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The term "ketogenic diet" (KD) is used for a wide variety of diets with diverse indications ranging from obesity to neurological diseases, as if it was the same diet. This terminology is confusing for patients and the medical and scientific community. The term "ketogenic" diet implies a dietary regimen characterized by increased levels of circulating ketone bodies that should be measured in blood (beta-hydroxybutyrate), urine (acetoacetate) or breath (acetone) to verify the "ketogenic metabolic condition". Our viewpoint highlights that KDs used for epilepsy and obesity are not the same; the protocols aimed at weight loss characterized by low-fat, low-CHO and moderate/high protein content are not ketogenic by themselves but may become mildly ketogenic when high calorie restriction is applied. In contrast, there are standardized protocols for neurological diseases treatment for which ketosis has been established to be part of the mechanism of action. Therefore, in our opinion, the term ketogenic dietary therapy (KDT) should be reserved to the protocols considered for epilepsy and other neurological diseases, as suggested by the International Study Group in 2018. We propose to adjust the abbreviations in VLCHKD for Very Low CarboHydrate Ketogenic Diet and VLEKD for Very Low Energy Ketogenic Diet, to clarify the differences in dietary composition. We recommend that investigators describe the researchers describing efficacy or side effects of KDs, to clearly specify the dietary protocol used with its unique acronym and level of ketosis, when ketosis is considered as a component of the diet's mechanism of action.
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Dieta Cetogênica , Epilepsia , Cetose , Humanos , Dieta Cetogênica/efeitos adversos , Obesidade/diagnóstico , Epilepsia/diagnóstico , Corpos Cetônicos , Cetose/diagnósticoRESUMO
BACKGROUND: Suboptimal antiretroviral (ART) adherence can lead to virologic failure with consequent HIV-1 resistance. Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a powerful biomarker of cumulative adherence, predictive of future viremia. It has been associated with resistance in Persons With HIV (PWH) in South Africa and the US. We explored the relationship of TFV-DP concentrations with antiretroviral drug resistance at the time of treatment failure in SA. METHODS: Adult PWH from health clinics in Cape Town, South Africa on efavirenz-based first-line ART containing tenofovir disoproxil fumarate (TDF) with an undetectable (< 50 copies/mL) HIV-1 viral load (VL) were prospectively enrolled in an observational cohort for 12 months. Monthly study visits included blood collection for HIV-1 VL and DBS for TFV-DP. The first confirmed viral breakthrough (VB) > 400 copies/mL triggered HIV-1 genotyping at the subsequent visit. An electronic adherence (EA) device monitored ART adherence in real-time, estimated as a percent for the 30-days prior to VB. Wilcoxon rank sum test was used to compare median [IQR] TFV-DP by genotype outcome. RESULTS: Of 250 individuals, (n = 195, 78% women), 21 experienced VB, with a median of 5 [4;7] months on study, and a median EA of 33.3 [13.3;53.3]%. Demographic characteristics between those with and without VB were similar. Median VL at VB was 4.0 [3.2;4.5] log copies/mL. TFV-DP concentrations trended down towards the VB visit. Median TFV-DP concentrations were significantly higher in those HIV-1 genotype did not amplify due to being virally suppressed at the subsequent visit (n = 10; 380 [227-661] fmol/punch, p = 0.035; EA 45 [24.9; 59.2]%); than in those who were successfully genotyped with evidence of drug resistance (n = 5, 241 [150-247] fmol/punch, EA 20 [6.7;36.7]%) and in individuals who did not have resistance (n = 3, 39.9 [16.6; 93.9] fmol/punch; EA 33.3 [16-38]%). Three genotype collections were not done. Only non-nucleoside reverse transcriptase inhibitor-associated mutations were identified on resistance testing. (K103N, E138K, Y118H). CONCLUSION: TFV-DP in DBS showed a step-wise inverse relationship with VB and drug resistance, with evidence of low cumulative ART adherence in PWH who developed antiretroviral resistance. Monitoring TFV-DP concentrations could be a valuable tool for predicting future VB and future resistance.
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Infecções por HIV , Soropositividade para HIV , HIV-1 , Adulto , Feminino , Humanos , Masculino , Antirretrovirais , Infecções por HIV/tratamento farmacológico , HIV-1/genética , África do Sul/epidemiologiaRESUMO
The popularity of unicompartmental knee arthroplasty (UKA) continues to grow among orthopaedic surgeons and robotic surgery may be helpful in obtaining a precise placement of the prosthetic components, thanks to the meticulous intra-operative computer study for simulating the prosthetic positioning. This may lead to longer implant survivorship as well as a reduction in intermediate and long-term prosthetic complications, despite the initial greater costs than those of manual UKA. In this preliminary study, from January 2017 and October 2017, 18 patients underwent UKA with MAKO robotic system assistance and 10 patients received UKA with NAVIO robotic system assistance. The two groups were homogeneous by age, BMI, degree of osteoarthritis involvement, and postoperative program. Patients were followed both clinically (Numeric Rating Scale NRS and Knee Injury Osteoarthritis Outcome Scores KOOS) and radiographically. At the end term follow up (2 years), no significant difference was observed for NRS and KOOS as well as for clinical parameters as an active range of motion. A significant discrepancy was detected regarding the duration of the surgery and time of using the robotic system, that appeared to be longer in the NAVIO group than that of MAKO group, likely due to the specific technical aspects that characterize these two different robotic systems. The main finding of this study is that favorable clinical and radiographical results may be obtained using a robotic approach (MAKO or NAVIO) for UKA positioning at a short follow up. Due to the lack of significant clinical differences observed between the two groups of patients at end term follow up, the "concept" of a robotic approach, more than a specific patented system, may be considered the key element for improving UKA technique and it is likely that in the near future the choice of a single specific robotic system will still be a "surgeon's preference". The results of the study add scientific evidence regarding the effective improvement of UKA results using different robotic approaches. They also show possible economic sustainability of this therapeutic strategy related to the optimal patients' performance obtained at short term follow up, suggesting that the robotic assistance may really become a key element for better long-term survivorship of unicompartmental knee arthroplasty.
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Artroplastia do Joelho , Prótese do Joelho , Procedimentos Cirúrgicos Robóticos , Seguimentos , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: It is controversial whether sentinel node biopsy (SNB) is adequate in breast cancer patients who become cN0 after primary chemotherapy. To address this we retrospectively compared outcomes in T2 cases given primary chemotherapy, comparing those given axillary dissection (AD) with those given SNB but no AD if sentinel nodes were clinically negative post-chemotherapy. METHODS: We examined overall survival (OS), disease-free survival (DFS), and axillary failure in 317 consecutive cT2 cN0/1 patients given primary chemotherapy followed by quadrantectomy/mastectomy, between January 2002 and December 2007. The approach to the axilla changed over time allowing division into three groups: 101 (31.9%) given upfront AD; 139 (43.8%) given SNB + AD; and 77 (24.3%) given SNB only because the SNs were negative. RESULTS: After median follow-ups of 92 (AD), 99 (SNB + AD) and 72 months (SNB-only), OS (p = 0.131) and DFS (p = 0.087) did not differ between the 3 groups, or between SNB-only and the ypN1 and ypN0 subgroups of SNB + AD, or between the cN0 and cN1 subgroups (before chemotherapy) of the SNB-only group. No SNB-only patient had axillary failure. OS (p = 0.004) and DFS (p = 0.002) were better in patients with complete response than those with partial response or stable/progressive disease. CONCLUSIONS: SNB is adequate in T2 patients who are cN0 after primary chemotherapy, irrespective of axillary status before. Better outcomes after complete pathological remission confirm the prognostic importance of response to primary chemotherapy, and suggest that all T2 patients should receive primary chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Biópsia de Linfonodo Sentinela , Adulto , Axila , Feminino , Humanos , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Linfocintigrafia , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Additive manufacturing (AM) techniques can produce complex, high-value metal parts, with potential applications as critical parts, such as those found in aerospace components. The production of AM parts with consistent and predictable properties requires input materials (e.g., metal powders) with known and repeatable characteristics, which in turn requires standardized measurement methods for powder properties. First, based on our previous work, we assess the applicability of current standardized methods for powder characterization for metal AM powders. Then we present the results of systematic studies carried out on two different powder materials used for additive manufacturing: stainless steel and cobalt-chrome. The characterization of these powders is important in NIST efforts to develop appropriate measurements and standards for additive materials and to document the property of powders used in a NIST-led additive manufacturing material round robin. An extensive array of characterization techniques was applied to these two powders, in both virgin and recycled states. The physical techniques included laser diffraction particle size analysis, X-ray computed tomography for size and shape analysis, and optical and scanning electron microscopy. Techniques sensitive to structure and chemistry, including X-ray diffraction, energy dispersive analytical X-ray analysis using the X-rays generated during scanning electron microscopy, and X-Ray photoelectron spectroscopy were also employed. The results of these analyses show how virgin powder changes after being exposed to and recycled from one or more Direct Metal Laser Sintering (DMLS) additive manufacturing build cycles. In addition, these findings can give insight into the actual additive manufacturing process.
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BACKGROUND AND AIMS: The measurement of resting energy expenditure (REE) is important to assess individual total energy requirements in older subjects. The validity of REE prediction equations in this population has not been thoroughly evaluated and therefore the main aim of this analysis was to assess the accuracy of REE prediction equations in older subjects. METHODS: Weight, height and body mass index (BMI) were measured. REE was measured by indirect calorimetry (IC) in 68 older subjects (age: 60-94 years, M/F: 13/55, BMI: 26.3 ± 5.0 kg/m(2)). Measured REE was compared to 14 equations for the calculation of REE estimates. In addition, two novel approaches (Aggregate model and meta-regression equations) for the prediction of REE were evaluated. Paired t test and Bland-Altman method were used to assess the agreement of the equations. RESULTS: The average measured REE was 1298 ± 264 kcal/day. The equation with the smallest bias was proposed by Muller (Bias ± 2SD = +3 ± 294 kcal/day) whereas the Mifflin equation was associated with the largest error (Bias ± 2SD = -172 ± 282 kcal/day). The Aggregate, Muller, Harris-Benedict and Fredrix equations were characterised by a prediction within ±10% of measured REE in more than 60% of subjects. Of the four algorithms, only the Aggregate equation did not show a significant association of the measurement bias with age, BMI and gender. CONCLUSIONS: The Aggregate algorithm was characterised by a higher, overall accuracy for the prediction of REE in older subjects and its use should be advocated in older subjects. However, due to the large variability of the estimates, the measurement of REE by IC is still recommended for an accurate assessment of individual REE.
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Metabolismo Basal/fisiologia , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Estatura , Índice de Massa Corporal , Peso Corporal , Calorimetria Indireta , Estudos Transversais , Ingestão de Energia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Necessidades Nutricionais , Valor Preditivo dos Testes , Reprodutibilidade dos TestesRESUMO
UNLABELLED: This study evaluated the agreement of novel anthropometric equations and established indirect methods (skinfold thickness and bioimpedance analysis) with reference methods [dual X-ray absorptiometry (DXA) and air displacement plethysmography (ADP)] for fat mass assessment (FM) in older subjects. METHODS: Forty subjects (M/F = 15/25, age = 61-84 years, BMI = 18-37 kg/m(2)) were recruited. The agreement of the following predictive equations was evaluated: body adiposity index (BAI), BAI-Fels and Clínica Universidad de Navarra-body adiposity estimator (CUN-BAE). RESULTS: BAI estimates were comparable to DXA (Δ ± 2SD = 0.4 ± 6.0 kg, p > 0.05) but not to ADP (Δ ± 2SD = -2.8 ± 7.2 kg, p < 0.001); BAI-Fels estimates were comparable to DXA (Δ ± 2SD = 0.8 ± 5.5 kg, p > 0.05) but not to ADP (Δ ± 2SD = -4.0 ± 6.9 kg, p < 0.001). The difference between CUN-BAE and ADP was not significant (Δ ± 2SD = -0.4 ± 5.6 kg, p > 0.05), whereas it significantly overestimated DXA (Δ ± 2SD = 2.8 ± 5.4 kg, p < 0.001). ADP significantly overestimated FM compared to DXA (Δ ± 2SD = 3.2 ± 5.4 kg, p < 0.001) and the measurement bias was significantly correlated with BMI in men (p = 0.004). CONCLUSIONS: The accuracy of the three anthropometric indexes is dependent on the choice of the reference method. The variability of the FM estimates was large and these indexes cannot be recommended for the assessment of FM in older subjects.
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Adiposidade , Envelhecimento/patologia , Antropometria/métodos , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Impedância Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pletismografia , Reprodutibilidade dos Testes , Dobras CutâneasRESUMO
OBJECTIVE: NLRP12 mutations have been described in patients affected with peculiar autoinflammatory symptoms. This study was undertaken to characterize NLRP12 mutations in patients with autoinflammatory syndromes, particularly a novel missense mutation, p.D294E, affecting a protein sequence crucial for ATP binding, which was identified in a Caucasian family with familial cold-induced autoinflammatory syndrome in some family members. METHODS: Fifty patients were tested for NLRP12 mutations. A Caucasian family with the p.D294E missense mutation of NLRP12 in some family members was clinically characterized. In vitro analysis of the effects of the mutation on NF-κB activity was performed in HEK 293 cells after cotransfection of the cells with a luciferase NF-κB-responsive element and mutant or wild-type (WT) NLRP12 expression plasmids. NF-κB activity was also evaluated 24 hours after stimulation with tumor necrosis factor α in monocytes from individual family members carrying the mutation. Furthermore, secretion of interleukin-1ß (IL-1ß), production of reactive oxygen species (ROS), and activation of antioxidant systems in patient and healthy donor monocytes, under resting conditions and after stimulation with pathogen-associated molecular patterns (PAMPs), were also assessed. RESULTS: In the family assessed, the p.D294E mutation segregated in association with a particular sensitivity to cold exposure (especially arthralgias and myalgia), but not always with an inflammatory phenotype (e.g., urticarial rash or fever). In vitro, the mutant protein maintained the same inhibitory activity as that shown by WT NLRP12. Consistently, NLRP12-mutated monocytes showed neither increased levels of p65-induced NF-κB activity nor higher secretion of IL-1ß. However, the kinetics of PAMP-induced IL-1ß secretion were significantly accelerated, and high production of ROS and up-regulation of antioxidant systems were demonstrated. CONCLUSION: Even with a variable range of associated manifestations, the extreme sensitivity to cold represents the main clinical hallmark in an individual carrying the p.D294E mutation of the NLRP12 gene. Although regulation of NF-κB activity is not affected in patients, redox alterations and accelerated secretion of IL-1ß are associated with this mild autoinflammatory phenotype.
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Temperatura Baixa/efeitos adversos , Síndromes Periódicas Associadas à Criopirina/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação de Sentido Incorreto , Adulto , Idoso , Síndromes Periódicas Associadas à Criopirina/imunologia , Síndromes Periódicas Associadas à Criopirina/metabolismo , Saúde da Família , Feminino , Células HEK293 , Humanos , Interleucina-1beta/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/imunologia , Linhagem , Fenótipo , População Branca/genéticaRESUMO
Electroluminescence characteristics of a heterojunction light-emitting diode, which was fabricated by depositing a layer of randomly assembled n-SnO(2) nanowires on p-GaN:Mg/sapphire substrate via vapor transport method, were investigated at room temperature. Peak wavelength emission at around 388 nm was observed for the diode under forward bias. This is mainly related to the radiative recombination of weakly bounded excitons at the shallow-trapped states of SnO(2) nanowires, Under reverse bias, near bandedge emission from the p-GaN:Mg/sapphire leads to the observation of emission peak at around 370 nm.
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Eletroquímica/métodos , Nanotecnologia/métodos , Óxido de Alumínio , Gálio/química , Luz , Luminescência , Magnésio/química , Microscopia Eletrônica de Varredura/métodos , Nanofios/química , Dióxido de Silício/química , Propriedades de Superfície , Temperatura , Raios UltravioletaRESUMO
Tumours have at least two mechanisms that can alter dendritic cell (DC) maturation and function. The first affects the ability of haematopoietic progenitors to differentiate into functional DCs; the second affects their differentiation from CD14+ monocytes, promoting an early but dysfunctional maturation. The aim of this study was to evaluate the in vivo relevance of these pathways in breast cancer patients. For this purpose, 53 patients with invasive breast cancer were compared to 68 healthy controls. To avoid isolation or culture procedures for enrichment of DCs, analyses were directly performed by flow cytometry on whole-blood samples. The expression of surface antigens and intracellular accumulation of regulatory cytokines upon LPS stimulation were evaluated. The number of DCs, and in particular of the myeloid subpopulation, was markedly reduced in cancer patients (P<0.001). Patient DCs were characterized by a more mature phenotype compared with controls (P=0.016), and had impaired production of IL-12 (P<0.001). These alterations were reverted by surgical resection of the tumour. To investigate the possible role of some tumour-related immunoactive soluble factors, we measured the plasmatic levels of vascular endothelial growth factor, IL-10 and spermine. A significant inverse correlation between spermine concentration and the percentage of DCs expressing IL-12 was found. Evidence was also obtained that in vitro exposure of monocyte-derived DCs to spermine promoted their activation and maturation, and impaired their function. Taken together, our results suggest that both the above-described mechanisms could concomitantly act in breast cancer to affect DC differentiation, and that spermine could be a mediator of dysfunctional maturation of DCs.
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Neoplasias da Mama/fisiopatologia , Diferenciação Celular , Células Dendríticas/fisiologia , Regulação Neoplásica da Expressão Gênica , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/imunologia , Estudos de Casos e Controles , Citocinas/biossíntese , Feminino , Citometria de Fluxo , Humanos , Pessoa de Meia-IdadeRESUMO
RATIONALE AND OBJECTIVES: To review magnetic resonance imaging (MRI) findings in lobular breast carcinoma, the in situ or infiltrating subtype, with special attention to the dynamic curves with the aim to evaluate possible differences with ductal carcinoma. METHODS: In 2 years, 27 patients with lobular and one with tubular carcinoma underwent MRI at the Istituto Nazionale Tumori of Milan. RESULTS: All lobular carcinomas demonstrated early or late enhancement (100% sensitivity), without significant differences in morphology compared with ductal carcinoma, but frequently with a different shape of the dynamic curves. CONCLUSIONS: Due to its infiltrative growth associated to only limited connective tissue reaction, lobular carcinoma often encounters difficulties in mammographic diagnosis. In contrast, MRI can be very helpful in evaluating the true extension of the disease, especially when breast conservation is considered. Due to a more consistent fibrotic stroma, these lesions sometimes show a delayed enhancement, which suggests that more than one set of subtracted images should be evaluated during MRI analysis.
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Neoplasias da Mama/patologia , Carcinoma Lobular/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Surgical removal of axillary lymph node and histologic examination for metastases are used to determine whether adjuvant treatment is necessary for patients with breast cancer. Axillary lymph node dissection (ALND) is a costly procedure associated with various side effects, and 80% or more of patients with tumors of 20 mm or less are lymph node negative and might avoid ALND. In this study, we evaluated whether an alternative, noninvasive method--i.e., positron emission tomography (PET) with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG)-- could be used to determine axillary lymph node status in patients with breast cancer. METHODS: One hundred sixty-seven consecutive patients with breast cancers of 50 mm or less (range = 5-50 mm; mean = 21 mm) scheduled for complete ALND were studied preoperatively with FDG-PET, and then PET and pathology results from ALND were compared. All statistical tests were two-sided. RESULTS: The overall sensitivity, specificity, and accuracy of lymph node staging with PET were 94.4% (PET detected 68 of 72 patients with axillary involvement; 95% confidence interval [CI] = 86.0% to 98.2%), 86.3% (82 of 95 patients without axillary involvement; 95% CI = 77.8% to 91.9%), and 89.8% (150 of 167 patients with breast cancer; 95% CI = 84.2% to 93.6%), respectively. Positive- and negative-predictive values were 84.0% (68 patients with histologically positive lymph nodes of 81 patients with positive FDG-PET scan; 95% CI = 74.2% to 90.5%) and 95.3% (82 patients with histologically negative lymph nodes of 86 patients with negative FDG-PET scan; 95% CI = 88.2% to 98.5%), respectively. When PET results for axillary metastasis were analyzed by tumor size, the diagnostic accuracy was similar for all groups (86.0%-94.2%), with higher sensitivity for tumors of 21-50 mm (98.0%) and higher specificity for tumors of 10 mm or less (87.8%), and the range was 93.5%-97.3% for negative-predictive values and 54.5%-94.1% for positive-predictive values. Among the 72 patients with axillary involvement, PET detected three or fewer metastatic lymph nodes in 27 (37.5%) patients, about 80% of whom had no clinically palpable axillary lymph nodes. CONCLUSIONS: Noninvasive FDG-PET appears to be an accurate technique to predict axillary status in patients with breast cancer and thus to identify patients who might avoid ALND. These results should be confirmed in large multicenter studies.
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Neoplasias da Mama/diagnóstico por imagem , Fluordesoxiglucose F18 , Linfonodos/diagnóstico por imagem , Compostos Radiofarmacêuticos , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Excisão de Linfonodo , Linfonodos/metabolismo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Compostos Radiofarmacêuticos/farmacocinética , Tomografia Computadorizada de EmissãoRESUMO
As for all materials, the performance of concrete is determined by its microstructure. Its microstructure is determined by its composition, its curing conditions, and also by the mixing method and mixer conditions used to process the concrete. This paper gives an overview of the various types of mixing methods and concrete mixers commercially available used by the concrete industry. There are two main types of mixers used: batch mixers and continuous mixers. Batch mixers are the most common. To determine the mixing method best suited for a specific application, factors to be considered include: location of the construction site (distance from the batching plant), the amount of concrete needed, the construction schedule (volume of concrete needed per hour), and the cost. Ultimately, the quality of the concrete produced determines its performance after placement. An important measure of the quality is the homogeneity of the material after mixing. This paper will review mixing methods in regards to the quality of the concrete produced. Some procedures used to determine the effectiveness of the mixing will be examined.
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We approached the issue of surgical margins in the conservative treatment of breast cancer by examining the literature germane to four precise questions: At what distance from the macroscopic margin of the tumour should the resection margin be? To what extent do histologically clear resection margins indicate complete local control of the disease? To what extent do histologically involved margins indicate persistence of disease? and Does the local recurrence rate correlate with the status of the resection margin? We propose categorizing margin involvement into five groups (absent, focal, minimal, moderate and extensive involvement) according to strict histological criteria, and assigning increasingly aggressive subsequent treatments according to the extent of any margin involvement.
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Recent work has shown remarkable plasticity between neural and hematopoeitic, as well as between hematopoeitic and muscle stem cells, depending on environmental stimuli (Fuchs, E. and Segre, J. A. (2000) Cell 100, 143-155). Stem cells give rise to a proliferative transient amplifying population (TA), which is generally considered to be irreversibly committed. Corneal epithelium provides a particularly useful system for studying the ability of TA cells to activate different genetic programs in response to a change in their fibroblast environment. Indeed, corneal stem and TA cells occupy different localities - stem cells at the periphery, and TA cells more central (Lehrer, M. S., Sun, T. T. and Lavker, R. M. (1998) J. Cell Sci. 111, 2867-2875) - and thus can be discretely dissected from each other. It is well known that pluristratified epithelia of cornea and skin display distinct programs of differentiation: corneal keratinocytes express keratin pair K3/K12 and epidermal keratinocytes keratin pair K1-2/K10; moreover, the epidermis forms cutaneous appendages, which express their own set of keratins. In our experiments, central adult rabbit corneal epithelium was thus associated either with a mouse embryonic dorsal, upper-lip or plantar dermis before grafting onto nude mice. Complementary experiments were performed using adult mouse corneal epithelium from the Rosa 26 strain. The origin of the differentiated structures were identified in the first case by Hoechst staining and in the second by the detection of beta-galactosidase activity. The results show that adult central corneal cells are able to respond to specific information originating from embryonic dermis. They give rise first to a new basal stratum, which does not express anymore corneal-type keratins, then to pilosebaceous units, or sweat glands, depending of the dermis, and finally to upper layers expressing epidermal-type keratins. Our results provide the first evidence that a distinct TA cell population can be reprogrammed.
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Epitélio Corneano/citologia , Epitélio Corneano/metabolismo , Animais , Quimera , Epitélio Corneano/embriologia , Regulação da Expressão Gênica , Cabelo/citologia , Cabelo/embriologia , Cabelo/metabolismo , Queratinas/genética , Queratinas/metabolismo , Camundongos , Camundongos Nus , Modelos Biológicos , Coelhos , Glândulas Sebáceas/metabolismo , Glândulas Sudoríparas/metabolismoRESUMO
We addressed the problem of the need for axillary dissection in clinically node-negative breast cancer by determining how the information provided by the dissection suggests a different treatment to that indicated by primary tumour characteristics and age alone. We examined retrospectively 260 cases of clinically node negative early breast cancer all of whom underwent breast surgery, radiotherapy and axillary dissection. We assigned adjuvant therapy according to accepted guidelines with and without consideration of pathological node status and compared the difference. Fifty-six patients had involved axillary nodes. There was no change in adjuvant chemotherapy indication for the 44 cases over 65 years. The change in indication for the remaining 216 cases was 18.5% to 6%, depending on whether none or all of the intermediate risk patients were originally assigned chemotherapy (all were originally assigned tamoxifen). Since the trend is for most intermediate risk patients is to be assigned adjuvant chemotherapy, and since tamoxifen is anyway considered effective therapy for low and intermediate risk patients, we conclude that the information provided by axillary dissection is probably not necessary if guidelines recommending wide application of systemic adjuvant chemotherapy are applied. Satisfactory prognostic information can be obtained by consideration of primary tumour characteristics, while new prognostic markers are likely to further refine prognostic precision in the near future.
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Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Linfonodos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticarcinógenos/uso terapêutico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Terapia Combinada , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática/patologia , Mastectomia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Tamoxifeno/uso terapêuticoRESUMO
OBJECTIVE: To evaluate the impact of breast carcinoma (T1-2N0) surgery without axillary dissection on axillary and distant relapses, and to evaluate the usefulness of a panel of pathobiologic parameters determined from the primary tumor, independent of axillary nodal status, in planning adjuvant treatment. METHODS: In a prospective nonrandomized pilot study, 401 breast cancer patients who underwent breast surgery without axillary dissection were accrued from January 1986 to June 1994. At surgery, all patients were clinically node-negative and lacked evidence of distant metastases after clinical or radiologic examination. A precise 4-month clinical and radiologic follow-up was performed to detect axillary or distant metastases. Patients with clinical evidence of axillary nodal relapse were considered for surgery as salvage treatment. Biologic characteristics of primary carcinomas were investigated by immunohistochemistry, and four pathologic and biologic parameters (size, grading, laminin receptor, and c-erbB-2 receptor) were analyzed to determine a prognostic score. RESULTS: The 5-year follow-up of these patients revealed a low rate of nodal relapses (6.7%), particularly for T1a and T1b patients (2% and 1.7%, respectively), whereas T1c and T2 patients showed a 10% and 18% relapse rate, respectively. Surgery was a safe and feasible salvage treatment without technical problems in all 19 cases of progressive disease at the axillary level. The low rate of distant metastases in T1a and T1b groups (<6%) increased to 15% in T1c and 34% in T2 patients. Analyzing the primary tumor with respect to the panel of pathologic and biologic parameters was predictive of metastatic spread and therefore can replace nodal status information for planning adjuvant treatment. CONCLUSIONS: Middle-term follow-up shows that the rate of axillary relapse in this patient population is lower than expected, suggesting that only a minimal number of microembolic nodal metastases become clinically evident. Avoidance of axillary dissection has a negligible effect on the outcome of T1 patients, particularly in T1a and T1b tumors with no palpable nodes, because the rate of axillary node relapse is very low for both. In T1 breast carcinoma, postsurgical therapy should be considered on the basis of biologic characteristics rather than nodal involvement. The authors' prognostic score based on the primary tumor identified patients who required postsurgical treatment, providing a practical alternative to axillary status for deciding on adjuvant treatment. Conversely, in the T2 group, the high rate of salvage surgery for axillary relapses, which is expected in tumors larger than 2.5 cm or 3.0 cm, represents a limit for avoiding axillary dissection. Preoperative evaluation of axillary nodes for modification of surgical dissection in this subgroup would be more useful more than in T1 breast cancer because of the high risk. Complete dissection is feasible without technical problems if precise follow-up detects progressive axillary disease.
Assuntos
Neoplasias da Mama/cirurgia , Excisão de Linfonodo , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais , Axila , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Estudos Prospectivos , Radioterapia AdjuvanteRESUMO
BACKGROUND: To evaluate survival rate, follow-up and renal function in patients treated with "nephron-sparing" approach due to cancer in a transplanted kidney. METHODS: During the 18 years' activity of our Transplantation Centre 3 renal carcinomas in transplanted kidneys (0.24%) have been found. Diagnoses were made in one case during transplantation procedures and, in the remaining two, 1 month and 10 years after. All tumours were unifocal, small (10, 12 and 18 mm of diameter), capsulated and low stage (T1). The resection of the mass ("nephron-sparing" surgery) and of a layer (1 cm thick) of the tissue surrounding the tumour was performed. The histological exam showed in all cases low grade (G2) renal cell carcinoma and negative surgical margins. RESULTS: 138, 94 and 15 months after transplant all patients are alive, without disease recurrence and with good renal function. In all cases the doses of immune-suppressive therapy were reduced. CONCLUSIONS: Renal cancer in transplanted kidneys is generally treated with nephrectomy. On the contrary, we decided to apply the same criteria which are accepted for the treatment of renal neoplasms in general and then to perform a "nephron-sparing" surgery when the tumour is small, capsulated and with negative surgical margins at the intraoperative histological exam. In personal experience good results from the oncologic and nephrologic point of view have been accomplished.
Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Transplante de Rim/efeitos adversos , Nefrectomia/métodos , Complicações Pós-Operatórias/cirurgia , Carcinoma de Células Renais/etiologia , Seguimentos , Humanos , Neoplasias Renais/etiologia , NéfronsRESUMO
The suitability of using the initial current from the rapid chloride test (ASTM C 1202) to determine specimen conductivity is tested using impedance spectroscopy with a frequency spectrum of 10 Hz to 1 MHz. The specimen conductivity has an analytical relationship to specimen diffusivity and so is a useful quantity in service life prediction. Measurements made on specimens of different lengths indicate that the total charge passed during the six hour conduction test carried out according to ASTM C 1202 is not a direct measure of specimen conductivity. Further, ohmic heating during the 6 hour test makes it nearly impossible to directly measure any specimen transport property from the results. The total charge passed during the 6 hour conduction test is, therefore, not a reliable quantity for service life prediction. Results indicate that the direct current (dc) measurement of resistance using a voltage of 60 V is sufficient to overwhelm polarization effects, thereby yielding an accurate estimate of the true specimen conductivity. Impedance spectroscopy measurements also indicate that corrosion may form on the brass electrodes, adding bias to a conductivity estimate based upon a dc measurement.