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1.
BJOG ; 117(7): 788-800, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20406227

RESUMO

BACKGROUND: Meta-analyses of postpartum blood loss and the effect of uterotonics are biased by visually estimated blood loss. OBJECTIVES: To conduct a systematic review of measured postpartum blood loss with and without prophylactic uterotonics for prevention of postpartum haemorrhage (PPH). SEARCH STRATEGY: We searched Medline and PubMed terms (labour stage, third) AND (ergonovine, ergonovine tartrate, methylergonovine, oxytocin, oxytocics or misoprostol) AND (postpartum haemorrhage or haemorrhage) and Cochrane reviews without any language restriction. SELECTION CRITERIA: Refereed publications in the period 1988-2007 reporting mean postpartum blood loss, PPH (> or =500 ml) or severe PPH (> or =1000 ml) following vaginal births. DATA COLLECTION AND ANALYSIS: Raw data were abstracted into Excel by one author and then reviewed by a co-author. Data were transferred to SPSS 17.0, and copied into RevMan 5.0 to perform random effects meta-analysis. MAIN RESULTS: The distribution of average blood loss (29 studies) is similar with any prophylactic uterotonic, and is lower than without prophylaxis. Compared with no uterotonic, oxytocin and misoprostol have lower PPH (OR 0.43, 95% CI 0.23-0.81; OR 0.73, 95% CI 0.50-1.08, respectively) and severe PPH rates (OR 0.61, 95% CI 0.29-1.29; OR 0.74, 95% CI 0.52-1.04, respectively). Oxytocin has lower PPH (OR 0.65, 95% CI 0.60-0.70) and severe PPH (OR 0.71, 95% CI 0.56-0.91) rates than misoprostol, but not in developing countries. CONCLUSION: Oxytocin is superior to misoprostol in hospitals. Misoprostol substantially lowers PPH and severe PPH. A sound assessment of the relative merits of the two drugs is needed in rural areas of developing countries, where most PPH deaths occur.


Assuntos
Ocitócicos , Hemorragia Pós-Parto/prevenção & controle , Feminino , Humanos , Terceira Fase do Trabalho de Parto , Hemorragia Pós-Parto/diagnóstico , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Manejo de Espécimes
2.
BJOG ; 114(5): 555-62, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17439563

RESUMO

OBJECTIVE: The objective of this study was to compare efficacy for four medical abortion regimens used in one clinic setting: (1) misoprostol alone, (2) oral methotrexate + buccal misoprostol, (3) oral methotrexate + vaginal misoprostol, and (4) intramuscular methotrexate + vaginal misoprostol. DESIGN: Retrospective analysis of data from clinical records. SETTING: An anonymous women's health centre in Latin America, providing medical abortion services since 2001 in a highly restrictive setting. POPULATION: A total of 8678 women with gestations <56 days, who sought a medical abortion between April 2002 and December 2004. METHODS: Chi-square test was performed to compare patient characteristics by abortion outcome (success/failure). The impact of selected variables on method success was explored through logistic regression. A second regression analysis was conducted with a subsample (n = 4022), for which data on parity and previous abortion(s) were available. MAIN OUTCOME MEASURE: Abortion outcome (success/failure) at 2-week follow up. RESULTS: Success rates for the three methotrexate regimens ranged from 81.7 to 83.5% and did not differ significantly; misoprostol-alone regimen had a success rate of 76.8%. Efficacy was significantly higher for the three combined methotrexate regimens compared with misoprostol alone and remained so in the multivariate model (OR = 1.35). In the final regression, lower gestational age, being nulliparous, and having no previous abortions were positively correlated with method success. CONCLUSIONS: In this real-use setting, methotrexate appears to confer a significant advantage over misoprostol alone for early medical abortion. This finding is important for settings where mifepristone remains unavailable. Additional factors such as gestational age limits and patient preference should be considered in regimen selection.


Assuntos
Abortivos não Esteroides/administração & dosagem , Aborto Induzido/métodos , Metotrexato/administração & dosagem , Misoprostol/administração & dosagem , Administração Intravaginal , Administração Oral , Adulto , Quimioterapia Combinada , Feminino , Humanos , Injeções Intramusculares , Gravidez , Estudos Retrospectivos
3.
Sex Transm Infect ; 81(2): 135-41, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15800091

RESUMO

OBJECTIVE: To assess Mexican physicians' knowledge about the human papillomavirus (HPV) and cervical cancer and their opinions and practices related to screening, managing, and counselling women on these topics. METHODOLOGY: In August 2002 we surveyed 1206 general practitioners (GPs) and obstetricians-gynaecologists (Ob-Gyns) working in a nationally representative sample of public and private facilities in urban Mexico. Eligible physicians completed a self administered questionnaire. We conducted a weighted analysis and used chi(2) tests to compare GPs and Ob-Gyns on outcome variables. RESULTS: 76% of recruited physicians responded to the survey. 43% of Ob-Gyns had performed a hysterectomy in the last year to treat a case of CIN I or II. With respect to HPV, while 80% of respondents identified the virus as the principal cause of cervical cancer, many lacked detailed knowledge about this association. Ob-Gyns were more likely than GPs to have heard about specific oncogenic strains of HPV (p<0.001). Nearly all respondents thought that women should be informed that HPV causes cervical cancer; nevertheless, physicians believed that positioning cervical cancer as a sexually transmitted infection (STI) could cause problems in partner relationships (60%), confusion (40%), and unnecessary anxiety among women (32%). CONCLUSIONS: Mexican physicians support patient education on the HPV-cervical cancer link. However, findings suggest the need to present clear messages to women (emphasising, for example, that only certain types of HPV are oncogenic), to consider the conflicts such information might create for couples, and to further educate physicians about this topic and about overall cervical cancer screening and treatment protocols.


Assuntos
Competência Clínica/normas , Medicina de Família e Comunidade/educação , Ginecologia/educação , Obstetrícia/educação , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Distribuição de Qui-Quadrado , Aconselhamento , Coleta de Dados , Medicina de Família e Comunidade/estatística & dados numéricos , Feminino , Ginecologia/estatística & dados numéricos , Humanos , Masculino , México , Pessoa de Meia-Idade , Obstetrícia/estatística & dados numéricos , Infecções por Papillomavirus/complicações , Prática Profissional/normas , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/normas , Esfregaço Vaginal/estatística & dados numéricos
4.
Int J Gynaecol Obstet ; 85 Suppl 1: S42-51, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15147853

RESUMO

OBJECTIVES: To identify new and underutilized technologies that may assist in reducing maternal mortality due to obstetric hemorrhage. METHODS: Review of published and unpublished literature, including systematic reviews of randomized trials and individual clinical studies. RESULTS: Hemorrhage, primarily postpartum, accounts for approximately 25% of maternal deaths globally. Uterotonic drugs offer great promise for both prevention and management of postpartum hemorrhage (PPH). Other technologies--such as anti-shock garments, umbilical vein injection of oxytocin, and simple anemia detection methods--represent potential new opportunities to reduce PPH-related mortality. CONCLUSIONS: Clinical and operational research is needed to answer remaining questions about misoprostol, the anti-shock garment, and umbilical vein injection of oxytocin for retained placenta. Efforts are needed to ensure the availability of technologies with proven value, such as oxytocin in Uniject prefilled injection devices. Equally important, technologies and techniques with proven efficacy--such as active management of third-stage labor and aortic compression--must be translated into general use by disseminating the evidence for them, incorporating them into national guidelines and training curricula, and ensuring the availability of supportive supplies and equipment.


Assuntos
Serviços de Saúde Materna/organização & administração , Hemorragia Pós-Parto/prevenção & controle , Países em Desenvolvimento , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Mortalidade Materna , Área Carente de Assistência Médica , Ocitócicos/administração & dosagem , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Arch Environ Health ; 56(4): 314-9, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11572274

RESUMO

Cancer cluster studies in North Carolina identified several communities in which there existed an elevated risk of brain cancer. These findings prompted a series of case-control studies. The current article, which originated from the results of the 3rd of such studies, is focused on inclusion of the earth's own geomagnetic fields that interact with electromagnetic fields generated from distribution power lines. This article also contains an assessment of the contribution of confounding by residential (e.g., urban, rural) and case characteristics (e.g., age, race, gender). Newly diagnosed brain cancer cases were identified for a 4-county region of central North Carolina, which the authors chose on the basis of the results of earlier observations. A 3:1 matched series of cancer cases from the same hospitals in which the cases were diagnosed served as the comparison group. Extensive geographic information was collected and was based on an exact place of residence at the time of cancer diagnosis, thus providing several strategic geophysical elements for assessment. The model for this assessment was based on the effects of these two sources of electromagnetic fields for an ion cyclotron resonance mechanism of disease risk. The authors used logistic regression models that contained the predicted value for the parallel component of the earth's magnetic field; these models were somewhat erratic, and the elements were not merged productively into a single statistical model. Interpretation of these values was difficult; therefore, the modeled values for the model elements, at progressive distances from the nearest power-line segments, are provided. The results of this study demonstrate the merits of using large, population-based databases, as well as using rigorous Geographic Information System techniques, for the assessment of ecologic environmental risks. The results also suggest promise for exposure classification that is compatible with the theoretical biological mechanisms posited for electromagnetic fields.


Assuntos
Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/etiologia , Campos Eletromagnéticos/efeitos adversos , Exposição Ambiental/efeitos adversos , Centrais Elétricas , Idoso , Estudos de Casos e Controles , Análise por Conglomerados , Fatores de Confusão Epidemiológicos , Ciclotrons , Bases de Dados Factuais , Exposição Ambiental/análise , Monitoramento Ambiental , Monitoramento Epidemiológico , Feminino , Geografia , Humanos , Incidência , Sistemas de Informação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Vigilância da População , Valor Preditivo dos Testes , Características de Residência/estatística & dados numéricos , Fatores de Risco
9.
Am J Prev Med ; 19(4): 316-20, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11064237

RESUMO

PURPOSE: In this population-based, random-digit-dial, cross-sectional survey, we assessed the lifetime victimization of intimate partner violence (IPV) and forced or coerced sex among 556 women and men in South Carolina, and the help-seeking behaviors of victims. RESULTS: Among women, 25.3% experienced IPV (sexual, physical, or emotional violence) compared with 13.2% of men. Although women were significantly more likely to report physical or sexual IPV (17.8%) than were men (4.9%), men (8.3%) were as likely as women (7.4%) to report perceived emotional abuse without physical or sexual IPV. One half of men and women with annual incomes <$15, 000 reported IPV. Among women experiencing physical or sexual IPV, 53% sought community-based or professional services for IPV; women with higher education levels and those experiencing more severe violence were most likely to seek services. CONCLUSIONS: These data show that IPV is common and that most victims do not receive services to address this violence.


Assuntos
Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Estupro/estatística & dados numéricos , Maus-Tratos Conjugais/estatística & dados numéricos , Maus-Tratos Conjugais/terapia , Adolescente , Adulto , Distribuição por Idade , Intervalos de Confiança , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Prevalência , Probabilidade , Medição de Risco , Distribuição por Sexo , South Carolina/epidemiologia
11.
Chemosphere ; 41(1-2): 59-67, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10819180

RESUMO

Environmental epidemiology is the specialized aspect of public health science that studies human health risk from environmental hazards. It is rises largely upon a foundation of public health surveillance, and relies heavily upon analyses of data for small areas and sparse population groups. To a degree, environmental epidemiology is assigned the role of discerning very subtle human health impacts, or discerning early evidence of a tragic sequence. In that context, environmental epidemiology has a substantial public education and risk communication role. Environmental epidemiology will be greatly advanced as effective biological markers of exposure and precursor health effects are developed. At this point in time, statistical methods are in place to monitor population-level disease rates in high-risk populations for early risk identification and sentinel event recognition. Advances in geographic methods have provided a boon to the discipline by advantaging spatial studies. These advances in the discipline still need further refinement and pilot experiences. The inclusion of environmental epidemiological considerations with instances of proposed industrial expansion, hazardous waste management, and contamination remediation is heartily recommended.


Assuntos
Medicina Ambiental , Estudos Epidemiológicos , Poluentes Ambientais/efeitos adversos , Humanos , Saúde Pública , Projetos de Pesquisa , Medição de Risco
13.
Epidemiology ; 11(3): 353-6, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10784259

RESUMO

We present arguments that suggest that historical average calculated fields, which are widely used to estimate biologically relevant exposure to electromagnetic fields, may be less accurate than contemporary spot measurements, which are made at a time following the biologically relevant period of exposure. We use data from the seminal Feychting and Ahlbom study of the health effects of electromagnetic field exposure in a Swedish population to illustrate our argument. We also show how the two types of measurements can produce divergent estimates of risk, and show how in the Feychting and Ahlbom study, the less accurate measurement, the historical average calculated fields, may have resulted in a spurious increase in the estimates of risk. Finally, we consider the implications of our arguments for other studies that rely on wire codes and historical calculations of personal exposure.


Assuntos
Campos Eletromagnéticos , Exposição Ambiental , Neoplasias/epidemiologia , Viés , Criança , Campos Eletromagnéticos/efeitos adversos , Exposição Ambiental/efeitos adversos , Projetos de Pesquisa Epidemiológica , Humanos , Suécia/epidemiologia
14.
J Occup Environ Med ; 41(12): 1104-15, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10609231

RESUMO

Fire departments have replaced traditional uniforms with modern, more thermal protective gear. Although the new uniforms afford superior burn protection, they may reduce work time. Our purpose was to determine if exercise time was (1) reduced by wearing the modern versus traditional uniform, and (2) increased by a design change to a modified modern uniform (T-shirt and short pants rather than a shirt and long pants under the outer uniform). Male firefighters (n = 23; age 27 to 59) performed a maximum exercise test in gym clothes (maximal oxygen consumption = 46 +/- 9 ml/kg/min) and then returned on separate days to exercise using a moderately high intensity, constant work rate treadmill protocol while wearing fire fighting breathing apparatus and each of three uniforms. Firefighters exceeded anaerobic threshold by 1 minute and eventually reached or exceeded maximum heart rate and maximal oxygen consumption. Exercise time in modern (15 +/- 3 min) was significantly less than in traditional (18 +/- 5 min) uniform. Exercise time in modified modern (17 +/- 5 min) was significantly greater than in modern and not significantly different than in traditional uniforms. The rate of change in oxygen consumption and water loss were significantly affected by uniform type, with faster rates in modern compared with modified modern or traditional uniforms. These findings show the impact that design changes have on energy demands and exercise duration.


Assuntos
Exercício Físico , Saúde Ocupacional , Aptidão Física , Roupa de Proteção , Adulto , Pessoal Técnico de Saúde , Incêndios , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Trabalho de Resgate , Equilíbrio Hidroeletrolítico
15.
Chest ; 116(5): 1183-93, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10559074

RESUMO

OBJECTIVE: The etiology of sarcoidosis is unknown, but epidemiology suggests that environmental agents are a factor. Because firefighters are exposed to numerous toxins, we questioned whether sarcoidosis was increased in this cohort. SETTING: The New York City Fire Department (FDNY), employing > 11,000 firefighters and nearly 3,000 emergency medical services (EMS) health-care workers (HCWs). DESIGN: In 1985, FDNY initiated a surveillance program to determine the incidence, prevalence, and severity of biopsy-proven sarcoidosis in firefighters. In 1995, EMS HCWs were added as control subjects. RESULTS: Between 1985 and 1998, 4 prior cases and 21 new cases of sarcoidosis were found in FDNY firefighters. Annual incidence proportions ranged from 0 to 43.6/100,000, and averaged 12.9/100,000. On July 1, 1998, the point prevalence was 222/100,000. For EMS HCWs, annual incidence proportions were zero. Radiographic stage 0 or stage 1 sarcoidosis was found in 19 firefighters (76%), and stage 3 was found in 1 firefighter (4%). Pulmonary function (FVC, FEV(1), and diffusing capacity for carbon monoxide) was normal in 17 firefighters (68%), and reduced to

Assuntos
Incêndios , Sarcoidose Pulmonar/epidemiologia , Índice de Gravidade de Doença , Adulto , Biópsia , Teste de Esforço , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Doenças Profissionais/diagnóstico , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Prevalência , Radiografia Torácica , Unidades de Cuidados Respiratórios/estatística & dados numéricos , Testes de Função Respiratória , Estudos Retrospectivos , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/etiologia , População Urbana
16.
Breast Cancer Res Treat ; 56(1): 59-66, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10517343

RESUMO

BACKGROUND: Research shows that rural populations are more likely than their urban counterparts to be diagnosed with late-stage cancer, but less is known about appropriateness of cancer treatment in rural locations after diagnosis. The objective of this analysis was to assess the degree to which rural breast cancer treatment was received in concordance with national recommendations. METHODS: Data came from 251 stage I and II breast cancer patients residing in rural North Carolina. State-of-the-art care was defined using the National Cancer Institute's (NCI) physician data query (PDQ) database, and cases were categorized into appropriate primary and/or adjuvant treatment. Chi-square and Fishers' exact tests were used to assess changes in appropriate treatment over time (1991-1996) and between stage. Multiple logistic regression was used to determine whether any patient or disease characteristics were associated with receipt of appropriate treatment. RESULTS: Most (81-90%) of the breast cancer cases received the appropriate primary therapy (mastectomy or lumpectomy followed by radiation therapy); of these, the majority received a mastectomy (66-72%). Fewer women received adjuvant therapy as recommended (27-61%), although significantly more stage II than stage I cases did so (p < or = 0.05). Regression showed that stage and estrogen-receptor (ER) status were associated with appropriate therapy. CONCLUSIONS: The findings suggest that there exist deviations from NCI established treatment recommendations among rural breast cancer patients. More research is needed to develop better methods for dissemination of state-of-the-art cancer information to rural physicians and patients, and to understand how treatment decisions are made.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Fidelidade a Diretrizes , Guias de Prática Clínica como Assunto , Serviços de Saúde Rural/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Tomada de Decisões , Feminino , Humanos , Serviços de Informação , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptores de Estrogênio/análise , População Rural
17.
Cancer Detect Prev ; 23(5): 428-34, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10468896

RESUMO

The purpose of this study was to determine the degree to which colon cancer treatment in rural North and South Carolina in 1991 and 1996 conformed to national treatment recommendations. Data came from medical records of colon cancer patients residing in rural North and South Carolina. The National Cancer Institute's Physician Data Query (PDQ) database was used to define state-of-the-art care and to categorize receipt of primary and/or adjuvant treatment. Changes in treatment over time, location, and stage and bivariate relationships between treatment and selected covariates were assessed with chi-square and Fisher's exact tests. Regression was used to control for possible interactions between patient and/or disease characteristics and treatment. The majority of colon cancer cases received primary therapy as suggested by the PDQ which was not significantly related to other factors examined. There was variation in provision of adjuvant therapy. Stage III patients received adjuvant therapy significantly more often than did stage II patients (p

Assuntos
Neoplasias do Colo/epidemiologia , Neoplasias do Colo/terapia , População Rural , Adulto , Idoso , Idoso de 80 Anos ou mais , População Negra , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Modelos Estatísticos , North Carolina , Razão de Chances , Fatores de Risco , Classe Social , South Carolina , População Branca
18.
J S C Med Assoc ; 95(6): 227-30, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10389384

RESUMO

In 1996, there were 34,035 deaths in South Carolina. Almost 70 percent of these deaths were due to chronic diseases. There are known ways to prevent chronic diseases from developing or at least delay their developmental process, thereby lengthening years of life. The purpose of this paper is to report modifiable risk factors for mortality related to leading causes of death. The top ten causes of death in South Carolina were obtained from the South Carolina Department of Health and Environmental Control. Estimates of the number of deaths due to certain modifiable risk factors were made using results of a study published by McGinnis and Foege. The percentage of deaths due to each cause was adapted to South Carolina death certificate data from the national estimates. Results indicate that small modifications in individual lifestyles could prevent or delay nearly 50 percent of deaths in South Carolina annually. Tobacco use, diet and physical activity, and misuse of alcohol contribute to the largest number of deaths. Other modifiable behaviors contributing to the 50 percent mortality are microbial agents, toxic agents, firearms, sexual behavior, motor vehicle accidents, and illicit use of drugs. The implication in these findings is that these risk factors for mortality are mainly modifiable. There are many causes of death that may be delayed due to these modifiable risk factors. By looking at preventable causes of death, rather than focusing on traditional causes of death, it becomes clear that prevention strategies are critically important.


Assuntos
Causas de Morte , Dieta , Humanos , Esforço Físico , Fatores de Risco , Fumar , South Carolina
19.
Urology ; 53(6): 1194-9, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10367851

RESUMO

OBJECTIVES: Although stage at diagnosis is one of the most important predictors of survival from prostate cancer, demographic factors, screening practices, and knowledge and beliefs associated with stage at diagnosis have not been well documented, particularly by race. METHODS: We conducted telephone interviews with 117 black and 114 white men diagnosed with prostate cancer to identify the demographic factors, healthcare-seeking behaviors, and prostate cancer-related knowledge, attitudes, and practices associated with stage. The sample was stratified by stage at diagnosis and was composed of men 50 to 74 years old who resided in a contiguous 63-county region in North Carolina and who were diagnosed at 1 of 16 participating hospitals. RESULTS: Among blacks, stage was inversely correlated with income (P = 0.04) and health insurance status (P < or = 0.001); among whites, stage was not associated with income or health insurance status, but approached significance with marital status (P = 0.06). Awareness of prostate cancer before diagnosis tended to decline with advancing stage among black men (P = 0.07), but was high for all stages (greater than 93%) among whites. Report of a prostate-specific antigen screen was inversely correlated with stage among black men (P = 0.01); a trend was observed among whites but was not significant (P = 0.20). Knowledge of prostate cancer risk factors was not significantly associated with stage for blacks or whites. Less than one third of men in each race and stage group knew that black men are at increased risk of prostate cancer. CONCLUSIONS: Demographic and other factors vary with stage and should be considered when designing and targeting interventions to reduce late diagnosis of prostate cancer.


Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias da Próstata/epidemiologia , População Branca/estatística & dados numéricos , Idoso , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , North Carolina/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde , Neoplasias da Próstata/patologia , Fatores Socioeconômicos
20.
Chem Biol ; 6(7): 429-39, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10381407

RESUMO

BACKGROUND: Lovastatin, an HMG-CoA reductase inhibitor produced by the fungus Aspergillus terreus, is composed of two polyketide chains. One is a nonaketide that undergoes cyclization to a hexahydronaphthalene ring system and the other is a simple diketide, 2-methylbutyrate. Fungal polyketide synthase (PKS) systems are of great interest and their genetic manipulation should lead to novel compounds. RESULTS: An A. terreus mutant (BX102) was isolated that could not synthesize the nonaketide portion of lovastatin and was missing a approximately 250 kDa polypeptide normally present under conditions of lovastatin production. Other mutants produced lovastatin intermediates without the methylbutyryl sidechain and were missing a polypeptide of approximately 220 kDa. The PKS inhibitor cerulenin reacted covalently with both polypeptides. Antiserum raised against the approximately 250 kDa polypeptide was used to isolate the corresponding gene, which complemented the BX102 mutation. The gene encodes a polypeptide of 269 kDa containing catalytic domains typical of vertebrate fatty acid and fungal PKSs, plus two additional domains not previously seen in PKSs: a centrally located methyltransferase domain and a peptide synthetase elongation domain at the carboxyl terminus. CONCLUSIONS: The results show that the nonaketide and diketide portions of lovastatin are synthesized by separate large multifunctional PKSs. Elucidation of the primary structure of the PKS that forms the lovastatin nonaketide, as well as characterization of blocked mutants, provides new details of lovastatin biosynthesis.


Assuntos
Aspergillus/metabolismo , Lovastatina/biossíntese , Complexos Multienzimáticos/genética , Sequência de Aminoácidos , Aspergillus/enzimologia , Aspergillus/genética , Clonagem Molecular , Biblioteca Gênica , Dados de Sequência Molecular , Complexos Multienzimáticos/metabolismo , Software
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