RESUMO
BACKGROUND: Human papillomavirus (HPV) vaccination protects against HPV, a necessary risk factor for cervical cancer. We now report results from population-based follow-up of randomised cohorts that vaccination provides HPV-type-specific protection against invasive cancer. METHODS: Individually and/or cluster randomised cohorts of HPV-vaccinated and non-vaccinated women were enrolled in 2002-2005. HPV vaccine cohorts comprised originally 16-17 year-old HPV 16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2465) and HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866). Altogether, 3341 vaccines were followed by the Finnish Cancer Registry in the same way as 16 526 non-HPV-vaccinated controls. The control cohort stemmed from 15 665 originally 18-19 years-old women enrolled in 2003 (6499) or 2005 (9166) and 861 placebo recipients of the FUTURE II trial. The follow-up started 6 months after the clinical trials in 2007 and 2009 and ended in 2019. It was age aligned for the cohorts. FINDINGS: During a follow-up time of up to 11 years, we identified 17 HPV-positive invasive cancer cases (14 cervical cancers, 1 vaginal cancer, 1 vulvar cancer and 1 tongue cancer) in the non-HPV-vaccinated cohorts and no cases in the HPV-vaccinated cohorts. HPV typing of diagnostic tumour blocks found HPV16 in nine cervical cancer cases, HPV18, HPV33 and HPV52 each in two cases and HPV45 in one cervical cancer case. The vaginal, vulvar and tongue cancer cases were, respectively, positive for HPV16, HPV52/66 and HPV213. Intention-to-treat vaccine efficacy against all HPV-positive cancers was 100% (95% CI 2 to 100, p<0.05). INTERPRETATION: Vaccination is effective against invasive HPV-positive cancer. TRIAL REGISTRATION NUMBER: NCT00122681, Post-results; NCT00169494, Post-results; NCT00092534, Post-results.
Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Adolescente , Adulto , Feminino , Seguimentos , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Eficácia de Vacinas , Adulto Jovem , Displasia do Colo do Útero/diagnósticoRESUMO
Persistent genital chlamydial infection may lead to tubal factor infertility (TFI). Chlamydia trachomatis TroA and HtrA are proteins expressed during persistent chlamydial infection in vitro. We studied serum IgG antibody response against these proteins by EIA in women with TFI and in subfertile women without tubal pathology. Altogether, 22 of 258 subfertile women (8.5%) had TFI which was unilateral in 17 cases and bilateral in 5 cases. Overall, 55 (21.3%) of the 258 women had TroA and 39 (15.1%) had HtrA antibodies. Seropositivity to TroA and HtrA was more common among women with TFI than women with other causes for subfertility (45.5 vs. 19.1%, p = 0.004 for TroA; 36.4 vs. 13.1%, p = 0.004 for HtrA). Mean absorbance values and the prevalence of TroA and HtrA antibodies increased with increasing severity of TFI. On the basis of our results, TroA and HtrA serology has the potential to be further developed to a specific biomarker for C. trachomatis-related TFI.
Assuntos
Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Infecções por Chlamydia/complicações , Infecções por Chlamydia/imunologia , Chlamydia trachomatis/imunologia , Infertilidade Feminina/etiologia , Adulto , Anticorpos Antibacterianos/sangue , Biomarcadores , Infecções por Chlamydia/sangue , Infecções por Chlamydia/epidemiologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Infertilidade Feminina/epidemiologia , Fatores de Risco , Adulto JovemRESUMO
We studied whether antibody to two chlamydial proteins (TroA and HtrA) could be used as biomarkers of Chlamydia trachomatis infection. METHODS: Recombinant proteins C. trachomatis TroA and HtrA were used as antigens in enzyme immunoassay (EIA). Both IgG and IgA antibody responses were studied. RESULTS: IgG or IgA antibody to either protein was infrequently detected in sera from healthy blood donors or virgin girls. Patients attending the STI Clinic and patients with perihepatitis had often IgG antibody against TroA (25 and 50 % respectively) and HtrA (21 and 38 % respectively). Especially in sera from patients with chlamydial perihepatitis, the A450nm values with TroA were high (mean 1.591). A positive correlation between C. trachomatis MIF antibody and TroA (r = 0.7) as well as HtrA (r = 0.5) antibody was observed in sera from STI clinic patients and perihepatitis patients. Individuals with C. trachomatis infection and positive serology already when seeking medical attention had higher A450nm values for TroA (0.638) and HtrA (0.836) than patients with no marker of previous exposure or with no infection (0.208 and 0.234 respectively). Diagnosis of genital C. trachomatis infection is often NAAT-based, whereas serology has little value in testing for uncomplicated genital C. trachomatis infection. TroA and HtrA antibodies are potential biomarkers for evaluation of ascending and repeated C. trachomatis infection.
Assuntos
Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Biomarcadores/sangue , Infecções por Chlamydia/diagnóstico , Chlamydia trachomatis/isolamento & purificação , Adolescente , Criança , Infecções por Chlamydia/patologia , Chlamydia trachomatis/imunologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Imunoglobulina A/sangue , Imunoglobulina G/sangueRESUMO
Chlamydia-like organisms (CLOs) are recently identified members of the Chlamydiales order. CLOs share intracellular lifestyles and biphasic developmental cycles, and they have been detected in environmental samples as well as in various hosts such as amoebae and arthropods. In this study, we screened bat feces for the presence of CLOs by molecular analysis. Using pan-Chlamydiales PCR targeting the 16S rRNA gene, Chlamydiales DNA was detected in 54% of the specimens. PCR amplification, sequencing, and phylogenetic analysis of the 16S rRNA and 23S rRNA genes were used to classify positive specimens and infer their phylogenetic relationships. Most sequences matched best with Rhabdochlamydia species or uncultured Chlamydia sequences identified in ticks. Another set of sequences matched best with sequences of the Chlamydia genus or uncultured Chlamydiales from snakes. To gain evidence of whether CLOs in bat feces are merely diet borne, we analyzed insects trapped from the same location where the bats foraged. Interestingly, the CLO sequences resembling Rhabdochlamydia spp. were detected in insect material as well, but the other set of CLO sequences was not, suggesting that this set might not originate from prey. Thus, bats represent another potential host for Chlamydiales and could harbor novel, previously unidentified members of this order. IMPORTANCE: Several pathogenic viruses are known to colonize bats, and recent analyses indicate that bats are also reservoir hosts for bacterial genera. Chlamydia-like organisms (CLOs) have been detected in several animal species. CLOs have high 16S rRNA sequence similarity to Chlamydiaceae and exhibit similar intracellular lifestyles and biphasic developmental cycles. Our study describes the frequent occurrence of CLO DNA in bat feces, suggesting an expanding host species spectrum for the Chlamydiales As bats can acquire various infectious agents through their diet, prey insects were also studied. We identified CLO sequences in bats that matched best with sequences in prey insects but also CLO sequences not detected in prey insects. This suggests that a portion of CLO DNA present in bat feces is not prey borne. Furthermore, some sequences from bat droppings not originating from their diet might well represent novel, previously unidentified members of the Chlamydiales order.
Assuntos
Quirópteros/microbiologia , Chlamydiales/genética , Chlamydiales/isolamento & purificação , Fezes/microbiologia , Animais , Chlamydiales/classificação , DNA Bacteriano/análise , Filogenia , RNA Ribossômico 16S/análise , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNARESUMO
OBJECTIVE: To evaluate the association of amniotic fluid (AF) matrix metalloproteinase-8 (MMP-8) and cathelicidin concentrations with microbial invasion of the amniotic cavity (MIAC) in pregnancies with preterm prelabor rupture of the membranes or intact membranes. STUDY DESIGN: Amniocentesis was performed in 54 singleton pregnancies between 22+0 and 34+2 gestational weeks with suspected intra-amniotic infection. AF-MMP-8 was analysed by immunoassay and AF-cathelicidin by commercial ELISA. Standard biochemical methods, molecular microbiology and culture techniques were used. RESULTS: MIAC was present in 18 (33%) women. The cutoff value for the diagnosis of MIAC was 41.5 ng ml-1 for AF-MMP-8, and 11.6 ng ml-1 for AF-cathelicidin. With these cutoff values AF-MMP-8 had a sensitivity of 100%, specificity of 69%, positive predictive value of 62% and negative predictive value of 100% for MIAC. The corresponding values for AF-cathelicidin were 89, 81, 70 and 94%. CONCLUSION: The performance of AF-cathelicidin in the prediction of MIAC is comparable to AF-MMP-8.
Assuntos
Líquido Amniótico/química , Peptídeos Catiônicos Antimicrobianos/análise , Ruptura Prematura de Membranas Fetais/diagnóstico , Metaloproteinase 8 da Matriz/análise , Adulto , Amniocentese , Líquido Amniótico/enzimologia , Líquido Amniótico/microbiologia , Peptídeos Catiônicos Antimicrobianos/metabolismo , Biomarcadores/análise , Corioamnionite/enzimologia , Corioamnionite/metabolismo , Feminino , Ruptura Prematura de Membranas Fetais/enzimologia , Idade Gestacional , Humanos , Metaloproteinase 8 da Matriz/metabolismo , Trabalho de Parto Prematuro/enzimologia , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Curva ROC , CatelicidinasRESUMO
OBJECTIVE: The aim of our study was to introduce outpatient induction of labor by Foley catheter, and to compare outcomes and preferences between in-patients and outpatients. STUDY DESIGN: This clinical cohort study was conducted in Helsinki University Hospital between January 2011 and January 2012. A total of 485 women scheduled for induction of labor by Foley catheter were included. The main outcome measures were cesarean delivery rate, and maternal and neonatal infectious morbidity. Maternal satisfaction of outpatients was measured after delivery. RESULTS: Two hundred and four (42.1%) women were managed as outpatients and 281 (57.9%) women as in-patients. The rates of cesarean delivery, and maternal or neonatal infections did not differ between outpatients and in-patients. Of the outpatients, 85.3% were satisfied. CONCLUSION: Induction of labor by Foley catheter appears suitable for outpatients, and resulted in no differences in cesarean delivery or infection rates compared with in-patients. Most women were satisfied with the outpatient induction.
Assuntos
Cesárea/estatística & dados numéricos , Trabalho de Parto Induzido/métodos , Pacientes Ambulatoriais/estatística & dados numéricos , Cateterismo Urinário/métodos , Adulto , Catéteres , Maturidade Cervical/fisiologia , Colo do Útero/cirurgia , Estudos de Coortes , Feminino , Finlândia , Humanos , Recém-Nascido , Pacientes Internados/estatística & dados numéricos , Modelos Logísticos , Masculino , Análise Multivariada , Gravidez , Resultado da GravidezRESUMO
OBJECTIVE: The objective of this study was to evaluate the association of amniotic fluid lactate dehydrogenase and glucose concentrations with microbial invasion of amniotic cavity and histologic chorioamnionitis before 37 pregnancy weeks in women with or without preterm premature rupture of membranes. STUDY DESIGN: Amniocentesis was performed on 70 women with suspected intra-amniotic infection. Standard biochemical methods, molecular microbiology and culture techniques were used. Histopathological examination of the placenta was performed. RESULTS: Thirty (48%) women had microbial invasion of the amniotic cavity (MIAC), 53 (76%) women had histological chorioamnionitis and 28 women had both. The cutoff values for MIAC and histological chorioamnionitis were 429 IU l(-1) for lactate dehydrogenase and 0.7 mmol l(-1) for glucose. Both end points occurred equally often regardless of the membrane status. CONCLUSION: Increased amniotic fluid lactate dehydrogenase and decreased glucose were associated with MIAC and histological chorioamnionitis. However, test performance was of limited value.
Assuntos
Líquido Amniótico/microbiologia , Corioamnionite/epidemiologia , Ruptura Prematura de Membranas Fetais/epidemiologia , Glucose/análise , L-Lactato Desidrogenase/análise , Adulto , Amniocentese , Líquido Amniótico/química , Biomarcadores/análise , Corioamnionite/microbiologia , Corioamnionite/patologia , Feminino , Finlândia , Idade Gestacional , Humanos , Placenta/patologia , Gravidez , Estudos Prospectivos , Curva ROCRESUMO
Inherited variance in the IL-12B gene is associated with susceptibility to Chlamydia trachomatis-induced tubal factor infertility and disease severity. In this study, our aim was to discover how polymorphisms in IL-12-coding genes influence C. trachomatis-induced immune responses and IL-12 production. The study population consisted of 240 women. IL-12A and IL-12B single nucleotide polymorphisms (SNPs) were determined from isolated DNA using the Sequenom system with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. We studied lymphocyte proliferative (LP) responses to C. trachomatis strains E and F elementary bodies (EBs) and recombinant chlamydial heat-shock protein 60 (CHSP60) antigen. IL-12p40 and IL-12p70 levels were measured using the BD Flex Set method. We found a statistically significant association between the C. trachomatis EB antigen-specific LP response and the rs2853694 SNP (P = 0.02). Our study demonstrates that the IL-12 cytokine family is involved in C. trachomatis-specific immune responses. Moreover, C. trachomatis-induced IL-12 production and the IL-12B rs2853694 SNP partially explain individual variation in the C. trachomatis LP response.
Assuntos
Infecções por Chlamydia/imunologia , Chlamydia trachomatis/imunologia , Subunidade p40 da Interleucina-12/genética , Subunidade p40 da Interleucina-12/imunologia , Adolescente , Adulto , Anticorpos Antibacterianos/imunologia , Chaperonina 60/imunologia , Feminino , Humanos , Imunidade Celular/genética , Imunidade Celular/imunologia , Infertilidade Feminina/microbiologia , Subunidade p40 da Interleucina-12/metabolismo , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Adulto JovemRESUMO
OBJECTIVE: To assess the long-term neurodevelopmental outcome of children born from singleton euploid pregnancies with increased fetal nuchal translucency (NT) in the first trimester ultrasound screening and without structural anomalies in the second trimester ultrasound screening. STUDY DESIGN: This is a register-based retrospective cohort study carried out at a tertiary referral centre from 2002 to 2007. Children were followed up until 2012. All fetuses had increased NT (>95th percentile) at the first trimester ultrasound screening and normal findings in the second trimester ultrasound screening. Data about the neurodevelopmental outcome was retrieved from the hospital databases, The National Institute for Health and Welfare, and the Finnish Causes of Death Statistics Database. Information about received disability allowances was gathered from the Social Insurance Institute of Finland. RESULTS: The study population consists of 691 children. The mean follow-up time was 6.5 years. Neurodevelopmental disorders occurred in 29 children (4.2%). Twelve of these 29 children (1.7%) had severe neurodevelopmental impairment. CONCLUSIONS: The long-term neurodevelopmental outcome of children after increased fetal NT is reassuring. This information should be added to the parental counselling of such cases. © 2014 John Wiley & Sons, Ltd.
Assuntos
Desenvolvimento Infantil , Transtornos do Neurodesenvolvimento/diagnóstico , Medição da Translucência Nucal/métodos , Adolescente , Adulto , Criança , Aberrações Cromossômicas , Estudos de Coortes , Feminino , Seguimentos , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Transtornos do Neurodesenvolvimento/epidemiologia , Gravidez , Resultado da Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Interleukin-12 (IL-12) and related cytokines induce activation and differentiation of T cells. Our aim was to investigate the associations between genetic differences in IL-12-family cytokines and the pathogenesis of chlamydial disease. METHODS: The final study population consisted of 100 women with Chlamydia trachomatis-induced tubal factor infertility (TFI) and 125 pregnant women as controls. Three single nucleotide polymorphisms (SNPs) of IL12A and seven SNPs of IL12B genes were determined from isolated DNA using the Sequenom system with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. RESULTS: We found that the IL12B SNP rs3212227 was associated with both susceptibility and severity of TFI. The minor allele C was rare and only one CC homozygote was found among the controls. AC heterozygotes were more common among TFI cases than among controls (P = 0.009) and were associated with increased risk of TFI [odds ratios (OR) = 2.44, 95% confidence intervals (CI) = 1.23-4.87]. Carrying the minor allele C was also associated with disease severity (P for trend = 0.008) and moderate (OR = 2.51, 95% CI = 1.06-5.95) and severe tubal damage (OR = 2.73, 95% CI = 1.15-6.52). CONCLUSIONS: The results suggest that variation in the IL12B gene partly explains inter-individual differences in disease susceptibility and severity.
Assuntos
Infecções por Chlamydia/complicações , Infecções por Chlamydia/genética , Chlamydia trachomatis/metabolismo , Infertilidade/complicações , Infertilidade/microbiologia , Subunidade p35 da Interleucina-12/genética , Subunidade p40 da Interleucina-12/genética , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Estudos de Casos e Controles , Tubas Uterinas/microbiologia , Tubas Uterinas/patologia , Feminino , Predisposição Genética para Doença , Variação Genética , Homozigoto , Humanos , Razão de Chances , Análise de Sequência de DNA , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
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 & controleRESUMO
OBJECTIVE: To compare, whether women with menorrhagia, treated with either hysterectomy or LNG-IUS, differ in their cardiovascular risk profile during 10-year follow-up. STUDY DESIGN: A total of 236 women were randomized to treatment by hysterectomy (n=117) or LNG-IUS (n=119). Their cardiovascular risk factors were analyzed at baseline, at 5 years, and at 10 years. As 55 originally randomized to the LNG-IUS group had hysterectomy during the follow-up, all analyzes were performed by actual treatment modality. MAIN OUTCOME MEASURES: Waist circumference, body-mass index (BMI), blood pressure, and the levels of blood lipids, serum high-sensitivity CRP (hsCRP) and tumor necrosis factor alpha (TNF-α) were measured, and the use of medication for hypertension, diabetes, hypercholesterolemia, and ischemic heart disease was analyzed. RESULTS: After 5 years, an increase in the use of diabetes medication during the follow-up was only detected in the hysterectomy group (from 1.7% to 6.7%, P=0.008 vs from 5.1% to 8.4%, P=0.08), as well as they had significantly higher serum levels of TNF-α (108.59 pg/ml vs 49.02 pg/ml, P=0.001) and hsCRP (1.55 µg/ml vs 0.78 µg/ml, P=0.038) at 5- and 10-years. There was no difference between the groups in the use of cardiovascular medication, neither was there difference in blood pressure, waist circumference, BMI, or concentrations of blood lipids. CONCLUSIONS: Hysterectomy seems to be associated with increased levels of serum inflammatory markers and increased diabetes medication, which in turn, may predispose individual to future cardiovascular events.
Assuntos
Doenças Cardiovasculares/etiologia , Diabetes Mellitus/etiologia , Histerectomia/efeitos adversos , Inflamação/complicações , Levanogestrel/efeitos adversos , Menorragia/terapia , Progestinas/efeitos adversos , Adulto , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/sangue , Diabetes Mellitus/sangue , Diabetes Mellitus/tratamento farmacológico , Feminino , Seguimentos , Humanos , Hipoglicemiantes/uso terapêutico , Inflamação/sangue , Dispositivos Intrauterinos Medicados , Levanogestrel/uso terapêutico , Menorragia/sangue , Pessoa de Meia-Idade , Progestinas/uso terapêutico , Fatores de Risco , Fator de Necrose Tumoral alfa/sangueRESUMO
Chlamydia trachomatis-induced fallopian tube damage leading to tubal factor infertility (TFI) is linked with TNF, IL-10, and probably IFNG gene polymorphisms. The aim of this study was to clarify the contribution of these cytokine gene polymorphisms to interindividual variation in C trachomatis-specific immune responses and the cross-regulation of secreted cytokines and single nucleotide polymorphisms (SNPs). Cytokine polymorphisms (IL-10 -1082A/G, -819T/C, and -592A/C, IFNG +874T/A, and TNF -308G/A) were genotyped by polymerase chain reaction in 139 women. C trachomatis-specific immune responses were measured using lymphocyte proliferation (LP) induced by C trachomatis E and F strains and chlamydial heat shock protein 60 antigens. Cytokine secretion was measured in culture supernatants of infected and uninfected mononuclear leukocytes. IL-10 -1082/-819/-592 and IFNG +874 SNPs were associated with the intensity of LP responses to C trachomatis antigens. These cytokines also interact with each other and a cumulative effect of IL-10 -1082 and IFNG +874 genotypes was seen in LP responses to C trachomatis antigens. Our data suggest that interleukin-10 and interferon-γ regulate C trachomatis-specific immune responses in humans and that genetic variation in the expression of their coding genes explains interindividual variation in host immune responses to C trachomatis infection.
Assuntos
Infecções por Chlamydia/genética , Infecções por Chlamydia/imunologia , Chlamydia trachomatis/imunologia , Infertilidade Feminina/genética , Interferon gama/genética , Interleucina-10/genética , Fator de Necrose Tumoral alfa/genética , Adolescente , Adulto , Anticorpos Antibacterianos/imunologia , Chaperonina 60/genética , Chaperonina 60/imunologia , Chlamydia trachomatis/genética , Doenças das Tubas Uterinas/imunologia , Doenças das Tubas Uterinas/microbiologia , Feminino , Expressão Gênica , Variação Genética , Genótipo , Humanos , Infertilidade Feminina/imunologia , Interferon gama/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/microbiologia , Contagem de Linfócitos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVE: To study whether elevated levels of decidual insulin-like growth factor binding protein-1 (IGFBP-1) in the cervical fluid of unselected asymptomatic women in early or mid-pregnancy are associated with spontaneous preterm delivery (PTD). DESIGN: Prospective population-based cohort study. SETTING: Maternity Clinics, University Central Hospital, Helsinki, Finland. POPULATION: A total of 5180 unselected pregnant women. METHODS: Cervical swab samples were collected during the first and second trimester ultrasound screening. The concentration of IGFBP-1 was measured by immunoenzymometric assay, which detects the decidual phosphoisoforms of IGFBP-1 (phIGFBP-1). Concentrations of 10 micrograms/l or more were considered to be elevated. MAIN OUTCOME MEASURE: Spontaneous PTD. Results In the first trimester, 24.5% of women, and in the mid-second trimester, 20.2% of women, had an elevated cervical fluid phIGFBP-1 level. The rates of spontaneous PTD before 32 and before 37 weeks of gestation were higher in women with an elevated cervical fluid phIGFBP-1 level, compared with women who had cervical phIGFBP-1 of <10 micrograms/l (1.1% versus 0.3% and 5.7% versus 3.2%, respectively). An elevated phIGFBP-1 level in the first trimester was an independent predictor for PTD before 32 and before 37 weeks of gestation, with odds ratios of 3.0 (95% CI 1.3-7.0) and 1.6 (95% CI 1.2-2.3), respectively. Cervical phIGFBP-1 levels of 10 micrograms/l or more in the first trimester predicted PTD before 32 and before 37 weeks of gestation, with sensitivities of 53.8% and 37.0%, respectively. The negative predictive values were 99.7% and 96.8%. CONCLUSIONS: Elevated cervical fluid phIGFBP-1 levels in the first trimester were associated with an increased risk of spontaneous PTD.
Assuntos
Colo do Útero/química , Colo do Útero/citologia , Decídua/química , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Trabalho de Parto Prematuro/prevenção & controle , Diagnóstico Pré-Natal/métodos , Adolescente , Adulto , Biomarcadores/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Trabalho de Parto Prematuro/metabolismo , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Estudos Prospectivos , Fatores de Risco , Sensibilidade e Especificidade , Adulto JovemRESUMO
OBJECTIVE: To evaluate the effect of hysterectomy and levonorgestrel-releasing intrauterine system (LNG-IUS) on lower urinary tract symptoms (LUTS) among women treated for menorrhagia. DESIGN: Randomised controlled trial analysed by actual treatment. SETTING: Five university hospitals in Finland. SAMPLE: A cohort of 236 women, aged 35-49 years, referred for menorrhagia between 1994 and 1997. METHODS: Women were randomly assigned to treatment by hysterectomy (n = 117) or LNG-IUS (n = 119). MAIN OUTCOME MEASURES: Lower urinary tract symptoms were evaluated by questionnaires at baseline, and after 6, 12 months, 5, and 10 years. Medications and operations for urinary incontinence were confirmed from medical records and national registries. RESULTS: Overall, 221 (94%) women took part in the 10-year follow-up evaluation. As 55 (46%) women originally randomised to the LNG-IUS group underwent hysterectomy, the results were analysed by actual treatment. Women treated by hysterectomy used more medication for urinary incontinence than LNG-IUS users (12% versus 1%) (OR 9.45, 95% CI 1.24-71.87, P = 0.006). Three hysterectomised women and one LNG-IUS user underwent surgery for stress urinary incontinence (SUI). Women treated by hysterectomy had more urinary tract infections (UTIs) than LNG-IUS users (OR 3.20, 95% CI 1.47-6.96, P = 0.002). Feeling of incomplete emptying (OR 3.00, 95% CI 1.00-9.05, P = 0.04) and SUI (OR 1.83, 95% CI 1.01-3.32, P = 0.04) were more common among women treated by hysterectomy. No differences between the study arms were noted in urge urinary incontinence or by the Urinary Incontinence Severity Score. A multivariate model showed that UTIs were associated with hysterectomy (P = 0.004). CONCLUSIONS: Hysterectomy increases the risks for incomplete emptying, lower UTIs and SUI.
Assuntos
Anticoncepcionais Femininos/administração & dosagem , Histerectomia/efeitos adversos , Levanogestrel/administração & dosagem , Menorragia/terapia , Infecções Urinárias/etiologia , Transtornos Urinários/etiologia , Adulto , Anticoncepcionais Femininos/efeitos adversos , Feminino , Finlândia , Seguimentos , Humanos , Dispositivos Intrauterinos Medicados , Levanogestrel/efeitos adversos , Pessoa de Meia-IdadeRESUMO
Susceptibility to Chlamydia trachomatis infections is 40% host based. microRNA-146a is a negative regulator of Tolllike receptor (TLR) signaling and possesses functional polymorphisms which decrease the production of premiR-146a and mature miR-146a. Single nucleotide polymorphisms (SNPs) in NLRP3 are associated with decreased NLRP3 expression and hypoproduction of interleukin (IL)-1beta. We investigated whether the SNPs miR-146a G>C (rs2910164), NLRP3 C>T (rs4925663) and G>A (rs12065526) are associated with the susceptibility to and severity of C. trachomatis infection. The genotypes of three SNPs were tested in two cohorts: cohort 1 consists of Dutch women (n = 318) attending a sexually transmitted disease (STD) clinic and cohort 2 (n = 277) consists of subfertile (n = 184) and healthy Finnish women (n=93). While in cohort 1 the analyzed SNPs were not associated with the susceptibility to C. trachomatis infections (C. trachomatis-positive vs. C. trachomatis-negative), we showed in C. trachomatis-positive women that the NLRP3 mutant AG and AA genotypes were a risk factor for the development of symptoms (P = 0.047, OR = 2.9) and more specifically for having lower abdominal pain (genotype AA: P = 0.022, OR = 31.3). In the Finnish tubal pathology group versus the control group no statistical significant differences in the incidences of the SNPs studied were found, nor for the degree of tubal pathology. In conclusion, the mutant NLRP3 A allele is a risk factor for the development of symptoms, specifically lower abdominal pain, after a C. trachomatis infection in women attending an STD clinic.
Assuntos
Proteínas de Transporte/genética , Infecções por Chlamydia/etiologia , Chlamydia trachomatis , Doenças das Tubas Uterinas/etiologia , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Infecções por Chlamydia/genética , Infecções por Chlamydia/imunologia , Doenças das Tubas Uterinas/genética , Doenças das Tubas Uterinas/imunologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Interleucina-1beta/fisiologia , Proteína 3 que Contém Domínio de Pirina da Família NLRRESUMO
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/virologiaRESUMO
BACKGROUND: Quadrivalent human papillomavirus (HPV types 6/11/16/18) L1 VLP vaccine is highly effective in preventing HPV 6/11/16/18-related cervical and external genital disease. Herein, we evaluated the impact of the quadrivalent HPV 6/11/16/18 L1 VLP vaccine on prevention of HPV-associated cervico-genital lesions in a broad population of sexually active European women. METHODS: Female subjects (N = 9265) aged 16-24 with four or fewer lifetime sexual partners were enrolled and randomized to quadrivalent HPV vaccine or placebo. Subjects underwent cervicovaginal sampling for HPV DNA detection. Papanicolaou testing and anti-HPV 6/11/16/18 serology testing was also performed. RESULTS: Vaccine efficacy against lesions representing immediate cervical cancer precursors (cervical intraepithelial neoplasia grade 2/3 or adenocarcinoma in situ) related to HPV 6/11/16/18 in the per-protocol population was 100.0%[95% confidence interval (95% CI), 89.8-100.0]. Efficacy against external genital lesions (vulvar or vaginal intraepithelial neoplasia, condyloma, vulvar or vaginal cancer) related to vaccine HPV types in the per-protocol European population was 99.0% (95% CI, 94.4-100.0). CONCLUSION: These data demonstrate that quadrivalent HPV 6/11/16/18 vaccination programs in 16- to 24-year-old European women can be beneficial. NCT0009252, NCT00092534, NCT00092495.
Assuntos
Adenocarcinoma/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Displasia do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Feminino , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18 , Humanos , Placebos , Ensaios Clínicos Controlados Aleatórios como Assunto , Parceiros Sexuais , Adulto JovemRESUMO
OBJECTIVE: The objective of this study was to study whether women surgically treated for cervical intraepithelial neoplasia (CIN) have increased mortality later in life. We also wanted to study whether pregnancy beyond 22 weeks post-treatment affects the risk. DESIGN: Register-based retrospective cohort study from Finland. SETTING: National data of the Hospital Discharge Register and the Cause-of-Death Register during 1986-2003. POPULATION: A total of 25 827 women who had surgical treatment for CIN during 1986-2003. METHODS: We calculated standardised mortality ratios (SMRs) by dividing the numbers of observed deaths (until 31 December 2006) by the numbers of expected deaths. MAIN OUTCOME MEASURES: SMRs for different causes-of-death groups. RESULTS: The overall mortality increased by 17% after treatment for CIN, including increased risk of dying from all diseases and medical conditions (SMR 1.13, 95% CI 1.01-1.26), cancers (SMR 1.09, 95% CI 0.91-1.27) and injury deaths (SMR 1.31, 95% CI 1.03-1.58). As expected, the mortality from cervical cancer was high (SMR 7.69, 95% CI 4.23-11.15). Women who had delivered post-treatment tended to have decreased overall mortality (SMR 0.78, 95% CI 0.52-1.04) and decreased disease mortality (SMR 0.63, 95% CI 0.37-0.90). However, the mortality rate was significantly increased for women who had subsequent preterm delivery (SMR 2.51, 95% CI 1.24-3.78). In this subgroup, there was a tendency of increased mortality from diseases of the circulatory system, alcohol-related causes and injury deaths. CONCLUSIONS: Mortality rate was increased after surgical treatment for CIN. However, women who had delivered post-treatment had decreased overall disease mortality rate. Subsequent preterm delivery may be a risk marker for increased long-term mortality.