RESUMEN
BACKGROUND: Cholelithiasis is a frequent complication in pediatric sickle cell disease (SCD). Though it is standard practice to perform a cholecystectomy in pediatric SCD patients with symptoms of cholelithiasis, the use of elective cholecystectomy for asymptomatic patients remains controversial. PROCEDURE: Records of 191 pediatric sickle cell patients with cholelithiasis who underwent cholecystectomy were retrospectively reviewed. Patients classified as follows: (i) elective-no preoperative symptoms, cholelithiasis on screening ultrasound, comprehensive preoperative plan; (ii) symptomatic-preoperative symptoms of cholelithiasis on diagnostic ultrasound, comprehensive preoperative plan; or (iii) emergent-hospitalization for acute cholecystitis symptoms, cholelithiasis on diagnostic ultrasound, limited preoperative preparation. We compared the morbidity of cholecystectomy by examining pre- and post-cholecystectomy hospital admission days, length of stay for cholecystectomy, and surgical complications. RESULTS: Patients with SCD underwent a total of 191 cholecystectomies over a 10-year period: 51 elective, 110 symptomatic, and 30 emergent. Patients who required emergent cholecystectomy had a longer postoperative hospitalization time than elective or symptomatic cholecystectomy (7.3 vs 4.3, P < 0.001). Baseline values for total bilirubin and aspartate aminotransferase (AST) were significantly elevated (P < 0.02 and P < 0.07, respectively) in patients requiring emergent cholecystectomy. CONCLUSIONS: This represents the largest reported retrospective review of pediatric cholelithiasis and cholecystectomy in SCD to date. These data strongly suggest that elective cholecystectomy decreases morbidity associated with emergent cholecystectomy. The overall outcomes for symptomatic and elective patients are favorable. However, our study indicates the need for prospective studies to identify clinical indicators for those emergent patients.
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Anemia de Células Falciformes/complicaciones , Colecistectomía/métodos , Colelitiasis/cirugía , Procedimientos Quirúrgicos Electivos/métodos , Tiempo de Internación/estadística & datos numéricos , Niño , Preescolar , Colelitiasis/etiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Morbilidad , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVE: To determine whether curve magnitude of scoliosis at presentation correlates with BMI. METHODS: Retrospective chart review of 180 patients presenting with scoliosis was performed. Curve pattern and magnitude, Risser status, occurrence of surgery, zip code, height and weight, race, and insurance status were recorded. Relationships were examined by Spearman rank and Pearson correlations, and logistic regression analysis was used to determine odds ratios. RESULTS: For both thoracic and lumbar curve patterns, there was a correlation between BMI and curve magnitude. Spearman rank correlation was 0.19 for thoracic (P = .03) and 0.24 for lumbar curves (P = .02). Overweight or obese patients were not more likely, however, to present with curves at higher risk of progression or more likely to have surgical intervention. With respect to potential confounding socioeconomic variables, thoracic curve magnitude was negatively correlated with median family income (Spearman rank correlation -0.17, P = .04). Curve magnitude was not correlated with race, distance, or insurance payer. CONCLUSIONS: Patients with high BMI and scoliosis are more likely to present with larger curves, but not more likely to require surgery. This is concerning because of the national trend of increasing childhood obesity and because scoliosis treatment may be more complicated in larger curves. Socioeconomic factors may also be barriers to access.
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Índice de Masa Corporal , Escoliosis/diagnóstico , Adolescente , Niño , Femenino , Instituciones de Salud , Humanos , Masculino , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Prevention of tumors induced by environmental carcinogens has not been achieved. Skin tumors produced by polyaromatic hydrocarbons, such as 7,12-dimethylbenz(a)anthracene (DMBA), often harbor an H-ras point mutation, suggesting that it is a poor target for early immunosurveillance. The application of pyrosequencing and allele-specific PCR techniques established that mutations in the genome and expression of the Mut H-ras gene could be detected as early as 1 d after DMBA application. Further, DMBA sensitization raised Mut H-ras epitope-specific CTLs capable of eliminating Mut H-ras(+) preneoplastic skin cells, demonstrating that immunosurveillance is normally induced but may be ineffective owing to insufficient effector pool size and/or immunosuppression. To test whether selective pre-expansion of CD8 T cells with specificity for the single Mut H-ras epitope was sufficient for tumor prevention, MHC class I epitope-focused lentivector-infected dendritic cell- and DNA-based vaccines were designed to bias toward CTL rather than regulatory T cell induction. Mut H-ras, but not wild-type H-ras, epitope-focused vaccination generated specific CTLs and inhibited DMBA-induced tumor initiation, growth, and progression in preventative and therapeutic settings. Transferred Mut H-ras-specific effectors induced rapid tumor regression, overcoming established tumor suppression in tumor-bearing mice. These studies support further evaluation of oncogenic mutations for their potential to act as early tumor-specific, immunogenic epitopes in expanding relevant immunosurveillance effectors to block tumor formation, rather than treating established tumors.
Asunto(s)
Vacunas contra el Cáncer/uso terapéutico , Genes ras/genética , Mutación Puntual/genética , Neoplasias Cutáneas/prevención & control , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Animales , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Vacunas contra el Cáncer/administración & dosificación , Carcinógenos/toxicidad , Citocinas/inmunología , Citocinas/metabolismo , Análisis Mutacional de ADN , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Epítopos/genética , Epítopos/inmunología , Femenino , Genes ras/inmunología , Células HEK293 , Humanos , Inmunoterapia Adoptiva/métodos , Ratones Endogámicos C3H , Ratones Endogámicos , Mutación Puntual/efectos de los fármacos , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/genética , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/metabolismo , Resultado del Tratamiento , Carga Tumoral/inmunologíaRESUMEN
BACKGROUND: Increased severity of illness in patient with acute hematogenous osteomyelitis (AHO) with methicillin-resistant Staphylococcus aureus (MRSA) necessitates prompt intervention, but overtreatment of methicillin-sensitive S. aureus (MSSA) may contribute to antibiotic resistance. Therefore, predicting methicillin sensitivity in suspected AHO is desirable. A previously published prediction algorithm has not performed well in settings with high prevalence of MRSA. We sought to develop a predictive equation using presenting factors to predict MRSA in our patient population with a predominance of MRSA. METHODS: A retrospective chart review was performed. Consecutive cases of AHO with positive blood or bone cultures were identified at a single children's hospital. Presenting features were recorded including duration of symptoms, weight-bearing, prior antibiotic use, vital signs, complete blood count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Univariate comparison was made between the groups with MRSA and MSSA. Continuous variables were compared with t tests and discrete variables were compared using the Fischer exact test. Logistic regression was performed using a forward stepwise regression to develop a model to predict MRSA. RESULTS: A total of 68 patients formed the study group, and 60% had MRSA (41 MRSA, 27 MSSA). Temperature, respiratory rate, heart rate, white blood cell count, absolute neutrophil count (ANC), ESR), and CRP were significantly higher in MRSA cases, whereas platelets were lower. Logistic regression resulted in a model utilizing temperature, ANC, and CRP. This model correctly predicted 87% of cases (92% of MRSA and 79% of MSSA) with an area under the curve of 0.919±0.035 with a 95% confidence interval of 0.851, 0.987. CONCLUSION: A logistic regression model incorporating temperature, ANC, and CRP correctly predicts methicillin resistance of S. aureus in 87% of cases. The model differs from one developed at an institution with a low rate of MRSA. Prediction of MRSA could help direct antibiotic management, whereas prediction of MSSA could help prevent overuse of antibiotics directed against MRSA. LEVEL OF EVIDENCE: Diagnostic study level IV.
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Proteína C-Reactiva/análisis , Fiebre/diagnóstico , Recuento de Leucocitos/métodos , Staphylococcus aureus Resistente a Meticilina , Osteomielitis , Infecciones Estafilocócicas , Enfermedad Aguda , Adolescente , Algoritmos , Niño , Preescolar , Femenino , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Osteomielitis/sangre , Osteomielitis/diagnóstico , Osteomielitis/epidemiología , Osteomielitis/microbiología , Osteomielitis/fisiopatología , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Estudios Retrospectivos , Infecciones Estafilocócicas/sangre , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/fisiopatología , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: To evaluate common duct (CD) dilation by computed tomography (CT) in patients with intact gallbladders and diameter change over time in remote and interval cholecystectomy patients, frequency of visualization of the CD, and its relationship to age. METHODS: This IRB-approved retrospective study evaluated baseline CD diameter, intrahepatic biliary dilation, and interval duct diameter change in patients with CTs ≥ 2 years apart (n = 324), in block-randomized order by two blinded board-certified radiologists. 272 patients were divided into three groups: (1) prior cholecystectomy before the first CT, (2) cholecystectomy between the first and last CTs, and (3) no cholecystectomy. A subset of 191 nonoperated patients was evaluated for age-related dilation. RESULTS: Group 1 ducts were significantly larger than the other groups at both baseline and follow-up CTs (p < 0.001). Group 2 showed a greater increase in duct size than the other groups at follow-up (p < 0.001). The CD was measurable in 89% of the CT studies. In nonoperated patients, there was a statistically significant correlation between CD size and increasing age (p < 0.001), although the CD size remained within normal size limits. CONCLUSION: Remote cholecystectomy patients have larger CD diameters than the nonoperated and interval cholecystectomy groups. Greater increase in ductal diameter occurred between studies in the interval cholecystectomy patients, suggesting that dilation occurs after cholecystectomy. Also, the CD dilates slightly with age in nonoperated patients.
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Colecistectomía , Conducto Colédoco/diagnóstico por imagen , Conducto Colédoco/patología , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/patología , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Dilatación Patológica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Estudios Retrospectivos , Adulto JovenRESUMEN
CASPASE-12 (CASP12) has a downregulatory function during infection and thus may protect against inflammatory disease. We investigated the distribution of CASP12 alleles (#rs497116) in African-Americans (AA) with rheumatoid arthritis (RA). CASP12 alleles were genotyped in 953 RA patients and 342 controls. Statistical analyses comparing genotype groups were performed using Kruskal-Wallis non-parametric ANOVA with Mann-Whitney U tests and chi-square tests. There was no significant difference in the overall distribution of CASP12 genotypes within AA with RA, but CASP12 homozygous patients had lower baseline joint-narrowing scores. CASP12 homozygosity appears to be a subtle protective factor for some aspects of RA in AA patients.
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Artritis Reumatoide/enzimología , Artritis Reumatoide/genética , Negro o Afroamericano/genética , Caspasa 12/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Artritis Reumatoide/inmunología , Estudios de Casos y Controles , Caspasa 12/inmunología , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Homocigoto , Humanos , Mediadores de Inflamación/metabolismo , Masculino , Persona de Mediana Edad , SeudogenesRESUMEN
PURPOSE: The purpose of this study was to evaluate intravenous (IV) contrast-enhanced single-source rapid kilovolt (peak)-switching dual-energy (RSDE) multidetector computed tomography (CT) material density assessment of hepatic steatosis compared to conventional unenhanced (CU) Multidetector computed tomography (MDCT). MATERIALS AND METHODS: This is an institutional review board-approved intrapatient study of 363 consecutive adults (189 men, 174 women; mean age, 59 years) evaluated with multiphasic IV abdominal RSDE. Material density virtual unenhanced water and fat hepatic parenchymal values were measured and correlated to Hounsfield units (HUs) on CU CT using linear regression. Study population was dichotomized into steatotic or nonsteatotic liver parenchyma on the basis of CU liver-spleen (L-S) difference. The RSDE fat(-iodine) values (in milligram per milliliter) were compared (t test), correlated to the L-S difference in HU, and a milligram-per-milliliter fat threshold for clinically significant steatosis was calculated using receiver operator curve (ROC) analysis. RESULTS: Regression analysis revealed r value of 0.86 for mg/mL water (P < 0.001) and 0.87 for milligram-per-milliliter fat (P < 0.001). Twenty-seven participants were excluded from the L-S analysis (splenectomy). A total of 107 (32%) had steatosis (mean L-S, - 6.3; mean fat(-iodine) milligram per milliliter, 1018.4); 229 (68%) had no steatosis (mean L-S, 9.4; milligram per milliliter, 1028.4 [P < 0.001]). The RSDE fat material density measurement correlated to L-S less than 1 with r value of 0.74 (P < 0.001), with an area under receiver operator curve of 0.847. A threshold of 1023-mg/mL fat had 71% sensitivity and 80% specificity, and a threshold of 1027-mg/mL fat had 90% sensitivity and 61% specificity for steatosis. CONCLUSIONS: The RSDE milligram-per-milliliter fat values correlate well with hepatic steatosis defined by the L-S difference less than 1 on conventional MDCT. A threshold of 1027 mg/mL can identify 90% of steatotic livers when post-IV contrast RSDE is used, without obtaining additional CU scans. However, regression equations were not helpful to convert an individual participant's milligram-per-milliliter fat or milligram-per-milliliter water-derived from RSDE material density images to CU MDCT HU for the estimation of liver fat content.
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Absorciometría de Fotón/métodos , Hígado Graso/diagnóstico por imagen , Yopamidol , Intensificación de Imagen Radiográfica/métodos , Imagen Radiográfica por Emisión de Doble Fotón/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Medios de Contraste , Femenino , Humanos , Infusiones Intravenosas , Yopamidol/administración & dosificación , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
PURPOSE: This study aimed to determine if a single-source rapid kilovolt (peak)-switching dual-energy (RSDE) multidetector computed tomography (CT) can differentiate high lipid content (HLC) from low lipid content (LLC) incidental adrenal lesions. METHODS: A retrospective intrapatient study of 40 consecutive adults with known hepatic or pancreatic pathology who underwent multiphasic abdominal RSDE for nonadrenal-related clinical indications and had adrenal lesions was done. Arterial phase was acquired with RSDE, conventional unenhanced (CU) images with standard MDCT. RSDE measurements included lesion attenuation in Hounsfield units on simulated monochromatic 140-keV images and density (in milligrams per milliliter) on material decomposition images, using water-iodine and fat-iodine basis pairs. Each variable was correlated with CU Hounsfield units (Pearson coefficient). RSDE lesion values were compared with analysis of variance and Tukey HSD test. Receiver operating characteristic (ROC) analysis was performed to identify RSDE thresholds comparable to 10 HU on unenhanced MDCT. RESULTS: Twenty-nine HLC and 18 LLC lesions were evaluated in 40 subjects (21 men; mean age, 66.5 years). RSDE variables correlated with CU Hounsfield units, r = 0.90-0.92, P < 0.001. Myelolipomas, HLC, and LLC lesions were different by analysis of variance, P < 0.001 for all dual-energy variables. Excluding myelolipomas from ROC curve analysis, ROC areas for Hounsfield unit 140-keV images, fat(-iodine), and water(-iodine) were 0.929 (0.039), 0.917 (0.046), and 0.912 (0.048), respectively (P < 0.001); using a specificity of 94.4%, 64% of adenomatous lesions had 140 keV values of less than 9.5 HU, 59% had fat(-iodine) values of less than 987 mg/mL, and 50% had water(-iodine) values of less than 994 mg/mL. CONCLUSIONS: There is a strong correlation between RSDE measures and accepted MDCT attenuation values for HLC and LLC adrenal lesions. In some patients undergoing postcontrast RSDE who are found to have incidental adrenal nodules, further unenhanced CT or adrenal-protocol CT or magnetic resonance imaging may not be necessary.
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Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/metabolismo , Biomarcadores de Tumor/metabolismo , Metabolismo de los Lípidos , Imagen Radiográfica por Emisión de Doble Fotón/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Previous gene microarray studies have shown that expression of 14-3-3θ is significantly decreased in an α-synuclein transgenic mouse model. In this study, we tested whether α-synuclein can regulate 14-3-3θ transcription. We demonstrate that the 14-3-3θ mRNA level is decreased in SH-SY5Y cells overexpressing α-synuclein. Luciferase activity under the control of the 14-3-3θ promoter is reduced both in stable SH-SY5Y cells constitutively overexpressing α-synuclein and in doxycycline-inducible SH-SY5Y cells upon α-synuclein induction, suggesting that the regulation of 14-3-3θ by α-synuclein occurs at the transcriptional level. Knockdown of α-synuclein by RNA interference does not increase the 14-3-3θ mRNA level. These findings suggest that α-synuclein represses 14-3-3θ transcription under pathologic conditions, but that regulation of 14-3-3θ expression is not a function of endogenous α-synuclein at baseline.
Asunto(s)
Proteínas 14-3-3/genética , Transcripción Genética , alfa-Sinucleína/genética , Proteínas 14-3-3/metabolismo , Línea Celular Tumoral , Humanos , Regiones Promotoras Genéticas , ARN Mensajero/genética , ARN Mensajero/metabolismo , alfa-Sinucleína/metabolismoRESUMEN
OBJECTIVES: To evaluate changes in the common duct diameter on sonography over time in patients with and without cholecystectomy. METHODS: We retrospectively evaluated the common duct diameter, central biliary dilatation, and interval change in 1079 patients who underwent sonography at least 2 years apart over a 6-year period. A board-certified radiologist, blinded to clinical and laboratory data, measured the duct diameter. A total of 893 patients (568 female and 325 male) were divided into 3 groups: group 1, remote cholecystectomy before sonography (mean, 9.7 years before sonography; n = 117); group 2, interval cholecystectomy between the first and second sonographic examinations (n = 56); and group 3, no cholecystectomy (n = 720). All groups were stratified by age, and group 3 was also stratified by the absence (n = 528) or presence (n=192) of gallstones. RESULTS: Duct diameters at baseline and follow-up averaged 4.5 and 5.2, 3.6 and 4.9, and 3.5 and 3.9 mm in groups 1, 2, and 3, respectively. Group 1 ducts were larger at baseline than in the other groups (P < .001). At follow-up, group 2 ducts showed a greater interval diameter increase than the other groups (P < .001). In a subanalysis of each group based on age, there was a mild increase in duct size with increasing age, although not clinically significant and within normal limits. In group 3 patients who never had gallstones, there was a significant small increase in duct size over decades (P < .001). The baseline duct sizes for patients with gallstones were not significantly different from those who never had gallstones (P = .15). CONCLUSIONS: Patients with remote cholecystectomy have larger common duct diameters than those with no or interval cholecystectomy. Most asymptomatic patients with or without cholecystectomy have a normal common duct diameter.
Asunto(s)
Colecistectomía/estadística & datos numéricos , Enfermedades del Conducto Colédoco/diagnóstico por imagen , Enfermedades del Conducto Colédoco/epidemiología , Conducto Colédoco/diagnóstico por imagen , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/epidemiología , Ultrasonografía/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alabama/epidemiología , Conducto Colédoco/patología , Dilatación Patológica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de Riesgo , Sensibilidad y Especificidad , Método Simple Ciego , Resultado del Tratamiento , Adulto JovenRESUMEN
The goal of the study was to assess the efficacy of combined extracellular matrix metalloprotease inducer (EMMPRIN)- and death receptor 5 (DR5)-targeted therapy for pancreatic adenocarcinoma in orthotopic mouse models with multimodal imaging. Cytotoxicity of anti-EMMPRIN antibody and anti-DR5 antibody (TRA-8) in MIA PaCa-2 and PANC-1 cell lines was measured by ATPlite assay in vitro. The distributions of Cy5.5-labeled TRA-8 and Cy3-labeled anti-EMMPRIN antibody in the 2 cell lines were analyzed by fluorescence imaging in vitro. Groups 1 to 12 of severe combined immunodeficient mice bearing orthotopic MIA PaCa-2 (groups 1-8) or PANC-1 (groups 9-12) tumors were used for in vivo studies. Dynamic contrast-enhanced-MRI was applied in group 1 (untreated) or group 2 (anti-EMMPRIN antibody). The tumor uptake of Tc-99m-labeled TRA-8 was measured in group 3 (untreated) and group 4 (anti-EMMPRIN antibody). Positron emission tomography/computed tomography imaging with (18)F-FDG was applied in groups 5 to 12. Groups 5 to 8 (or groups 9 to 12) were untreated or treated with anti-EMMPRIN antibody, TRA-8, and combination, respectively. TRA-8 showed high killing efficacy for both MIA PaCa-2 and PANC-1 cells in vitro, but additional anti-EMMPRIN treatment did not improve the cytotoxicity. Cy5.5-TRA-8 formed cellular caps in both the cell lines, whereas the maximum signal intensity was correlated with TRA-8 cytotoxicity. Anti-EMMPRIN therapy significantly enhanced the tumor delivery of the MR contrast agent, but not Tc-99m-TRA-8. Tumor growth was significantly suppressed by the combination therapy, and the additive effect of the combination was shown in both MIA PaCa-2 and PANC-1 tumor models.
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Adenocarcinoma/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Basigina/inmunología , Neoplasias Pancreáticas/tratamiento farmacológico , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/inmunología , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Animales , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Basigina/metabolismo , Carbocianinas/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Humanos , Imagen por Resonancia Magnética , Ratones , Ratones Endogámicos BALB C , Ratones SCID , Microscopía Fluorescente/métodos , Imagen Multimodal/métodos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Tomografía de Emisión de Positrones , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Tomografía Computarizada por Rayos X , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The objective of this study was to evaluate extracellular matrix metalloproteinase (EMMPRIN) as a novel target in orthotopic pancreatic cancer murine models. MIA PaCa-2 human pancreatic tumor cells were implanted in groups 1 and 3-7, whereas MIA PaCa-2 EMMPRIN knockdown cells were implanted in group 2. Dosing with anti-EMMPRIN antibody started immediately after implantation for groups 1-3 (residual tumor model) and at 21 days after cell implantation for groups 4-7 (established tumor model). Groups 3, 5, and 7 were treated with anti-EMMRPIN antibody (0.2-1.0 mg) twice weekly for 2-3 weeks, whereas the other groups served as the control. In the residual tumor model, tumor growth of anti-EMMPRIN-treated group was successfully arrested for 21 days (15 ± 4 mm(3)), which was significantly lower than that of the EMMPRIN knockdown group (80 ± 15 mm(3); P=0.001) or the control group (240 ± 41 mm(3); P<0.001). In the established tumor model, anti-EMMPRIN therapy lowered tumor volume increase by approximately 40% compared with the control, regardless of the dose amount. Ki67-expressed cell density of group 5 was 939 ± 150 mm(-2), which was significantly lower than that of group 4 (1709 ± 145 mm(-2); P=0.006). Microvessel density of group 5 (30 ± 6 mm(-2)) was also significantly lower than that of group 4 (53 ± 5 mm(-2); P=0.014), whereas the microvessel size of group 5 (191 ± 22 µm(2)) was significantly larger than that of group 4 (113 ± 26 µm(2); P=0.049). These data show the high potential of anti-EMMPRIN therapy for pancreatic cancer and support its clinical translation.
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Anticuerpos Antiidiotipos/farmacología , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Basigina/inmunología , Basigina/metabolismo , Antígeno Ki-67/biosíntesis , Metaloproteinasas de la Matriz/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Animales , Anticuerpos Antiidiotipos/inmunología , Anticuerpos Monoclonales de Origen Murino/inmunología , Basigina/biosíntesis , Línea Celular Tumoral , Evaluación Preclínica de Medicamentos , Matriz Extracelular/metabolismo , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Antígeno Ki-67/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones SCID , Terapia Molecular Dirigida , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Radioinmunoensayo , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Children with sickle cell anemia are at risk for brain injury. Physicians obtain brain magnetic resonance imaging (MRI) for clinical indications to determine if a patient has developed a brain injury. Controversy exists whether all children with sickle cell anemia should undergo MRI screening. This retrospective study evaluates the clinical and laboratory correlates for brain injury in 124 MRIs obtained for a variety of clinical indications. Seizure, sensory, or motor events were statistically associated with the highest risk for brain injury while less specific neurologic complaints of headache or poor school performance were not associated. Children with high systolic blood pressure, leukocytosis, and severe anemia demonstrate a higher probability for brain injury. These results indicate that brain MRI should be obtained on all children with seizure, sensory, or motor events. These data suggest that less specific neurologic symptoms should be screened if physical findings or abnormal lab or vital signs exist.
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Anemia de Células Falciformes/complicaciones , Lesiones Encefálicas/diagnóstico , Lesiones Encefálicas/etiología , Encéfalo/patología , Imagen por Resonancia Magnética , Adolescente , Anemia de Células Falciformes/diagnóstico por imagen , Presión Sanguínea , Lesiones Encefálicas/diagnóstico por imagen , Niño , Preescolar , Femenino , Cefalea/etiología , Hemoglobinas/metabolismo , Humanos , Lactante , Modelos Logísticos , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética/métodos , Masculino , Trastornos del Movimiento/etiología , Estudios Retrospectivos , Convulsiones/etiología , Ultrasonografía Doppler Transcraneal , Adulto JovenRESUMEN
Early pancreatic cancer response following cetuximab and/or irinotecan therapies was measured by serial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) before and during therapy. Groups 1 to 4 (n â=â 6/group) of SCID mice bearing orthotopic pancreatic adenocarcinoma xenografts expressing luciferase were treated with phosphate-buffered saline, cetuximab, irinotecan, or cetuximab combined with irinotecan, respectively, twice weekly for 3 weeks. DCE-MRI was performed on days 0, 1, 2, and 3 after therapy initiation, whereas anatomic magnetic resonance imaging was performed on days 0, 1, 2, 3, 6, and 13. Bioluminescence imaging was performed on days 0 and 21. At day 21, all tumors were collected for further histologic analyses (Ki-67 and CD31 staining), whereas tumor dimensions were measured by calipers. The Ktrans values in the 0.5 mm-thick peripheral tumor region were calculated, and the changes in Ktrans during the 3 days posttherapy were compared to tumor volume changes, bioluminescent signal changes, and histologic findings. The Ktrans changes in the peripheral tumor region after 3 days of therapy were linearly correlated with 21-day decreases in tumor volume (p < .001), bioluminescent signal (p â=â .050), microvessel densities (p â=â .002), and proliferating cell densities (p â=â .001). This study supports the clinical use of DCE-MRI for pancreatic cancer patients for early assessment of an anti-epidermal growth factor receptor therapy combined with chemotherapy.
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Anticuerpos Monoclonales/uso terapéutico , Camptotecina/análogos & derivados , Medios de Contraste , Imagen por Resonancia Magnética/métodos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Anticuerpos Monoclonales Humanizados , Camptotecina/uso terapéutico , Línea Celular Tumoral , Cetuximab , Humanos , Irinotecán , Ratones , Ratones SCID , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos X , Carga TumoralRESUMEN
PURPOSE: To measure reader agreement in determining whether lung nodules detected at baseline screening computed tomography (CT) had changed at subsequent screening examinations and to evaluate the variability in recommendations for further follow-up. MATERIALS AND METHODS: All subjects were enrolled in the National Lung Screening Trial (NLST), and each participant consented to the use of their de-identified images for research purposes. The authors randomly selected 100 cases of nodules measuring at least 4.0 mm at 1-year screening CT that were considered by the original screening CT reader to be present on baseline CT scans; nodules considered by the original reader to have changed were oversampled. Selected images from each case showing the entire nodule at both examinations were preloaded on a picture archiving and communication system workstation. Nine radiologists served as readers, and they evaluated whether the nodule was present at baseline and recorded the bidimensional measurements and nodule characteristics at each examination, presence or absence of change, results of screening CT, and follow-up recommendations (high-level follow-up, low-level follow-up, no follow-up). RESULTS: On the basis of reviews during case selection, five nodules seen at follow-up were judged not to have been present at baseline; for 19 of the remaining 95 cases, at least one reader judged the nodule not to have been present at baseline. For the 76 nodules that were unanimously considered to have been present at baseline, 21%-47% (mean ± standard deviation, 30% ± 9) were judged to have grown. The κ values were similar for growth (κ = 0.55) and a positive screening result (κ = 0.51) and were lower for a change in margins and attenuation (κ = 0.27-0.31). The κ value in the recommendation of high- versus low-level follow-up was high (κ = 0.66). CONCLUSION: Reader agreement on nodule growth and screening result was moderate to substantial. Agreement on follow-up recommendations was lower.
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Tamizaje Masivo/estadística & datos numéricos , Derivación y Consulta/estadística & datos numéricos , Nódulo Pulmonar Solitario/diagnóstico por imagen , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Prevalencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) measured the early vascular changes after administration of TRA-8, bevacizumab, or TRA-8 combined with bevacizumab in breast tumor xenografts. PROCEDURES: Groups 1-4 of nude mice bearing human breast carcinoma were injected with phosphate-buffered saline, TRA-8, bevacizumab, and TRA-8 + bevacizumab on day 0, respectively. DCE-MRI was performed on days 0, 1, 2, and 3, and thereafter tumors were collected for terminal deoxynucleotidyl transferase-mediated dUT nick end labeling and CD31 staining. RESULTS: DCE-MRI measured a significant K (trans) change within 3 days after TRA-8 therapy that correlated with tumor growth arrest, which was not shown with statistical significance by histopathology at these early time points posttreatment. The K (trans) changes followed quadratic polynomial curves. CONCLUSION: DCE-MRI detected significantly lower K (trans) levels in breast tumor xenografts following TRA-8 monotherapy or combined therapy with bevacizumab.
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Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/irrigación sanguínea , Imagen por Resonancia Magnética/métodos , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales Humanizados , Bevacizumab , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Humanos , Ratones , Ratones Desnudos , Trasplante HeterólogoRESUMEN
OBJECTIVE: The purpose of the study was to determine whether a difference in patient preference exists between iohexol (Omnipaque) and diatrizoate sodium (Gastroview) as oral contrast medium for abdominal-pelvic CT. A secondary objective was to evaluate whether there are significant differences in bowel opacification and adverse effect profile for the two agents. SUBJECTS AND METHODS: From August 2007 through March 2009, 300 patients were enrolled in this prospective study after informed consent was obtained. Eligible patients were identified from those scheduled for outpatient abdominal-pelvic CT. Subjects were randomly assigned to receive one of two oral contrast agents in a double-blinded fashion. Subjects graded the taste using a 5-point scale, and data regarding demographics, total volume, and adverse effects were collected. A direct comparison of 30 mL of each of the two diluted agents in randomized order was then performed. CT images were graded for bowel opacification by two blinded abdominal radiologists. RESULTS: Of 287 subjects who expressed a preference, 233 patients (81%) preferred dilute iohexol compared with 54 patients (19%) who preferred dilute diatrizoate sodium (p < 0.001). Ten patients had no preference, and three patients did not complete the taste comparison study. No difference in bowel opacification was identified between the oral contrast agents (p = 0.27), nor was there a significant difference in adverse effects (p = 0.352). CONCLUSION: Patents preferred dilute iohexol over dilute diatrizoate sodium for oral contrast for abdominal-pelvic CT. There was no significant difference in bowel opacification or adverse effect profile.
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Medios de Contraste , Diatrizoato , Intestinos/diagnóstico por imagen , Yohexol , Prioridad del Paciente , Tomografía Computarizada por Rayos X/métodos , Administración Oral , Adulto , Medios de Contraste/administración & dosificación , Diatrizoato/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Yohexol/administración & dosificación , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Imagen de Cuerpo EnteroRESUMEN
INTRODUCTION: It is often not possible to determine whether small nodules detected on computed tomography (CT) in oncology patients are metastatic. We evaluated a group of oncology patients to determine the outcome of small pulmonary nodules and whether they can be ignored in the therapeutic decision process. MATERIALS AND METHODS: Radiology reports of thoracic CTs from a 2-year period were searched for keywords indicating a small pulmonary nodule. All CT images were evaluated by two thoracic radiologists for nodules 4 mm or less. There were 102 cases that met criteria for inclusion. RESULTS: Forty-seven had follow-up CT of less than 365 days, and 55 had follow-up CT for more than 365 days. For those with less than 365 days, the observed nodule was increased (17, 36%), increased and new nodules (9, 19%); stable (19, 40%); stable but new nodules developed (1); and decreased (1). For those with greater than 365 days follow-up, the observed nodule was increased (3, 5%); stable (51, 93%); and stable but new nodule developed (1). Combined, 28% of patient';s nodules increased (90% were within 365 days; 25% within 203 days; and 14% within 14 days). CONCLUSION: In oncologic patients, 28% of small pulmonary nodules detected at initial CT will increase in size, suggesting metastasis. This increase in size tends to occur early, and follow-up CT in 3 months and 6 months would be appropriate in further evaluation. Small nodules that are stable in size for more than 365 days are unlikely to be pulmonary metastasis.
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Neoplasias Pulmonares/diagnóstico por imagen , Nódulo Pulmonar Solitario/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estudios Retrospectivos , Nódulo Pulmonar Solitario/patologíaRESUMEN
BACKGROUND: This study evaluated the effect of 17ß-estradiol (E2) administration on cardiovascular parameters in male rats after trauma-hemorrhage and for an extended period (3 hours) of severe hypotension, based on blood-pool single photon emission computed tomography imaging. METHODS: After a 5-cm midline laparotomy, male Sprague-Dawley rats were injected intravenously with Tc-bovine serum albumin; the animals were then bled for >45 minutes to reach maximum bleedout (MBO; removal of 60% of the circulating blood volume). E2 (1 mg/kg body weight, 0.4 mL/kg) or vehicle (cyclodextrin [CD], 0.4 mL/kg) was injected intravenously at MBO; no additional fluid was administered for 3 hours. Imaging was performed continually for a maximum of 3 hour post-MBO. The percentages of injected dose in heart, brain, liver, and kidney were quantified from the imaging (n = 8/group) at 0 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, and 180 minutes post-MBO. Mixed model analysis of variance was used to analyze the difference between the two groups over six imaging time points (30-180 minutes post-MBO). RESULTS: The percentages of injected dose of Tc-bovine serum albumin in heart, kidney, and liver after E2 administration were significantly higher than those after CD administration (p = 0.036, 0.025, and 0.028 for heart, kidney, and liver, respectively), whereas those in brain were not different between E2 and CD administration (p = 0.343). CONCLUSIONS: The significantly larger blood volume maintained in heart, kidney, and liver of rats after E2 therapy compared with control supports the notion that E2 produces salutary effects on the cardiovascular system after trauma-hemorrhage and even extended periods of severe hypotension.
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Hipotensión/tratamiento farmacológico , Choque Hemorrágico/tratamiento farmacológico , Tomografía Computarizada de Emisión de Fotón Único , Heridas y Lesiones/complicaciones , Animales , Presión Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Estradiol/uso terapéutico , Hipotensión/diagnóstico por imagen , Hipotensión/etiología , Masculino , Ratas , Ratas Endogámicas F344 , Ratas Sprague-Dawley , Choque Hemorrágico/diagnóstico por imagen , Choque Hemorrágico/etiología , Heridas y Lesiones/fisiopatologíaRESUMEN
OBJECTIVE: The purpose of this study was to determine whether preoperative neoadjuvant therapy in patients with locally advanced pancreatic cancer affects the ability of multiphasic MDCT to predict successful surgical resection. MATERIALS AND METHODS: From 2000 to 2006, there were 12 patients with prior neoadjuvant therapy successfully downstaged by CT and 31 age-matched pancreatic cancer patients without preoperative therapy who underwent pancreatic MDCT followed by attempted pancreaticoduodenectomy. Three readers blinded to surgical findings independently analyzed immediate preoperative MDCT scans of 43 patients comprising the retrospective data set in random order for vascular involvement (degree of contact and narrowing) and distant metastases. Individual reader sensitivity and specificity for resectability prediction were compared for study and control groups using the Fisher's exact test. Interobserver agreement was assessed using the kappa statistic. RESULTS: Seven (58%) of 12 neoadjuvant-treated adenocarcinomas and 10 (32%) of 31 control pancreatic carcinomas were resectable (p > 0.05). For resectable disease, sensitivities were 86%, 71%, and 14% for the neoadjuvant group and 90%, 90%, and 60% for the control group (p > 0.05). Specificities were 80%, 100%, and 100% for the neoadjuvant group and 57%, 43%, and 76% for the control group (reader 2 specificity difference, p = 0.04). The multi rater kappa value of resectability prediction for neoadjuvant patients was 0.28, and that for control subjects was 0.63 (p < 0.001). In the neoadjuvant group, the majority of individual reader errors were false-negative resectability interpretations resulting from overestimation of vascular involvement. Consideration of degrees of venous abutment did not improve estimation of resectability in patients with neoadjuvant therapy. CONCLUSION: Sensitivity for prediction of resectability tends to be lower for patients with locally advanced pancreatic cancer that has been downstaged by neoadjuvant therapy, but this trend is not statistically significant. Interobserver variability for determination of resectability is statistically higher than for controls who did not receive preoperative therapy.