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1.
Urol Oncol ; 35(3): 119, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28159492

RESUMO

PURPOSE: Percutaneous biopsy obtained from a single location is prone to sampling error in large heterogeneous renal masses, leading to nondiagnostic results or failure to detect poor prognostic features. We evaluated the accuracy of percutaneous biopsy for large renal masses using a modified multi-quadrant technique vs. a standard biopsy technique. MATERIALS AND METHODS: Clinical and pathological data for all patients with cT2 or greater renal masses who underwent percutaneous biopsy from 2009 to 2014 were reviewed. The multi-quadrant technique was defined as multiple core biopsies from at least 4 separate solid enhancing areas in the tumor. The incidence of nondiagnostic findings, sarcomatoid features and procedural complications was recorded, and concordance between biopsy specimens and nephrectomy pathology was compared. RESULTS: A total of 122 biopsies were performed for 117 tumors in 116 patients (46 using the standard biopsy technique and 76 using the multi-quadrant technique). Median tumor size was 10cm (IQR: 8-12). Biopsy was nondiagnostic in 5 of 46 (10.9%) standard and 0 of 76 (0%) multi-quadrant biopsies (P = 0.007). Renal cell carcinoma was identified in 96 of 115 (82.0%) tumors and nonrenal cell carcinoma tumors were identified in 21 (18.0%). One complication occurred using the standard biopsy technique and no complications were reported using the multi-quadrant technique. Sarcomatoid features were present in 23 of 96 (23.9%) large renal cell carcinomas studied. Sensitivity for identifying sarcomatoid features was higher using the multi-quadrant technique compared to the standard biopsy technique at 13 of 15 (86.7%) vs. 2 of 8 (25.0%) (P = 0.0062). CONCLUSIONS: The multi-quadrant percutaneous biopsy technique increases the ability to identify aggressive pathological features in large renal tumors and decreases nondiagnostic biopsy rates.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Biópsia , Humanos , Rim , Estudos Retrospectivos
2.
World J Urol ; 35(5): 729-735, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27631325

RESUMO

INTRODUCTION: A significant proportion of patients that fail active surveillance (AS) for prostate cancer management do so because of cancer upgrading. A previously validated upgrading nomogram generates a score that predicts risk of biopsy Gleason 6 upgrading following radical prostatectomy in lower-risk populations that are candidates for Active Surveillance (Cancer, 2013). OBJECTIVES: We hypothesize that the upgrading risk (UR) score generated by this nomogram at diagnosis improves the ability to predict patients that will subsequently fail AS. METHODS: To evaluate the nomogram, retrospective data from several institutional cohorts of patients who met AS criteria, group 1 (n = 75) and group 2 (n = 1230), were independently examined. A UR score was generated using the coefficients from the nomogram consisting of PSA density (PSAD), BMI, maximum % core involvement (MCI), and number of positive cores. AS failure was defined as Gleason score (GS) >6, >50 % maximum core involvement, or >2 positive cores on biopsy. Univariate and multivariate Cox proportional-hazards regression models, upgrading risk score, and other clinicopathologic features were each assessed for their ability to predict AS failure. RESULTS: Clinicopathologic parameters were similar in both groups with the exception of mean PSAD (0.13 vs. 0.11, p < 0.01) and follow-up (2.1 vs. 3.2 years, p = 0.2). Most common cause of AS failure was GS > 6 (group 1) compared to >2 positive cores (group 2). On univariate analysis in both populations, features at diagnosis including PSAD and the UR score were significant in predicting AS failure by upgrading (Gleason > 6) and any failure. Multivariate analysis revealed the UR score predicts AS failure by GS upgrading (HR 1.8, 95 % CI 1.12-2.93; p = 0.01) and any failure criteria (HR 1.7, 95 % CI 1.06-2.65); p = 0.02) for group 1. Likewise, the UR score in group 2 predicts AS failure with GS upgrading (HR 1.3, 95 % CI 1.15-1.42; p < 0.0001) and any failure criteria (HR 1.18, 95 % CI 1.18-1.38; p < 0.0001). An ROC generated an AUC of 0.66. Decision curve analysis demonstrated a high net benefit for the UR score across a range of threshold probabilities. Based on these outcomes, at 3 years, patients in the lowest risk quartile have a 15 % risk of AS failure versus a 46 % risk in the highest quartile (p < 0.0001). CONCLUSIONS: The UR score was predictive of pathologic AS failure on multivariate analysis in several AS cohorts. It outperformed single clinicopathologic criteria and may provide a useful adjunct using clinicopathologic data to stratify patients considering AS.


Assuntos
Algoritmos , Neoplasias da Próstata/patologia , Conduta Expectante , Fatores Etários , Idoso , Biópsia com Agulha de Grande Calibre , Índice de Massa Corporal , Estudos de Coortes , Gerenciamento Clínico , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Prognóstico , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/terapia , Estudos Retrospectivos , Medição de Risco
3.
J Cutan Pathol ; 43(12): 1226-1230, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27696488

RESUMO

Glandular and pseudoglandular tumors of the penile skin are extremely uncommon and can present diagnostic challenges. Primary adenosquamous carcinoma of the penis is an extremely rare tumor, composed of distinct areas of malignant squamous and glandular cells, making it a diagnostically challenging entity. The World Health Organization (WHO) recognizes several subtypes of squamous cell carcinoma (SCC), each with its own distinctive pathologic appearance, clinical associations and prognosis. Among these variants is the exceedingly uncommon adenosquamous carcinoma (ASC), representing 1%-2% of all SCC of the penis. Recent large studies have interrogated the presence of human papillomavirus (HPV) in malignant penile tumors and have shown specific morphologic patterns and clinical presentations to associate with HPV status. However, given the rarity of the adenosquamous variant of SCC, it has largely been excluded from these studies. The glandular components of these lesions can present a confusing appearance, particularly when a large tumor is represented on a small biopsy. Here we describe a difficult histologic presentation of this rare tumor, with the first published characterization of the HPV status of this subtype. This case represents a distinctly unusual case of metastatic HPV-positive primary cutaneous adenosquamous carcinoma of the penis.


Assuntos
Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/virologia , Infecções por Papillomavirus/complicações , Neoplasias Penianas/patologia , Neoplasias Penianas/virologia , Adulto , Biomarcadores Tumorais/análise , Humanos , Imuno-Histoquímica , Masculino , Papillomaviridae , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/virologia
4.
Bladder Cancer ; 2(2): 139-149, 2016 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-27376136

RESUMO

Patient-reported outcomes (PRO), including health-related quality of life (HRQOL) measures, represent important means for evaluating patients' health outcomes and for guiding health care decisions made by patients, practitioners, investigators, and policy makers. In spite of the large number of studies examining HRQOL in patients with bladder cancer, very few review articles investigated this topic. Because these review studies report mixed results, incorporating bladder cancer HRQOL measures into standard urological practice is not a viable option. In this non-systematic review of the literature and commentary we note some general concerns regarding PRO research, but our primary focus is on the HRQOL methodology within the context of two types of bladder cancer: muscle invasive and non-muscle invasive bladder cancer. Considering bladder cancer HRQOL as the interaction of four areas of the assessment process (i.e., what model of HRQOL to choose, what instruments are available to fit the choice, how interpretation of the resulting data fits the model, and how to derive some utility from the chosen model) and the two types of disease (i.e., muscle invasive and non-muscle invasive) may move us toward a better understanding of bladder cancer HRQOL. Establishing a useful model of perceived general health or specific symptoms is the first and most important step in developing the responsive bladder cancer HRQOL measures necessitated by clinical settings.

5.
Adv Urol ; 2014: 746298, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24982672

RESUMO

Objectives. Level 1 evidence supports the use of neoadjuvant chemotherapy (NAC) to improve overall survival in muscle invasive bladder cancer; however utilization rates remain low. The aims of our study were to determine factors associated with NAC use, to more clearly define reasons for low utilization, and to determine the current rate of NAC use among urologic oncologists. Materials and Methods. Active members of the Society for Urologic Oncology were provided a 20-question survey. Descriptive statistical analysis was conducted for each question and univariate analysis was performed. Results. We achieved a response rate of 21%. Clinical T3/T4 disease was the most often selected reason for recommending NAC (87%). Concerns with recommending NAC were age and comorbidities (54%) followed by delay in surgery (35%). An association was identified between urologic oncologists who discussed NAC with >90% of their patients and medical oncologists "always" recommending NAC (P = 0.0009). NAC utilization rate was between 30 and 57%. Conclusions. Amongst this highly specialized group of respondents, clinical T3-T4 disease was the most common reason for implementation of NAC. Respondents who frequently discussed NAC were more likely to report their medical oncologist always recommending NAC. Reported NAC use was higher in this surveyed group (30-57%) compared with recently published rates.

6.
Prostate Cancer Prostatic Dis ; 13(4): 328-32, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20877308

RESUMO

The aim of this study is to evaluate the outcomes of robot-assisted laparoscopic prostatectomy (RALP) in prostate cancer (PCa) patients with human immunodeficiency virus (HIV). This is a prospective cohort study of HIV patients undergoing RALP, comparing the demographics, tumor characteristics, complications, and short-term oncological outcomes of HIV-positive men to HIV-negative men using univariate (χ(2), Mann-Whitney test) and multivariable (logistic regression) analyses. From 2007 to 2010, 298 men underwent RALP, 8 of whom were known to be HIV positive. Preoperatively, all eight were taking highly active antiretroviral therapy (HAART) and had undetectable viral loads (<50); mean CD4 count was 634 cells per mm(3). HIV-positive men were younger (54 versus 62 years, P=0.010) and less likely to be white (P=0.007). There were no significant differences between groups with respect to clinical staging, pathological and oncological outcomes or most complication rates. However, the prevalence of perioperative transfusions (P=0.031) and ileus (P=0.021) were higher in HIV-positive patients. HIV remained significantly associated with risk of transfusion after adjustment for age, race, Gleason sum and clinical T stage (P=0.002). After a median of 2.6 (range 0.03-19.2) months of follow-up, PSA remained undetectable in all eight HIV patients. These data suggest that RALP is safe for, and demonstrates short-term oncological efficacy in, HIV-positive patients with PCa.


Assuntos
Carcinoma/cirurgia , Infecções por HIV/cirurgia , Laparoscopia/métodos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Robótica/métodos , Adulto , Idoso , Carcinoma/complicações , HIV/fisiologia , Infecções por HIV/complicações , Humanos , Laparoscopia/instrumentação , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Prostatectomia/instrumentação , Neoplasias da Próstata/complicações
7.
Prostate Cancer Prostatic Dis ; 12(1): 6-12, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-18711409

RESUMO

Malignancy occurs with increased frequency in the HIV-positive population. The true incidence of prostate cancer in this population is unknown. In the few cases that have been presented in the literature, prostate cancer in HIV-positive men appears to behave much like it does in HIV-negative men. Prostate cancer is the most common malignancy in men and the second leading cause of cancer death. Approximately 800,000 men in the United States are HIV positive, and innovative therapies have dramatically improved survival. HIV disproportionately impacts ethnic groups with increased risk of prostate cancer and has been associated with increases in the incidence of certain malignancies. Despite the high prevalence of both diseases, there is relatively little literature about prostate cancer in HIV-positive patients. There is no consensus on how to screen or treat this patient population. We review the literature with regards to incidence, screening, treatment, and outcomes of this poorly characterized population. We briefly discuss the impact of highly active antiretroviral therapy and testosterone supplementation in the development of prostate cancer. A systematic review of the literature was conducted using MEDLINE key words 'HIV,' 'prostate,' 'prostate cancer' and 'AIDS.' Manual bibliographic review of cross-referenced items was also performed. A total of 176 unique abstracts and publications were reviewed; many authors provided data on the incidence of HIV and various malignancies including prostate cancer. Twelve unique publications providing detailed information on 60 patients with HIV and prostate cancer were identified. Prostate cancer is a common malignancy in HIV-positive men. With improved therapies for HIV and increasing survival, the importance for screening and treating prostate cancer is increasing. Acute outcomes of treatment do not demonstrate increased acute morbidity; however long-term outcomes have not been reported.


Assuntos
Infecções por HIV/complicações , Neoplasias da Próstata/complicações , Idoso , Infecções por HIV/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/epidemiologia
8.
Health policy ; 83(2/3): 144-161, Oct. 2007. ilus, tab
Artigo em Inglês | CidSaúde - Cidades saudáveis | ID: cid-59811

RESUMO

Biomedical interventions promise achievement of health-related Millennium Development Goals provided social-, capacity- and knowledge-based constraints to scaling up and reaching marginalized people at risk, are addressed, and balance between prevention and treatment is struck. We argue for a new approach: multi-stakeholder capacity building and learning for empowerment: MuSCLE. MuSCLE is used as a way to frame three systemic weaknesses in traditional health science and policy approaches: (1) a lack of engagement with people at risk to build a collective understanding of the contexts of health problems, including social drivers; (2) a lack of multi-criteria evaluation of alternative interventions; (3) a lack of attention paid to integrated capacity building. The MuSCLE framework responds in three ways: (1) participatory assessment of the ecological, socio-cultural, economic and political contexts of health, identifying priorities using risk and vulnerability science, and modeling drivers; (2) selection among intervention alternatives that makes ecological, socio-cultural, economic and political tradeoffs transparent; (3) integrated capacity building for sustainable and adaptive interventions. Literature and field lessons support the argument, and guidelines are set down. A MuSCLE approach argues for a transformation in health science and policy in order to achieve Millennium Development Goals for health. (AU)


Assuntos
Humanos , Participação da Comunidade , Promoção da Saúde/organização & administração , Prioridades em Saúde , Comportamento Cooperativo , Objetivos Organizacionais , Cultura , Nações Unidas
9.
Prostate Cancer Prostatic Dis ; 9(4): 448-51, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16683012

RESUMO

Prostate cancer has a distinctly recognized pattern of metastases: multifocal and osteoblastic lesions involving the axial skeleton and non-calcified lymph nodes in the pelvic and lumbar aortic groups. Most adenocarcinomas are capable of producing macrocalcification. We report a case of prostate cancer with de novo calcified metastases to the liver and retroperitoneal lymph nodes mimicking the pattern usually seen in mucin-producing adenocarcinomas arising from the gastrointestinal tract. To our knowledge, this is the first such case to be reported in the literature. We propose a multifactorial mechanism that supports dystrophic calcification in this case. The knowledge of atypical presentation of metastatic disease can prevent diagnostic delay and prompt initiation of therapy.


Assuntos
Adenocarcinoma Mucinoso/patologia , Calcinose/etiologia , Neoplasias Hepáticas/secundário , Linfonodos/patologia , Neoplasias da Próstata/patologia , Neoplasias Retroperitoneais/secundário , Adenocarcinoma Mucinoso/secundário , Biomarcadores Tumorais/sangue , Diagnóstico Diferencial , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia Computadorizada por Raios X
10.
Artigo em Inglês | MEDLINE | ID: mdl-18238154

RESUMO

This paper is concerned with the use of scientific visualization methods for the analysis of feedforward neural networks (NNs). Inevitably, the kinds of data associated with the design and implementation of neural networks are of very high dimensionality, presenting a major challenge for visualization. A method is described using the well-known statistical technique of principal component analysis (PCA). This is found to be an effective and useful method of visualizing the learning trajectories of many learning algorithms such as backpropagation and can also be used to provide insight into the learning process and the nature of the error surface.

11.
Cogn Affect Behav Neurosci ; 1(3): 239-49, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12467124

RESUMO

In the present study, functional magnetic resonance imaging was used to examine the neural mechanisms involved in the imagined spatial transformation of one's body. The task required subjects to update the position of one of four external objects from memory after they had performed an imagined self-rotation to a new position. Activation in the rotation condition was compared with that in a control condition in which subjects located the positions of objects without imagining a change in self-position. The results indicated similar networks of activation to other egocentric transformation tasks involving decisions about body parts. The most significant area of activation was in the left posterior parietal cortex. Other regions of activation common among several of the subjects were secondary visual, premotor, and frontal lobe regions. These results are discussed relative to motor and visual imagery processes as well as to the distinctions between the present task and other imagined egocentric transformation tasks.


Assuntos
Encéfalo/fisiologia , Imaginação/fisiologia , Cinestesia/fisiologia , Imageamento por Ressonância Magnética , Orientação/fisiologia , Adulto , Mapeamento Encefálico , Cerebelo/fisiologia , Córtex Cerebral/fisiologia , Dominância Cerebral/fisiologia , Feminino , Giro do Cíngulo/fisiologia , Humanos , Masculino , Rede Nervosa/fisiologia , Rotação
12.
Int J Occup Environ Health ; 6(3): 220-37, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10926727

RESUMO

The dispersion of persistent, bioaccumulative toxic chemicals poses risks to human health and the integrity of the ecosystem on a continental scale. Mexico, the United States, and Canada sought to add two pollutants to an existing list of four subject to North American Regional Action Plans (chlordane, DDT, mercury, PCBs). Mexican negotiators used results from an internal selection process, applying 14 criteria in five categories-physicochemical, health-endpoint, data quality/quantity, exposure potential, and control feasibility-to a baseline group of over 4,700 substances. Using policy analysis by the multiattribute maximum-utility method, progressive application of criteria and weighting algorithms acted like successive filters to identify priority lists of 15 and 7 substances/substance groups for Mexico. The 15 are: 1) benzo-a-pyrene (1 other PAHs); 2) cadmium; 3) heptachlor; 4) hexachlorobenzene; 5) lead; 6) lindane (+ other HCH isomers); 7) 2,3, 7,8-tetrachlorodibenzo-p-dioxin (&plus other PCDDs); 8) aldrin; 9) arsenic; 10) chromium; 11) carbon tetrachloride; 12) 3-3'-dichlorobenzidine; 13) dieldrin; 14) nickel; and 15) toxaphene. The first seven are the priority list of seven.


Assuntos
Algoritmos , Poluição Ambiental/prevenção & controle , Substâncias Perigosas , Política de Saúde , Prioridades em Saúde/organização & administração , Cooperação Internacional , Programas Médicos Regionais/organização & administração , Carga Corporal (Radioterapia) , Canadá , Árvores de Decisões , Substâncias Perigosas/efeitos adversos , Humanos , México , Neoplasias/induzido quimicamente , Probabilidade , Prática de Saúde Pública , Gestão de Riscos , Estados Unidos
13.
Environ Health Perspect ; 107(7): 553-61, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10398590

RESUMO

Untreated wastewater from the Mexico City basin has been used for decades to irrigate cropland in the Mezquital Valley, State of Hidalgo, Mexico. Excess irrigation water recharges the near-surface aquifer that is used as a domestic water supply source. We assessed the groundwater quality of three key groundwater sources of domestic water by analyzing for 24 trace metals, 67 target base/neutral/acid (BNA) organic compounds, nontarget BNA organics, 23 chlorinated pesticides, 20 polychlorinated biphenyls, and nitrate, as well as microbiological contaminants--coliforms, Vibrio cholerae, and Salmonella. Study participants answered a questionnaire that estimated ingestion and dermal exposure to groundwater; 10% of the sample reported frequent diarrhea and 9% reported persistent skin irritations. Detection of V. cholerae non-01 in surface waters at all sites suggested a potential risk (surrogate indicator present) of diarrheal disease for canal and river bathers by accidental ingestion, as well as potential Vibrio contamination of near-surface groundwater and potential cholera risk, magnified by lapses in disinfection. High total coliform levels in surface water and lower levels in groundwater at all sites indicated fecal contamination and a potential risk of gastrointestinal disease in populations exposed to inadequately disinfected groundwater. Using chemical criteria, no significant risk from ingestion or dermal contact was identified at the method detection limits at any site, except from nitrate exposure: infants and young children are at risk from methemoglobinemia at all sites. Results suggest that pathogen risk interventions are a priority, whereas nitrate risk needs further characterization to determine if formal treatment is needed. The risks exist inside and outside the irrigation district. The method was highly cost-effective.


Assuntos
Esgotos , Microbiologia da Água , Poluentes Químicos da Água/toxicidade , Humanos , Inseticidas/toxicidade , Metais/toxicidade , Nitratos/toxicidade , Bifenilos Policlorados/toxicidade , Risco , Fatores Socioeconômicos
14.
J Immunol ; 162(4): 2399-405, 1999 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-9973521

RESUMO

Combination therapy with intravesical bacillus Calmette-Guérin (BCG) plus IFN-alpha for superficial bladder cancer has been demonstrated to be more effective than either single agent alone in animal studies and of suggested greater efficacy in clinical studies. However, the mechanism by which IFN-alpha enhances BCG-mediated antitumor activity is poorly understood. Using PBMCs from bladder cancer patients, IFN-alpha was found to substantially enhance the efficacy of BCG to induce IFN-gamma production. Among 34 patients tested, 80% showed >4-fold increase. This effect of IFN-alpha was observed in both initial and memory responses to BCG. In addition, IFN-alpha up-regulated BCG-induced IL-12 and TNF-alpha and down-regulated BCG-induced IL-10. Neutralizing endogenous IL-10 or adding exogenous IL-12 provided further synergy for IFN-gamma production. In clinical practice, intravesical IFN-alpha 2B (50 million units (MU)/dose) was observed to accelerate urinary IFN-gamma production to low-dose BCG (one-tenth or one-third of a full dose) in patients treated with combination therapy compared with BCG alone. These results suggest that IFN-alpha is a potent BCG enhancer that polarizes the BCG-induced immune response toward the cellular immune pathway by promoting Th1 cytokine expression and reducing Th2 cytokine expression. This study provides an immunological basis for future rational use of IFN-alpha in conjunction with intravesical BCG for bladder cancer immunotherapy.


Assuntos
Adjuvantes Imunológicos/farmacologia , Vacina BCG/imunologia , Citocinas/biossíntese , Interferon-alfa/farmacologia , Células Th1/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/imunologia , Administração Intravesical , Vacina BCG/uso terapêutico , Células Cultivadas , Citocinas/urina , Quimioterapia Combinada , Humanos , Imunização Secundária , Memória Imunológica/efeitos dos fármacos , Interferon alfa-2 , Interferon gama/biossíntese , Proteínas Recombinantes , Taquifilaxia/imunologia , Células Th1/efeitos dos fármacos , Neoplasias da Bexiga Urinária/terapia
15.
Exp Hematol ; 27(1): 110-6, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9923449

RESUMO

Recent progress in the culture of human megakaryocytes (MKs) has led to the capacity to produce platelets in vitro. This capability enables investigation into the possibility of modifying platelet structure and/or function by genetically altering the MK. To this end, a cDNA for the murine CD9 (mCD9) cell surface protein was introduced into MK progenitors by retrovirally mediated gene transfer and subsequently detected in cultured MKs with a monoclonal antibody (MoAb) that specifically recognizes the murine protein. CD34+ human peripheral blood or marrow progenitors, enriched by immunomagnetic bead selection, were cultured for 5 days in the presence of growth factors, including stem cell factor and thrombopoietin, to induce MK progenitors into the cell cycle. The stimulated cells were then cocultured with the mCD9 retroviral producer cell line for 3 days, followed by culture in serum-depleted medium for 3 to 7 additional days. Flow cytometry analysis using the anti-CD9 MoAb and TAB, a MoAb recognizing human GPIIb, revealed that a large proportion (40-100%) of the MKs expressed mCD9. To ascertain whether these cells were capable of producing mCD9+ platelets, flow cytometry analysis was performed at a time when proplatelets were observed in the culture. mCD9 was detected in up to 59% of the TAB+ platelet-sized particles. Because deteriorating MKs can produce platelet-sized particles in vitro, experiments were performed to determine whether mCD9+ TAB+ particles were functionally active. Addition of phorbol myristate acetate resulted in the redistribution of P-selectin (CD62) from the alpha granule to the platelet surface as detected by MoAbs S12 and G5 in three-color flow cytometry analyses. These studies showed that up to 76% of the mCD9+ TAB+ particles were functionally active. The data show that retrovirally mediated gene transfer is a viable approach for genetically altering MK progenitors, resulting in platelets that express heterologous proteins.


Assuntos
Antígenos CD/biossíntese , Antígenos CD/genética , Plaquetas/metabolismo , Expressão Gênica/genética , Técnicas de Transferência de Genes , Megacariócitos/metabolismo , Animais , Antígenos CD34/análise , Plaquetas/citologia , Linhagem Celular , Hematopoese , Humanos , Leucócitos Mononucleares/imunologia , Megacariócitos/citologia , Camundongos , Plasmídeos/genética , Ativação Plaquetária/efeitos dos fármacos , Retroviridae/genética , Acetato de Tetradecanoilforbol/farmacologia , Transdução Genética
16.
Curr Opin Urol ; 9(1): 9-14, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10726066

RESUMO

Two of the most common problems presenting to urologists are benign prostatic hyperplasia and sexual dysfunction, with an increasing number of patients presenting for treatment as a result of the proliferation of less invasive therapies. How such therapies for lower urinary tract symptoms affect sexual function in men is important to both urologists and their patients, and is the focus of this review.


Assuntos
Disfunção Erétil/etiologia , Hiperplasia Prostática/complicações , Envelhecimento/fisiologia , Tratamento Farmacológico , Disfunção Erétil/fisiopatologia , Disfunção Erétil/terapia , Humanos , Masculino , Hiperplasia Prostática/terapia , Sexualidade/fisiologia , Procedimentos Cirúrgicos Urológicos Masculinos
17.
Am J Physiol ; 276(6 Pt 2): S39-54, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16211666

RESUMO

There is increasing demand on science faculty to develop authentic assessment measures for both individual courses and undergraduate programs. We report here on a quarter-long group project used in a neurophysiology course that can be used for either purpose. Small groups of four to five students critically analyze at least 10 articles from the primary scientific literature. The end result of this process is the equivalent of a scientific review article that is presented in two formats, a 10-min oral presentation and a scientific poster presentation. Students perform better on application tasks than on analysis, synthesis, or evaluation tasks associated with the project (P < 0.025) and generally respond positively to process questions (59-82%) but less positively to task questions (36-76%) about group dynamics. The cognitive skills and basic content knowledge required to complete this project are developed throughout the undergraduate program. Thus the project is a type of culminating program experience. However, the project also assesses basic course proficiency, because students cannot analyze primary neuroscience research without an understanding of neurophysiological principles.


Assuntos
Educação de Graduação em Medicina/métodos , Avaliação Educacional/métodos , Aprendizagem Baseada em Problemas , Humanos , Literatura de Revisão como Assunto
18.
Arch Biochem Biophys ; 353(1): 109-15, 1998 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-9578606

RESUMO

Cytochrome P450scc (P450scc) catalyzes the first step in steroid hormone synthesis, the conversion of cholesterol to pregnenolone. Human P450scc has been poorly studied due to the difficulty of purifying reasonable quantities of enzyme from human tissue. To provide a more convenient source of the human enzyme and to enable structure-function studies to be done using site-directed mutagenesis, we expressed the mature form of human P450scc in Escherichia coli. The expression system enabled us to produce larger quantities of active cytochrome than have previously been isolated from placental mitochondria. The expressed P450scc was purified to near homogeneity and shown to have catalytic properties comparable to the enzyme purified from the human placenta. The mature form of human adrenodoxin was also expressed in E. coli and supported cholesterol side chain cleavage activity with the same Vmax as that observed using bovine adrenodoxin but with a higher Km. Mutation of Ile-462 to Leu in human P450scc caused a decrease in the catalytic rate constant (kcat) with cholesterol as substrate, increased the Km for 22R-hydroxycholesterol, but did not affect the kinetic constants for 20 alpha-hydroxycholesterol. This suggests that Ile-462 lies close to the side chain binding site and that the side chains of cholesterol, 22R-hydroxycholesterol, and 20 alpha-hydroxycholesterol occupy slightly different positions in the active site.


Assuntos
Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Isoleucina , Animais , Catálise , Bovinos , Enzima de Clivagem da Cadeia Lateral do Colesterol/biossíntese , Enzima de Clivagem da Cadeia Lateral do Colesterol/isolamento & purificação , Clonagem Molecular/métodos , Primers do DNA , Escherichia coli , Feminino , Humanos , Cinética , Mitocôndrias/enzimologia , Mutagênese Sítio-Dirigida , Placenta/enzimologia , Gravidez , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Especificidade por Substrato
19.
J Expo Anal Environ Epidemiol ; 8(2): 231-52, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9577753

RESUMO

A method is presented which links on-site electromagnetic field monitoring data with pre-existing work history data. The linkage is used to estimate cumulative and average annualized magnetic field exposure for a case-control study. On-site electromagnetic field monitoring data for 1,966 volunteer utility employees, at 59 sites in the United States and three other countries, were obtained from a large project (the EMDEX project) designed to collect, analyze, and document 60-Hz electric and magnetic field exposures for a diverse population. These data represent 9 primary work environments, and 16 job classification categories, amounting to 144 unique job categories which were consolidated using the job-exposure matrix presented into 282 three-digit Dictionary of Occupational Title (DOT) codes. The DOT code categories were then linked to lifetime occupational histories from a case-control study of leukemia. The method may be extended to link additional job titles with monitoring information. Job titles linked with electromagnetic field monitoring information provide more specific estimates of exposure intensity than previous ordinal estimates of exposure. Therefore, estimates of cumulative electromagnetic field exposure are achievable, as well as high and low level exposure estimates.


Assuntos
Bases de Dados Factuais , Campos Eletromagnéticos , Monitoramento Ambiental , Exposição Ocupacional/análise , Estudos de Casos e Controles , Humanos , Descrição de Cargo , Leucemia/etiologia , Fatores de Risco , Inquéritos e Questionários
20.
South Med J ; 91(2): 173-81, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9496871

RESUMO

BACKGROUND: Vital statistics data were used to describe the burden of cancer in Texas. METHODS: Average annual age-adjusted mortality data in Texas (1986 to 1990) for 17 cancer types were compared with the US data for whites and blacks and with California data for Hispanics. Trends were examined from 1980 to 1990 for the entire state and from 1976 to 1989 for 24 geographic regions within the state. RESULTS: Mortality excesses were detected for lung and liver cancer, and deficits for colorectal, breast, and prostate cancers. Rates were generally stable from 1980 to 1990 with several exceptions (lung, liver, colon). Six areas of Texas, including four areas along the Gulf Coast, had relatively more excesses of various cancers, without a discernible pattern by cancer type. CONCLUSIONS: Overall, Texas has fared favorably in cancer mortality when compared with the United States. Enhanced evaluation of the frequency of cancer, as well as the conduct of etiologic research, must await the availability of statewide long-term cancer incidence data.


Assuntos
Neoplasias/mortalidade , Negro ou Afro-Americano/estatística & dados numéricos , California/epidemiologia , Feminino , Hispânico ou Latino , Humanos , Masculino , Neoplasias/etnologia , Texas/epidemiologia , Estados Unidos/epidemiologia , Estatísticas Vitais , População Branca/estatística & dados numéricos
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