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1.
Pediatr Blood Cancer ; 64(1): 113-120, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27643455

RESUMO

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.


Assuntos
Anemia Falciforme/complicações , Colecistectomia/métodos , Colelitíase/cirurgia , Procedimentos Cirúrgicos Eletivos/métodos , Tempo de Internação/estatística & dados numéricos , Criança , Pré-Escolar , Colelitíase/etiologia , Feminino , Seguimentos , Humanos , Masculino , Morbidade , Prognóstico , Estudos Retrospectivos
2.
J Immunol ; 194(6): 2683-95, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25694611

RESUMO

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.


Assuntos
Vacinas Anticâncer/uso terapêutico , Genes ras/genética , Mutação Puntual/genética , Neoplasias Cutâneas/prevenção & controle , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Vacinas Anticâncer/administração & dosagem , Carcinógenos/toxicidade , Citocinas/imunologia , Citocinas/metabolismo , Análise Mutacional de DNA , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Epitopos/genética , Epitopos/imunologia , Feminino , Genes ras/imunologia , Células HEK293 , Humanos , Imunoterapia Adotiva/métodos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos , Mutação Puntual/efeitos dos fármacos , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/genética , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Resultado do Tratamento , Carga Tumoral/imunologia
3.
Abdom Imaging ; 40(6): 1581-6, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25421790

RESUMO

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.


Assuntos
Colecistectomia , Ducto Colédoco/diagnóstico por imagem , Ducto Colédoco/patologia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/patologia , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Dilatação Patológica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto Jovem
4.
J Pediatr Orthop ; 35(4): 426-30, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25171681

RESUMO

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.


Assuntos
Proteína C-Reativa/análise , Febre/diagnóstico , Contagem de Leucócitos/métodos , Staphylococcus aureus Resistente à Meticilina , Osteomielite , Infecções Estafilocócicas , Doença Aguda , Adolescente , Algoritmos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Osteomielite/sangue , Osteomielite/diagnóstico , Osteomielite/epidemiologia , Osteomielite/microbiologia , Osteomielite/fisiopatologia , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Retrospectivos , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/fisiopatologia , Estados Unidos/epidemiologia
5.
Immunogenetics ; 66(4): 281-5, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24515649

RESUMO

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.


Assuntos
Artrite Reumatoide/enzimologia , Artrite Reumatoide/genética , Negro ou Afro-Americano/genética , Caspase 12/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Artrite Reumatoide/imunologia , Estudos de Casos e Controles , Caspase 12/imunologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Homozigoto , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Pseudogenes
6.
J Comput Assist Tomogr ; 37(6): 904-10, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24270112

RESUMO

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.


Assuntos
Absorciometria de Fóton/métodos , Fígado Gorduroso/diagnóstico por imagem , Iopamidol , Intensificação de Imagem Radiográfica/métodos , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Humanos , Infusões Intravenosas , Iopamidol/administração & dosagem , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
7.
J Comput Assist Tomogr ; 37(6): 937-43, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24270116

RESUMO

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.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/metabolismo , Biomarcadores Tumorais/metabolismo , Metabolismo dos Lipídeos , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
8.
J Ultrasound Med ; 32(8): 1385-91, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23887947

RESUMO

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.


Assuntos
Colecistectomia/estatística & dados numéricos , Doenças do Ducto Colédoco/diagnóstico por imagem , Doenças do Ducto Colédoco/epidemiologia , Ducto Colédoco/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/epidemiologia , Ultrassonografia/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alabama/epidemiologia , Ducto Colédoco/patologia , Dilatação Patológica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Método Simples-Cego , Resultado do Tratamento , Adulto Jovem
9.
Mol Imaging ; 10(3): 153-67, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21496446

RESUMO

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  =  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  =  .050), microvessel densities (p  =  .002), and proliferating cell densities (p  =  .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.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Camptotecina/análogos & derivados , Meios de Contraste , Imageamento por Ressonância Magnética/métodos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Anticorpos Monoclonais Humanizados , Camptotecina/uso terapêutico , Linhagem Celular Tumoral , Cetuximab , Humanos , Irinotecano , Camundongos , Camundongos SCID , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Carga Tumoral
10.
Radiology ; 259(1): 263-70, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21248232

RESUMO

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.


Assuntos
Programas de Rastreamento/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Prevalência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estados Unidos/epidemiologia
11.
Anticancer Drugs ; 22(9): 864-74, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21730821

RESUMO

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.


Assuntos
Anticorpos Anti-Idiotípicos/farmacologia , Anticorpos Monoclonais Murinos/uso terapêutico , Basigina/imunologia , Basigina/metabolismo , Antígeno Ki-67/biossíntese , Metaloproteinases da Matriz/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Anticorpos Anti-Idiotípicos/imunologia , Anticorpos Monoclonais Murinos/imunologia , Basigina/biossíntese , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Matriz Extracelular/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Antígeno Ki-67/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Terapia de Alvo Molecular , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Radioimunoensaio , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Clin Gastroenterol Hepatol ; 8(3): 303-8; quiz e33, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19879963

RESUMO

BACKGROUND & AIMS: A goal of radiologists is to use computed tomography (CT) imaging less frequently in younger patients because of radiation exposure. We evaluated abdominal CT use among patients hospitalized for acute pancreatitis at a tertiary care hospital and compared estimated radiation doses with disease severity and patient age. METHODS: We performed a retrospective analysis of numbers and types of CTs performed on patients with acute pancreatitis (1036 admissions, 869 patients; mean age, 50.8 y); 566 had 1081 abdominopelvic CTs performed from October 1, 2001, to September 30, 2006. Effective dose estimates for abdominopelvic CTs were used to estimate exposure. Disease severities were stratified using Balthazar CT grades and severity indexes. RESULTS: The mean number of abdominopelvic CTs per patient, per hospitalization, was 1.9 (range, 1-12); the mean number was 3.0 over the 5-year period (range, 1-19). During hospitalization, each patient was exposed to a mean estimated radiation dose of 31.03 +/- 26.4 mSv (range, 14.7-176.9 mSv). Patients with pancreatitis grades D or E (n = 233) compared with grades A through C (n = 333) had longer periods of hospitalization (mean, 23.3 vs 10.8 d; P < .001), more days as an inpatient (mean, 2.54 vs 1.45 d; P < .001), more total CT scans (mean, 4.02 vs 2.37; P < .001), and higher total effective radiation doses (mean, 53.5 vs 35 mSv; P < .0001). Linear regression revealed a relationship between dose and disease grade, but not patient age. CONCLUSIONS: Regardless of age, patients with severe acute pancreatitis undergo more abdominopelvic CTs as inpatients and outpatients and are exposed to higher doses of radiation compared with patients with less severe disease. Awareness of CT ordering patterns for patients with acute pancreatitis may aid in the development of alternate imaging strategies to reduce radiation exposure in this population, especially for younger patients.


Assuntos
Pâncreas/patologia , Pâncreas/efeitos da radiação , Pancreatite Necrosante Aguda/diagnóstico , Radiografia Abdominal/efeitos adversos , Radiografia Abdominal/estatística & dados numéricos , Tomografia/efeitos adversos , Tomografia/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto Jovem
13.
AJR Am J Roentgenol ; 195(5): 1137-41, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20966319

RESUMO

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.


Assuntos
Meios de Contraste , Diatrizoato , Intestinos/diagnóstico por imagem , Iohexol , Preferência do Paciente , Tomografia Computadorizada por Raios X/métodos , Administração Oral , Adulto , Meios de Contraste/administração & dosagem , Diatrizoato/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Iohexol/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Imagem Corporal Total
14.
AJR Am J Roentgenol ; 194(3): 615-22, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20173136

RESUMO

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.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma/patologia , Meios de Contraste , Feminino , Humanos , Iohexol , Iopamidol , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Sensibilidade e Especificidade
15.
J Trauma ; 69(5): 1266-73, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20571453

RESUMO

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.


Assuntos
Hipotensão/tratamento farmacológico , Choque Hemorrágico/tratamento farmacológico , Tomografia Computadorizada de Emissão de Fóton Único , Ferimentos e Lesões/complicações , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Estradiol/uso terapêutico , Hipotensão/diagnóstico por imagem , Hipotensão/etiologia , Masculino , Ratos , Ratos Endogâmicos F344 , Ratos Sprague-Dawley , Choque Hemorrágico/diagnóstico por imagem , Choque Hemorrágico/etiologia , Ferimentos e Lesões/fisiopatologia
16.
AJR Am J Roentgenol ; 190(3): 650-5, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18287435

RESUMO

OBJECTIVE: The purpose of our study was to evaluate the causes, waveform morphology, and clinical outcomes of high-resistance reversed diastolic flow in transplanted kidneys. MATERIALS AND METHODS: To identify patients with reversed diastolic flow, we performed a review of 5,089 renal transplant Doppler sonograms obtained over a 10-year period. Waveform morphology was correlated with surgical-histologic findings and clinical outcomes. RESULTS: Fifty-nine patients (33 male, 26 female; age range, 14-69 years) with reversed diastolic flow fell into three chronologic groups: acute group (six patients), transplant < 24 hours; perioperative group (34 patients), transplant < or = 30 days; and long-term group (19 patients), transplant > 30 days. Acute reversed diastolic flow was associated with higher likelihood of graft survival (p = 0.001, Fisher's exact test) compared with reversed diastolic flow discovered in the perioperative or long-term group. In the acute group, hematoma, acute tubular necrosis, renal vein thrombosis, and vascular kink produced reversed diastolic flow. The causes of reversed diastolic flow for the perioperative group were acute tubular necrosis, rejection, and renal vein thrombosis; for the long-term group, reasons for diastolic reversal were rejection, glomerulosclerosis, low cardiac output, and diabetic nephrosclerosis. The causes of reversed diastolic flow were not differentiated by waveform morphology. CONCLUSION: The causes of reversed diastolic flow cannot be distinguished by waveform morphology. Patients with reversed diastolic flow < 24 hours after transplantation warrant emergent exploration because correction of treatable causes may lead to recovered function. Long-standing renal transplants with reversed diastolic flow are not likely salvageable.


Assuntos
Sobrevivência de Enxerto/fisiologia , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Circulação Renal/fisiologia , Resistência Vascular/fisiologia , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Falência Renal Crônica/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler
17.
AJR Am J Roentgenol ; 191(5): 1552-8, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18941100

RESUMO

OBJECTIVE: The objective of our study was to examine the correlation between CT-based and radionuclide renography-based measures of split renal function in a healthy population of live potential kidney donors using 3D models generated from CT angiography. MATERIALS AND METHODS: The records of 173 renal donor candidates who had undergone CT and radionuclide renography between March 1, 2005, and February 28, 2006, were retrospectively evaluated; of those 173 patients, 152 met study inclusion criteria. A blinded investigator using 3D models that were created semiautomatically from the unenhanced, arterial, and excretory phase data made measurements of CT renal volumes and attenuations. The mean renal attenuation and volume were used to calculate the net accumulation of contrast material and split renal function for comparison with radionuclide renography. Split function from CT was calculated in the arterial and excretory phases as well as based on split renal volume and the Patlak method. RESULTS: All four CT-based methods for the calculation of split renal function showed correlation with no significant difference from radionuclide renography (p > 0.05, Student's t test). Pearson's correlation coefficients varied from 0.36 to 0.63 (p < 0.001 for each). Difference scores revealed that the excretory and renal volume splits had the narrowest range and showed a linear, nonzero relationship to the renography splits. Bland-Altman analysis confirmed that the majority of difference scores between each CT method and the radionuclide renography were within the 95% CI of the differences. CONCLUSION: Split renal function based on 3D CT models can provide a "one-stop" evaluation of both the anatomic and the functional characteristics of the kidneys of living potential kidney donors. The excretory phase data and the split renal volume data show the best correlation and the smallest difference scores compared with radionuclide renography data.


Assuntos
Angiografia/métodos , Câmaras gama , Imageamento Tridimensional/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Renografia por Radioisótopo/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Feminino , Humanos , Testes de Função Renal/métodos , Masculino , Pessoa de Meia-Idade , Intensificação de Imagem Radiográfica/métodos , Renografia por Radioisótopo/instrumentação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
J Assoc Nurses AIDS Care ; 19(1): 75-84, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18191771

RESUMO

This study evaluated an intervention to facilitate adaptive coping by persons living with HIV (PLWH), with the participation of their cohabiting partners as a dimension of the intervention. An experimental design with randomization was used, and 84 PLWH and their partners were recruited. The intervention was based on a psychosocial educational model that incorporated four 2-hour sessions focused on communication, stress appraisal, adaptive coping strategies, and building social support. Both members of the dyad were included in each session. The comparison control included four supportive phone calls to the PLWH alone. Data were collected from both the PLWH and their partner in each of the two groups at baseline, immediately following the intervention, and 3 months and 6 months posttreatment. Data were analyzed using repeated measures analysis of variance, with change scores from the partner data being covariates. Results indicated that the design was a feasible model, which demonstrated potential for the management of stress and possibly problems such as adherence in PLWH. A manual was developed as a part of this intervention and is currently available.


Assuntos
Adaptação Psicológica , Infecções por HIV/psicologia , Educação em Saúde/organização & administração , Modelos Educacionais , Apoio Social , Cônjuges/educação , Adulto , Análise de Variância , Atitude Frente a Saúde , Comunicação , Conflito Psicológico , Currículo , Estudos de Viabilidade , Feminino , Infecções por HIV/complicações , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Promoção da Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos , Pesquisa em Avaliação de Enfermagem , Avaliação de Programas e Projetos de Saúde , Cônjuges/psicologia , Estresse Psicológico/etiologia , Estresse Psicológico/prevenção & controle
19.
Diabetes Technol Ther ; 9 Suppl 1: S102-10, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17563298

RESUMO

BACKGROUND AND METHODS: Delivery of insulin to the deep lung presents unique challenges to the body's mucosal defense system. Pulmonary mucosal defense has the ability to discriminate between self and non-self antigens and has the potential for induction of immunologic tolerance. Published data concerning the immunogenicity of inhaled human insulin in drug trials will be reviewed, and data regarding the possible adverse effects of anti-insulin antibody development will be presented. Examination of the immunologic safety of inhaled human insulin will include discussion of comparator studies, factors affecting immunogenicity, the effects of insulin immunity on glycemic control and pulmonary function, and the relationship of insulin antibodies to dose requirements, pharmacodynamics, and hypoglycemia. CONCLUSIONS: Inhaled human insulin, whether formulated as a powder or liquid, has been shown to be more immunogenic than comparator insulins given by subcutaneous routes; however, adverse effects of antibody formation have not been demonstrated.


Assuntos
Administração por Inalação , Anticorpos Anti-Insulina/sangue , Insulina/administração & dosagem , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/imunologia , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Imunoglobulina G/sangue , Insulina/uso terapêutico , Nebulizadores e Vaporizadores
20.
AJR Am J Roentgenol ; 188(3): 745-50, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17312063

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the sensitivity and specificity of seven CT signs in the diagnosis of internal hernia after laparoscopic Roux-en-Y gastric bypass. MATERIALS AND METHODS: With institutional review board approval, the CT scans of 18 patients (17 women, one man) with surgically proven internal hernia after laparoscopic Roux-en-Y gastric bypass were retrieved, as were CT studies of a control group of 18 women who had undergone gastric bypass but did not have internal hernia at reoperation. The scans were reviewed by three radiologists for the presence of seven CT signs of internal hernia: swirled appearance of mesenteric fat or vessels, mushroom shape of hernia, tubular distal mesenteric fat surrounded by bowel loops, small-bowel obstruction, clustered loops of small bowel, small bowel other than duodenum posterior to the superior mesenteric artery, and right-sided location of the distal jejunal anastomosis. Sensitivity and specificity were calculated for each sign. Stepwise logistic regression was performed to ascertain an independent set of variables predictive of the presence of internal hernia. RESULTS: Mesenteric swirl was the best single predictor of hernia; sensitivity was 61%, 78%, and 83%, and specificity was 94%, 89%, and 67% for the three reviewers. The combination of swirled mesentery and mushroom shape of the mesentery was better than swirled mesentery alone, sensitivity being 78%, 83%, and 83%, and specificity being 83%, 89%, and 67%, but the difference was not statistically significant. CONCLUSION: Mesenteric swirl is the best indicator of internal hernia after laparoscopic Roux-en-Y gastric bypass, and even minor degrees of swirl should be considered suspicious.


Assuntos
Derivação Gástrica/efeitos adversos , Hérnia/diagnóstico por imagem , Hérnia/etiologia , Laparoscopia/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Adulto , Feminino , Humanos , Masculino , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como Assunto , Resultado do Tratamento
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