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1.
Khirurgiia (Mosk) ; (11): 113-117, 2023.
Artículo en Ruso | MEDLINE | ID: mdl-38010025

RESUMEN

Primary intraosseous cavernous hemangioma (PICH) is a rare benign vascular tumor. This neoplasm is common in the spine and less common in skull. Toynbee J. first described this tumor in 1845. PICH of the cranium does not always have typical X-ray features and should be always differentiated with other more common skull lesions. Surgical resection is preferable since total resection is followed by favorable prognosis. We present a 65-year-old patient with asymptomatic tumor of the right parietal bone. CT revealed osteolytic lesion that required total resection and skull repair. Histopathological analysis revealed intraosseous cavernous hemangioma.


Asunto(s)
Hemangioma Cavernoso , Neoplasias Craneales , Neoplasias Vasculares , Humanos , Anciano , Neoplasias Craneales/diagnóstico , Neoplasias Craneales/cirugía , Neoplasias Craneales/patología , Cráneo , Hemangioma Cavernoso/diagnóstico por imagen , Hemangioma Cavernoso/cirugía
2.
Artículo en Ruso | MEDLINE | ID: mdl-35170277

RESUMEN

OBJECTIVE: To improve technique of intraoperative ultrasound-assisted microsurgery of spinal tumors. MATERIAL AND METHODS: There were 68 patients with 70 spinal tumors who underwent intraoperative ultrasound-assisted resection between 2007 and 2018. Age of patients varied from 21 to 80 (mean 48.5±14.3). Intradural tumors were diagnosed in 54 (79.4%) patients (of them intramedullary in 16 (23.5%) and extramedullary in 38 (55.9%) cases). Fourteen patients (20.6%) had extradural tumors. Intraoperative ultrasound was used to determine localization, margins and structure of tumors, interrelations with neural structures, zones of dura opening and myelotomy. We also assessed quality of resection and spinal decompression. RESULTS: In surgery of spinal tumors, intraoperative ultrasound allows to localize the tumor with 95.3% sensitivity, determine the character of its growth, shape, size and internal structure. One can also differentiate the margins of neoplasm, control accuracy of approach, select the optimal zone for dura opening and myelotomy, objectively assess spinal cord and nerve roots decompression in real-time mode. Quality of intraoperative ultrasonography images is comparable to preoperative MRI, and even exceed resolution of MR scans in some cases. CONCLUSION: In our study, intraoperative ultrasound has proven to be a method complementing preoperative CT and MRI. This approach provides additional data in real-time mode to form a complete picture of surgical area, increase accuracy of manipulations and reduce surgical trauma.


Asunto(s)
Neoplasias de la Médula Espinal , Neoplasias de la Columna Vertebral , Duramadre , Humanos , Procedimientos Neuroquirúrgicos , Médula Espinal , Neoplasias de la Médula Espinal/diagnóstico por imagen , Neoplasias de la Médula Espinal/cirugía , Neoplasias de la Columna Vertebral/cirugía , Ultrasonografía
3.
Khirurgiia (Mosk) ; (2): 21-31, 2020.
Artículo en Ruso | MEDLINE | ID: mdl-32105252

RESUMEN

OBJECTIVE: To analyze advisability of intraoperative ultrasound during lumbar microdiscectomy. MATERIAL AND METHODS: We used intraoperative ultrasound to identify and localize various tissues and structures of the spinal canal, optimize surgical approach to the herniated disc and assess decompression of neural structures. The study was conducted in 48 patients with herniated discs of the lumbar spine who were operated for the period from 2014 to 2017. We used ultrasound devices BK Medical Pro Focus 2202 and BK Medical Flex Focus 400 with neurosurgical transducer Craniotomy 8862 and Burr-Hole 8863. Examinations were performed before and after flavotomy during neural decompression and after decompression. All patients underwent laboratory, clinical and instrumental survey. We analyzed changes of functional and neurological status and investigated various possibilities of intraoperative ultrasound and its impact on postoperative outcomes. RESULTS: Intraoperative ultrasound is valuable to verify various tissues and structures of the lumbar spine. On-line scanning gives a correct volumetric representation of the various anatomical structures and their spatial relationships that is essential for less traumatic and more radical surgery. CONCLUSION: Intraoperative ultrasound is easy, harmless, inexpensive and widely available method of intraoperative imaging. US data may be comparable with those of intraoperative CT and MRI. Intraoperative ultrasound during lumbar microdiscectomy results better postoperative outcomes.


Asunto(s)
Discectomía , Degeneración del Disco Intervertebral , Desplazamiento del Disco Intervertebral , Microcirugia , Descompresión Quirúrgica , Discectomía/métodos , Humanos , Degeneración del Disco Intervertebral/diagnóstico por imagen , Degeneración del Disco Intervertebral/cirugía , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/cirugía , Vértebras Lumbares , Microcirugia/métodos , Resultado del Tratamiento , Ultrasonografía
4.
Acta Neurochir Suppl ; 126: 39-45, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29492529

RESUMEN

OBJECTIVES: Validated optimal cerebral perfusion pressure (CPP) treatment thresholds in children do not exist. To improve the intensive care unit (ICU) management of the paediatric traumatic brain injury (TBI) population, we are forming a new paediatric multi-centre collaboration to recruit standardised ICU data for running and reporting upon models for assessing autoregulation and optimal CCP (CPPopt). MATERIALS AND METHODS: We are adapting the adult BrainIT group's approach to develop a new Paediatric Brain Monitoring and Information Technology Group (KidsBrainIT), which will include a repository to store prospectively collected high-resolution physiological, clinical, and outcome data. In the first phase of this project there are 7 UK Paediatric Intensive Care Units, 1 Spanish, 1 Belgium, and 1 Romanian Centre interested in participating. In subsequent phases, we plan to open recruitment to other centres both within Europe, US and abroad. We are collaborating with the Leuven Group and plan to use their LAx (low-frequency autoregulation index), DATACAR (dynamic adaptive target of active cerebral autoregulation), CPPopt and visualisation methodologies. We also plan to use the continuous diffuse optical monitoring and tomography technology developed in Barcelona as an acute surrogate end-point for optimising brain perfusion. This technology allows non-invasive continuous monitoring of deep tissue perfusion and oxygenation in adults but its clinical application in infants and children with TBI has not been studied previously. RESULTS: We report on the current status of setting up this new collaboration and also on pilot analyses in two centres which are the basis of our rationale for the need for a prospective validation study of CPPopt in children. Specifically, we demonstrated that CPPopt varied with time for each patient during their paediatric intensive care unit (PICU) stay, and the median overall CPPopt levels for children aged 2-6 years, 7-11 years and 12-16 years were 68.83, 68.09, and 72.17 mmHg respectively. Among survivors and patients with favourable outcome (GOS 4 and 5), there were significantly higher proportions with CPP monitoring time within CPPopt (p = 0.04 and p = 0.01 respectively). CONCLUSIONS: There is a need and an interest in forming a multi-centre PICU collaboration for acquiring data and performing analyses for determining validated CPPopt thresholds in the paediatric TBI population. KidsBrainIT is being formed to meet that need.


Asunto(s)
Lesiones Traumáticas del Encéfalo/terapia , Encéfalo/fisiopatología , Circulación Cerebrovascular , Presión Intracraneal/fisiología , Monitoreo Fisiológico , Adolescente , Bélgica , Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/fisiopatología , Niño , Preescolar , Conducta Cooperativa , Manejo de la Enfermedad , Europa (Continente) , Femenino , Homeostasis , Humanos , Unidades de Cuidado Intensivo Pediátrico , Masculino , Proyectos Piloto , Rumanía , España , Tomografía Computarizada por Rayos X , Reino Unido , Estados Unidos
5.
Clin Anat ; 31(1): 81-85, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29265651

RESUMEN

Current medical literature does not describe precisely the activation and mechanisms of prostate orgasms. This brief review describes what we know about the anatomy and physiology of the prostate and its involvement in reproduction and especially its stimulation for sexual recreation. It is illustrated with a highly relevant case history. Clin. Anat. 31:81-85, 2018. © 2017 Wiley Periodicals, Inc.


Asunto(s)
Eyaculación/fisiología , Orgasmo/fisiología , Próstata/fisiología , Conducta Adictiva , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/fisiopatología , Próstata/anatomía & histología , Próstata/inervación , Prostatectomía , Neoplasias de la Próstata/cirugía , Prostatitis/terapia , Disfunciones Sexuales Psicológicas/fisiopatología
6.
Lupus ; 26(8): 825-834, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27852935

RESUMEN

Blood-borne RNA circulating in association with autoantibodies is a potent stimulator of interferon production and immune system activation. RSLV-132 is a novel fully human biologic Fc fusion protein that is comprised of human RNase fused to the Fc domain of human IgG1. The drug is designed to remain in circulation and digest extracellular RNA with the aim of preventing activation of the immune system via Toll-like receptors and the interferon pathway. The present study describes the first clinical study of nuclease therapy in 32 subjects with systemic lupus erythematosus. The drug was well tolerated with a very favorable safety profile. The approximately 19-day serum half-life potentially supports once monthly dosing. There were no subjects in the study that developed anti-RSLV-132 antibodies. Decreases in B-cell activating factor correlated with decreases in disease activity in a subset of patients.


Asunto(s)
Autoanticuerpos/sangre , Lupus Eritematoso Sistémico/tratamiento farmacológico , ARN/sangre , Proteínas Recombinantes de Fusión/uso terapéutico , Adulto , Autoanticuerpos/inmunología , Factor Activador de Células B/metabolismo , Método Doble Ciego , Esquema de Medicación , Femenino , Semivida , Humanos , Inmunoglobulina G/inmunología , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Ribonucleasas/inmunología , Índice de Severidad de la Enfermedad
7.
Artículo en Ruso | MEDLINE | ID: mdl-28665387

RESUMEN

The prevalence of syringomyelia (SM) caused by adhesive arachnoiditis (AA) is 2 to 4 cases per 100000 population. Surgical treatment of this pathology usually includes implantation of shunts into the cyst cavity or opening and drainage of the cavity. In this case, SM continues to progress in 72-100% of patients. Unsatisfactory outcomes of this surgical approach necessitate searching for other treatment options. PURPOSE: To define the optimal amount of surgery for SM associated with AA and the criteria for assessment of surgery outcomes. MATERIAL AND METHODS: The authors treated 47 SM patients in the period from 2010 to 2015. Of these, 34 (72.3%) patients underwent surgery; a total of 40 operations were performed. The patients' age ranged from 18 to 64 years (mean, 43.5 years). Tethering of the spinal cord was eliminated in 25 patients; 9 patients underwent cyst shunting. RESULTS: Among operated patients, 5 patients had grade 1 arachnopathy, 13 patients had grade 2 arachnopathy, 12 patients had grade 3 arachnopathy, and 4 patients had grade 4 arachnopathy. The minimal postoperative follow-up period was 11 months. After shunting, the condition improved in 8 of 9 patients; in 7 patients, the condition returned to the baseline level within the first postoperative year; in 6 (66.7%) of these patients, the disease continued to progress. After surgical release of spinal cord tethering, satisfactory long-term results were achieved in 13 (86.6%) patients with grade 1-2 arachnopathy. In 3 (50%) patients with grade 3 arachnopathy, the condition was stabilized. Among patients with grade 4 arachnopathy, progression of the disease was stopped in 1 patient; the condition worsened in 2 (50%) patients. Among all the operated patients, complications developed in 7 patients. There were no lethal outcomes. CONCLUSIONS: In grade 1-2 arachnopathy, progression of SM after release of spinal cord tethering occurs only in 13.4% of patients. Therefore, release of spinal cord tethering is recommended for these patients. In grade 3-4 arachnopathy, the rate of relapse after this surgery is more than 80%. Therefore, given the simplicity and a lower risk of complications of cyst shunting, this procedure is advisable for these patients.


Asunto(s)
Aracnoiditis/cirugía , Procedimientos Neuroquirúrgicos/métodos , Enfermedades de la Médula Espinal/cirugía , Siringomielia/cirugía , Adherencias Tisulares/cirugía , Adolescente , Adulto , Aracnoiditis/complicaciones , Humanos , Persona de Mediana Edad , Enfermedades de la Médula Espinal/complicaciones , Siringomielia/etiología , Adherencias Tisulares/complicaciones , Resultado del Tratamiento , Adulto Joven
8.
Osteoporos Int ; 25(2): 763-8, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24002542

RESUMEN

UNLABELLED: Despite sharing common risk factors and biological pathways, the relationship between frailty and osteoporosis (OP) is not clear. This prospective study has shown that frailty defined by the Vulnerable Elders Survey can predict a decrease in bone mineral density after 1 year. Thus, frail older women should be assessed for osteoporosis. INTRODUCTION: Frailty and OP share common risk factors such as age, sarcopenia, lack of physical activity, low body weight, and smoking. Despite shared risk factors and biological pathways, the relationship between frailty and OP is not clear. The purpose of our prospective study was to examine this relationship in a community sample of older women. METHODS: A sample of 235 community-dwelling women was assessed for demographic, medical, frailty and OP status at baseline, and after at least 1 year. Frailty was assessed using the Cardiovascular Health study (CHS) frailty phenotype and using the Vulnerable Elders Survey (VES-13). OP was measured using dual photon absorptiometry bone mineral density (BMD). Descriptive statistics and regression models were used. RESULTS: At baseline, 235 women with a mean age of 77.6 (SD = 5.4), body mass index (BMI) of 28.3 (SD = 5.2) kg/m(2), and BMD of 0.7 (SD = 0.2) g/cm(2)were assessed. No correlation was found between BMD and the CHS (BMD spine, r = 0.009, p = 0.889; BMD hips, r = 0.050, p = 0.473) or the VES-13 (BMD spine, r = 0.034, p = 0.605; BMD hips, r = -0.042, p = 0.537) frailty scales. One hundred fifty-two (63.9 %) women were assessed after 1 year. In a regression model, women who were frail at baseline (VES-13) were found to have a statistically significantly lower hip and spine BMD at follow-up (controlling for BMI) than women who were non-frail at baseline (p = 0.0393, hip; p = 0.0069, spine). CONCLUSIONS: Frailty status as defined by the VES-13 predicts a decrease in BMD after 1 year.


Asunto(s)
Anciano Frágil/estadística & datos numéricos , Osteoporosis Posmenopáusica/etiología , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Densidad Ósea/fisiología , Femenino , Evaluación Geriátrica , Encuestas Epidemiológicas , Humanos , Israel/epidemiología , Osteoporosis Posmenopáusica/epidemiología , Osteoporosis Posmenopáusica/fisiopatología , Estudios Prospectivos , Factores de Riesgo
9.
Br J Psychiatry ; 205(1): 44-51, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23929443

RESUMEN

BACKGROUND: All antipsychotic medications carry warnings of increased mortality for older adults, but little is known about comparative mortality risks between individual agents. AIMS: To estimate the comparative mortality risks of commonly prescribed antipsychotic agents in older people living in the community. METHOD: A retrospective, claims-based cohort study was conducted of people over 65 years old living in the community who had been newly prescribed risperidone, olanzapine, quetiapine, haloperidol, aripiprazole or ziprasidone (n = 136 393). Propensity score-adjusted Cox proportional hazards models assessed the 180-day mortality risk of each antipsychotic compared with risperidone. RESULTS: Risperidone, olanzapine and haloperidol showed a dose-response relation in mortality risk. After controlling for propensity score and dose, mortality risk was found to be increased for haloperidol (hazard ratio (HR) = 1.18, 95% CI 1.06-1.33) and decreased for quetiapine (HR = 0.81, 95% CI 0.73-0.89) and olanzapine (HR = 0.82, 95% CI 0.74-0.90). CONCLUSIONS: Significant variation in mortality risk across commonly prescribed antipsychotics suggests that antipsychotic selection and dosing may affect survival of older people living in the community.


Asunto(s)
Antipsicóticos/efectos adversos , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/mortalidad , Anciano , Anciano de 80 o más Años , Antipsicóticos/uso terapéutico , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Mortalidad , Características de la Residencia , Estudios Retrospectivos , Riesgo
10.
Biomed Phys Eng Express ; 9(4)2023 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-37141866

RESUMEN

Purpose.Patient-specific quality assurance (PSQA) failures in radiotherapy can cause a delay in patient care and increase the workload and stress of staff. We developed a tabular transformer model based directly on the multi-leaf collimator (MLC) leaf positions (without any feature engineering) to predict IMRT PSQA failure in advance. This neural model provides an end-to-end differentiable map from MLC leaf positions to the probability of PSQA plan failure, which could be useful for regularizing gradient-based leaf sequencing optimization algorithms and generating a plan that is more likely to pass PSQA.Method.We retrospectively collected DICOM RT PLAN files of 968 patient plans treated with volumetric arc therapy. We constructed a beam-level tabular dataset with 1873 beams as samples and MLC leaf positions as features. We trained an attention-based neural network FT-Transformer to predict the ArcCheck-based PSQA gamma pass rates. In addition to the regression task, we evaluated the model in the binary classification context predicting the pass or fail of PSQA. The performance was compared to the results of the two leading tree ensemble methods (CatBoost and XGBoost) and a non-learned method based on mean-MLC-gap.Results.The FT-Transformer model achieves 1.44% Mean Absolute Error (MAE) in the regression task of the gamma pass rate prediction and performs on par with XGBoost (1.53 % MAE) and CatBoost (1.40 % MAE). In the binary classification task of PSQA failure prediction, FT-Transformer achieves 0.85 ROC AUC (compared to the mean-MLC-gap complexity metric achieving 0.72 ROC AUC). Moreover, FT-Transformer, CatBoost, and XGBoost all achieve 80% true positive rate while keeping the false positive rate under 20%.Conclusions.We demonstrated that reliable PSQA failure predictors can be successfully developed based solely on MLC leaf positions. FT-Transformer offers an unprecedented benefit of providing an end-to-end differentiable map from MLC leaf positions to the probability of PSQA failure.


Asunto(s)
Radioterapia de Intensidad Modulada , Humanos , Radioterapia de Intensidad Modulada/métodos , Estudios Retrospectivos , Planificación de la Radioterapia Asistida por Computador/métodos , Algoritmos
11.
Int J Androl ; 35(1): 79-85, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21696395

RESUMEN

There is a growing body of evidence to support the direct link between obstructive bladder dysfunction and erectile dysfunction (ED). However, there have been few pathophysiological studies to determine the relationship between lower urinary tract syndrome (LUTS) and ED. As the transforming growth factor-ß1 (TGF-ß1) that induces the synthesis of collagen in the penile tissues is critical for the development of ED, the first aim of this study was to investigate the expression of TGF-ß1 in the penis from male rabbits with chronic partial bladder outlet obstruction (PBOO). Besides, it has been suggested that oxidative stress plays a significant role in the pathophysiological mechanism of ED. Thus, the second aim of this study was to further investigate whether the urinary or serum oxidative stress markers are involved in chronic PBOO-induced penile dysfunction. A total of 16 male New Zealand White rabbits were separated equally into four groups: a control group and PBOO groups obstructed for 2, 4 and 8 weeks respectively. Using the RT-PCR and Western blot analysis, a progressive increase of TGF-ß1 in penis was found at 2, 4 and 8 weeks after obstruction. Moreover, the biomarkers for oxidative stress or oxidative damage were significantly detected in the penis of rabbits after PBOO, which include the enhancement of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine and plasma, plasma malondialdehyde (MDA) and total antioxidant capacity (TAC), as well as reduction of glutathione (GSH). On the basis of our results, the increase of TGF-ß1 and elevated systemic oxidative stress may play key roles to contribute to penile dysfunction after chronic PBOO.


Asunto(s)
Estrés Oxidativo , Pene/metabolismo , Factores de Crecimiento Transformadores/metabolismo , Obstrucción del Cuello de la Vejiga Urinaria/metabolismo , Animales , Western Blotting , Masculino , Reacción en Cadena de la Polimerasa , Conejos
12.
iScience ; 25(6): 104371, 2022 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-35620429

RESUMEN

Aggression is a behavior common in most species; it is controlled by internal and external drivers, including hormones, environmental cues, and social interactions, and underlying pathways are understood in a broad range of species. To date, though, effects of gut microbiota on aggression in the context of gut-brain communication and social behavior have not been completely elucidated. We examine how manipulation of Drosophila melanogaster microbiota affects aggression as well as the pathways that underlie the behavior in this species. Male flies treated with antibiotics exhibited significantly more aggressive behaviors. Furthermore, they had higher levels of cVA and (Z)-9 Tricosene, pheromones associated with aggression in flies, as well as higher expression of the relevant pheromone receptors and transporters OR67d, OR83b, GR32a, and LUSH. These findings suggest that aggressive behavior is, at least in part, mediated by bacterial species in flies.

13.
J Exp Med ; 186(9): 1615-20, 1997 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-9348321

RESUMEN

The complete healing of wounds is the final step in a highly regulated response to injury. Although many of the molecular mediators and cellular events of healing are known, their manipulation for the enhancement and acceleration of wound closure has not proven practical as yet. We and others have established that adenosine is a potent regulator of the inflammatory response, which is a component of wound healing. We now report that ligation of the G alpha s-linked adenosine receptors on the cells of an artificial wound dramatically alters the kinetics of wound closure. Excisional wound closure in normal, healthy mice was significantly accelerated by topical application of the specific A2A receptor agonist CGS-21680 (50% closure by day 2 in A2 receptor antagonists. In rats rendered diabetic (streptozotocin-induced diabetes mellitus) wound healing was impaired as compared to nondiabetic rats; CGS-21680 significantly increased the rate of wound healing in both nondiabetic and diabetic rats. Indeed, the rate of wound healing in the CGS-21680-treated diabetic rats was greater than or equal to that observed in untreated normal rats. These results appear to constitute the first evidence that a small molecule, such as an adenosine receptor agonist, accelerates wound healing in both normal animals and in animals with impaired wound healing.


Asunto(s)
Adenosina/análogos & derivados , Fenetilaminas/administración & dosificación , Agonistas del Receptor Purinérgico P1 , Cicatrización de Heridas/efectos de los fármacos , Adenosina/administración & dosificación , Administración Tópica , Animales , Línea Celular , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatología , Endotelio Vascular/metabolismo , Femenino , Fibroblastos/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratas , Ratas Sprague-Dawley , Receptor de Adenosina A2A , Receptores Purinérgicos P1/biosíntesis , Receptores Purinérgicos P1/genética , Piel , Venas Umbilicales
15.
Br J Cancer ; 101(10): 1717-23, 2009 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-19844230

RESUMEN

BACKGROUND: Myelosuppression has been observed with several multikinase angiogenesis inhibitors in clinical studies, although the frequency and severity varies among the different agents. Inhibitors targeting vascular endothelial growth factor receptor (VEGFR) often inhibit other kinases, which may contribute to their adverse-event profiles. METHODS: Kinase selectivity of pazopanib, sorafenib, and sunitinib was evaluated in a panel of 242 kinases. Cellular potency was measured using autophosphorylation assays. Effect on human bone marrow progenitor growth in the presence of multiple growth factors was evaluated and correlated with the kinase selectivity. RESULTS: Sunitinib inhibited more kinases than pazopanib and sorafenib, at potencies within 10-fold of VEGFR-2. All three compounds potently inhibited VEGFR-2, platelet-derived growth factor receptor-beta and c-Kit, However, pazopanib was less active against Flt-3 in both kinase and cellular assays. The inhibitory properties of pazopanib, sorafenib, and sunitinib were dependent on the growth factor used to initiate bone marrow colony formation. Addition of stem cell factor and/or Flt-3 ligand with granulocyte-macrophage colony stimulating factor resulted in significant shifts in potency for sorafenib and sunitinib but less so for pazopanib. CONCLUSION: Activity against c-kit and Flt-3 by multikinase angiogenesis inhibitors provide a potential explanation for the differences in myelosuppression observed with these agents in patients.


Asunto(s)
Bencenosulfonatos/farmacología , Indoles/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/farmacología , Pirimidinas/farmacología , Pirroles/farmacología , Sulfonamidas/farmacología , Inhibidores de la Angiogénesis/farmacología , Línea Celular Tumoral , Enfermedades Hematológicas/inducido químicamente , Enfermedades Hematológicas/enzimología , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Indazoles , Concentración 50 Inhibidora , Mielopoyesis/efectos de los fármacos , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-kit/antagonistas & inhibidores , Receptores del Factor de Crecimiento Derivado de Plaquetas/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Sorafenib , Especificidad por Sustrato , Sunitinib , Tirosina Quinasa 3 Similar a fms/antagonistas & inhibidores
16.
Osteoporos Int ; 20(10): 1735-47, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19266138

RESUMEN

SUMMARY: Weekly bisphosphonates are the primary agents used to treat osteoporosis. Although these agents are generally well tolerated, serious gastrointestinal adverse events, including hospitalization for gastrointestinal bleed, may arise. We compared the gastrointestinal safety between weekly alendronate and weekly risedronate and found no important difference between new users of these agents. INTRODUCTION: Weekly bisphosphonates are the primary agents prescribed for osteoporosis. We examined the comparative gastrointestinal safety between weekly bisphosphonates. METHODS: We studied new users of weekly alendronate and weekly risedronate from June 2002 to August 2005 among enrollees in a state-wide pharmaceutical benefit program for seniors. Our primary outcome was hospitalization for upper gastrointestinal bleed. Secondary outcomes included outpatient diagnoses for upper gastrointestinal disease, symptoms, endoscopic procedures, use of gastroprotective agents, and switching between therapies. We used Cox proportional hazard models to compare outcomes between agents within 120 days of treatment initiation, adjusting for propensity score quintiles. We also examined composite safety outcomes and stratified results by age and prior gastrointestinal history. RESULTS: A total of 10,420 new users were studied, mean age = 79 years (SD, 6.9), and 95% women. We observed 31 hospitalizations for upper gastrointestinal bleed (0.91 per 100 person-years) within 120 days of treatment initiation. Adjusting for covariates, there was no difference in hospitalization for upper gastrointestinal bleed among those treated with risedronate compared with alendronate (HR, 1.12; 95%CI, 0.55 to 2.28). Risedronate switching rates were lower; otherwise, no differences were observed for secondary or composite outcomes. CONCLUSIONS: We found no important difference in gastrointestinal safety between weekly oral bisphosphonates.


Asunto(s)
Conservadores de la Densidad Ósea/efectos adversos , Difosfonatos/efectos adversos , Enfermedades Gastrointestinales/inducido químicamente , Administración Oral , Anciano , Anciano de 80 o más Años , Alendronato/administración & dosificación , Alendronato/efectos adversos , Conservadores de la Densidad Ósea/administración & dosificación , Difosfonatos/administración & dosificación , Esquema de Medicación , Métodos Epidemiológicos , Ácido Etidrónico/administración & dosificación , Ácido Etidrónico/efectos adversos , Ácido Etidrónico/análogos & derivados , Femenino , Enfermedades Gastrointestinales/epidemiología , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/epidemiología , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Osteoporosis/tratamiento farmacológico , Osteoporosis/epidemiología , Pennsylvania/epidemiología , Ácido Risedrónico , Resultado del Tratamiento
17.
Science ; 163(3871): 1083-4, 1969 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-5764876

RESUMEN

Postpartum female rats deprived of suckling stimulation while being kept continuously with pups nonetheless suspended ovarian cyclicity for an average of 16 days and responded to uterine trauma by forming deciduomata. These results show that the extramammary stimulation afforded by young is alone capable of sustaining prolactin output from the adenohypophysis of the postpartum rat.


Asunto(s)
Lactancia , Preñez , Prolactina/metabolismo , Animales , Estro , Femenino , Glándulas Mamarias Animales/fisiología , Embarazo , Ratas
18.
Ann Rheum Dis ; 67(5): 609-13, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-17728328

RESUMEN

BACKGROUND: Uric acid lowering therapy (UALT) is considered a chronic treatment for gout. Relatively little is known about adherence to UALT. METHODS: We assessed adherence with UALT over a 1-year study period among 9823 older adults enrolled in a pharmacy benefit program. Two adherence measures were calculated, the percentage of days covered (PDC) and the time until an extended break (at least 60 days) in treatment. A PDC <80% was considered poor adherence and its predictors were examined in multivariable logistic models. RESULTS: The mean (SD) PDC was 54% (36%) with 64% of patients considered poorly compliant over the study period. A total of 56% had experienced an extended break in UALT. Predictors of poor adherence included younger age (odds ratio (OR) 1.50, 95% CI 1.33-1.69 for ages 65-74 compared with 85 and above) and African-American race (OR 1.86, 95% CI 1.52-2.27 compared with Caucasian race). Most patients (93%) received their initial UALT prescription from a non-specialist and this also predicted poor adherence (OR 1.15, 95% CI 0.96-1.38 compared with rheumatologists or nephrologists). CONCLUSION: Adherence with UALT is poor. While uric acid levels were not measured in this study, poor adherence with UALT is likely to reduce attainment of goal uric acid levels.


Asunto(s)
Supresores de la Gota/uso terapéutico , Gota/tratamiento farmacológico , Gota/psicología , Cooperación del Paciente , Negro o Afroamericano , Factores de Edad , Anciano , Anciano de 80 o más Años , Alopurinol/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Estudios de Cohortes , Esquema de Medicación , Quimioterapia Combinada , Femenino , Gota/etnología , Humanos , Modelos Logísticos , Masculino , Massachusetts , Probenecid/uso terapéutico , Sulfinpirazona/uso terapéutico , Población Blanca
19.
J Appl Microbiol ; 104(3): 728-34, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18081775

RESUMEN

AIMS: To develop a PCR strategy for Vibrio vulnificus in irradiated foods. METHODS AND RESULTS: Real-time PCR was used to discriminate between DNA from gamma-irradiated and nonirradiated cells. gamma-Irradiation at 1.08 KGy and above of cell suspensions containing 1 x 10(6) CFU ml(-1) resulted in 0 CFU ml(-1). Real-time PCR was able to detect 86.6% destruction by 1.08 KGy, while ethidium bromide monoazide (EMA) real-time PCR was able to detect 93.2% destruction at this dose. With 3.0 and 5.0 KGy, EMA real-time PCR was able to detect 99.3% and 100% destruction, respectively. CONCLUSIONS: The inability to detect via PCR extensively degraded DNA resulting from gamma-irradiation can be taken as evidence of cell death. The increased ability of EMA to further reduce the detectable number of target sequences via PCR, with DNA from cells exposed to increased doses of gamma-irradiation, can be considered to reflect the accompanying increase in membrane damage which allows EMA to penetrate the cells. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study that has made use of the PCR to discriminate between gamma-irradiated and nonirradiated bacterial cells and has led to insights regarding the ability of the PCR to discriminate between nonirradiated and gamma-irradiation destroyed cells.


Asunto(s)
Irradiación de Alimentos , Microbiología de Alimentos , Vibrio vulnificus/aislamiento & purificación , Rayos gamma , Viabilidad Microbiana , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Vibrio vulnificus/fisiología , Vibrio vulnificus/efectos de la radiación
20.
J Clin Invest ; 75(2): 657-66, 1985 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-3156151

RESUMEN

During blood coagulation human polymorphonuclear leukocytes release elastase in amounts that can exceed 100 nmol/liter. We therefore studied the effect of elastase on platelet structure and function. Physiologic concentrations of elastase specifically inhibited thrombin-induced platelet aggregation and ristocetin-induced agglutination of washed platelets in a time- and dose-dependent manner. This was associated with a decrease in the number of high affinity thrombin binding sites on the platelet surface (analysis by "Ligand" program) from 31 per platelet to 12 per platelet (P less than 0.05). As analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, treatment of 3H-labeled platelets with elastase resulted in a decrease in the percent glycoprotein at 130,000-150,000 Mr = and an increase in the percent protein at Mr = 102,000. The supernatant from elastase-treated platelets contained a Mr = 88,000 glycoprotein not found in the supernatant from untreated platelets. Immunoprecipitation studies with monoclonal antiglycoprotein Ib demonstrated that treatment of whole platelets with physiologic concentrations of elastase resulted in proteolytic cleavage of glycoprotein Ib. Elastase treatment of glycoprotein immunoisolated with monoclonal antiglycoprotein Ib antibody resulted in formation of a glycopeptide with the same electrophoretic mobility as the Mr = 102,000 membrane-related glycopeptide. In contrast, analysis by Western blot technique using antiglycoprotein IIb and IIIa antibodies demonstrated that elastase did not degrade glycoproteins IIb or IIIa. We conclude that elastase inhibition of thrombin-induced platelet stimulation is accompanied by (a) a reduction in the number of thrombin binding sites per platelet and (b) proteolysis of glycoprotein Ib.


Asunto(s)
Plaquetas/efectos de los fármacos , Glicoproteínas/sangre , Proteínas de la Membrana/sangre , Neutrófilos/enzimología , Elastasa Pancreática/farmacología , Plaquetas/fisiología , Humanos , Técnicas In Vitro , Agregación Plaquetaria/efectos de los fármacos , Glicoproteínas de Membrana Plaquetaria , Serotonina/metabolismo , Trombina/metabolismo , Trombina/farmacología
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