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1.
Hum Vaccin Immunother ; 15(7-8): 1986-1994, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31184976

RESUMO

There has been a noticeable shift in discussions about cervical cancer, moving from prevention to elimination. Interventions such as FASTER, human papillomavirus (HPV) vaccination and HPV screening are innovative intervention strategies which can be utilized to begin a path to elimination. To explore the feasibility of the FASTER strategy, an evaluation was carried out in eight primary health-care centers within the Tlalpan Health-Jurisdiction of Mexico City between March 2017 and August 2018. A mixed methods approach was used to evaluate three components: infrastructure, patient acceptability, and health-care professionals' perceptions. This included checklists of requirements for the infrastructure rollout of FASTER and interviews with women and health-care professionals. Nearly all (93%) of the 3,474 women aged 25-45 years accepted HPV vaccination as part of a combined vaccination and screening program. The main reason for acceptance was prevention, while having doubts about the vaccine's benefits was the main reason for refusal. Most of the 24 health-care professionals had a positive opinion toward HPV vaccination and identified the need to increase dissemination, inform the population clearly and concisely and currently extend the age range for vaccination. The evaluation of eight primary health-care centers showed they had the necessary infrastructure for the development of a joint HPV prevention strategy, but many centers required improvements to become more efficient. Together these findings suggest that although HPV vaccine acceptance was high, there is the need to increase education and awareness among potential vaccine recipients and health-care professionals to implement the FASTER strategy.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Programas de Rastreamento , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Atenção Primária à Saúde/estatística & dados numéricos , Vacinação/métodos , Adulto , Estudos de Viabilidade , Feminino , Humanos , México , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia
2.
Climacteric ; 22(1): 97-104, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30601066

RESUMO

OBJECTIVE: This study aimed to investigate the association of seven single nucleotide polymorphisms (SNPs) on the RMND1, CCDC170, and ESR1 genes with osteoporosis or hip fracture in a postmenopausal Mexican population. METHODS: We included a group of 400 postmenopausal women from the Health Workers Cohort Study from the Mexican Institute of Social Security. As a replication sample, we recruited 423 postmenopausal women from the National Institute of Rehabilitation. Demographic data were collected through a structured questionnaire. Bone mineral density was assessed using dual X-ray absorptiometry. Individuals were classified as normal, osteopenia, osteoporosis, and fracture, according to World Health Organization criteria. Genotyping was performed using predesigned TaqMan Probes. Linear regression analysis was used to investigate association. RESULTS: All of the analyzed SNPs showed association with at least one of the phenotypes of the study groups. In addition, we observed a region with linkage disequilibrium within the ESR1 gene in all groups. CONCLUSION: This study shows that an association of the SNPs can exist with osteopenia, osteoporosis, or fragility fracture. Our results agree with data published elsewhere, supporting the potential of these loci for the identification of the population at risk. However, additional studies are required to determine the extent of this association for other geographic regions of Mexico.


Assuntos
Densidade Óssea/genética , Fraturas do Quadril/genética , Osteoporose Pós-Menopausa/genética , Polimorfismo de Nucleotídeo Único , Pós-Menopausa , Absorciometria de Fóton , Idoso , Proteínas de Transporte/genética , Proteínas de Ciclo Celular/genética , Estudos de Coortes , Receptor alfa de Estrogênio/genética , Feminino , Frequência do Gene , Haplótipos , Humanos , Modelos Lineares , Desequilíbrio de Ligação , México , Pessoa de Meia-Idade , Ossos Pélvicos/patologia
3.
Oral Dis ; 22(8): 781-790, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27470907

RESUMO

OBJECTIVES: This cross-sectional study examined the distribution and correlates of salivary secretory leukocyte protease inhibitor (SLPI) concentrations within a multinational cohort of men. METHODS: Extracellular SLPI was measured in oral gargle cell supernatants of 378 men from three countries using an ELISA-based assay. Risk factor data were collected by a questionnaire. Factors associated with SLPI were assessed using linear and logistic regression for continuous and categorical SLPI, respectively. RESULTS: Among men aged 18-73 years, the median SLPI concentration was 492.0 ng ml-1 (range: 2.3-1919.9). In multivariable modeling, men in Brazil and younger men (18-30 years) were more likely to have higher levels of SLPI [adjusted odds ratio (aOR) 3.84; 95% confidence interval (CI): 1.94-7.59, and aOR 3.84; 95% CI: 1.98-7.43, respectively]. Men with a self-reported sexually transmitted diseases diagnosis in the past 6 months were more likely to have higher SLPI levels (aOR 2.98; 95% CI: 1.1-7.83) and men reporting bleeding/swollen gums were less likely to have higher SLPI (aOR 0.34; 95% CI: 0.15-0.79). Similar results were observed for linear regression models. CONCLUSIONS: Secretory leukocyte protease inhibitor concentrations varied significantly by country and decreased with increasing age. The interaction between SLPI, modifiable factors, and oral infections that influence cancer risk warrants further investigation.


Assuntos
Saliva/química , Inibidor Secretado de Peptidases Leucocitárias/análise , Adolescente , Adulto , Fatores Etários , Idoso , Estudos Transversais , Gengivite/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Sexualmente Transmissíveis/metabolismo , Adulto Jovem
4.
Eur J Cancer ; 50(16): 2846-54, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25155250

RESUMO

AIM: This work describes the human papillomavirus (HPV) prevalence and the HPV type distribution in a large series of vaginal intraepithelial neoplasia (VAIN) grades 2/3 and vaginal cancer worldwide. METHODS: We analysed 189 VAIN 2/3 and 408 invasive vaginal cancer cases collected from 31 countries from 1986 to 2011. After histopathological evaluation of sectioned formalin-fixed paraffin-embedded samples, HPV DNA detection and typing was performed using the SPF-10/DNA enzyme immunoassay (DEIA)/LiPA25 system (version 1). A subset of 146 vaginal cancers was tested for p16(INK4a) expression, a cellular surrogate marker for HPV transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance. RESULTS: HPV DNA was detected in 74% (95% confidence interval (CI): 70-78%) of invasive cancers and in 96% (95% CI: 92-98%) of VAIN 2/3. Among cancers, the highest detection rates were observed in warty-basaloid subtype of squamous cell carcinomas, and in younger ages. Concerning the type-specific distribution, HPV16 was the most frequently type detected in both precancerous and cancerous lesions (59%). p16(INK4a) overexpression was found in 87% of HPV DNA positive vaginal cancer cases. CONCLUSIONS: HPV was identified in a large proportion of invasive vaginal cancers and in almost all VAIN 2/3. HPV16 was the most common type detected. A large impact in the reduction of the burden of vaginal neoplastic lesions is expected among vaccinated cohorts.


Assuntos
Carcinoma de Células Escamosas/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Neoplasias Vaginais/virologia , Idoso , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/epidemiologia , Estudos Transversais , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , DNA Viral/análise , Feminino , Papillomavirus Humano 16/isolamento & purificação , Humanos , Técnicas Imunoenzimáticas , Cooperação Internacional , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Distribuição de Poisson , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/virologia , Prevalência , Análise de Regressão , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Vaginais/complicações , Neoplasias Vaginais/epidemiologia
5.
Eur J Trauma Emerg Surg ; 40(6): 693-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26814784

RESUMO

OBJECTIVE: A high perception of risk may exert a preventive effect against the initiation of risky activities. The aims of the present study were (1) to analyze the risk perception for traumatic incidents according to drug intake (alcohol, cannabis, cocaine, no consumption) by trauma patients admitted to our hospital, and (2) to explore the influence of drugs on trauma recidivism. METHODS: Between 1 November 2011 and 1 April 2012, 404 patients aged between 16 and 70 years were admitted to our hospital for trauma cases. In 363 (89.9 %) of the patients, data were gathered on age, the trauma mechanism, and the consumption of alcohol and other drugs. Out of these 363 patients, 286 (78.8 %) attended a motivational interview and reported their consumption habits and their perception of the risk of trauma after alcohol and/or illegal drug consumption, as well as the antecedents of previous traumatisms. RESULTS: Alcohol and/or illegal drugs were detected in 37 % of the sample, with alcohol being the most frequently detected, followed by cannabis, cocaine, and other drugs. Among the trauma patients with no consumption, a high perception of trauma risk was associated with alcohol intake by 95.9 %, with cannabis consumption by 68.4 %, and with cocaine consumption by 53.4 %, whereas these percentages were significantly lower for patients testing positive for substances (79.3, 21.1, and 8.3 % respectively). Among the patients experiencing their first trauma, the mean age was almost 15 years younger in those who were positive for these substances than in those who were negative (p < 0.001). Finally, a history of previous trauma was reported by a majority (64 %) of the trauma patients testing positive for alcohol and/or drugs, but by a minority (36 %) of those testing negative (p < 0.001). CONCLUSIONS: The low perception of risk associated with alcohol, cannabis, or cocaine consumption by trauma patients under the influence of these substances on admission may be a predisposing factor for recidivism. Recommendations for both primary and secondary prevention are presented.

6.
Mater Sci Eng C Mater Biol Appl ; 33(3): 1183-92, 2013 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-23827558

RESUMO

Gemcitabine is a chemotherapy drug used in different carcinomas, although because it displays a short biological half-life, its plasmatic levels can quickly drop below the effective threshold. Nanoparticle-based drug delivery systems can provide an alternative approach for regulating the bioavailability of this and most other anticancer drugs. In this work we describe a new model of composite nanoparticles consisting of a core of magnetite nanoparticles, coated with successive layers of high molecular weight poly(acrylic acid) and chitosan, and a final layer of folic acid. The possibility of using these self-assembled nanostructures for gemcitabine vehiculization is explored. First, the surface charge of the composite particles is studied by means of electrophoretic mobility measurements as a function of pH for poly(acrylic acid) (carbopol) of different molecular weights. The adsorption of folic acid, aimed at increasing the chances of the particles to pass the cell membrane, is followed up by optical absorbance measurements, which were also employed for drug adsorption determinations. As a main result, it is shown that gemcitabine adsorbs onto the surface of chitosan/carbopol-coated magnetite nanoparticles. In vitro experiments show that the functionalized magnetic nanoparticles are able to deliver the drug to the nuclei of liver, colon and breast tumor cells.


Assuntos
Antineoplásicos/farmacologia , Fenômenos Químicos , Desoxicitidina/análogos & derivados , Sistemas de Liberação de Medicamentos , Nanopartículas de Magnetita/química , Neoplasias/tratamento farmacológico , Resinas Acrílicas/química , Adsorção , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Eletroforese , Ácido Fólico/análise , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Nanopartículas de Magnetita/ultraestrutura , Microscopia Confocal , Imagem Óptica , Tamanho da Partícula , Gencitabina
7.
Histol Histopathol ; 27(4): 459-66, 2012 04.
Artigo em Inglês | MEDLINE | ID: mdl-22374723

RESUMO

AIMS: To study liver lesions in morbidly obese patients who underwent liver biopsy at the time of bariatric surgery to define histological lesions, especially inflammatory infiltrate, diagnostic categories and the possible influence of gender in this respect. METHODS AND RESULTS: 110 biopsies (36 males-M- and 76 females -F-) were evaluated and categorised, according to the NAS (NAFLD -non alcoholic fatty liver disease- Activity Score) system and other criteria, as non-NAFLD (15.5%, F predominance), non-alcoholic steatohepatitis (NASH) (16.5%, M predominance), non-alcoholic hepatosteatosis (NAHS) (21%, F predominance) and, the most numerous group, NASH-borderline (NASH-BORD) (47%), with three subgroups, characterised by centrozonal lesions, portal area preferential involvement or affecting both areas. The predominant form of hepatocytesteatosis was mixed with a multivesicular component that was present in most cases with fibroinflammatory portal involvement. Nuclear glycogenosomes were found in greater number of biopsies in patients in the third and sixth decades. Portal inflammation was present in a large number of cases (M predominance); the application of immunohistochemical techniques (myeloperoxidase and CD68 antibodies) to evaluate lobular inflammation revealed "surgical hepatitis" in one third of the cases, and the presence of microgranulomas (CD68+) (M predominance), which were more abundant with increasing lesion severity. CONCLUSIONS: Portal inflammation and multivesicular hepatocytesteatosis are highly prevalent in morbidly obese patients. This study identifies a new subtype of NASH-BORD characterized by centrizonal and porto-periportal area involvement and the existence of liver biopsies without steatosis. CD68+ microgranulomas constitute an unequivocal marker of lobular inflammation in surgical biopsies and of lesion severity, which is gender-related.


Assuntos
Fígado Gorduroso/patologia , Fígado/patologia , Obesidade Mórbida/diagnóstico , Adulto , Fatores Etários , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Cirurgia Bariátrica , Biomarcadores/metabolismo , Biópsia , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/cirurgia , Feminino , Fibrose/patologia , Granuloma/metabolismo , Granuloma/patologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida/metabolismo , Obesidade Mórbida/cirurgia , Sistema Porta/patologia , Fatores Sexuais
8.
Int J Cancer ; 131(1): 106-16, 2012 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-21858807

RESUMO

In the Phase III PATRICIA study (NCT00122681), the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (Cervarix(®), GlaxoSmithKline Biologicals) was highly efficacious against HPV-16/18 infections and precancerous lesions in women HPV-16/18 deoxyribose nucleic acid (DNA) negative and seronegative at baseline. We present further data on vaccine efficacy (VE) against HPV-16/18 in the total vaccinated cohort including women who may have been exposed to HPV-16/18 infection before vaccination. In women with no evidence of current or previous HPV-16/18 infection (DNA negative and seronegative), VE was 90.3% (96.1% confidence interval: 87.3-92.6) against 6-month persistent infection (PI), 91.9% (84.6-96.2) against cervical intraepithelial neoplasia (CIN)1+ and 94.6% (86.3-98.4) against CIN2+ [97.7% (91.1-99.8) when using the HPV type assignment algorithm (TAA)]. In women HPV-16/18 DNA negative but with serological evidence of previous HPV-16/18 infection (seropositive), VE was 72.3% (53.0-84.5) against 6-month PI, 67.2% (10.9-89.9) against CIN1+, and 68.8% (-28.3-95.0) against CIN2+ [88.5% (10.8-99.8) when using TAA]. In women with no evidence of current HPV-16/18 infection (DNA negative), regardless of their baseline HPV-16/18 serological status, VE was 88.7% (85.7-91.1) against 6-month PI, 89.1% (81.6-94.0) against CIN1+ and 92.4% (84.0-97.0) against CIN2+ [97.0% (90.6-99.5) when using TAA]. In women who were DNA positive for one vaccine type, the vaccine was efficacious against the other vaccine type. The vaccine did not impact the outcome of HPV-16/18 infections present at the time of vaccination. Vaccination was generally well tolerated regardless of the woman's HPV-16/18 DNA or serological status at entry.


Assuntos
Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Adjuvantes Imunológicos , Adolescente , Adulto , Anticorpos Antivirais/sangue , Estudos de Coortes , DNA Viral/sangue , Feminino , Humanos , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/efeitos adversos , Resultado do Tratamento , Vacinação , Adulto Jovem , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/prevenção & controle
9.
Clin Pharmacol Ther ; 90(5): 712-21, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21993426

RESUMO

Chronic hepatitis C (CHC) is a worldwide health problem that is highly related to liver fibrosis, cirrhosis, and hepatocellular carcinoma. The achievement of response to the current standard of care-pegylated interferon plus ribavirin-has recently been described to be associated with single-nucleotide polymorphisms (SNPs) near the IL-28B gene. Additionally, baseline expression levels of genes involved in interferon (IFN)-stimulated genes (ISGs) have been found to be related to treatment outcome. In the present study, 285 patients were genotyped for 63 SNPs within genes of the IFN signaling pathway (IPGs) and ISGs. Two ISG polymorphisms-OASL rs12819210 (odds ratio (OR)=2.1, P=0.03) and IFIT1 rs304478 (OR=2.5, P=0.01)-were found to be independent predictive factors of sustained virological response (SVR) after adjusting for other clinical covariates. Furthermore, the predictive value of IL-28B SNP was notably improved by simultaneous genotyping of rs12819210 and rs304478, particularly in patients with the worst prognosis (viral genotype 1, area under the curve (AUC)=0.74). In conclusion, ISG SNPs could constitute a valuable tool for individualizing CHC therapy.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferons/genética , Interleucinas/genética , Transdução de Sinais/genética , Adulto , Quimioterapia Combinada , Feminino , Variação Genética , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Polimorfismo de Nucleotídeo Único , Prognóstico , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Ribavirina/uso terapêutico , Resultado do Tratamento
10.
Cancer Lett ; 301(1): 47-56, 2011 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-21093979

RESUMO

The purpose of this study was to investigate whether PARP-1 inhibition sensitizes human liver cancer cell lines to doxorubicin treatment. Both the addition of PARP-1 inhibitor (ANI) and depletion by means of stable siRNA significantly enhanced the growth inhibition induced by the DNA damage agents used. This effect was associated with an accumulation of unrepaired DNA, with a reduction in EGFR and Bcl-xL gene expression as well as with positive annexin-V staining. These results provide novel evidence of the direct role of PARP-1 in tumour chemoresistance in relation to its effects on the transcription of key genes involved in tumour survival.


Assuntos
1-Naftilamina/análogos & derivados , Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Inibidores Enzimáticos/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Naftalimidas/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases , Quinolonas/farmacologia , 1-Naftilamina/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Sinergismo Farmacológico , Receptores ErbB/análise , Humanos , Neoplasias Hepáticas/patologia , Proteína bcl-X/análise
12.
Lancet ; 374(9686): 301-14, 2009 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-19586656

RESUMO

BACKGROUND: The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic, generally well tolerated, and effective against HPV-16 or HPV-18 infections, and associated precancerous lesions in an event-triggered interim analysis of the phase III randomised, double-blind, controlled PApilloma TRIal against Cancer In young Adults (PATRICIA). We now assess the vaccine efficacy in the final event-driven analysis. METHODS: Women (15-25 years) were vaccinated at months 0, 1, and 6. Analyses were done in the according-to-protocol cohort for efficacy (ATP-E; vaccine, n=8093; control, n=8069), total vaccinated cohort (TVC, included all women receiving at least one vaccine dose, regardless of their baseline HPV status; represents the general population, including those who are sexually active; vaccine, n=9319; control, n=9325), and TVC-naive (no evidence of oncogenic HPV infection at baseline; represents women before sexual debut; vaccine, n=5822; control, n=5819). The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2+ (CIN2+) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline, and DNA negative at baseline and month 6 for the corresponding type (ATP-E). This trial is registered with ClinicalTrials.gov, number NCT00122681. FINDINGS: Mean follow-up was 34.9 months (SD 6.4) after the third dose. Vaccine efficacy against CIN2+ associated with HPV-16/18 was 92.9% (96.1% CI 79.9-98.3) in the primary analysis and 98.1% (88.4-100) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types (ATP-E cohort). Vaccine efficacy against CIN2+ irrespective of HPV DNA in lesions was 30.4% (16.4-42.1) in the TVC and 70.2% (54.7-80.9) in the TVC-naive. Corresponding values against CIN3+ were 33.4% (9.1-51.5) in the TVC and 87.0% (54.9-97.7) in the TVC-naive. Vaccine efficacy against CIN2+ associated with 12 non-vaccine oncogenic types was 54.0% (34.0-68.4; ATP-E). Individual cross-protection against CIN2+ associated with HPV-31, HPV-33, and HPV-45 was seen in the TVC. INTERPRETATION: The HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2+ associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes. FUNDING: GlaxoSmithKline Biologicals.


Assuntos
Papillomavirus Humano 16 , Papillomavirus Humano 18 , Infecções por Papillomavirus , Vacinas contra Papillomavirus/imunologia , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Adolescente , Adulto , Método Duplo-Cego , Feminino , Humanos , Vacinação em Massa , Estadiamento de Neoplasias , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Lesões Pré-Cancerosas/prevenção & controle , Lesões Pré-Cancerosas/virologia , Segurança , Comportamento Sexual , Resultado do Tratamento , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Adulto Jovem , Displasia do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/virologia
13.
J Virol ; 82(13): 6644-53, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18448540

RESUMO

Mutations in several subgenomic regions of hepatitis C virus (HCV) have been implicated in influencing the response to interferon (IFN) therapy. Sequences within HCV NS5A (PKR binding domain [PKRBD], IFN sensitivity-determining region [ISDR], and variable region 3 [V3]) were analyzed for the pretreatment serum samples of 60 HCV genotype 1-infected patients treated with pegylated IFN plus ribavirin (1b, n = 47; 1a, n = 13) but with different treatment outcomes, those with sustained virologic responses (SVR; n = 36) or nonresponders (NR; n = 24). Additionally, the sequence of the PKR/eIF-2alpha phosphorylation homology domain (E2-PePHD) region was determined for 23 patients (11 SVR and 12 NR). The presence of > 4 mutations in the PKRBD region was associated with SVR (P = 0.001) and early virologic responses (EVR; 12 weeks) (P = 0.037) but not rapid virologic responses (4 weeks). In the ISDR, the difference was almost statistically significant (68% of SVR patients with mutations versus 45% without mutations; P = 0.07). The V3 region had a very high genetic variability, but this was not related to SVR. Finally, the E2-PePHD (n = 23) region was well conserved. The presence of > 4 mutations in the PKRBD region (odds ratio [OR] = 9.9; P = 0.006) and an age of < or = 40 years (OR = 3.2; P = 0.056) were selected in a multivariate analysis as predictive factors of SVR. NS5A sequences from serum samples taken after 1 month of treatment and posttreatment were examined for 3 SVR and 15 NR patients to select treatment-resistant viral subpopulations, and it was found that in the V3 and flanking regions, the mutations increased significantly in posttreatment sera (P = 0.05). The genetic variability in the PKRBD (> 4 mutations) is a predictive factor of SVR and EVR in HCV genotype 1 patients treated with pegylated IFN and ribavirin.


Assuntos
Variação Genética , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Filogenia , Estrutura Terciária de Proteína/genética , Proteínas do Envelope Viral/genética , Proteínas não Estruturais Virais/genética , Adulto , Fatores Etários , Alanina Transaminase/metabolismo , Sequência de Bases , Análise por Conglomerados , Feminino , Genótipo , Hepatite C/genética , Humanos , Interferons/uso terapêutico , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação/genética , Razão de Chances , Estudos Prospectivos , Ribavirina/uso terapêutico , Análise de Sequência de DNA
14.
Int J Oral Maxillofac Surg ; 37(4): 398-400, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18022345

RESUMO

Inclusion of the third molar is relatively frequent in oral and maxillofacial surgery, but ectopic placement is quite rare. Only a few cases of third molar inclusion in the condyle region of the mandible have been reported. Presented here are two cases of ectopic location of a third molar in the condyle of the mandible. A description of the management of this pathology through open surgery and extraction of the molar is given, while preserving the anatomy of the condylar region.


Assuntos
Corpos Estranhos/cirurgia , Côndilo Mandibular/cirurgia , Dente Serotino/anormalidades , Erupção Ectópica de Dente/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dente Serotino/cirurgia
15.
AJR Am J Roentgenol ; 181(3): 831-8, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12933490

RESUMO

OBJECTIVE: The goal of our study was to investigate the contributing factors, clinical repercussions, and implications for prognosis of high-resistance flow at the hepatic artery detected on Doppler sonography during the period immediately after orthotopic liver transplantation. MATERIALS AND METHODS: We retrospectively studied the transplanted livers of 90 patients who had been examined on Doppler sonography within the first 3 days after grafting. Seventeen variables from organ donors, transplant recipients, graft characteristics, and surgical procedures were investigated. Early clinical evolution was also analyzed. Follow-up was performed for 5 years. RESULTS: Forty-one (45.6%) of the 90 patients showed a high resistive index at the hepatic artery during the first 72 hr after transplantation. Two factors showed a statistically significant effect on the occurrence of a high resistive index at the hepatic artery immediately after transplantation: an older liver donor (p = 0.008) and extended preservation time (p = 0.005). No relation with early graft function was detected. The incidence of bile duct complications, retransplantation, or death was not higher at follow-up in patients with high-resistance flow than in those with normal flow. CONCLUSION: High-resistance flow at the hepatic artery detected on Doppler sonography during the period immediately after transplantation is a frequent finding and is related to older donor age and prolonged period of ischemia. This finding has neither significant clinical repercussions nor prognosis implications for early and long-term follow-up.


Assuntos
Artéria Hepática/diagnóstico por imagem , Artéria Hepática/fisiopatologia , Falência Hepática/diagnóstico por imagem , Falência Hepática/cirurgia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias , Ultrassonografia Doppler , Resistência Vascular/fisiologia , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Falência Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Período Pós-Operatório , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
16.
An Med Interna ; 20(6): 317-26, 2003 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-12848605

RESUMO

Cystinuria is an autosomal recessive disorder with an estimated incidence of 1 case in 7000 live births, that results in elevated urinary excretion of cystine and dibasic aminoacids: ornithine, lysine and arginine. Discussed by Sir Archibald Edward Garrod, in 1908, as one of the four first known inborn errors of metabolism, it is characterized by a defect in transport of cystine and dibasic aminoacids, that affects their reabsortion in both renal tubule and gastrointestinal tract. To date, according to the recent molecular findings, two genes have been identified as responsible for this disease: SLC3A1 and SLC7A9. A more accurate pheno/genotyping identification of cystinuric patients will allow to improve prophilaxis and therapy for this illness. Cystinuria only causes recurrent urolithiasis (about 1-2 / of renal calculi in adults) and its associated complications as clinical feature because of poor cystine solubility at low pH. An accurate control over prohylaxis (based on high water intake and potassium citrate treatment, on first line, and tiol-derivatives treatment, on second line) must be taken in patients -like homozygous type I- with high lithiasis risk. However, approximately one half of patients under prophylaxis control will develop recurrent lithiasis; in this case, only urology or surgical approaches would be possible. 474 Updated knowledge about biochemical, genetic, clinical, diagnosis, prevention, treatment and prognosis aspects of this, relatively unusual, disease has been reviewed in this article.


Assuntos
Sistemas de Transporte de Aminoácidos Básicos , Proteínas de Transporte de Cátions , Cistinúria , Aminoácidos/farmacocinética , Transporte Biológico , Proteínas de Transporte/genética , Cistinúria/complicações , Cistinúria/epidemiologia , Cistinúria/genética , Cistinúria/terapia , Humanos , Absorção Intestinal , Glicoproteínas de Membrana/deficiência , Glicoproteínas de Membrana/genética , Mutação , Cotransportador de Sódio-Sulfato , Simportadores/deficiência , Simportadores/genética , Cálculos Urinários/etiologia
17.
BMC Anesthesiol ; 2(1): 2, 2002 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-11991809

RESUMO

BACKGROUND: Several neuromuscular blocking (NMB) agents are available for clinical use in anesthesia. The present study was performed in order to identify preferences and behaviors of anesthesiologists for using vecuronium, rocuronium or other NMB agents in their clinical practice. MATERIAL AND METHODS: The cross-sectional survey was applied at the Updated Course of the Colegio Mexicano de Anestesiología performed last year. Of 989, 282 (28.5%) surveys were returned. RESULTS: Most anesthesiologists were working at both public and private hospitals, performed anesthetic procedures for hospitalized and ambulatory patients, and anesthetized children as well as adults. Respondents did not consider mechanomyography as the gold standard method for neuromuscular monitoring. The T25 was not recognized as a pharmacodynamic parameter that represents the clinical duration of the neuromuscular block. Most answered that vecuronium induces less histamine release than rocuronium, had never used any neuromuscular monitor, did not know the cost of vecuronium and rocuronium, and preferred rocuronium in multiple-sampling vials and vecuronium in either a vial for single or multiple sampling. Rocuronium was preferred for emergency surgery in patients with full stomach only. Almost all of anesthesiologists that conserve the unused drug did it without refrigeration and more than 30% conserve the unused drug in one syringe for further use. CONCLUSION: Vecuronium was preferred for most clinical situations, and the decision for this choice was not based on costs. Storage of unused drugs without refrigeration in a single syringe for purpose of future use in several patients represented a dangerous common practice.

18.
J Natl Cancer Inst ; 93(17): 1325-30, 2001 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-11535707

RESUMO

BACKGROUND: Human papillomavirus 16 (HPV16) has a number of variants, each with a different geographic distribution and some that are associated more often with invasive neoplasias. We investigated whether the high incidence of cervical cancer in Mexico (50 cases per 100 000 women) may be associated with a high prevalence of oncogenic HPV16 variants. METHODS: Cervical samples were collected from 181 case patients with cervical cancer and from 181 age-matched control subjects, all from Mexico City. HPV16 was detected with an E6/E7 gene-specific polymerase chain reaction, and variant HPV classes and subclasses were identified by sequencing regions of the E6 and L1/MY genes. Clinical data and data on tumor characteristics were also collected. All statistical tests were two-sided. RESULTS: HPV16 was detected in cervical scrapes from 50.8% (92 of 181) of case patients and from 11% (20 of 181) of control subjects. All HPV16-positive samples, except one, contained European (E) or Asian-American (AA) variants. AA and E variants were found statistically significantly more often in case patients (AA = 23.2% [42 of 181]; E = 27.1% [49 of 181]) than in control subjects (AA = 1.1% [two of 181]; E = 10% [18 of 181]) (P<.001 for case versus control subjects for either E or AA variants, chi2 test). However, the frequency of AA variants was 21 times higher in cancer patients than in control subjects, whereas that ratio for E variants was only 2.7 (P =.006, chi2 test). The odds ratio (OR) for cervical cancer associated with AA variants (OR = 27.0; 95% confidence interval [CI] = 6.4 to 113.7) was higher than that associated with E variants (OR = 3.4; 95% CI = 1.9 to 6.0). AA-positive case patients (46.2 +/- 12.5 years [mean +/- standard deviation]) were 7.7 years younger than E-positive case patients (53.9 +/- 12.2 years) (P =.004, Student's t test). AA variants were associated with squamous cell carcinomas and adenocarcinomas, but E variants were associated with only squamous cell carcinomas (P =.014, Fisher's exact test). CONCLUSIONS: The high frequency of HPV16 AA variants, which appear to be more oncogenic than E variants, might contribute to the high incidence of cervical cancer in Mexico.


Assuntos
Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções Tumorais por Vírus/complicações , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/virologia , Adulto , Idoso , Ásia/etnologia , Povo Asiático/genética , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/virologia , Estudos de Casos e Controles , DNA Viral/genética , Europa (Continente)/etnologia , Feminino , Variação Genética , Humanos , Incidência , México/epidemiologia , Pessoa de Meia-Idade , Razão de Chances , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Prevalência , Análise de Sequência de DNA , Infecções Tumorais por Vírus/virologia , População Branca/genética
19.
Arch Med Res ; 32(3): 243-7, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11395192

RESUMO

BACKGROUND: A scenario that must be considered when testing prophylactic human papillomavirus (HPV) vaccines in teenagers is the parents' acceptability of their daughters' participation in the study. METHODS: A survey was carried out in a random sample of 880 women between the ages of 15 and 49 years in the metropolitan area of Cuernavaca, Mexico. These women were interviewed to obtain information concerning their knowledge of risk factors for cervical cancer and their perception of the usefulness of vaccines. Afterward, they were provided with information on the main risk factors for cervical cancer and the future availability of a human papillomavirus (HPV) vaccine to prevent cervical cancer. Finally, we explored, with parents, the possible acceptability of an HPV vaccine for their teenaged daughters. The degree of acceptability and its association with a series of sociodemographic and reproductive factors were assessed. RESULTS: The respondents had little knowledge regarding the etiology of cervical cancer. Only 1.9% said that the principal risk factor was infection with HPV; however, 84.2% were aware of the usefulness of vaccines and 83.6% of the women indicated that they would allow their daughters to participate in a trial to evaluate the effectiveness of an HPV vaccine that helps prevent cervical cancer. The main factor associated with the acceptance of a possible vaccine against HPV was the knowledge of the usefulness of vaccines [odds ratio (OR) = 6.5, 95% confidence interval (CI) 5.2-8.2]. Likewise, a history of two or more sexual partners (OR = 2.2, 95% CI 1.3-3.6) increased acceptability. Acceptance was not associated with the number of live births (never vs. ever OR = 0.9, 95% CI 0.3-2.1). There were 525 women with children over the age of 10 years (59.6%); prevalence of acceptability among these women was 80.1%, not statistically different from the remainder of the sample (p >0.05). CONCLUSIONS: Acceptance of a potential HPV vaccine was high in this sample of Mexican women. Initiation of HPV vaccine clinical trials and immunization campaigns that target school children and/or teenagers who are not sexually active should include educational programs aimed at mothers of these individuals. Knowledge of the benefits of a preventive vaccine as well as the etiology and risk factors of cervical cancer should be emphasized.


Assuntos
Atitude Frente a Saúde , Mães , Papillomaviridae/imunologia , Vacinas contra Papillomavirus , Infecções Tumorais por Vírus/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Vacinas Virais/administração & dosagem , Adolescente , Adulto , Feminino , Humanos , Entrevistas como Assunto , México , Pessoa de Meia-Idade , Fatores de Risco , Infecções Tumorais por Vírus/virologia , Neoplasias do Colo do Útero/virologia
20.
Hepatology ; 33(5): 1124-9, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11343240

RESUMO

Radiofrequency (RF) ablation is an alternative to percutaneous ethanol injection (PEI) for single nonsurgical hepatocellular carcinoma (HCC) and is currently used as adjuvant therapy before liver transplantation. This phase II study assesses the treatment-related complications and response rate of RF for the treatment of single HCC < or = 5 cm. Percutaneous RF was performed under conscious sedation and ultrasound (US) guidance with an electrical generator connected to a single cooled-tip electrode. Neoplastic cells in peripheral blood (reverse transcription-polymerase chain reaction for alpha fetoprotein [AFP] messenger RNA) were analyzed before and after RF. Treatment response was assessed by spiral computed tomography (CT) at 1 month and every 3 months by US or spiral CT thereafter. Thirty-two patients (20 men; age 67 +/- 4 years; 78% hepatitis C virus; 24 Child-Pugh A) with a mean tumor size of 2.8 cm (25 patients < or = 3 cm) were treated by RF (1.25 sessions; mean time, 22.1 +/- 2 minutes). Adjuvant PEI was performed in 9 cases. Complete response was achieved in 21 patients (65%), being significantly higher for HCC < or = 3 cm (76% vs. 29%, P = .03). After a median follow-up of 10 months, 8 patients showed treatment-related morbidity. Four of them (12.5%) showed biopsy-proven needle-track seeding detected between 4 to 18 months. Neoplastic seeding was related to subcapsular location (P = .009), poor differentiation degree (P = .02), and baseline AFP levels (P = .02). Thus, RF ablation with cooled-tip needle for HCC is associated with a high risk of neoplastic seeding. Iatrogenic dissemination was related to subcapsular location or an invasive tumoral pattern, and has to be considered when selecting curative treatments for HCC or adjuvant therapies before liver transplantation.


Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/efeitos adversos , Neoplasias Hepáticas/cirurgia , Inoculação de Neoplasia , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Fatores de Risco , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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