RESUMO
Dairy farms producing 98% of the US milk supply participate in the Farmers Assuring Responsible Management (FARM) Animal Care Program. Producers who sell milk to cooperatives or processors participating in FARM must follow program standards. The objectives of this study were to assess producer perceptions about the knowledge, experience, and value of FARM and to determine whether perceptions differ based on demographics. A concurrent triangulation design was implemented through collecting quantitative and qualitative data using a 30-question survey instrument. Quantitative questions aimed to address project objectives, and qualitative data were provided through 1 open-ended survey question that asked participants what they thought the main goal of the FARM program was. Participants offered additional feedback through providing text in comment boxes, writing on the back of the survey, or writing a separate letter and returning it with their survey. Quantitative data were analyzed using principal components analysis and modeling, and qualitative data were analyzed through thematic analysis. Dairy producers from cooperatives or processors that participate in the FARM program were recruited via electronic and postal mail. A total of 487 respondents from 40 states completed the survey. Of the survey participants, 414 (85.0%) answered the open-ended question and 190 (39.0%) provided additional qualitative feedback. Thematic analysis revealed 5 main themes: distrust of program, producers on the defense, anger, efficiency, and nostalgia. Of respondents, 73.6% reported being knowledgeable about the FARM Animal Care Program. Greater level of formal education and larger herd size were associated with greater producer knowledge. More dairy producer input in the revisions of FARM was identified as a need by 83.3% of respondents. Although 89.3% of respondents reported positive experiences with evaluations and relationships with evaluators, 45.6% did not think that the program had value overall. Respondent age was positively associated with perceived value of FARM. Respondent age was also significant in determining the reasons why FARM was considered to be important. Results indicate that to increase buy-in and positive perceptions from producers, future versions of FARM should solicit producer input during the development of program standards, target specific producer demographics for program promotion, and address perceived communication deficits and program inequalities. Findings from this study can be used to inform future versions of the program.
Assuntos
Criação de Animais Domésticos , Indústria de Laticínios , Fazendeiros , Adulto , Idoso , Criação de Animais Domésticos/métodos , Animais , Bovinos , Indústria de Laticínios/métodos , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Leite , Percepção , Inquéritos e QuestionáriosRESUMO
One hundred thirty-seven spring-born yearling beef heifers of British breed types were used to determine the relationships between residual feed intake (RFI) and growth rate, body composition, mature size, and fertility. Heifers were housed in a dry lot facility during the experimental period, and data were collected over a 2-yr period (yr 1, n = 67; yr 2, n = 70). Individual feed intake, BW, BCS, hip height, and ultrasonic measurements [subcutaneous rib fat (UBF), rump fat (URF), LM area (LMA), and intramuscular fat (IMF)] of body composition were recorded. Individual feed intakes (kg of TDN consumed/d) were used to calculate RFI combining both years of data. Heifers averaged 387.0 ± 19.4 d of age and 337.1 ± 29.9 kg of BW at initiation of the experiment. Mean ADG was 1.14 ± 0.21 kg/d during the trial. Based on RFI, with year of test and farm of origin included in the model as covariates, heifers were classified into groups: positive (POS; 0.74 kg of TDN/d) or negative (NEG; -0.73 kg TDN/d) for first analysis and high (HI), medium (MED), or low (LO; mean RFI = 1.06, -0.01, and -1.13 kg of TDN/d, respectively) subsequently. An initial phenotypic relationship (P < 0.05) between RFI and both UBF and URF (r = 0.19 and 0.17, respectively) was sustained (P < 0.01) with UBF (r = 0.27) and URF (r = 0.24) to trial conclusion. No other correlations with RFI were significant. Heifers classified as POS reached puberty earlier than those classified as NEG (414 ± 3.83 vs. 427 ± 4.67 d of age, P = 0.03), and possessed greater LMA per 100 kg of BW (LMACWT) at conclusion of the trial (P < 0.01). Medium heifers exhibited less URF (P < 0.05) compared with either HI or LO heifers at trial initiation. Low heifers possessed less LM area (cm(2)) per 100 kg of BW (P < 0.05) than HI but did not differ (P > 0.10) from MED heifers at either the beginning or the end of test. Additionally, a negative linear relationship was observed between RFI and age at puberty (P < 0.05). Each 1-unit increase in RFI corresponded to a decrease of 7.5 d in age at puberty, but did not affect pregnancy or conception rates (P > 0.10). Differences in body fat and rate of metabolism associated with RFI could delay reproductive maturity.
Assuntos
Composição Corporal , Tamanho Corporal , Bovinos/fisiologia , Fertilidade , Ração Animal , Animais , Bovinos/crescimento & desenvolvimento , Feminino , Desenvolvimento Muscular , Necessidades Nutricionais , Gravidez , Maturidade SexualRESUMO
BACKGROUND: This analysis was performed in order to determine whether primary tumor location in breast cancer affects the axillary sentinel lymph node (SLN) identification (ID) rate, the false negative (FN) rate, incidence of axillary nodal metastases, or the number of SLN identified. METHODS: In this prospective multi-institutional study, SLN biopsy was performed on clinical stage T1-2, N0 breast cancer patients using blue dye alone or in combination with radioactive colloid, followed by completion axillary LN dissection. RESULTS: Central tumor location was associated with an improved FN rate, which may be related to reliable drainage from the subareolar lymphatic plexus. Tumor location did not significantly affect the SLN ID rate or the mean number of SLN identified. Medial tumor location was associated with a decreased rate of axillary nodal metastasis. CONCLUSIONS: Breast cancers drain reliably to the axillary lymph nodes regardless of tumor location within the breast.
Assuntos
Neoplasias da Mama/patologia , Linfa/fisiologia , Axila , Mama/patologia , Reações Falso-Negativas , Feminino , Humanos , Linfonodos/fisiopatologia , Metástase Linfática , Pessoa de Meia-Idade , Estudos Prospectivos , Vigilância de Evento SentinelaRESUMO
Laminin-5, the major extracellular matrix protein produced by mammary epithelial cells, is composed of three chains (designated alpha3A, beta3, and gamma2), each encoded by a separate gene. Laminin-5 is markedly down-regulated in breast cancer cells. Little is known about the regulation of laminin gene transcription in normal breast cells, nor about the mechanism underlying the down-regulation seen in cancer. In the present study, we cloned the promoter of the gene for the human laminin alpha3A chain (LAMA3A) and investigated its regulation in functionally normal MCF10A breast epithelial cells and several breast cancer cell lines. Using site-directed mutagenesis of promoter-reporter constructs in transient transfection assays in MCF10A cells, we find that two binding sites for Kruppel-like factor 4 (KLF4/GKLF/EZF) are required for expression driven by the LAMA3A promoter. Electrophoretic mobility shift assays reveal absence of KLF4 binding activity in extracts from T47D, MDA-MB 231, ZR75-1, MDA-MB 436, and MCF7 breast cancer cells. Transient transfection of a plasmid expressing KLF4 activates transcription from the LAMA3A promoter in breast cancer cells. A reporter vector containing duplicate KLF4-binding sites in its promoter is expressed at high levels in MCF10A cells but at negligible levels in breast cancer cells. Thus, KLF4 is required for LAMA3A expression and absence of laminin alpha3A in breast cancer cells appears, at least in part, attributable to the lack of KLF4 activity.
Assuntos
Mama/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/fisiologia , Células Epiteliais/metabolismo , Laminina/biossíntese , Fatores de Transcrição/metabolismo , Fatores de Transcrição/fisiologia , Sítios de Ligação , Western Blotting , Linhagem Celular , Núcleo Celular/metabolismo , Clonagem Molecular , Regulação para Baixo , Regulação da Expressão Gênica , Genes Reporter , Humanos , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like , Modelos Genéticos , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Plasmídeos/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , Fatores de Tempo , Fator de Transcrição AP-1/metabolismo , Transcrição Gênica , Transfecção , Células Tumorais CultivadasRESUMO
OBJECTIVE: To determine the optimal experience required to minimize the false-negative rate of sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: Before abandoning routine axillary dissection in favor of SLN biopsy for breast cancer, each surgeon and institution must document acceptable SLN identification and false-negative rates. Although some studies have examined the impact of individual surgeon experience on the SLN identification rate, minimal data exist to determine the optimal experience required to minimize the more crucial false-negative rate. METHODS: Analysis was performed of a large prospective multiinstitutional study involving 226 surgeons. SLN biopsy was performed using blue dye, radioactive colloid, or both. SLN biopsy was performed with completion axillary LN dissection in all patients. The impact of surgeon experience on the SLN identification and false-negative rates was examined. Logistic regression analysis was performed to evaluate independent factors in addition to surgeon experience associated with these outcomes. RESULTS: A total of 2,148 patients were enrolled in the study. Improvement in the SLN identification and false-negative rates was found after 20 cases had been performed. Multivariate analysis revealed that patient age, nonpalpable tumors, and injection of blue dye alone for SLN biopsy were independently associated with decreased SLN identification rates, whereas upper outer quadrant tumor location was the only factor associated with an increased false-negative rate. CONCLUSIONS: Surgeons should perform at least 20 SLN cases with acceptable results before abandoning routine axillary dissection. This study provides a model for surgeon training and experience that may be applicable to the implementation of other new surgical technologies.
Assuntos
Neoplasias da Mama/patologia , Competência Clínica/normas , Biópsia de Linfonodo Sentinela , Reações Falso-Negativas , Feminino , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Although numerous studies have demonstrated that sentinel lymph node (SLN) biopsy can accurately determine the axillary nodal status for early breast cancer some studies have suggested that SLN biopsy may be less reliable for tumors >2 cm in size. This analysis was performed to determine whether tumor size affects the accuracy of SLN biopsy. The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective multi-institutional study involving 226 surgeons. The study was approved by the Institutional Review Board of each institution, and informed consent was obtained from all patients. Patients with clinical stage T1-2 N0 breast cancer were eligible for the study. Some patients with T3 tumors were included because they were clinically staged as T2 but on final pathology were found to have tumors >5 cm. This analysis includes 2148 patients who were enrolled from August 1997 through October 2000. All patients underwent SLN biopsy using a combination of radioactive colloid and blue dye injection followed by completion Level I/II axillary dissection. Statistical comparison was performed by chi-square analysis. The SLN identification rate, false negative rate, and overall accuracy of SLN biopsy were not significantly different among tumor stages T1, T2, and T3. We conclude that SLN biopsy is no less accurate for T2-3 breast cancers compared with T1 tumors.
Assuntos
Neoplasias da Mama/patologia , Biópsia de Linfonodo Sentinela , Reações Falso-Negativas , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , PalpaçãoRESUMO
OBJECTIVE: To determine the optimal radioactive colloid injection technique for sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: The optimal radioactive colloid injection technique for breast cancer SLN biopsy has not yet been defined. Peritumoral injection of radioactive colloid has been used in most studies. Although dermal injection of radioactive colloid has been proposed, no published data exist to establish the false-negative rate associated with this technique. METHODS: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a multiinstitutional study involving 229 surgeons. Patients with clinical stage T1-2, N0 breast cancer were eligible for the study. All patients underwent SLN biopsy, followed by level I/II axillary dissection. Peritumoral, subdermal, or dermal injection of radioactive colloid was performed at the discretion of the operating surgeon. Peritumoral injection of isosulfan blue dye was performed concomitantly in most patients. The SLN identification rates and false-negative rates were compared. The ratios of the transcutaneous and ex vivo radioactive SLN count to the final background count were calculated as a measure of the relative degree of radioactivity of the nodes. One-way analysis of variance and chi-square tests were used for statistical analysis. RESULTS: A total of 2,206 patients were enrolled. Peritumoral, subdermal, or dermal injection of radioactive colloid was performed in 1,074, 297, and 511 patients, respectively. Most of the patients (94%) who underwent radioactive colloid injection also received peritumoral blue dye injection. The SLN identification rate was improved by the use of dermal injection compared with subdermal or peritumoral injection of radioactive colloid. The false-negative rates were 9.5%, 7.8%, and 6.5% (not significant) for peritumoral, subdermal, and dermal injection techniques, respectively. The relative degree of radioactivity of the SLN was five- to sevenfold higher with the dermal injection technique compared with peritumoral injection. CONCLUSIONS: Dermal injection of radioactive colloid significantly improves the SLN identification rate compared with peritumoral or subdermal injection. The false-negative rate is also minimized by the use of dermal injection. Dermal injection also is associated with SLNs that are five- to sevenfold more radioactive than with peritumoral injection, which simplifies SLN localization and may shorten the learning curve.
Assuntos
Neoplasias da Mama/patologia , Compostos Radiofarmacêuticos , Biópsia de Linfonodo Sentinela , Coloide de Enxofre Marcado com Tecnécio Tc 99m , Humanos , Injeções Intradérmicas , Injeções Intralesionais , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Core biopsy findings of atypical ductal hyperplasia (ADH) underestimates the diagnosis of malignancy by 18% to 88%. Using the Mammotome biopsy technique, more accurate assessment of the lesion is possible, making selective excision of these lesions a consideration. METHODS: The records of 62 patients who were found to have ADH at Mammotome biopsy and subsequently underwent excision of the lesion were reviewed. Patient data were statistically analyzed for predictors of malignancy at the time of surgical excision. RESULTS: Of the 62 patients, 9 (15%) had malignancy at excision. Variables predicting for malignancy included markedly atypical hyperplasia and incomplete removal of calcifications at Mammotome biopsy, a previous contralateral breast cancer, and a family history of breast cancer, with a combined sensitivity of 100% and specificity of 80%. CONCLUSIONS: Mild ADH found on Mammotome, not associated with a personal or family history of breast cancer, may not need excision if all calcifications have been removed.
Assuntos
Biópsia por Agulha/instrumentação , Mama/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha/métodos , Biópsia por Agulha/estatística & dados numéricos , Doenças Mamárias/patologia , Neoplasias da Mama/patologia , Calcinose/patologia , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Humanos , Hiperplasia/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
INTRODUCTION: Multiple radioactive lymph nodes are often removed during the course of sentinel lymph node (SLN) biopsy for breast cancer when both blue dye and radioactive colloid injection are used. Some of the less radioactive lymph nodes are second echelon nodes, not true SLNs. The purpose of this analysis was to determine whether harvesting these less radioactive nodes, in addition to the "hottest" SLNs, reduces the false-negative rate. METHODS: Patients were enrolled in this multicenter (121 surgeons) prospective, institutional review board-approved study after informed consent was obtained. Patients with clinical stage T1-2, N0, M0 invasive breast cancer were eligible. This analysis includes all patients who underwent axillary SLN biopsy with the use of an injection of both isosulfan blue dye and radioactive colloid. The protocol specified that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest node should be removed and designated SLNs. All patients underwent completion level I/II axillary dissection. RESULTS: SLNs were identified in 672 of 758 patients (89%). Of the patients with SLNs identified, 403 patients (60%) had more than 1 SLN removed (mean, 1.96 SLN/patient) and 207 patients (31%) had nodal metastases. The use of filtered or unfiltered technetium sulfur colloid had no impact on the number of SLNs identified. Overall, 33% of histologically positive SLNs had no evidence of blue dye staining. Of those patients with multiple SLNs removed, histologically positive SLNs were found in 130 patients. In 15 of these 130 patients (11.5%), the hottest SLN was negative when a less radioactive node was positive for tumor. If only the hottest node had been removed, the false-negative rate would have been 13.0% versus 5.8% when all nodes with 10% or more of the ex vivo count of the hottest node were removed (P =.01). CONCLUSIONS: These data support the policy that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest SLN should be harvested for optimal nodal staging.
Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Excisão de Linfonodo , Linfonodos/diagnóstico por imagem , Biópsia/normas , Neoplasias da Mama/diagnóstico por imagem , Reações Falso-Negativas , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cintilografia , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Corantes de Rosanilina , Coloide de Enxofre Marcado com Tecnécio Tc 99mRESUMO
PURPOSE: Previous studies have demonstrated the feasibility of sentinel lymph node (SLN) biopsy for nodal staging of patients with breast cancer. However, unacceptably high false-negative rates have been reported in several studies, raising doubt about the applicability of this technique in widespread surgical practice. Controversy persists regarding the optimal technique for correctly identifying the SLN. Some investigators advocate SLN biopsy using injection of a vital blue dye, others recommend radioactive colloid, and still others recommend the use of both agents together. PATIENTS AND METHODS: A total of 806 patients were enrolled by 99 surgeons. SLN biopsy was performed by single-agent (blue dye alone or radioactive colloid alone) or dual-agent injection at the discretion of the operating surgeon. All patients underwent attempted SLN biopsy followed by completion level I/II axillary lymph node dissection to determine the false-negative rate. RESULTS: There was no significant difference (86% v 90%) in the SLN identification rate among patients who underwent single- versus dual-agent injection. The false-negative rates were 11.8% and 5.8% for single- versus dual-agent injection, respectively (P <.05). Dual-agent injection resulted in a greater mean number of SLNs identified per patient (2. 1 v 1.5; P <.0001). The SLN identification rate was significantly less for patients older than 50 years as compared with that of younger patients (87.6% v 92.6%; P =.03). Upper-outer quadrant tumor location was associated with an increased likelihood of a false-negative result compared with all other locations (11.2% v 3. 9%; P <.05). CONCLUSION: In multi-institutional practice, SLN biopsy using dual-agent injection provides optimal sensitivity for detection of nodal metastases. The acceptable SLN identification and false-negative rates associated with the dual-agent injection technique indicate that this procedure is a suitable alternative to routine axillary dissection across a wide spectrum of surgical practice and hospital environments.
Assuntos
Biópsia , Neoplasias da Mama/patologia , Excisão de Linfonodo , Linfonodos/patologia , Axila , Reações Falso-Negativas , Feminino , Humanos , Injeções , Metástase Linfática , Corantes de Rosanilina , Sensibilidade e Especificidade , Coloide de Enxofre Marcado com Tecnécio Tc 99mRESUMO
The relationship of the neutralizing activity (NA) profile of sera from human immunodeficiency virus (HIV)-infected individuals to the HIV viral load and the absolute CD4 count was examined. The NA of 24 serum samples against autologous isolates (AI) and HIV type 1 strain MN was examined. Three NA patterns were recognized. Nine sera neutralized both AI and MN (+/+), six sera neutralized MN but not AI (-/+), and nine sera failed to neutralize both AI and MN (-/-). The identification of the three neutralization patterns (+/+, -/+, and -/-) indicated that resistance to neutralization was progressive. A reciprocal relationship between the viral burden of the patients and the NA profiles was observed. The nine subjects with a -/- NA profile had a plasma viral load of > or =5 x 10(4) copies/ml and a cellular viral burden of > or =1,122 infectious units per million viable cells, which were significantly different from those of the other groups (P < 0.02). These patterns were independent of the phenotypic characteristics of the virus. Longitudinally, subjects with a -/- profile at baseline gained their HIV-specific NA by 24 weeks of antiretroviral therapy when this was associated with a >/=1-log(10) decline in the plasma HIV viral load. The sera from week 24 from some patients were able to neutralize both the 24-week and the baseline dominant virus isolates. A change in CD4 cell count of 50 or more in either direction predicted a -/- or +/+ profile. The verification of the autologous NA profile might be important in selecting patients who may benefit from immune-based therapies involving neutralizing monoclonal antibodies.
Assuntos
Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da Imunodeficiência Adquirida/imunologia , Contagem de Linfócito CD4 , Antígenos HIV/análise , HIV/imunologia , Carga Viral , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/sangue , Biomarcadores , Progressão da Doença , Feminino , HIV/genética , Humanos , Imunoglobulinas Intravenosas , Imunofenotipagem , Masculino , Mutação , Testes de Neutralização , RNA Viral/sangue , Especificidade da Espécie , Viremia/diagnóstico , Viremia/tratamento farmacológico , Viremia/imunologiaRESUMO
OBJECTIVE: To evaluate the role of preoperative lymphoscintigraphy in sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: Numerous studies have demonstrated that SLN biopsy can be used to stage axillary lymph nodes for breast cancer. SLN biopsy is performed using injection of radioactive colloid, blue dye, or both. When radioactive colloid is used, a preoperative lymphoscintigram (nuclear medicine scan) is often obtained to ease SLN identification. Whether a preoperative lymphoscintigram adds diagnostic accuracy to offset the additional time and cost required is not clear. METHODS: After informed consent was obtained, 805 patients were enrolled in the University of Louisville Breast Cancer Sentinel Lymph Node Study, a multiinstitutional study involving 99 surgeons. Patients with clinical stage T1-2, N0 breast cancer were eligible for the study. All patients underwent SLN biopsy, followed by level I/II axillary dissection. Preoperative lymphoscintigraphy was performed at the discretion of the individual surgeon. Biopsy of nonaxillary SLNs was not required in the protocol. Chi-square analysis and analysis of variance were used for statistical comparison. RESULTS: Radioactive colloid injection was performed in 588 patients. In 560, peritumoral injection of isosulfan blue dye was also performed. A preoperative lymphoscintigram was obtained in 348 of the 588 patients (59%). The SLN was identified in 221 of 240 patients (92.1%) who did not undergo a preoperative lymphoscintigram, with a false-negative rate of 1.6%. In the 348 patients who underwent a preoperative lymphoscintigram, the SLN was identified in 310 (89.1%), with a false-negative rate of 8.7%. A mean of 2.2 and 2. 0 SLNs per patient were removed in the groups without and with a preoperative lymphoscintigram, respectively. There was no statistically significant difference in the SLN identification rate, false-negative rate, or number of SLNs removed when a preoperative lymphoscintigram was obtained. CONCLUSIONS: Preoperative lymphoscintigraphy does not improve the ability to identify axillary SLN during surgery, nor does it decrease the false-negative rate. Routine preoperative lymphoscintigraphy is not necessary for the identification of axillary SLNs in breast cancer.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Axila , Biópsia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Reações Falso-Negativas , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Cintilografia , Compostos Radiofarmacêuticos , Corantes de Rosanilina , Coloide de Enxofre Marcado com Tecnécio Tc 99mRESUMO
Chronic inflammation is a significant risk factor for the development of urinary bladder cancer. We have shown that inflammation induced by killed Escherichia coli and also by its lipopolysaccharide (LPS) strikingly enhances N-methyl-N-nitrosourea (MNU)-initiated rat bladder carcinogenesis. Aspirates from the bladder lumen contained a large quantity of hydrogen peroxide (H2O2) and several cytokines. In this study, we tested the hypothesis that reactive oxygen intermediates (ROI) released from activated polymorphonuclear leukocytes (PMN) are involved in inflammation-associated bladder carcinogenesis. Using an immortalized nontumorigenic rat urothelial cell line, MYP3, we examined the effect of LPS-activated PMN on malignant transformation. MYP3 cells pretreated with or without MNU were exposed daily to LPS-activated PMN for one week and were then tested for growth in soft agar. In contrast to no colony formation by the parental cells, a varying number of colonies developed from cells treated with LPS-activated PMN. Although combined treatment with MNU and PMN was most effective (P<0.01), cells treated with LPS-activated PMN alone also formed a small number of colonies. Addition of catalase, which decomposes H2O2, and/or an antioxidant, alpha-tocopherol, reduced the number of colonies induced by LPS-activated PMN (P<0.05). Cells derived from colonies were tumorigenic in athymic nude mice. However, tumorigenicity in mice was greater with cells treated with both MNU and PMN than with cells treated with PMN alone. Our results suggest that ROI released from LPS-activated PMN may be one of the mechanisms involved in the carcinogenesis associated with active urinary tract infection.
Assuntos
Transformação Celular Neoplásica/metabolismo , Lipopolissacarídeos/farmacologia , Neutrófilos/metabolismo , Urotélio/patologia , 8-Hidroxi-2'-Desoxiguanosina , Animais , Catalase/farmacologia , Linhagem Celular , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/imunologia , Desoxiguanosina/análogos & derivados , Desoxiguanosina/biossíntese , Cultura em Câmaras de Difusão , Genes p53/genética , Genes ras/genética , Humanos , Peróxido de Hidrogênio/metabolismo , Ativação Linfocitária , Camundongos , Camundongos Nus , Transplante de Neoplasias , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Ratos , Ensaio Tumoral de Célula-Tronco , Urotélio/efeitos dos fármacos , Urotélio/metabolismo , Vitamina E/farmacologiaRESUMO
We examined expression of N-methylpurine-DNA glycosylase (MPG), a DNA repair enzyme that removes N-alkylpurine damage, in normal, malignant, and immortalized breast epithelial cells, and breast cancer cell lines (MDA-MB-231, MCF7, T47D). Northern analysis showed increased expression in cancer versus normal breast epithelial cells (2-24-fold). Southern blots revealed no gene amplification or polymorphisms. Immunofluorescence, immunohistochemistry, and Western blot analysis demonstrated increased MPG protein expression in the tumor cells that correlated with elevated glycosylase activity. Since MPG overexpression has been shown to be paradoxically associated with increased susceptibility to DNA damage, up-regulation of this gene may suggest a functional role in breast carcinogenesis.
Assuntos
Neoplasias da Mama/enzimologia , DNA Glicosilases , Reparo do DNA , N-Glicosil Hidrolases/biossíntese , Adenina/análogos & derivados , Adenina/metabolismo , Sequência de Aminoácidos , Mama/metabolismo , Neoplasias da Mama/genética , Células Cultivadas , Humanos , Dados de Sequência Molecular , N-Glicosil Hidrolases/metabolismo , RNA Mensageiro/metabolismo , Células Tumorais CultivadasRESUMO
Image-guided core biopsy (IGCB) of nonpalpable mammographic abnormalities has gained attention as an alternative to needle-localized breast biopsy (NLB). This study evaluated IGCB in the diagnostic workup of patients with nonpalpable mammographic lesions suspicious for cancer. Eighty-six patients who underwent IGCB were compared to 85 patients who underwent NLB for the diagnosis of mammographic lesions suspicious for cancer. The incidence of positive margins was less in patients who subsequently underwent needle-localized resection in the IGCB group than in the NLB group (29 and 65%; P < 0.0001). The volume of excision was greater for patients in the IGCB group than for the NLB group (106 cm3 and 52 cm3; P < 0.0001). Patients in the IGCB group averaged 1.1 operative procedures compared with patients in the NLB group, who required an average of 1.9 operative procedures. The mean charge for an IGCB was $1011 compared to $2975 for a NLB. Subset analysis of 32 spiculated masses from the IGCB group and 21 from the NLB group showed similar advantages of IGCB over NLB. The preoperative use of IGCB for mammographically suspicious lesions can reduce the incidence of positive surgical margins and the number of surgical procedures required. The use of IGCB allows for a more efficient diagnostic workup and less expense to the patient.
Assuntos
Biópsia por Agulha/métodos , Neoplasias da Mama/diagnóstico , Diagnóstico por Imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/economia , Biópsia/métodos , Biópsia por Agulha/economia , Feminino , Humanos , Mamografia , Pessoa de Meia-Idade , Palpação , Estudos RetrospectivosRESUMO
The recent shift toward the diagnosis of smaller breast cancers has led to the reevaluation of their treatment. Because of the low incidence of nodal involvement, recent studies have recommended selective axillary lymph node dissection (AxLND) for early breast cancer. The incidence of nodal involvement is a critical factor in defining the role of AxLND. Large series based on cancer registry data report the incidence of nodal positivity in stage T1a cancer to be 16 to 23 per cent. In contrast, data that include only pathologically reviewed cases report the incidence to be 0 to 6 per cent. We reviewed the medical records of 148 stage T1a breast cancer patients from 1987 through 1994 in two community hospitals as identified by the local tumor registry. After chart review, 115 cases with AxLND underwent pathologic review; 82 were confirmed as stage T1a. Only 3 of 82 (4%) patients were node positive. All three node-positive tumors were of infiltrating ductal histology. No tumor characteristic was predictive of nodal metastasis. Data from the tumor registry and from pathology reports overstated the incidence of nodal involvement (5 and 9%, respectively). In light of the limited clinical benefit and associated cost and morbidity of AxLND, selected informed patients may be spared AxLND.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Excisão de Linfonodo , Linfonodos/patologia , Axila , Carcinoma Ductal de Mama/secundário , Carcinoma Ductal de Mama/cirurgia , Feminino , Humanos , Incidência , Excisão de Linfonodo/estatística & dados numéricos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Sistema de Registros , Estudos RetrospectivosRESUMO
OBJECTIVES: This study examined the extent of variation by race/ethnicity in the prevalence of adverse birth outcomes, whether differentials persisted after other risk factors were controlled for, and whether the direction and magnitude of relationships differed by type of outcome. METHODS: A revised system of measurement was used to estimate multinomial logistic models in a large, nationally representative US data set. RESULTS: Considerable racial/ethnic variation was found across birth outcome categories; differences persisted in the adjusted parameter estimates; and the effects of other risk factors on birth outcomes were similar as to direction, but varied somewhat in magnitude. The odds of compromised birth outcomes were much higher among African Americans than among Mexican Americans and non-Hispanic Whites. CONCLUSIONS: In addition to persistent racial inequality, we found strong adverse effects of both inadequate and "adequate-plus" prenatal care and smoking. Risk of intrauterine growth retardation was higher in the absence of medical insurance, and risk of all adverse birth outcomes was lower among mothers participating in the Special Supplemental Food Program for Women, Infants, and Children.
Assuntos
Negro ou Afro-Americano , Retardo do Crescimento Fetal/etnologia , Hispânico ou Latino , Resultado da Gravidez/etnologia , População Branca , Adolescente , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Feminino , Retardo do Crescimento Fetal/genética , Humanos , Recém-Nascido , Modelos Logísticos , Masculino , Razão de Chances , Vigilância da População , Gravidez , Resultado da Gravidez/genética , Cuidado Pré-Natal , Prevalência , Características de Residência , Fatores de Risco , Fumar/etnologia , Fatores Socioeconômicos , Estados Unidos/epidemiologia , População Branca/estatística & dados numéricosRESUMO
BACKGROUND: Although the technique of isolated pelvic perfusion dates back to the time of Creech (1959) and has been used by a variety of authors to treat unresectable neoplasms, the inherent complexity of the open procedure limited its widespread use. We simplified the technique through use of the balloon-occlusion technique for aortic and caval control. Our initial efforts used this technique for unresectable pelvic cancer, but recently we used this as preoperative therapy for advanced pelvic malignancy. METHODS: Isolated pelvic perfusion was accomplished by placement of balloon-occlusion catheters (Fogerty 8) in the aorta and inferior vena cava (IVC) at L3 vertebral body level via the common femoral artery and vein and establishing inflow and outflow catheter connections to a hemodialysis pump that generated a flow rate of 150-300 ml/min. Chemotherapy drugs were infused at times 0, 10, and 20 min. 5-Fluorouracil (5-FU; 1,500 mg/M2), cis-platinum (50-100 mg/M2), and mitomycin (15-20 mg/M2) were given by normothermic perfusion over a 45-min period. Forty isolated perfusions were carried out in 25 patients. Patients were evaluated by clinical examination, biochemical tests, computed tomography (CT) and magnetic resonance imaging (MRI) scans, and surgical exploration. RESULTS: Pelvic perfusion generally achieved pelvic systemic exposure ratios (area under the curve) between 5 and 10:1 for all three drugs: mean ratios were 11.4 (5-FU), 6.0 (cisplatin), and 9.0 (mitomycin). The amount of leaking to the systemic circuit ranged from 28 to 38%. Of 15 patients treated for palliation, there was one objective partial response (PR). Ten patients had symptomatic improvement of pain, two had complete pain relief (CR), and eight had partial pain relief, ranging from 3 weeks to 3 months (median, 5 weeks). Six of 10 patients with adequate carcinoembryonic antigen (CEA) follow-up data had a reduction in CEA levels (mean change, 35 units). Of 10 preoperative patients, there was one CR among five rectal cancer patients; and four of five PRs among patients with other pelvic malignancies: two PRs in patients with epidermoid cancer and one PR each in patients with endometrial cancer and metastatic anorectal melanoma. CONCLUSION: Pelvic perfusion by a simplified balloon-occlusion technique provides palliation for most patients with advanced pelvic malignancy and may increase resectability and improve tumor control in patients amenable to resection.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cateterismo , Neoplasias Pélvicas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia do Câncer por Perfusão Regional , Cisplatino/administração & dosagem , Cisplatino/farmacocinética , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/farmacocinética , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Mitomicina/farmacocinética , Cuidados Paliativos , Neoplasias Pélvicas/terapia , Pelve , Indução de RemissãoRESUMO
8-OH-deoxyguanosine can diminish the ability of the restriction endonucleases Hpa II and Msp I to cleave DNA. The exact position of the adduct within the recognition site appears to determine the extent of the effect.
Assuntos
Enzimas de Restrição do DNA/metabolismo , DNA/metabolismo , Desoxiguanosina/metabolismo , Desoxirribonuclease HpaII/metabolismo , Sequência de Bases , Radicais Livres/metabolismo , Humanos , Dados de Sequência Molecular , Oligonucleotídeos , Espécies Reativas de OxigênioRESUMO
Injury of the cervical spine involving the spinal cord such as results from diving into shallow water causes very severe disability. In spite of progress in medical science, results of the treatment and rehabilitation of such patients are not satisfactory. Every effort should be undertaken to give young swimmers, the most frequent victims of diving injuries, proper instructions to prevent spinal cord injury. A broadly conceived national prevention programme, developed under the catch-phrase 'Do Not Jump into the Unknown', has been under way in Slovenia during the past 3 years, and has been promoted in collaboration with the Health Protection Institute of Slovenia. In these years the number of new spinal cord injuries decreased (one-two per year), but it is too early to conclude that this is the result of the prevention activities. But it is obvious that knowledge of this type of injury is now much more widespread.