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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
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
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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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
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
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
Pluristratified epithelia of adult vertebrate skin continuously regenerate from stem cells, and the question still arises as to whether those cells are committed to the production of only one cell lineage, or in contrast they conserve their embryonic pluripotentiality. In order to investigate the abilities of adult cultured as well as wound healing epidermis, heterospecific fibroblast-keratinocyte recombinations were performed, which allow unquestionable identification of the cells implicated in the structures that differentiate. Adult human cultured breast epidermal cells and full-thickness wound healing from human facial skin and foreskin were associated with either rabbit embryonic trichogenic dermis or cultured dermal papilla cells of adult rat, before grafting onto nude mice for two weeks to one month. In situ hybridization with a human specific sequence Alu probe labeled the human cells, whereas implanted rabbit or rat and host mouse cells were distinguished by the Hoechst staining of their nuclei. The results show that human adult cultured breast epidermal cells are able to form hair buds and to participate in hair follicle formation, while adult healing epidermis from a sparsely hairy skin as the human face or the dorsal skin of nude mouse, or even from a glabrous epidermis as the human foreskin, are able to differentiate pilosebaceous units. Although a follicular origin of the involved keratinocytes cannot be excluded in the three first cases, the formation of hair and sebaceous glands by foreskin keratinocytes of children 2 to 10 years-old establishes the cutaneous appendage ability of the interfollicular epidermal stem cells. The formation of interspecies mosaic follicles also highlights the fact that there must be a significant level of commonality in the interactive signaling molecules used by epithelial cells from different species.
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Diferenciação Celular/fisiologia , Folículo Piloso/crescimento & desenvolvimento , Queratinócitos/fisiologia , Glândulas Sebáceas/crescimento & desenvolvimento , Pele/crescimento & desenvolvimento , Idoso , Animais , Comunicação Celular , Células Cultivadas , Criança , Pré-Escolar , Feminino , Humanos , Hibridização In Situ , Masculino , Camundongos , Camundongos Nus , Coelhos , Ratos , Cicatrização/fisiologiaRESUMO
Sixteen of 19 enrolled patients with minimal residual disease of ovarian cancer (macroscopic disease < 5 mm or positive blind biopsies and/or positive peritoneal washing), demonstrated by surgical second-look, underwent intraperitoneal radioimmunotherapy (RIT) with the radiolabelled monoclonal antibody I-131 MOv18 (mean dose 14 mg of MOv18 with 3700 GBq of I-131) 30-40 days after the second-look procedure. Clinical follow-up and/or third-look evaluation performed 90 days after RIT showed complete response (CR) in 5 patients, no change (NC) in 6 patients and progressive disease (PD) in 5 patients. Follow-up study showed long-term maintained CR in 1 patient (34 months) and relapses in the other 4 patients after a mean disease-free period of 10.5 months. 5 NC patients showed clinical or instrumental progression after a mean disease-free period of 13 months. The toxicity of RIT was negligible. Only 1 patient showed mild and transient bone marrow suppression (platelet count nadir 52,000 mm3 after 30 days). HAMA production was demonstrated in 94% (15/16) of patients. In conclusion, RIT appears to be a very promising therapeutic approach to treat minimal residual disease of ovarian cancer.
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Anticorpos Monoclonais/uso terapêutico , Radioisótopos do Iodo/uso terapêutico , Neoplasia Residual/radioterapia , Neoplasias Ovarianas/radioterapia , Radioimunoterapia , Adulto , Idoso , Feminino , Humanos , Laparoscopia , Pessoa de Meia-Idade , Cavidade Peritoneal , ReoperaçãoRESUMO
The relevance of 3H-thymidine labeling index (3H-dt LI) on clinical outcome was evaluated on 85 patients with advanced ovarian cancers treated with carboplatin or cisplatin alone (39 cases) or cisplatin in association with doxorubicin and/or cyclophosphamide (46 cases). 3H-dT LI of the primary tumour was significantly related to the 3-year probability of survival in patients treated by monochemotherapy (low LI, 63%; high LI, 21%; P = 0.013) but not in those treated with polychemotherapy. Analysis of the relation between cell kinetics and clinical outcome as a function of treatment showed that in patients with rapidly proliferating tumours the 3-year survival was significantly higher following polychemotherapy than monochemotherapy (51 vs. 21%; P = 0.04). In patients with slowly proliferating tumours no significant difference in survival was observed following the two types of treatment for the overall series, whereas in patients not achieving a complete response survival was significantly higher following monochemotherapy than polychemotherapy (61 vs. 9%; P = 0.008).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Carboplatina/uso terapêutico , Divisão Celular , Cisplatino/uso terapêutico , Feminino , Seguimentos , Humanos , Neoplasias Ovarianas/mortalidadeRESUMO
Response to a second-line weekly cisplatin chemotherapy in ovarian cancer previously treated with cisplatin- or carboplatin-based regimens was analysed in a clinical series observed between 1984 and 1991. Women who achieved pathological complete response or pathological optimal partial remission after first-line cisplatin- or carboplatin-based regimens were treated at recurrence or progression, occurring at least 4 months after first-line treatment, with second-line chemotherapy. A total of 72 women were included in the analysis. Second-line chemotherapy regimens were: cisplatin 1 mg/kg weekly for seven courses plus epirubicin 70 mg/m2 intravenously (i.v.) every 3 weeks for three courses (28 subjects), cisplatin 1 mg/kg plus etoposide 90 mg/m2 i.v. weekly for a total of seven courses (11 subjects) and cisplatin 1 mg/kg weekly for nine courses plus carboplatin 250 mg/m2 every 3 weeks for three courses (33 subjects). Of the 72 women, 22 (31%, 14 clinical, 8 pathological) had a complete response and 28 (39%), a partial response (24 clinical, 4 pathological). The 24-month cumulative survival probability was 63% in women with complete response, 32% in those who had partial response, but all the 22 non-responders died within 24 months from diagnosis of recurrence (log rank test P < 0.05). The frequency of complete response and partial response increased with the interval between first diagnosis and recurrence: among the 33 women who had recurrent disease to < 18 months from first diagnosis, complete response or partial response was obtained in 20 (61%) subjects, this figure was 67% (14 out of 21 women) among subjects who had recurrent disease between 18 and < 36 months from first diagnosis and 89% (16/18) among those who had recurrence > or = 36 months. In comparison with women who had recurrence 4- < 18 months from first diagnosis, the OR of response was 1.3 (95% CI 0.4-4.1) for those who had recurrence between 18 and < 36 and 5.2 (95% CI 1.1-24.3) for those who had recurrence > or = 36 months from surgery (chi 1(2) trend p < 0.05). Survival rate after the end of second line chemotherapy for women who relapsed 4- < 18 months, 18- < 36 or 36 months or more after surgery were, respectively, 24, 20 and 67% (log rank test, P < 0.05). Age at first diagnosis, histology, stage, and grading of the disease at first diagnosis and site of recurrence were not associated with response to second-line therapy.
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Carboplatina/uso terapêutico , Cisplatino/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Ovarianas/mortalidade , PrognósticoRESUMO
We conducted a phase I-II study with escalating paclitaxel doses plus carboplatin at a fixed dose for previously untreated patients with advanced ovarian cancer in order to define the maximum tolerated dose. Eligible for the study were women with a histologically confirmed diagnosis of ovarian cancer stage III-IV according to the FIGO classification. In the first phase of the study, 6 patients were allocated escalating paclitaxel doses with fixed-dose carboplatin in order to establish the maximum tolerated dose. The starting dose of paclitaxel was 150 mg/m2 given after carboplatin (300 mg/m2) every 4 weeks for a total of six courses. The paclitaxel dose step was 25 mg/m2 up to 250 mg/m2. The study then progressed to a phase II trial using the maximum tolerated paclitaxel dosage reached during the escalating dose phase. A total of 27 patients entered phase I and 23 phase II. Neurotoxicity was observed in 47 patients (94%; 29 grade 1, 17 grade 2, 1 grade 3, according to the WHO classification). The intensity of neurotoxicity tended to be dose related: out of the 15 patients who received < or = 200 mg paclitaxel, a total of 14 grade 1, but no grade 2 or 3 neurotoxicities, were observed. The frequency of grade 1, 2 and 3 neurotoxicity was 15, 17 and 1, respectively, in the 35 women who received > or = 225 paclitaxel +300 mg carboplatin. There was no clear relationship between median WBC and platelet nadir and dose level. Among other toxicities, alopecia was observed in all 50 cases, hypersensitivity in two (4%) and myalgia in 41 (82%; 34 grade 1 and 7 grade 2). These frequencies tended to increase with the dose, but the relationship was not statistically significant. The overall response rate was 78% (39/50) with a complete response rate of 62% (31/50). In conclusion, this study suggests that carboplatin and paclitaxel can be administered safely to patients with advanced ovarian carcinoma. The maximum dose reached was 250 mg/m2 paclitaxel and 300 mg/m2 for carboplatin, but from a clinical point of view the maximum paclitaxel dose we would consider safe is 225 mg/m2.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagemRESUMO
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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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
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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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.
RESUMO
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 authors present a case of renal agenesis and seminal vesicle cyst in a young man, diagnosed because of several micturion disorders partially cleared up with antibiotic therapy. We discuss about the diagnosis technique which includes Ultrasound Scanner, Computed Tomography, Magnetic Resonance and pelvic arteriography. Then we describe the surgical approach and finally we discuss about embryogenesis.
Assuntos
Cistos/patologia , Rim/anormalidades , Glândulas Seminais/patologia , Adulto , Diagnóstico Diferencial , Humanos , MasculinoRESUMO
A group of 463 general surgery patients received topical applications of lincomycin and gentamycin, which significantly reduced the incidence of infected wounds compared to the untreated control group. This confirmed the prophylactic efficacy of topical antibiotic treatment which is also less dangerous than parenteral administration.