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1.
J Endocrinol Invest ; 47(1): 235-243, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37354247

RESUMEN

BACKGROUND: There are evidences showing that sitagliptin and spironolactone can potentially improve the clinical outcomes of COVID-19 cases. In this observational study on acutely symptomatic outpatient COVID-19 cases, we investigated the effects of spironolactone and sitagliptin on the outcomes of the disease. METHODS: This is a prospective, naturally randomized cohort study. We followed mild to moderate symptomatic COVID-19 patients, who were treated with either combination (spironolactone 100 mg daily and sitagliptin 100 mg daily) or standard (steroid, antiviral and/or supportive care) therapy up to 30 days. The primary outcome was hospitalization rate. The secondary outcomes included ER visit, duration of disease, and complications, such as hypoglycemia, low blood pressure or altered mental status. RESULTS: Of the 206 patients referred to clinics randomly, 103 received standard therapy and 103 treated with combination therapy. There were no significant differences in baseline characteristics, except for slightly higher clinical score in control group (6.92 ± 4.01 control, 4.87 ± 2.92 combination; P < 0.0001). Treatment with combination therapy was associated with lower admission rate (5.8% combination, 22.3% control; P = 0.0011), ER visits (7.8% combination, 23.3% control; P = 0.0021) and average duration of symptoms (6.67 ± 2.30 days combination, 18.71 ± 6.49 days control; P ≤ 0.0001). CONCLUSIONS: The combination of sitagliptin and spironolactone reduced duration of COVID infection and hospital visits better than standard therapeutic approaches in outpatients with COVID-19. The effects of combination of sitagliptin and spironolactone in COVID-19 patients should be further verified in a double-blind, randomized, placebo-controlled trial.


Asunto(s)
COVID-19 , Fosfato de Sitagliptina , Humanos , Fosfato de Sitagliptina/uso terapéutico , Espironolactona/uso terapéutico , Pacientes Ambulatorios , Estudios Prospectivos , Estudios de Cohortes , Resultado del Tratamiento , Método Doble Ciego
2.
Eur J Vasc Endovasc Surg ; 51(5): 682-9, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-27021777

RESUMEN

BACKGROUND: The incidence of coagulopathy in patients presenting with rAAA is not clear. The lack of high-quality evidence has led to various speculations, reliance on anecdotal experience, and suggestions about their appropriate haemostatic resuscitation. The aim of this systematic review is to establish the baseline coagulation status of infra renal ruptured abdominal aortic aneurysms (rAAA) against defined standards and definitions. METHODS: An electronic search of literature in Medline, CINHAL, Scopus Embase, and Cochrane library was performed in accordance with the PRISMA guidelines. Quality assessment of articles was performed using the Oxford critical appraisal skills programme (CASP) and their recommendation for practice was examined through National Institute for Health and Care Excellence (NICE). Information on platelet count, international normalisation ratio (INR), activated partial prothrombin time (aPTT), prothrombin time (PT) fibrinogen and D-dimer was extracted, and pooled analysis was performed in accordance with the definition of coagulopathy and its subtypes. Pooled prevalence of coagulopathies and 95% CI were estimated with a variance weighted random effects model. RESULTS: Seven studies, comprising 461 patients were included in this systematic review. Overall weighted prevalence of coagulopathy was 12.3% (95% CI 10.7-13.9), 11.7% for INR (95% CI 1-31.6), 10.1% for platelet count (95% CI 1-26.8), and 11.1% for aPTT (95% CI 0.78-31). Fibrinogen serum concentration level was normal in 97%, and 46.2% (n = 55) of patients had elevated D-dimer. Only 6% of the entire population demonstrated significant coagulopathy. DIC was noted in 2.4% of the population. CONCLUSION: This first systematic review of literature on baseline coagulation of rAAAs suggests that the majority of these patients do not present with coagulopathy and only a minor proportion of patients present with significant coagulopathy.


Asunto(s)
Aneurisma de la Aorta Abdominal/sangre , Rotura de la Aorta/sangre , Fibrinógeno , Humanos , Incidencia
3.
PLoS One ; 19(7): e0306868, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39083456

RESUMEN

The endocannabinoid system (ECS) plays a major role in the maintenance of bodily homeostasis and adaptive response to external insults. It has been shown to regulate crucial physiological processes and behaviors, spanning nervous functions, anxiety, cognition, and pain sensation. Due to this broad activity, the ECS has been explored as a potential therapeutic target in the treatment of select diseases. However, until there is a more comprehensive understanding of how ECS activation by exogenous and endogenous ligands manifests across disparate tissues and cells, discretion should be exercised. Previous work has investigated how endogenous cannabinoid signaling impacts skeletal muscle development and differentiation. However, the effects of activation of the ECS by delta-9-tetrahydrocannabinol (THC, the most psychoactive component of cannabis) on skeletal muscle development, particularly in utero, remain unclear. To address this research gap, we used a highly translational non-human primate model to examine the potential impact of chronic prenatal THC exposure on fetal and infant musculoskeletal development. RNA was isolated from the skeletal muscle and analyzed for differential gene expression using a Nanostring nCounter neuroinflammatory panel comprised of 770 genes. Histomorphological evaluation of muscle morphology and composition was also performed. Our findings suggest that while prenatal THC exposure had narrow overall effects on fetal and infant muscle development, the greatest impacts were observed within pathways related to inflammation and cytokine signaling, which suggest the potential for tissue damage and atrophy. This pilot study establishes feasibility to evaluate neuroinflammation due to prenatal THC exposure and provides rationale for follow-on studies that explore the longer-term implications and functional consequences encountered by offspring as they continue to mature.


Asunto(s)
Dronabinol , Músculo Esquelético , Efectos Tardíos de la Exposición Prenatal , Dronabinol/farmacología , Animales , Femenino , Embarazo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/crecimiento & desarrollo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Desarrollo Musculoesquelético/efectos de los fármacos , Macaca mulatta , Desarrollo Fetal/efectos de los fármacos , Masculino
4.
J Neurooncol ; 99(3): 423-31, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20853019

RESUMEN

To formulate Functional Assessment of Cancer Therapy-Meningioma (FACT-MNG), a web-based tumor site-specific outcome instrument for assessing intracranial meningioma patients following surgical resection or stereotactic radiosurgery. We surveyed the relevant literature available on intracranial meningioma surgery and subsequent outcomes (38 papers), making note of which, if any, QOL/outcome instruments were utilized. None of the surgveyed papers included QOL assessment specific to tumor site. We subsequently developed questions that were relevant to the signs and symptoms that characterize each of 11 intracranial meningioma sites, and incorporated them into a modified combination of the Functional Assessment of Cancer Therapy-Brain (FACT-BR) and SF36 outcome instruments, thereby creating a new tumor site-specific outcome instrument, FACT-MNG. With outcomes analysis of surgical and radiosurgical treatments becoming more important, measures of the adequacy and success of treatment are needed. FACT-MNG represents a first effort to formalize such an instrument for meningioma patients. Questions specific to tumor site will allow surgeons to better assess specific quality of life issues not addressed in the past by more general questionnaires.


Asunto(s)
Internet , Neoplasias Meníngeas/cirugía , Meningioma/cirugía , Evaluación de Resultado en la Atención de Salud , Calidad de Vida , Radiocirugia , Humanos
5.
Br J Ophthalmol ; 91(1): 26-8, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16973656

RESUMEN

AIMS: To evaluate a possible relationship between central corneal thickness (CCT) and optic disc area in patients with primary open-angle glaucoma (POAG). METHODS: Patients with POAG underwent eye examination, optic disc imaging with the Heidelberg Retina Tomograph II (HRT II) and ultrasound corneal pachymetry. Exclusion criteria were prior ocular surgery and low-quality HRT II images (HRT standard deviation (SD) >50). Pearson's correlation coefficients were calculated to assess the associations between CCT and optic disc area. RESULTS: 212 eyes of 137 patients with POAG were examined. In all, 66 (48%) subjects were women, 104 (76%) were Caucasian, 26 (19%) African-American and 7 (5%) other races. 72 eyes remained after excluding those with prior intraocular surgery and low-quality HRT II images. In a univariate analysis of this group, CCT was inversely correlated with optic disc surface area (Pearson's correlation coefficient r = -0.284, p = 0.036, n = 72). Mean (SD) disc area was 2 (0.53) mm(2) (n = 160). Caucasians had significantly smaller discs (p<0.001) than other races (Caucasian 1.9 (0.47) mm(2) (n = 119), African-Americans 2.4 (0.54) mm(2) (n = 31), other races 2.3 (0.45) mm(2) (n = 10)). CONCLUSION: CCT is inversely correlated to optic disc area. Although thicker corneas have been recognised to cause slight overestimation of true intraocular pressure (IOP), they may also indicate the presence of a substantially smaller, and thus more robust, optic nerve head. People with thinner corneas which slightly underestimate the true IOP may also have larger and more deformable optic discs.


Asunto(s)
Córnea/patología , Glaucoma de Ángulo Abierto/patología , Disco Óptico/patología , Negro o Afroamericano , Anciano , Técnicas de Diagnóstico Oftalmológico , Susceptibilidad a Enfermedades/patología , Femenino , Glaucoma de Ángulo Abierto/etnología , Humanos , Masculino , Estudios Prospectivos , Factores Sexuales , Tomografía/métodos , Población Blanca
6.
Ann Biomed Eng ; 45(5): 1328-1340, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-27933406

RESUMEN

In the contact activation pathway of the coagulation, zymogen factor XII (FXII) is converted to FXIIa, which triggers activation of FXI leading to the activation of FIX and subsequent thrombin generation and fibrin formation. Feedback activation of FXI by thrombin has been shown to promote thrombin generation in a FXII-independent manner and FXIIa can bypass FXI to directly activate FX and prothrombin in the presence of highly negatively charged molecules, such as long-chain polyphosphates (LC polyP). We sought to determine whether activation of FXII or FXI differentially regulate the physical biology of fibrin formation. Fibrin formation was initiated with tissue factor, ellagic acid (EA), or LC polyP in the presence of inhibitors of FXI and FXII. Our data demonstrated that inhibition of FXI decreased the rate of fibrin formation and fiber network density, and increased the fibrin network strength and rate of fibrinolysis when gelation was initiated via the contact activation pathway with EA. FXII inhibition decreased the fibrin formation and fibrin density, and increased the fibrinolysis rate only when fibrin formation was initiated via the contact activation pathway with LC polyP. Overall, we demonstrate that inhibition of FXI and FXII distinctly alter the biophysical properties of fibrin.


Asunto(s)
Inhibidores de Factor de Coagulación Sanguínea/química , Factor XII , Factor XI , Fibrina/química , Fibrinólisis , Factor XI/antagonistas & inhibidores , Factor XI/química , Factor XII/antagonistas & inhibidores , Factor XII/química , Humanos , Polifosfatos/química
7.
ASAIO J ; 51(5): 495-7, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16322703

RESUMEN

Heart transplantation (HTx) is an ultimate treatment for children with end-stage heart failure or inoperable congenital heart disease. The supply of hearts is inadequate; therefore, different mechanical support systems must be used as bridge to HTx in pediatric patients with postoperative low output. The use of ventricular assist devices (VADs) as bridge to HTx in children is limited because of size differences. The purpose of this study was to evaluate the overall long-term outcome of pediatric circulatory support before pediatric HTx. From 1989 through 2004, 91 pediatric patients underwent isolated HTx. Seven of them required mechanical support before transplantation. We reviewed retrospectively the course of 91 children (mean age 14.7 years) who underwent HTx. Group A consisted of elective HTx patients who were treated as outpatients before HTx, whereas group B was the VAD-HTx bridging group (n=7; mean age 12.31 +/- 2.8 years). Mean duration of VAD support was 108 +/- 98 days (minimum 1 day, maximum 258 days). Overall survival rate after HTx was 80% at 1 year without significant differences between groups. Five of seven patients survived and could be discharged after successful HTx, for a survival rate of 77%. The mean follow-up period was 16.76 +/- 10.6 months. No differences in posttransplantation long-term survival and rejection episodes occurred between patients transplanted with or without VAD. VAD therapy can keep pediatric patients with end-stage heart failure alive until successful HTx, and bridge to HTx is a safe procedure in pediatric patients. After HTx, survival rates of these children are similar to those of patients awaiting elective HTx.


Asunto(s)
Trasplante de Corazón , Corazón Auxiliar , Adolescente , Niño , Diseño de Equipo , Estudios de Seguimiento , Alemania , Cardiopatías Congénitas/terapia , Insuficiencia Cardíaca/terapia , Humanos , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
8.
Cardiovasc J Afr ; 26(1): 13-6, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25784312

RESUMEN

BACKGROUND: Although for decades there has been controversy regarding the relationship between obesity and coronary artery disease (CAD), it has been assumed that high body mass index (BMI) is a risk factor for CAD. However, the findings of some recent studies were paradoxical. OBJECTIVES: The aim of this study was to find a relationship between high BMI and waist-to-hip ratio (WHR) with severity of CAD. METHODS: This study was a cross-sectional, prospective study where 414 patients with suspected coronary artery disease, in whom coronary angiography was performed, were enrolled. The mean ± SD of their ages was 61.2 ± 27.4 years (range 25-84), and 250 (60.4%) were male. Regarding cardiovascular risk factors, 113 (27.3%) patients had a history of diabetes mellitus (DM), 162 (39.1%) had hypercholesterolaemia, 238 (57.4%) had hypertension, 109 (26.3%) were current smokers and 24 (5.8%) had a family history of CAD. The mean ± SD of the patients' BMI was 26.04 ± 4.08 kg/m(2) (range 16-39) and means ± SD of their WHR ranged from 0.951 ± 0.07 to 0.987 ± 0.05. The mean ± SD of the severity of CAD according to the SYNTAX and Duke scores were 17.7 ± 9.6 (range 0-64) and 3.2 ± 1.7 (range 0-12), respectively. RESULTS: In this study, findings showed a negative correlation between the severity of CAD and BMI, according to both SYNTAX and Duke scores (p ≤ 0.001 and p = 0.001, respectively). However, there was a positive correlation between WHR and severity of CAD, according to the Duke score (p = 0.03). CONCLUSION: BMI had a negative correlation with the severity of CAD, but waist-to-hip ratio had a positive correlation with severity of CAD.


Asunto(s)
Índice de Masa Corporal , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Obesidad/diagnóstico , Relación Cintura-Cadera , Adulto , Anciano , Anciano de 80 o más Años , Comorbilidad , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/prevención & control , Estudios Transversales , Femenino , Humanos , Irán/epidemiología , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Valor Predictivo de las Pruebas , Prevalencia , Estudios Prospectivos , Factores Protectores , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto Joven
9.
Neurosurgery ; 48(6): 1231-7; discussion 1237-8, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11383724

RESUMEN

OBJECTIVE: Central neurocytomas are benign neoplasms with neuronal differentiation typically located in the lateral ventricles of young adults. Although the treatment of choice is complete surgical excision, patients may experience local recurrence. Adjuvant therapy for patients with residual or recurrent tumor has included reoperation, radiotherapy, or chemotherapy. To avoid the side effects of conventional radiotherapy in young patients, we present a series of patients with clear evidence of tumor progression who were treated with gamma knife radiosurgery. METHODS: Four patients (ages 20-49 yr; mean, 28 yr) who presented with an intraventricular mass on magnetic resonance imaging scans and underwent craniotomy for tumor resection were reviewed retrospectively. Histopathological analysis confirmed central neurocytoma in all cases. Each patient was followed up clinically and radiographically with serial magnetic resonance imaging. When radiographic signs of tumor progression were evident, patients were treated with radiosurgery. RESULTS: Complete radiographic tumor resection was achieved in all patients. There were no major postoperative complications. Local tumor progression was detected on magnetic resonance imaging scans 9 to 25 months after surgery (median, 17.5 mo). All patients achieved complete response to radiosurgery with reduction in tumor size. There have been no complications from radiosurgery. Follow-up ranged from 12 to 28 months (mean, 16.5 mo) after radiosurgery, and from 24 to 84 months (mean, 54.5 mo) after initial presentation. CONCLUSION: Radiosurgery with the gamma knife unit provides safe and effective adjuvant therapy after surgical resection of central neurocytomas. Radiosurgery may eliminate the need for reoperation and avoid the possible long-term side effects from conventional radiotherapy in young patients.


Asunto(s)
Neoplasias del Ventrículo Cerebral , Neoplasias del Ventrículo Cerebral/cirugía , Radiocirugia , Adulto , Neoplasias del Ventrículo Cerebral/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/cirugía , Resultado del Tratamiento
10.
Neurosurgery ; 49(3): 681-8; discussion 688-9, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11523680

RESUMEN

OBJECTIVE: Acquired immunity has been demonstrated in Fischer rats bearing syngeneic 9L tumors after herpes simplex virus (HSV) thymidine kinase (TK) gene transfection and ganciclovir treatment. The nature of this immunity in rats and its relevance to the HSV TK/ganciclovir protocol for human subjects remain to be determined. In this study, levels of major histocompatibility complex (MHC) Class I and II antigen expression were measured before and after HSV TK transfection, in an effort to document immunomodulatory changes caused by gene therapy. METHODS: Tumor cells from the 9L gliosarcoma cell line, three primary human glioma cultures, and the human glioma cell line U87 MG were transduced with HSV TK vector-containing supernatant from fibroblast-producing cells (titer of 5 x 10(6) colony-forming units/ml) and selected in G418 medium for neomycin resistance. Clones were pooled or individually selected for cell-killing assays with ganciclovir, to confirm TK expression (10(3) cells/well in a 96-well dish). Northern analyses using MHC Class I and Class II complementary deoxyribonucleic acid probes were performed on blots containing total ribonucleic acid from wild-type tumor cells and HSV TK transfectants. A beta-actin complementary deoxyribonucleic acid probe served as an internal control. Cell surface expression was confirmed with flow cytometry. The induction of MHC Class I was tested for cycloheximide and genistein sensitivity. RESULTS: All cell cultures exhibited increases in MHC Class I but not MHC Class II expression, as determined by Northern analysis densitometry and flow cytometry. Cycloheximide treatment did not diminish the up-regulation of MHC Class I after retroviral transfection, implicating a signal transduction pathway that does not require ongoing protein synthesis. Genistein pretreatment of cell cultures did diminish the up-regulation of MHC Class I, implicating a tyrosine kinase in the signaling cascade. CONCLUSION: Induction of MHC Class I in rat and human glioma cells after HSV TK retroviral gene therapy is a primary effect that is dependent on tyrosine kinase activity. Specific immune responses generated after transfection may represent an important general side effect of gene therapy protocols. Elucidation of the mechanism of immunomodulation after gene therapy will likely yield safer and more effective clinical protocols.


Asunto(s)
Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/terapia , Terapia Genética/métodos , Gliosarcoma/inmunología , Gliosarcoma/terapia , Complejo Mayor de Histocompatibilidad/genética , Complejo Mayor de Histocompatibilidad/inmunología , Neuroinmunomodulación/fisiología , Animales , Modulación Antigénica/genética , Modulación Antigénica/inmunología , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/inmunología , Antígenos de Superficie/genética , Antígenos de Superficie/inmunología , Northern Blotting , Citometría de Flujo , Expresión Génica/genética , Técnicas de Transferencia de Gen , Vectores Genéticos , Técnicas In Vitro , Ratas , Ratas Endogámicas F344 , Simplexvirus/enzimología , Simplexvirus/genética , Simplexvirus/inmunología , Timidina Quinasa/genética , Timidina Quinasa/inmunología , Timidina Quinasa/metabolismo , Transfección/métodos , Regulación hacia Arriba
11.
Neurosurgery ; 47(6): 1391-8; discussion 1398-9, 2000 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11126910

RESUMEN

OBJECTIVE: Intracerebral clysis is a drug delivery technique that depends on convection-enhanced microinfusion to achieve therapeutic drug levels within the brain. In this study, brain tumor-bearing rats were treated with topotecan delivered systemically and by the intracerebral clysis method. Our objective was to determine the efficacy and tissue distribution of topotecan delivered by intracerebral clysis. METHODS: The C6/Wistar rat glioma model was used after a thymidine incorporation assay determined topotecan sensitivity of C6 cells in vitro. Long-term survival of animals provided objective measurements of efficacy; records of animal weight during treatment and neurological status served to approximate toxicity. Topotecan tissue penetration was measured in samples of ex vivo tumor and surrounding brain tissue with high-pressure liquid chromatography. RESULTS: Dose escalation demonstrated significant sensitivity of C6 glioma cells to topotecan (median lethal dose, 0.19 micromol/L). Eleven of 12 rats bearing established intracerebral C6 glioma and receiving topotecan by intracerebral clysis survived beyond the end point of 120 days; no untreated control or systemically treated animal survived beyond 26 days (n = 18; P < 0.005). Histopathological assessment of animals demonstrated significant tumor masses in the brains of intraperitoneally treated animals and untreated control animals. In contrast, no residual tumor was found in the brains of intracerebral clysis groups. Animal weights during treatment were markedly reduced by intraperitoneal dosing (n = 6) but not by low-dose intracerebral clysis (32 microg/kg/d for 5 d; n = 6). None of the low-dose intracerebral clysis-treated animals demonstrated neurological toxicity, and one high-dose intracerebral clysis-treated animal (160 microg/kg/d for 2 d; n = 6) died during follow-up. Topotecan was detected well beyond the boundaries of the tumor and even in the contralateral hemisphere in animals treated with intracerebral clysis. CONCLUSION: Topotecan delivered by the intracerebral clysis method is effective for treatment of brain tumors in the rat glioma model. These studies provide compelling justification for further preclinical testing to formally evaluate toxicity and efficacy with variable dosing schedules.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Glioma/tratamiento farmacológico , Glioma/metabolismo , Topotecan/farmacocinética , Topotecan/uso terapéutico , Animales , Neoplasias Encefálicas/patología , Sistemas de Liberación de Medicamentos , Glioma/patología , Inyecciones Intraperitoneales , Trasplante de Neoplasias , Ratas , Ratas Wistar , Distribución Tisular , Topotecan/administración & dosificación , Topotecan/toxicidad , Células Tumorales Cultivadas
12.
Neurosurgery ; 39(1): 135-40, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8805149

RESUMEN

OBJECTIVE: To further investigate the role of Type 2 neurofibromatosis (NF2) gene transcript mutations in the sporadically occurring counterparts of NF2-associated tumors. METHODS: Reverse transcription-polymerase chain reaction followed by agarose gel electrophoresis, single strand conformation polymorphism analysis, and automated deoxyribonucleic acid sequence analysis were used to screen for mutations in the NF2 gene transcript in seven unrelated patients with sporadic intramedullary spinal cord ependymomas. RESULTS: Five of seven intramedullary spinal cord ependymomas harbored detectable mutations. All of these mutations occurred in the region of the transcript that is homologous to known cytoskeletal proteins and resulted in significant truncation of the predicted protein product. CONCLUSION: Mutations of the NF2 transcript occur in the majority of sporadic intramedullary spinal cord ependymomas. These mutations are frequent in a region of the transcript that is homologous to a family of cytoskeletal proteins, and they probably render the protein product inactive. These results add to the body of knowledge concerning the role of the NF2 gene transcript in tumorigenesis.


Asunto(s)
Ependimoma/genética , Genes de la Neurofibromatosis 2/genética , Mutación/genética , Neoplasias de la Médula Espinal/genética , Transcripción Genética/genética , Adulto , Proteínas del Citoesqueleto/genética , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Análisis de Secuencia
13.
Neurosurgery ; 47(4): 993-9; discussion 999-1000, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11014444

RESUMEN

OBJECTIVE: Intracranial rat glioma models are a useful method for evaluating the efficacy and toxicity of novel therapies for malignant glioma. The C6/Wistar model has been used extensively as a reproducible in vivo model for studying primary brain tumors including anti-glioma immune responses. The objective of the present study is to provide in vivo evidence that the C6 rat glioma model is allogeneic within Wistar rats and is therefore inappropriate for evaluating immune responses. METHODS: Growth patterns and immune responses of C6 cells implanted into the brain and flank of Wistar rats were analyzed and compared to an immunogenic syngeneic model (9L/Fischer). RESULTS: Wistar rats with C6 tumors developed a potent humoral and cellular immune response to the tumor. Wistar rats given simultaneous flank and intracerebral tumors had a survival rate of 100% compared to an 11% survival rate in control animals receiving only intracranial C6 cells. CONCLUSION: The C6 rat glioma induces a vigorous immune reaction that may mimic a specific anti-tumor response in Wistar rats. Efficacy of immunotherapy within this model must be cautiously interpreted.


Asunto(s)
Neoplasias Encefálicas/terapia , Glioma/terapia , Inmunoterapia/normas , Ratas Wistar , Animales , Formación de Anticuerpos , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , División Celular , Glioma/inmunología , Glioma/metabolismo , Glioma/patología , Inmunidad Celular , Masculino , Trasplante de Neoplasias , Ratas , Ratas Endogámicas F344/inmunología , Ratas Wistar/inmunología , Análisis de Supervivencia , Topotecan/administración & dosificación , Topotecan/uso terapéutico , Células Tumorales Cultivadas
14.
Neurosurgery ; 46(3): 683-91, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10719865

RESUMEN

OBJECTIVE: Intracerebral clysis (ICC) is a new term we use to describe convection-enhanced microinfusion into the brain. This study establishes baseline parameters for preclinical, in vivo, drug investigations using ICC in a rat glioma model. METHODS: Intracranial pressure was measured, with an intraparenchymal fiber-optic catheter, in male Fischer rats 10, 15, 20, and 25 days after implantation of C6 glioma cells in the right frontal lobe (n = 80) and in control rats without tumor (n = 20), before and during ICC. A 25% albumin solution (100 microl) was infused through an intratumoral catheter at 0.5, 1.0, 2.0, 3.0, and 4.0 microl/min. Infusate distribution was assessed by infusion of fluorescein isothiocyanate-dextran (Mr 20,000), using the aforementioned parameters (n = 36). Brains were sectioned and photographed under ultraviolet light, and distribution was calculated by computer analysis (NIH Image for Macintosh). Safe effective drug distribution was demonstrated by measuring tumor sizes and apoptosis in animals treated with N,N'-bis(2-chloroethyl)-N-nitrosourea via ICC, compared with untreated controls. Magnetic resonance imaging noninvasively confirmed tumor growth before treatment. RESULTS: Intracranial pressure increased with tumor progression, from 5.5 mm Hg at baseline to 12.95 mm Hg on Day 25 after tumor cell implantation. Intracranial pressure during ICC ranged from 5 to 21 mm Hg and was correlated with increasing infusion volumes and increasing rates of infusion. No toxicity was observed, except at the higher ends of the tumor size and volume ranges. Fluorescein isothiocyanate-dextran distribution was greater with larger infusion volumes (30 microl versus 10 microl, n = 8, P < 0.05). No significant differences in distribution were observed when different infusion rates were compared while the volume was kept constant. At tolerated flow rates, the volumes of distribution were sufficient to promote adequate drug delivery to tumors. N,N'-Bis(2-chloroethyl)-N-nitrosourea treatment resulted in significant decreases in tumor size, compared with untreated controls. CONCLUSION: The C6 glioma model can be easily modified to study aspects of interstitial delivery via ICC and the application of ICC to the screening of potential antitumor agents for safety and efficacy.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Glioma/tratamiento farmacológico , Animales , Antineoplásicos Alquilantes/administración & dosificación , Encéfalo/metabolismo , Encéfalo/patología , Neoplasias Encefálicas/fisiopatología , Carmustina/administración & dosificación , Dextranos/farmacocinética , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/farmacocinética , Glioma/fisiopatología , Procesamiento de Imagen Asistido por Computador , Inyecciones , Presión Intracraneal , Imagen por Resonancia Magnética , Masculino , Ratas , Ratas Endogámicas F344 , Ratas Wistar , Distribución Tisular
15.
Dentomaxillofac Radiol ; 43(2): 20130329, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24265395

RESUMEN

The aim of this study was to assess the influence of different object locations in different fields of view (FOVs) of two cone beam CT (CBCT) systems on trabecular bone microstructure measurements of a human mandible. A block of dry human mandible was scanned at five different locations (centre, left, right, anterior and posterior) using five different FOVs of two CBCT systems (NewTom™ 5G; QR Verona, Verona, Italy and Accuitomo 170; Morita, Kyoto, Japan). Image analysis software (CTAn software v. 1.1; SkyScan, Kontich, Belgium) was used to assess the trabecular bone microstructural parameters (thickness, Tb.Th; spacing, Tb.Sp; number, Tb.N; bone volume density, BV/TV). All measurements were taken twice by one trained observer. Tb.Th, Tb.Sp and Tb.N varied significantly across different FOVs in the NewTom 5G (p < 0.001) and the Accuitomo 170 (p < 0.001). For location, a significant difference was observed only when measuring BV/TV (p = 0.03) using the NewTom 5G. The trabecular bone microstructural measurements obtained from CBCT systems are influenced by the size of FOVs. Not all trabecular bone parameters measured using different CBCT systems are affected when varying the object location within the FOVs.


Asunto(s)
Tomografía Computarizada de Haz Cónico/métodos , Mandíbula/diagnóstico por imagen , Intensificación de Imagen Radiográfica/métodos , Densidad Ósea/fisiología , Tomografía Computarizada de Haz Cónico/instrumentación , Humanos , Procesamiento de Imagen Asistido por Computador/métodos
16.
Dentomaxillofac Radiol ; 43(7): 20140019, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25135316

RESUMEN

OBJECTIVES: The aim of this study was to investigate if the metal artefact reduction (MAR) tool used in the software of the ORTHOPANTOMOGRAPH(®) OP300 (Instrumentarium Dental, Tuusula, Finland) can improve the gray value levels in post-operative implant scans. METHODS: 20 potential implant sites were selected from 5 edentulous human dry mandibles. Each mandible was scanned by a CBCT scanner, and images were produced under three different conditions: implant sites drilled but no implants inserted, implants inserted without application of MAR and implants inserted with application of MAR. Using Geomagic(®) Studio 2012 (Geomagic, Morrisville, NC) and 3Diagnosys(®) v. 5.3.1 (3Diemme(®) SRL, Cantù, Italy) software, three scans of each mandible were superimposed. The mean gray value of identical regions of bone around the implants was derived for each condition. The differences between gray value measurements at implant sites derived from different conditions were assessed. RESULTS: A significant difference was found between mean gray values from the scans with no implants inserted and with implants inserted (with and without MAR) (p = 0.012). No significant difference was revealed for gray values measured from scans with and without MAR (p = 0.975). CONCLUSIONS: The MAR tool in the software of the ORTHOPANTOMOGRAPH OP300 CBCT scanner does not significantly correct the voxel gray values affected by the metal artefact in the vicinity of an implant in human dry mandibles.

17.
Dentomaxillofac Radiol ; 42(3): 20120075, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23420864

RESUMEN

Several dental implant studies have reported that radiographic evaluation of bone quality can aid in reducing implant failure. Bone quality is assessed in terms of its quantity, density, trabecular characteristics and cells. Current imaging modalities vary widely in their efficiency in assessing trabecular structures, especially in a clinical setting. Most are very costly, require an extensive scanning procedure coupled with a high radiation dose and are only partially suitable for patient use. This review examines the current literature regarding diagnostic imaging assessment of trabecular microstructure prior to oral implant placement and suggests cone beam CT as a method of choice for evaluating trabecular bone microstructure.


Asunto(s)
Proceso Alveolar/anatomía & histología , Proceso Alveolar/diagnóstico por imagen , Implantación Dental Endoósea , Densidad Ósea , Tomografía Computarizada de Haz Cónico , Humanos , Imagen por Resonancia Magnética , Planificación de Atención al Paciente , Radiografía Panorámica , Reproducibilidad de los Resultados , Tomografía Computarizada por Rayos X/métodos , Microtomografía por Rayos X
18.
Comput Biol Med ; 43(9): 1142-53, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23930807

RESUMEN

In this paper, the semi-numerical techniques known as the optimal homotopy analysis method (HAM) and Differential Transform Method (DTM) are applied to study the magneto-hemodynamic laminar viscous flow of a conducting physiological fluid in a semi-porous channel under a transverse magnetic field. The two-dimensional momentum conservation partial differential equations are reduced to ordinary form incorporating Lorentizian magnetohydrodynamic body force terms. These ordinary differential equations are solved by the homotopy analysis method, the differential transform method and also a numerical method (fourth-order Runge-Kutta quadrature with a shooting method), under physically realistic boundary conditions. The homotopy analysis method contains the auxiliary parameter ℏ, which provides us with a simple way to adjust and control the convergence region of solution series. The differential transform method (DTM) does not require an auxiliary parameter and is employed to compute an approximation to the solution of the system of nonlinear differential equations governing the problem. The influence of Hartmann number (Ha) and transpiration Reynolds number (mass transfer parameter, Re) on the velocity profiles in the channel are studied in detail. Interesting fluid dynamic characteristics are revealed and addressed. The HAM and DTM solutions are shown to both correlate well with numerical quadrature solutions, testifying to the accuracy of both HAM and DTM in nonlinear magneto-hemodynamics problems. Both these semi-numerical techniques hold excellent potential in modeling nonlinear viscous flows in biological systems.


Asunto(s)
Viscosidad Sanguínea , Simulación por Computador , Campos Magnéticos , Modelos Cardiovasculares , Velocidad del Flujo Sanguíneo , Humanos , Porosidad
19.
Dentomaxillofac Radiol ; 42(3): 79884780, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-22933535

RESUMEN

OBJECTIVES: The aim of this study was to determine the grey value variation at the implant site with different scan settings, including field of view (FOV), spatial resolution, number of projections, exposure time and dose selections in two cone beam CT (CBCT) systems and to compare the results with those obtained from a multislice CT system. METHODS: A partially edentulous human mandibular cadaver was scanned by three CT modalities: multislice CT (MSCT) (Philips, Best, the Netherlands), and two CBCT systems: (Accuitomo 170(®), Morita, Japan) and (NewTom 5G(®), QR, Verona, Italy). Using different scan settings 36 and 24 scans were obtained from the Accuitomo and the NewTom, respectively. The scans were converted to digital imaging and communications in medicine 3 format. The analysis of the data was performed using 3Diagnosys(®) software (v. 3.1, 3diemme, Cantù, Italy) and Geomagic studio(®) 2012 (Morrisville, NC). On the MSCT scan, one probe designating the site for pre-operative implant placement was inserted. The inserted probe on MSCT was transformed to the same region on each CBCT scan using a volume-based three-dimensional registration algorithm. The mean voxel grey value of the region around the probe was derived separately for each CBCT. The influence of scanning parameters on the measured mean voxel grey values was assessed. RESULTS: Grey values in both CBCT systems significantly deviated from Hounsfield unit values measured with MSCT (p = 0.0001). In both CBCT systems, scan FOV and spatial resolution selections had a statistically significant influence on grey value measurements (p = 0.0001). The number of projections selection had a statistically significant influence in the Accuitomo system (p = 0.0001) while exposure time and dose selections had no statistically significant influence on grey value measurements in the NewTom (p = 0.43 and p = 0.37, respectively). CONCLUSIONS: Grey-level values from CBCT images are influenced by device and scanning settings.


Asunto(s)
Tomografía Computarizada de Haz Cónico/métodos , Implantación Dental Endoósea , Arcada Parcialmente Edéntula/diagnóstico por imagen , Algoritmos , Densidad Ósea , Cadáver , Tomografía Computarizada de Haz Cónico/instrumentación , Marcadores Fiduciales , Humanos , Mandíbula/diagnóstico por imagen , Dosis de Radiación , Tomografía Computarizada por Rayos X/métodos
20.
Dentomaxillofac Radiol ; 42(10): 20130206, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24404603

RESUMEN

The objective of this study was to investigate the effect of different cone beam CT scan parameters on trabecular bone microstructure measurements. A human mandibular cadaver was scanned using a cone beam CT (3D Accuitomo 170; J.Morita, Kyota, Japan). 20 cone beam CT images were obtained using 5 different fields of view (4×4 cm, 6×6 cm, 8×8 cm, 10×10 cm and 10×5 cm), 2 types of rotation steps (180° and 360°) and 2 scanning resolutions (standard and high). Image analysis software was used to assess the trabecular bone microstructural parameters (number, thickness and spacing). All parameters were measured twice by one trained observer. Intraclass correlation coefficients showed high intraobserver repeatability (intraclass correlation coefficient, 0.95­0.97) in all parameters across all tested scan parameters. Trabecular bone microstructural measurements varied significantly, especially in smaller fields of view (p = 0.001). There was no significant difference in the trabecular parameters when using different resolutions (number, p = 0.988; thickness, p = 0.960; spacing, p = 0.831) and rotation steps (number, p = 1.000; thickness, p = 0.954; spacing, p = 0.759). The scan field of view significantly influences the trabecular bone microstructure measurements. Rotation steps (180° or 360°) and resolution (standard or high) selections are not relevant.


Asunto(s)
Tomografía Computarizada de Haz Cónico/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Mandíbula/diagnóstico por imagen , Cadáver , Humanos , Imagenología Tridimensional/métodos , Arcada Parcialmente Edéntula/diagnóstico por imagen , Mandíbula/ultraestructura , Intensificación de Imagen Radiográfica/métodos , Rotación
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