiting toxicity was established at the fourth dose level; consequently, maximal tolerable dose was assessed at the third dose level. Before treatment, the serum levels of IL-1beta, IL-6, and TNF-alpha were significantly greater in the patients than in healthy persons. The comparison between pretreatment and posttreatment serum values of IL-1beta, IL-6, TNF-alpha, and sIL-2R did not reveal significant differences in the patients. Similar results were obtained when the patients were considered as responders (partial response) or non-responders (stable or progressive disease) to therapy. Only IL-6 serum levels were increased (p = 0.014) after treatment.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Apetito/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Esquema de Medicación , Epirrubicina/administración & dosificación , Epirrubicina/efectos adversos , Femenino , Humanos , Interleucina-1/sangre , Interleucina-2/administración & dosificación , Interleucina-2/efectos adversos , Interleucina-6/sangre , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/cirugía , Masculino , Acetato de Medroxiprogesterona/administración & dosificación , Acetato de Medroxiprogesterona/efectos adversos , Persona de Mediana Edad , Desempeño Psicomotor/efectos de los fármacos , Receptores de Interleucina-2/sangre , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Sardinian population can be instrumental in defining the molecular basis of cancer, using the identity-by-descent method. We selected seven Sardinian breast cancer families originating from the northern-central part of the island with multiple affected members in different generations. We genotyped 106 members of the seven families and 20 control nuclear families with markers flanking BRCA2 locus at 13q12-q13. The detection of a common haplotype shared by four out of seven families (60%) suggests the presence of a founder BRCA2 mutation. Direct sequencing of BRCA2 coding exons of patients carrying the shared haplotype, allowed the identification of a 'frame-shift' mutation at codon 2867 (8765delAG), causing a premature termination-codon. This mutation was found in breast cancer patients as well as one prostate and one bladder cancer patient with shared haplotype. We then investigated the frequency of 8765delAG in the Sardinian breast cancer population by analysing 270 paraffin-embedded normal tissue samples from breast cancer patients. Five patients (1.7%) were found to be positive for the 8765delAG mutation. Discovery of a founder mutation in Sardinia through the identity-by-descent method demonstrates that this approach can be applied successfully to find mutations either for breast cancer or for other types of tumours.