RESUMO
AIM: To quantify and correlate the diagnostic error rates in radiological interpretation with the experience of the attending neuroradiologist at a tertiary academic medical centre. MATERIALS AND METHODS: The institution's Neuroradiology Quality Assurance Database of diagnostic errors was searched for misses from 2014-2020. Attendance at Head and Neck (H&N), Brain, and Paediatric Neuroradiology (PN) tumour boards (TB) as the presenting radiologist was recorded. Number of post-fellowship years of clinical practice (CPY) and frequency of TB attendance were considered separate metrics of a radiologist's experience. Radiological errors were categorised as Total, H&N, Skull Base (SKB), Brain, or PN diagnostic errors. Diagnostic error rates per attending neuroradiologist within each category were correlated with the frequency of TB participation and CPY using Spearman's rank correlation coefficients. RESULTS: A total 607 examinations contained a diagnostic error. Spearman's rank correlation coefficients between Total TB participation and Total, H&N, SKB, Brain error rates were: -0.89 (p=0.0002); -0.81 (p=0.002); -0.66 (p=0.03); -0.82 (p=0.002); respectively. Spearman's rank correlation coefficients between CPY and Total, H&N, SKB, Brain and PN error rates were: 0.05 (p=0.88); 0.08 (p=0.82); 0.28 (p=0.41); -0.10 (p=0.77); -0.16 (p=0.63), respectively. Spearman's rank correlation coefficients between H&N TB and H&N, SKB error rates; and between Brain TB attendance and Brain error rates were statistically significant (p<0.05). CONCLUSION: The present study shows a strong correlation between high TB participation rates and low diagnostic error rates. The number of years in practice did not appear to influence error rate.
Assuntos
Médicos , Radiologia , Criança , Erros de Diagnóstico , Bolsas de Estudo , Humanos , RadiologistasRESUMO
AIM: To analyse errors in head and neck (H&N) pathology made by attending neuroradiologists at a single tertiary-care centre. MATERIALS AND METHODS: A neuroradiology quality assurance (QA) database of radiological errors was searched for attending physician errors in H&N pathology from 2014-2020. Data were limited to computed tomography (CT) and magnetic resonance imaging (MRI) reports. Data were collected on missed pathologies and study types. Misses were grouped into three categories: central neck (thyroid gland, aerodigestive tract), lateral neck (salivary glands, lymph nodes, soft tissues), and face/orbits (orbits, sinuses, masticator space). RESULTS: During the study period, a total of 283,248 CT and MRI neuroradiology examinations were interpreted (all indications). Seventy-four H&N misses were identified comprising 85.1% perceptual and 14.9% interpretive errors. The distribution of errors was face/orbits (37.8%), central neck (36.5%), and lateral neck (25.7%). Clinically significant errors were found most commonly in the aerodigestive tract (21%), orbits (17.7%), masticator space, and parotid glands (14.5% each). The majority (67.6%) of the misses were detected on examinations that were not performed for a primary H&N indication; MRI brain was the most common examination (27%). Clearly malignant or potentially malignant masses accounted for 48.6% of all misses. CONCLUSION: The majority of H&N misses were perceptual and were detected on examinations not performed for a H&N indication. Clearly malignant or potentially malignant masses represented half of all misses.
Assuntos
Erros de Diagnóstico/estatística & dados numéricos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Radiologistas , Tomografia Computadorizada por Raios X/métodos , Centros Médicos Acadêmicos , Humanos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Centros de Atenção TerciáriaRESUMO
AIM: To investigate whether apical periodontitis lesions infected by Epstein-Barr virus (EBV) exhibit higher levels of oxidative stress biomarkers [8-hydroxydeoxyguanosine (8-OHdG) and oxidized glutathione (GSSG)] and bone resorption regulators [receptor activator of nuclear factor (NF-κB) ligand (RANKL) and osteoprotegerin (OPG)] compared to EBV-negative periapical lesions and healthy pulp tissues. METHODOLOGY: The experimental group consisted of 30 EBV-positive and 30 EBV-negative periapical lesions collected in conjunction with apicoectomy. The pulp tissues of 20 impacted third molars were used as healthy controls. The qualitative and quantitative analysis of EBV was performed by nested and real-time polymerase chain reaction (PCR), respectively. The levels of RANKL and OPG were analysed by reverse transcriptase real-time PCR. The levels of 8-OHdG and GSSG were determined by enzyme-linked immunosorbent assay (ELISA). Mann-Whitney U-test and Spearman's correlation were used for statistical analysis. RESULTS: The levels of RANKL, OPG, 8-OHdG and GSSG were significantly higher in apical periodontitis lesions compared to healthy pulp controls (P = 0.001, P < 0.001, P < 0.001 and P < 0.05, respectively). RANKL and OPG mRNA expression was significantly higher in EBV-positive compared to EBV-negative periapical lesions (P < 0.05). There was no significant correlation between EBV copy numbers and levels of RANKL, OPG, 8OH-dG and GSSG in apical periodontitis. CONCLUSION: Levels of bone resorption regulators and oxidative stress biomarkers were increased in apical periodontitis compared to healthy pulp tissues. EBV-positive periapical lesions exhibited higher levels of RANKL and OPG compared to EBV-negative periapical lesions. EBV may contribute to progression of apical periodontitis via enhanced production of bone resorption regulators.
Assuntos
Reabsorção Óssea/metabolismo , Reabsorção Óssea/virologia , Infecções por Vírus Epstein-Barr/metabolismo , Herpesvirus Humano 4 , Estresse Oxidativo , Periodontite Periapical/metabolismo , Periodontite Periapical/virologia , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Glutationa/metabolismo , Humanos , Masculino , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND AND OBJECTIVE: Due to increased life expectancy, the risk profile of the patients undergoing cardiac surgery changed dramatically. This is especially important in case of concomitant coronary artery disease and carotid artery stenosis (CAS). Careful decision making and appropriate surgical strategy in these patients is critical for the success of the operation. Controversy about relationship between staged and concomitant carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) still exists. In the current study, we present our case lood in treating patients with concomitant carotid artery stenosis and coronary artery disease. PATIENTS AND METHODS: CABG with additional CEA due to neurologic symptoms or high grade (>80%) CAS has been performed in 835 patients in the period of 1982-2010. Results of evaluation of perioperative mortality and morbidity in regard to the surgical approach have been discussed. RESULTS: The average patient age was 62.6 +/- 8.7 years. Echocardiography revealed that 28% of the patients had poor left ventricle ejection fraction (<30%). Coronarography demonstrated that 21.4% of the operated patients had significant left main coronary artery stenosis (>60%). In terms of neurological status, majority of the patients (88.3%) were neurologically asymptomatic. The overall mortality regardless the sequence of procedures was 2.3% (19 patients). In the group of concomitantly treated patients 44.6% (50 patients) required triple coronary bypass while the mean number of coronary bypasses was 2.6. Postoperative neurologic complications were present in 102 patients (12.2%). Eighty-four patients (10.0%) have had TIA, while 18 patients (2.2%) have had permanent neurologic deficit while 4 patients (0.5%) died as a result of it. CONCLUSIONS: It is imperative that every patient being considered for CABG should undergo ultrasonic evaluation of the carotid arteries regardless the neurological symptomatology. Concomitant surgery on patients with severe CAS and coronary disease carries a slightly higher operative risk and, therefore, should be avoided. Concomitant surgical treatment should only be considered in patients with unstable angina and significant CAS in whom we may expect higher morbidity and mortality.
Assuntos
Estenose das Carótidas/cirurgia , Ponte de Artéria Coronária , Estenose Coronária/cirurgia , Endarterectomia das Carótidas , Idoso , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico , Estenose das Carótidas/mortalidade , Transtornos Cerebrovasculares/etiologia , Distribuição de Qui-Quadrado , Angiografia Coronária , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Estenose Coronária/complicações , Estenose Coronária/diagnóstico , Estenose Coronária/mortalidade , Ecocardiografia , Endarterectomia das Carótidas/efeitos adversos , Endarterectomia das Carótidas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Sérvia , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia DopplerRESUMO
PURPOSE: To prospectively and intraindividually compare breast magnetic resonance imaging (MRI) at 1.5 Tesla (T) and 3.0T. METHODS: A prospective intraindividual Ethics Committee- approved study was performed in 31 women (average age 58.6±12.3 years), with 114 lesions (9 benign, 105 breast cancers; 24 patients with unilateral and 7 with bilateral cancers). Axial bilateral breast high-spatial resolution contrast-enhanced dynamic MRI was performed at 1.5T using 3 dimensional (3D) dynamic gradient-echo sequences in all patients (spatial resolution 1.1×0.7×2 mm; temporal resolution 41 sec per dynamic acquisition), and after 24-48 h at 3.0T (0.6×0.6×1.7 mm; temporal resolution 65 and 72 sec per dynamic acquisition). Contrast enhancement ratio, number and features of enhancing lesions, image quality and reliability were compared by two radiologists independently. RESULTS: 102 cancer lesions were detected at 1.5T and 105 cancer lesions were detected in 31 patients at 3.0T. One cancer lesion was observed at 1.5T which was missed at 3.0T, and 3 cancer lesions and one high-risk lesion (LCIS) were detected at 3.0T while missed at 1.5T. Enhancement rates were significantly higher at 1.5T (224.5±100.2) compared to 3.0T (133.7±38.3). Better image quality was observed at 3.0T. Interobserver reliability was higher at 3.0T (p= 0.684) compared to 1.5T (p= 0.351). CONCLUSION: Detection of breast cancer shows a trend of better performance at 3.0T than at 1.5T.
Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
BACKGROUND AND PURPOSE: Diagnostic errors affect 2%-8% of neuroradiology studies, resulting in significant potential morbidity and mortality. This retrospective analysis of a large database at a single tertiary academic institution focuses on diagnostic misses in cerebrovascular pathology and suggests error-reduction strategies. MATERIALS AND METHODS: CT and MR imaging reports from a consecutive database spanning 2015-2020 were searched for errors of attending physicians in cerebrovascular pathology. Data were collected on missed findings, study types, and interpretation settings. Errors were categorized as ischemic, arterial, venous, hemorrhagic, and "other." RESULTS: A total of 245,762 CT and MR imaging neuroradiology examinations were interpreted during the study period. Vascular diagnostic errors were present in 165 reports, with a mean of 49.6 (SD, 23.3) studies on the shifts when an error was made, compared with 34.9 (SD, 19.2) on shifts without detected errors (P < .0001). Seventy percent of examinations occurred in the hospital setting; 93.3% of errors were perceptual; 6.7% were interpretive; and 93.9% (n = 155) were clinically significant (RADPEER 2B or 3B). The distribution of errors was arterial and ischemic each with 33.3%, hemorrhagic with 21.8%, and venous with 7.5%. Most errors involved brain MR imaging (30.3%) followed by head CTA (27.9%) and noncontrast head CT (26.1%). The most common misses were acute/subacute infarcts (25.1%), followed by aneurysms (13.7%) and subdural hematomas (9.7%). CONCLUSIONS: Most cerebrovascular diagnostic errors were perceptual and clinically significant, occurred in the emergency/inpatient setting, and were associated with higher-volume shifts. Diagnostic errors could be minimized by adjusting search patterns to ensure vigilance on the sites of the frequently missed pathologies.
Assuntos
Cabeça , Tomografia Computadorizada por Raios X , Humanos , Estudos Retrospectivos , Erros de Diagnóstico , Tomografia Computadorizada por Raios X/métodos , Hematoma SubduralRESUMO
The serine protease inhibitor antithrombin III (AT-III), an α2-globulin synthesized in the liver and endothelial cells, is the principal in vivo inhibitor of blood coagulation inactivating mainly thrombin. AT-III deficiency presents a rare hereditary or acquired disorder that most often comes to light when a patient suffers recurrent venous thrombosis and pulmonary embolism. Triggers for the onset of the thrombosis include various mechanisms such as pregnancy, delivery, surgery, trauma, and contraceptive pill use. Decreased response to heparin may be the first sign of AT-III deficiency. Since heparin is a conditio sine qua non for cardiopulmonary bypass, rapid consumption of AT-III promoted by heparin may lead to systemic thrombosis. The effect of heparin on graft patency after CABG in patients with AT-III deficiency, particularly with respect to early graft thrombosis, has not been fully investigated. The early detection and timely treatment of this disorder may impact perioperative morbidity. We present a case of simultaneous thrombosis of three venous grafts after elective coronary artery bypass surgery in a patient with AT-III deficiency.
Assuntos
Deficiência de Antitrombina III/diagnóstico , Deficiência de Antitrombina III/etiologia , Ponte de Artéria Coronária/efeitos adversos , Cardiopatias/diagnóstico , Cardiopatias/etiologia , Trombose/diagnóstico , Trombose/etiologia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
AIM: To compare the reproducibility of three electronic apex locators (EALs), Dentaport ZX, RomiApex A-15 and Raypex 5, under clinical conditions. METHODOLOGY: Forty-eight root canals of incisors, canines and premolars with or without radiographically confirmed periapical lesions required root canal treatment in 42 patients. In each root canal, all three EALs were used to determine the working length (WL) that was defined as the zero reading and indicated by 'Apex', '0.0' or 'red square' markings on the EAL display. A new K-file of the same size was used for each measurement. The file length was fixed with a rubber stop and measured to an accuracy of 0.01 mm. Measurements were undertaken by two calibrated operators. Differences in zero readings between the three EALs in the same root canal were statistically analysed using paired t-tests with the Bonferroni correction, Bland-Altman plot and Linn's concordance correlation coefficients at α = 0.05. RESULTS: Mean and standard deviation values measured by the three EALs showed no statistically significant differences. Identical readings by all three EALs were found in 10.4% of root canals. Forty-three per cent of readings differed by less than ± 0.5 mm and 31.3% exceeded a difference of ± 1 mm. CONCLUSIONS: The clinical reproducibility of Dentaport ZX, RomiApex A-15 and Raypex 5 was confirmed with the majority of readings within the ± 1.0 mm range. However, the small number of identical zero readings suggests that EALs are not reliable as the sole means of WL determination under clinical conditions.
Assuntos
Odontometria/instrumentação , Ápice Dentário/anatomia & histologia , Adulto , Idoso , Instrumentos Odontológicos , Impedância Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Unilateral decreased/nonvisualization of a transverse dural sinus on MRV poses a diagnostic dilemma when gadolinium administration is contraindicated. We determined the frequency of unilateral decreased/nonvisualization of the transverse dural sinus and the performance of pregadolinium MR imaging sequences in diagnosing transverse sinus thrombosis in the presence of unilateral decreased/nonvisualization on phase-contrast MRV. MATERIALS AND METHODS: We conducted a retrospective review of consecutive 3D phase-contrast MRV (VENC, 30 cm/s) and routine brain imaging (noncontrast sagittal T1, axial T2, FLAIR, DWI, GRE, and postgadolinium 3D-MPRAGE images) performed during a 3-year period for a total of 208 patients. Nonvisualization of a transverse dural sinus was defined as ≥50% nonvisualization of the transverse sinus caliber versus the contralateral side on MRV. Noncontrast imaging findings were considered abnormal when hyperintense signal was present on T2, FLAIR, T1, and DWI, and there were T2* blooming artifacts on GRE and DWI. Postgadolinium 3D-MPRAGE was used to confirm the diagnosis of transverse sinus thrombosis. RESULTS: Nonvisualization of a transverse dural sinus was observed in 72/208 (34.6%) patients on MRV; 56/72 (77.8%) were without transverse sinus thrombosis, and 16/72 (22.2%) patients had transverse dural sinus thrombosis. Nonvisualization of a transverse dural sinus was seen in 56/192 (29.2%) patients without transverse sinus thrombosis and 16/16 (100%) with transverse sinus thrombosis. Abnormal findings on DWI (transverse sinus hyperintense signal or T2* blooming artifact) are 93.8% sensitive and 100.0% specific for transverse sinus thrombosis. Other noncontrast MR imaging sequences ranged from 56.3%-68.8% sensitive and 91.1%-100.0% specific. CONCLUSIONS: Nonvisualization of a transverse dural sinus is a frequent phenomenon on phase-contrast MRV. DWI can be effectively used to exclude sinus thrombosis when nonvisualization of a transverse dural sinus is a diagnostic conundrum on phase-contrast MRV and contrast-enhanced studies are contraindicated.
Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Trombose do Seio Lateral/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Seios Transversos/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Gadolínio , Humanos , Imageamento Tridimensional/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemAssuntos
Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Neoplasias da Próstata/sangue , Fator de Crescimento Transformador beta/sangue , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Ensaio de Imunoadsorção Enzimática , Humanos , Masculino , Invasividade Neoplásica , Estadiamento de Neoplasias , Projetos Piloto , Antígeno Prostático Específico/sangue , Prostatectomia , Hiperplasia Prostática/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgiaRESUMO
In the present study, the induction of base-pair reversion mutations from trp to Trp+ in the wild type and in uvrA, recA, and lexA mutants of Escherichia coli B/r was used to analyze the mechanism of benzo(a)pyrene-7,8-dihydrodiol 9,10-oxide (BPDE) mutagenesis. BPDE mutagenesis was compared to that of two well characterized mutagens: ethyl methanesulfonate and 4-nitroquinoline 1-oxide. We found that a uvrA mutant was about 20 times more sensitive to BPDE killing and BPDE-induced mutations than was wild-type E. coli. This suggests that BPDE-DNA lesions are removed by an excision repair mechanism similar to that which excises pyrimidine dimers. Although strains carrying either recA or lexA mutations were also more sensitive to BPDE killing, BPDE was not mutagenic in these strains. The recA+ and lexA+ gene products coordinately control the regulation of a set of genes that are expressed in response to DNA-damaging agents (SOS functions). Therefore, our results indicate that in E. coli BPDE is an indirect mutagen that acts through host-mediated functions, i.e., the SOS pathway, in the process of mutation fixation. The possible significance of these findings to carcinogenesis are discussed.
Assuntos
Benzopirenos/toxicidade , Escherichia coli/efeitos dos fármacos , Mutação/efeitos dos fármacos , 4-Nitroquinolina-1-Óxido/toxicidade , 7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido , Composição de Bases , Reparo do DNA , DNA Bacteriano , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Metanossulfonato de Etila/toxicidade , Genes , Mutagênicos , Raios UltravioletaRESUMO
A pilot study was conducted to assess whether plasma levels of transforming growth factor-beta1 (TGF-beta1) might facilitate biological subgrouping of postmenopausal metastatic breast cancer patients, and, accordingly, its applicability in clinical oncology. This study included 29 postmenopausal metastatic breast cancer patients. Plasma TGF-beta1 levels were detected by enzyme-linked immunosorbent assay (ELISA). Estrogen and progesterone receptors were assayed by radioligand binding, in accordance with the recommendation of the EORTC. Concentrations of 17-beta estradiol were determined by using ELISA-microwell method (DIALAB). Overall survival was followed for 24 months for each individual patient. Stratification of the patients by ER/PR status showed that 14 patients with estrogen receptor-negative, progesterone receptor-negative carcinomas displayed a statistically significant increase in plasma TGF-beta1 levels when compared to plasma TGF-beta1 levels of 6 patients with ER-positive, PR-positive carcinomas (P=0.04). In this study, 7 out of 14 patients with negative receptors' status had no plasma TGF-beta1 values overlapping with patients having positive receptors' status. The TGF-beta1 cut-off value was defined as the highest plasma TGF-beta1 level of ER-positive, PR-positive patients: 3.28 ng/ml. This plasma TGF-beta1 cut-off value defined low-risk subgroup of 19 patients (< or = 3.28 ng/ml) and high-risk subgroup of 10 patients (> 3.28 ng/ml) (P=0.047). Plasma TGF-beta1-related survival was independent of the classical prognostic factors of metastatic breast cancer. Accordingly, a clinical significance of elevated plasma TGF-beta1 levels may be suggested.
Assuntos
Neoplasias da Mama/fisiopatologia , Pós-Menopausa , Análise de Sobrevida , Fator de Crescimento Transformador beta/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Ensaio de Imunoadsorção Enzimática , Estradiol/sangue , Feminino , Humanos , Metástase Neoplásica , Ensaio Radioligante , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Fator de Crescimento Transformador beta1RESUMO
Fluorescence spectra of DNA isolated from hamster embryo cells incubated with 7,12-dimethylbenz(a)anthracene, or DNA modified in a microsomal system by reaction with this carcinogen or its 7-hydroxymethyl derivative, were compared to various model compounds. The spectra indicate that the DMBA derivative bound to DNA, in all 3 cases, has a 9,10-dimethylanthracene-like chromophore. They also provide the first evidence of the similarity in structure of the DNA-bound products between 7,12-dimethylbenz(a)anthracene and its 7-hydroxymethyl derivative. Our results are consistent with an activation mechanism that involves saturation of the 1,2,3,4-ring positions.
Assuntos
9,10-Dimetil-1,2-benzantraceno/metabolismo , Benzo(a)Antracenos/metabolismo , DNA/metabolismo , Microssomos/metabolismo , 9,10-Dimetil-1,2-benzantraceno/análogos & derivados , Animais , Células Cultivadas , Fenômenos Químicos , Química , Cricetinae , Técnicas In Vitro , Espectrometria de FluorescênciaRESUMO
In the present study, in vitro binding of 14C-labeled pinacolyl methylphosphonochloridate (PiCl) to calf-thymus DNA has been investigated. The data reveal that, at PiCl concentrations of 0.038-0.26 mM, the binding is rapid and saturable at the extent of modification of 1 PiCl molecule per 2000 nucleotides. A similar range of PiCl concentrations was toxic, but did not produce a significant increase in mutagenicity in Salmonella typhimurium TA100 and TA98. Our results are of relevance with regard to the in vitro assessment of Soman-like organophosphates and the mutagenic risk of these agents and related pesticides.
Assuntos
Mutagênicos , Compostos Organofosforados/toxicidade , Soman/toxicidade , Fenômenos Químicos , Química , DNA , Testes de Mutagenicidade , Salmonella typhimurium/efeitos dos fármacos , Soman/análogos & derivadosRESUMO
Although overexpression of TGF-beta1 protein has been demonstrated in advanced breast cancer (BC) patients, as well as in other solid tumours, the molecular mechanism of this process remains obscure. This paper proposes that a genetic/epigenetic alteration might occur in the TGF-beta1 gene, within the region coding for the recognition site with TGFbeta receptor type II, leading to a disruption of the ligand-receptor interaction and triggering the TGF-beta1 cascade-related BC progression. To establish the operational framework for this hypothesis, in the present study, this recognition site was identified by the Informational Spectrum Method (ISM) to comprise two TGF-beta1 peptides (positions 47-66 aa and 83-112 aa) and one receptor peptide at positions 112-151 aa of the extracellular domain of the receptor (TbetaRIIM). The TbetaRIIM locus was further evaluated by ISM-derived deletion analysis of the TbetaRII sequences. To provide experimental support for the proposed model, a pilot study of plasma TGF-beta1 analysis was performed in advanced BC patients (n = 8). Two commercial ELISA assays, one with specific alphaTGF-beta1 MAb (MAb) and other with TbetaRIIM as the immobilized phase, revealed pronounced differences in the pattern of plasma TGF-beta1 elevation. In MAb-profile, the TGF-beta1 increase was detected in 7 of 8 patients, whereas analogous TbetaRIIM-profile revealed the elevation in 3 of 8 patients, taking a 50% of maximal elevation as the cut-off value. These findings are consistent with the proposed aberration of TGF-beta1 ligand within the TbetaRII recognition site. Summarizing, this model system is a good starting point for further genetic studies, particularly on genetic/epigenetic alterations of sequences involved in TGF-beta1 and TbetaRIIM interaction, with putative prognostic value for breast cancer.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Análise de Sequência de Proteína/métodos , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos , Sítios de Ligação/genética , Neoplasias da Mama/epidemiologia , Feminino , Perfilação da Expressão Gênica/métodos , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Dados de Sequência Molecular , Ligação Proteica , Proteínas Serina-Treonina Quinases , Receptor do Fator de Crescimento Transformador beta Tipo II , Iugoslávia/epidemiologiaRESUMO
PURPOSE OF STUDY: To determine the rate of formation of tertiary dentine in dogs' teeth, in response to five commonly used lining materials. Also, to record the resulting differences in quality of the formed dentine. MATERIALS AND METHODS: Representatives of five types of materials commonly used in general practice in the UK were placed in deep standardised cavities with a remaining dentine thickness of 400-500 microns, and sealed to the cavo-surface with zinc oxide-eugenol. The daily rate of tertiary dentine formed in response to each material was measured over a period of 119 days using a tetracycline staining method. A concomitant study to show the quality of the formed dentine was undertaken using the same materials and experimental conditions. RESULTS: There was a significant difference between the rates of tertiary dentine formation for all materials except zinc oxide-eugenol and Ledermix paste. For each material there was a increased rate of tertiary dentine formation in the second period (29-49 days) compared to the first period (0-28 days). This is considered to be due, in part, to a lag period when damaged odontoblasts are differentiating from mesenchymal elements. The rate of tertiary dentine formation in response to all the test materials was always greater than that of normal physiological dentine formation in unprepared teeth. Qualitatively, there was difference in the formed tertiary dentine beneath each material. All the materials caused odontoblast destruction, altered ground substance production and alterations in the calcification process. CONCLUSION: None of the materials routinely used at present can be considered to be 'ideal' as odontoblast destruction, altered ground substance production and altered calcification occur beneath zinc oxide-eugenol preparations, calcium hydroxide preparations as well as in response to corticosteroid-containing materials such as Ledermix paste and cement.
Assuntos
Forramento da Cavidade Dentária , Dentina Secundária/crescimento & desenvolvimento , Dentinogênese/efeitos dos fármacos , Análise de Variância , Animais , Compostos de Cálcio/farmacologia , Hidróxido de Cálcio/farmacologia , Demeclociclina/farmacologia , Polpa Dentária/efeitos dos fármacos , Dentina/efeitos dos fármacos , Dentina Secundária/induzido quimicamente , Cães , Combinação de Medicamentos , Eugenol , Formaldeído , Minerais/farmacologia , Odontoblastos/efeitos dos fármacos , Óxidos/farmacologia , Fatores de Tempo , Triancinolona Acetonida/farmacologia , Óxido de Zinco , Cimento de Óxido de Zinco e Eugenol/farmacologiaRESUMO
The value of blind terminal subcultures (7 and 30 days) and prolonged incubation (30 days) of blood cultures from immunosuppressed patients was analyzed in the Fundación Favaloro, the Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia and the Hospital de Niños Ricardo Gutiérrez. A total of 2707 blood cultures and 369 patients were included (transplantation of solid organs 154, oncohematologic disorders 106 and solid tumors 109). Bact-Alert bottles were incubated at 35 degrees C for 30 days in the Bact-Alert System. Bottles with positive signals were routinely removed, and aliquots of the broth were Gram stained and subcultured aerobically in chocolate agar and Sabouraud agar. A total of 136 bacteremic episodes were obtained. The positivization time of blood cultures was 81.6% at 24 h, 93.3% at 48 h, 94.5% at 72 h and 97.7% within 7 days. Only 3 (2.2%) episodes were positive by blind terminal subcultures and 1 (0.75%) by prolonged incubation (14 days). The median time and range of positivization in hours were 13.8 and 2.2-168, respectively. The microorganisms isolated were coagulase negative staphylococci (n = 24), Klebsiella pneumoniae (n = 22), Staphylococcus aureus (n = 21), Escherichia coli (n = 18), Acinetobacter spp (n = 9), Candida spp (n = 8), Pseudomonas aeruginosa (n = 6), Enterobacter cloacae (n = 5), Stenotrophomonas maltophilia (n = 5), Enterococcus faecalis, Salmonella spp and Capnocytophaga sputigena (n = 2), Enterobacter aerogenes, Enterococcus faecium, Citrobacter diversus, Candida albicans, Klebsiella oxytoca, Chryseomonas luteola, Serratia marcescens, Abiotrophia spp, Campylobacter jejuni, Moraxella catarrhalis, Moraxella urethralis, Neisseria sicca, beta hemolytic group G streptococci, Rhodococcus equi, Micrococcus spp, Cryptococcus neoformans and Streptococcus mitis (n = 1). In our experience, blind terminal subcultures and prolonged incubation of blood cultures from immunosuppressed patients are unnecessary and cost expensive.
Assuntos
Bacteriemia/microbiologia , Bactérias/isolamento & purificação , Técnicas Bacteriológicas , Sangue/microbiologia , Hospedeiro Imunocomprometido , Bacteriemia/diagnóstico , Técnicas Bacteriológicas/economia , Meios de Cultura , Humanos , Neoplasias/sangue , Neoplasias/complicações , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/microbiologia , Método Simples-Cego , Fatores de Tempo , TransplanteRESUMO
UNLABELLED: The aim of this study was to determine and localize culprit lesion by myocardial perfusion imaging (MPI) in cases of angiographically detected coronary narrowing >or= 75% of at least one coronary artery. MATERIAL AND METHODS: One hundred and thirty-two (132) patients with angiographically detected significant coronary narrowing (>or= 75% luminal stenosis of at least one major coronary artery) were studied. All the patients submitted MPI (99m)Tc-MIBI, with pharmacologic dipyridamole stress protocol with concomitant low level bicycle exercise 50W (DipyEX). We measured relative uptake (99m)Tc-MIBI for each myocardial segment using short-axis myocardial tomogram study. A 5-point scoring system was used to assess the difference between uptake degree in stress and rest studies for the same segments, and we created two indices: Sum reversibility score (SRS), Index of sum reversibility score (ISRS). RESULTS: A total of 396 vascular territories (2244 segments) were analyzed before elective percutaneous coronary intervention (ePCI). Overall sensitivity, specificity and accuracy using SRS were 90.2%, 87.5%, and 89.4%, with a positive predictive value of 94.1%. Overall sensitivity, specificity, and accuracy using ISRS were 94.4%, 90.6%, 93.2% and the positive predictive value was 95.7%. CONCLUSION: DipyEX MPI with the two indices created, SRS and ISRS, significantly improves sensitivity, specificity and accuracy in the determination and localization of culprit lesions in patients undergoing elective PCI.