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To create reproducible emotional probes, affective scientists rely on sets of standardized pictures that are normed using subjective ratings of valence and emotional arousal. However, when emotional responses are investigated using neurophysiological measures, it might be more appropriate to select pictures integrating information from normative subjective reports and normative neurophysiological responses. Here, we provide electrophysiological normative responses for 323 emotional pictures (215 from the IAPS) covering a wide range of categories (erotica, romantic, appetizing foods, landscapes, people engaged in mundane activities, household objects, disgusting objects, accidents, sad people, violence, mutilations, and cigarette-related contents). Event-related potentials (ERPs) and subjective ratings of pleasure and emotional arousal were collected from 763 individuals (52% females, 41% white) aged between 18 and 65 (mean = 43). For each image, the mean amplitude of the late positive potential (LPP, an electrophysiological index of motivational relevance) and the mean subjective ratings of valence and arousal were calculated. We validated our procedure by showing that the subjective ratings of valence and arousal from this sample were highly correlated to the IAPS' published norms (Pearson r = .97 for pleasure and r = .82 for emotional arousal). LPP responses and subjective ratings of emotional arousal also were correlated (Pearson r = .61), but some categories reported being significantly more arousing than neutral (i.e., food, landscapes, and unpleasant objects) did not evoke LPPs significantly different from those evoked by neutral pictures. Researchers interested in probing the brain's affective systems can use these electrophysiological normative responses to create emotional probes that evoke reliable neuroaffective responses.
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Emoções , Produtos do Tabaco , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Emoções/fisiologia , Potenciais Evocados/fisiologia , Nível de Alerta/fisiologia , Motivação , Estimulação LuminosaRESUMO
INTRODUCTION: By improving our understanding of the neurobiological mechanisms underlying addiction, neuroimaging research is helping to identify new targets for personalized treatment interventions. When trying to quit, smokers with larger electrophysiological responses to cigarette-related, compared with pleasant, stimuli ("C > P") are more likely to relapse than smokers with the opposite brain reactivity profile ("P > C"). AIM AND METHOD: The goal was to (1) build a classification algorithm to identify smokers characterized by P > C or C > P neuroaffective profiles and (2) validate the algorithm's classification outcomes in an independent data set where we assessed both smokers' electrophysiological responses at baseline and smoking abstinence during a quit attempt. We built the classification algorithm applying discriminant function analysis on the event-related potentials evoked by emotional images in 180 smokers. RESULTS: The predictive validity of the classifier showed promise in an independent data set that included new data from 177 smokers interested in quitting; the algorithm classified 111 smokers as P > C and 66 as C > P. The overall abstinence rate was low; 15 individuals (8.5% of the sample) achieved CO-verified 12-month abstinence. Although individuals classified as P > C were nearly 2.5 times more likely to be abstinent than smokers classified as C > P (12 vs. 3, or 11% vs. 4.5%), this result was nonsignificant, preliminary, and in need of confirmation in larger trials. CONCLUSION: These results suggest that psychophysiological techniques have the potential to advance our knowledge of the neurobiological underpinnings of nicotine addiction and improve clinical applications. However, larger sample sizes are necessary to reliably assess the predictive ability of our algorithm. IMPLICATIONS: We assessed the clinical relevance of a neuroimaging-based classification algorithm on an independent sample of smokers enrolled in a smoking cessation trial and found those with the tendency to attribute more relevance to rewards than cues were nearly 2.5 times more likely to be abstinent than smokers with the opposite brain reactivity profile (11% vs. 4.5%). Although this result was not statistically significant, it suggests our neuroimaging-based classification algorithm can potentially contribute to the development of new precision medicine interventions aimed at treating substance use disorders. Regardless, these findings are still preliminary and in need of confirmation in larger trials.
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Algoritmos , Neuroimagem/métodos , Medicina de Precisão , Fumantes/psicologia , Abandono do Hábito de Fumar/estatística & dados numéricos , Tabagismo/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Abandono do Hábito de Fumar/métodos , Tabagismo/epidemiologia , Tabagismo/psicologia , Estados Unidos/epidemiologiaRESUMO
Introduction: Varenicline and bupropion are two effective smoking cessation pharmacotherapies. Researchers have hypothesized that they might be effective, in part, because they reduce cue reactivity and cue-induced cravings. Here, we used event-related potentials (ERPs) to directly measure brain responses to cigarette-related and other motivationally relevant images during a pharmacologically aided quit attempt. Methods: Smokers involved in a 12-week placebo-controlled double-blind clinical trial of smoking cessation medications (varenicline, bupropion, placebo) took part in the study. We assessed participants at two time points: 24 h (n = 140) and 4 weeks (n = 176) after the quit date. At both sessions, we measured the amplitude of the late positive potential (LPP), an ERP component reliably associated with motivational relevance, and self-reported tonic craving using the brief version of the Questionnaire of Smoking Urges (QSU-Brief). Results: At both sessions, emotional and cigarette-related images evoked significantly larger LPPs than neutral images. Neither drug type nor smoking abstinence altered this effect at either session. At both sessions, varenicline and bupropion significantly reduced self-reported tonic craving relative to the placebo condition. Conclusions: While both varenicline and bupropion reduced self-reported tonic craving, neither medication altered the amplitude of the LPP to cigarette-related or emotional pictures in smokers attempting to quit. These medications may influence abstinence by means other than by reducing neuroaffective responses to cigarette-related cues. Smokers should be prepared for the likelihood that even after several weeks of successful abstinence, once treatment ends, cigarette-related cues may remain motivationally relevant and trigger cravings that might lead to relapse. Implications: Bupropion and varenicline do not alter electrophysiological responses, as measured by the LPP, to cigarette-related and emotional images. These findings help explain why cigarette-related cues can trigger relapse when smoking cessation medication treatments end.
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Encéfalo/fisiologia , Bupropiona/uso terapêutico , Fumar Cigarros/terapia , Emoções/fisiologia , Agentes de Cessação do Hábito de Fumar/uso terapêutico , Vareniclina/uso terapêutico , Adulto , Encéfalo/efeitos dos fármacos , Bupropiona/farmacologia , Fumar Cigarros/fisiopatologia , Fumar Cigarros/psicologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa/métodos , Fumantes/psicologia , Abandono do Hábito de Fumar/métodos , Agentes de Cessação do Hábito de Fumar/farmacologia , Resultado do Tratamento , Vareniclina/farmacologiaRESUMO
Neurobiological models of addiction posit that drug use can alter reward processes in two ways: (1) by increasing the motivational relevance of drugs and drug-related cues and (2) by reducing the motivational relevance of non-drug-related rewards. Here, we discuss the results from a series of neuroimaging studies in which we assessed the extent to which these hypotheses apply to nicotine dependence. In these studies, we recorded smokers' and nonsmokers' brain responses to a wide array of motivationally relevant visual stimuli that included pleasant, unpleasant, cigarette-related, and neutral images. Based on these findings, we highlight the flaws of the traditional cue reactivity paradigm and we conclude that responses to non-drug-related motivationally relevant stimuli should be used to appropriately gauge the motivational relevance of cigarette-related cues and to identify smokers attributing higher motivational relevance to drug-related cues than to non-drug-related rewards. Identifying these individuals is clinically relevant as they achieve lower rates of long-term smoking abstinence when attempting to quit. Finally, we show how this approach may be extended beyond nicotine dependence to inform theoretical and clinical research in the study of obesity. Implications: The cue reactivity paradigm (ie, comparing responses evoked by drug-related cues to those evoked by neutral cues) cannot provide conclusive information about the motivational relevance of drug-related cues. Responses to non-drug-related motivationally relevant stimuli should be used to appropriately gauge the level of motivational relevance that substance-dependent individuals attribute to drug-related cues.
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Encéfalo , Sinais (Psicologia) , Motivação , Recompensa , Tabagismo , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Humanos , NeuroimagemRESUMO
Sleep deprivation has been shown recently to alter emotional processing possibly associated with reduced frontal regulation. Such impairments can ultimately fail adaptive attempts to regulate emotional processing (also known as cognitive control of emotion), although this hypothesis has not been examined directly. Therefore, we explored the influence of sleep deprivation on the human brain using two different cognitive-emotional tasks, recorded using fMRI and EEG. Both tasks involved irrelevant emotional and neutral distractors presented during a competing cognitive challenge, thus creating a continuous demand for regulating emotional processing. Results reveal that, although participants showed enhanced limbic and electrophysiological reactions to emotional distractors regardless of their sleep state, they were specifically unable to ignore neutral distracting information after sleep deprivation. As a consequence, sleep deprivation resulted in similar processing of neutral and negative distractors, thus disabling accurate emotional discrimination. As expected, these findings were further associated with a decrease in prefrontal connectivity patterns in both EEG and fMRI signals, reflecting a profound decline in cognitive control of emotion. Notably, such a decline was associated with lower REM sleep amounts, supporting a role for REM sleep in overnight emotional processing. Altogether, our findings suggest that losing sleep alters emotional reactivity by lowering the threshold for emotional activation, leading to a maladaptive loss of emotional neutrality. Significance statement: Sleep loss is known as a robust modulator of emotional reactivity, leading to increased anxiety and stress elicited by seemingly minor triggers. In this work, we aimed to portray the neural basis of these emotional impairments and their possible association with frontal regulation of emotional processing, also known as cognitive control of emotion. Using specifically suited EEG and fMRI tasks, we were able to show that sleep deprivation alters emotional reactivity by triggering enhanced processing of stimuli regarded previously as neutral. These changes were further accompanied by diminished frontal connectivity, reduced REM sleep, and poorer performance. Therefore, we suggest that sleep loss alters emotional reactivity by lowering the threshold for emotional activation, leading to a maladaptive loss of emotional neutrality.
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Mapeamento Encefálico , Encéfalo/fisiopatologia , Potenciais Evocados Visuais/fisiologia , Transtornos do Humor/etiologia , Transtornos do Humor/patologia , Privação do Sono/complicações , Adulto , Análise de Variância , Encéfalo/irrigação sanguínea , Eletroencefalografia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Oxigênio/sangue , Estimulação Luminosa , Tempo de Reação , Adulto JovemRESUMO
Emotionally arousing cues automatically attract attentional resources, which may be at the cost of processing task-related information. Of central importance is how the visual system resolves competition for processing resources among stimuli differing in motivational salience. Here, we assessed the extent and time-course of competition between emotionally arousing distractors and task-related stimuli in a frequency-tagging paradigm. Steady-state visual evoked potentials (ssVEPs) were evoked using random-dot kinematograms that consisted of rapidly flickering (8.57 Hz) dots, superimposed upon emotional or neutral distractor pictures flickering at 12 Hz. The time-varying amplitude of the ssVEP evoked by the motion detection task showed a significant reduction to the task-relevant stream while emotionally arousing pictures were presented as distractors. Competition between emotionally arousing pictures and moving dots began 450 ms after picture onset and persisted for an additional 2600 ms. Competitive effects of the overlapping task and picture stream revealed cost effects for the motion detection task when unpleasant pictures were presented as distractors between 450 and 1650 ms after picture onset, where an increase in ssVEP amplitude to the flickering picture stimulus was at the cost of ssVEP amplitude to the flickering dot stimulus. Cost effects were generalized to all emotionally arousing contents between 1850 and 3050 ms after picture onset, where the greatest amount of competition was evident for conditions in which emotionally arousing pictures, compared to neutral, served as distractors. In sum, the processing capacity of the visual system as measured by ssVEPs is limited, resulting in prioritized processing of emotionally relevant cues.
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Atenção , Emoções , Potenciais Evocados Visuais , Desempenho Psicomotor , Córtex Visual/fisiologia , Adolescente , Adulto , Sinais (Psicologia) , Feminino , Humanos , Tempo de ReaçãoRESUMO
Prader-Willi Syndrome (PWS) is characterized by hyperphagia, an extreme and persistent hunger that emerges in early childhood. We used event-related potentials (ERPs) to objectively investigate brain responses to low- and high-calorie foods, animals, and household objects in 20 satiated adolescents with PWS. Late Positive Potential (LPP) responses to food images did not differ from non-food images. Rather, we observed larger ERPs to high-calorie foods relative to animal images (p=.001) in an earlier time window. These responses correlated with greater severity of hyperphagia (p = .01). Thus, hyperphagia associated with PWS may be due to altered satiety regulation rather than increased motivational salience.
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Síndrome de Prader-Willi , Pré-Escolar , Animais , Humanos , Adolescente , Síndrome de Prader-Willi/complicações , Sinais (Psicologia) , Hiperfagia , Encéfalo , RecompensaRESUMO
Continuing to eat even when full leads to excessive calorie consumption and obesity. Thus, understanding brain responses to food cues when satiated has important implications for weight control interventions. We used the late positive potential (LPP, a component of the event-related potentials (ERP) indexing motivational relevance) to determine the extent to which satiety affects brain responses to images of highly palatable foods (high-fat, high-sugar), high and low motivationally relevant (pleasant, unpleasant) and neutral stimuli in a sample of obese (body mass index [BMI] ≥ 30 kg/m2) and lean (BMI < 25 kg/m2) individuals. Satiated individuals (N = 55, 21 with BMI ≥ 30 kg/m2) were fed a nutritional drink prior to the experimental session and were individually matched with 55 unsatiated individuals who saw the same images during a passive viewing task. Satiety did not affect LPP response to food-related or motivationally relevant cues in either BMI < 25 kg/m2 or BMI ≥ 30 kg/m2 individuals (p = .6). Irrespective of satiety, all participants showed larger LPPs as a function of the images' motivational relevance. There were no differences in LPP amplitude between BMI < 25 kg/m2 and BMI ≥ 30 kg/m2 individuals for any picture category, including food. However, within-group comparisons showed that BMI < 25 kg/m2 individuals had larger LPPs to low motivationally relevant pleasant images than to food-related cues (p < .001); this difference was not significant for BMI ≥ 30 kg/m2 individuals. Although satiety does not affect LPP responses to food-related cues, these results highlight the importance of evaluating reactivity to food-related cues in relation to other motivationally relevant stimuli. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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Sinais (Psicologia) , Emoções , Potenciais Evocados , Alimentos , Humanos , MotivaçãoRESUMO
While some individuals can defy the lure of temptation, many others find appetizing food irresistible. The goal of this study was to investigate the neuropsychological mechanisms that increase individuals' vulnerability to cue-induced eating. Using ERPs, a direct measure of brain activity, we showed that individuals with larger late positive potentials in response to food-related cues than to erotic images are more susceptible to cue-induced eating and, in the presence of a palatable food option, eat more than twice as much as individuals with the opposite brain reactivity profile. By highlighting the presence of individual brain reactivity profiles associated with susceptibility to cue-induced eating, these findings contribute to the understanding of the neurobiological basis of vulnerability to obesity.
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Sinais (Psicologia) , Literatura Erótica , Potenciais Evocados/fisiologia , Comportamento Alimentar/fisiologia , Alimentos , Sobrepeso/fisiopatologia , Adulto , Idoso , Suscetibilidade a Doenças , Eletroencefalografia , Endofenótipos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Adulto JovemRESUMO
When trying to quit, women are less likely than men to achieve long-term smoking abstinence. Identifying the neuropsychological mechanisms underlying women's higher relapse vulnerability will help clinicians to develop effective tailored smoking cessation interventions. Here we used event-related potentials (ERPs), a direct measure of brain activity, to evaluate the extent to which neurophysiological responses to cigarette-related and other emotional stimuli differ between female and male smokers. Both women and men showed similar patterns of brain reactivity across all picture categories; pleasant and unpleasant images prompted larger Late Positive Potentials (LPPs, a robust measure of motivational relevance) than neutral images in both groups, and cigarette-related images prompted lower LPPs than high arousing emotional images in both groups. Unlike previous studies, there were no differences between male and female smokers with regard to LPP responses to cigarette-related images. This suggests that the LPP may not be ideally suited to discriminate neurophysiological gender differences or that there are simply no gender differences in the neurophysiological responses to cigarette-related stimuli. We collected ERPs from 222 non-nicotine-deprived smokers (101 women) while they watched a slideshow that included high and low emotionally arousing pleasant and unpleasant pictures, cigarette-related, and neutral pictures. We used the mean amplitude of the LPP to assess the affective significance that participants attributed to these pictures.
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Emoções/fisiologia , Potenciais Evocados/fisiologia , Imageamento Tridimensional , Caracteres Sexuais , Fumantes , Produtos do Tabaco , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
BACKGROUND: While the notion that smokers reliably show higher reactivity to cigarette-related versus neutral cues is both theoretically and empirically supported, it is unclear why never-smokers also show enhanced brain responses to cigarette-related cues. METHODS: Using a repetitive picture viewing paradigm, in which responses evoked by affective cues are more resistant to habituation, we assessed the effects of stimulus repetition on event-related potentials (ERPs) evoked by pleasant, unpleasant, cigarette-related, and neutral images in 34 smokers (SMO) and 34 never-smokers (NEV). We examined the early posterior negativity (EPN) and the late positive potential (LPP), two ERP components which are sensitive to a picture's motivational qualities. RESULTS: Before stimulus repetition, pleasant, unpleasant, and cigarette-related cues produced greater EPN and LPP amplitudes than neutral cues in all subjects. During stimulus repetition, both components were similarly modulated by emotional arousal, such that pleasant, unpleasant, and cigarette-related cues evoked greater EPN and LPP amplitude, relative to neutral. Smoking status did not modulate these effects. While there were no group differences in self-reported stimulus ratings of valence for pleasant, unpleasant, or neutral stimuli, NEV rated cigarette-related cues as unpleasant. We observed a moderate, negative correlation between LPP amplitude and self-reported valence ratings of cigarette-related cues among NEV. CONCLUSIONS: These data suggest that cigarette-related cues capture attentional resources of both SMO and NEV, but for different reasons. For SMO, cigarette-related cues have acquired motivational significance through repeated associations with nicotine delivery, whereas for NEV, cigarette-related cues are perceived as unpleasant.
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Atenção/fisiologia , Sinais (Psicologia) , Potenciais Evocados/fisiologia , Fumantes/psicologia , Fumar/psicologia , Produtos do Tabaco , Adulto , Nível de Alerta/fisiologia , Encéfalo/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Through Pavlovian conditioning, reward-associated neutral stimuli can acquire incentive salience and motivate complex behaviors. In smokers, cigarette-associated cues may induce cravings and trigger smoking. Understanding the brain mechanisms underlying conditioned responses to cigarette-associated relative to other inherently pleasant stimuli might contribute to the development of more effective smoking cessation treatments that emphasize the rehabilitation of reward circuitry. Here we measured brain responses to geometric patterns (the conditioned stimuli, CSs) predicting cigarette-related, intrinsically pleasant and neutral images (the unconditioned stimuli, USs) using event-related potentials (ERPs) in 29 never-smokers, 20 nicotine-deprived smokers, and 19 non-deprived smokers. Results showed that during US presentation, cigarette-related and pleasant images prompted higher cortical positivity than neutral images over centro-parietal sensors between 400 and 800ms post-US onset (late positive potential, LPP). The LPP evoked by pleasant images was significantly larger than the LPP evoked by cigarette images. During CS presentation, ERPs evoked by geometric patterns predicting pleasant and cigarette-related images had significantly larger amplitude than ERPs evoked by CSs predicting neutral images. These effects were maximal over right parietal sites between 220 and 240ms post-CS onset and over occipital and frontal sites between 308 and 344ms post-CS onset. Smoking status did not modulate these effects. Our results show that stimuli with no intrinsic reward value (e.g., geometric patterns) may acquire rewarding properties through repeated pairings with established reward cues (i.e., cigarette-related, intrinsically pleasant).
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Córtex Cerebral/fisiologia , Condicionamento Psicológico/fisiologia , Sinais (Psicologia) , Estimulação Luminosa/métodos , Fumar/psicologia , Produtos do Tabaco , Adulto , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , AutorrelatoRESUMO
Background: Official guideline "indications and methods of hysterectomy" to assign indications for the different methods published and coordinated by the German Society of Gynecology and Obstetrics (DGGG), the Austrian Society of Gynecology and Obstetrics (OEGGG) and the Swiss Society of Gynecology and Obstetrics (SGGG). Besides vaginal and abdominal hysterectomy, three additional techniques have been implemented due to the introduction of laparoscopy. Organ-sparing alternatives were also integrated. Methods: The guideline group consisted of 26 experts from Germany, Austria and Switzerland. Recommendations were developed using a structured consensus process and independent moderation. A systematic literature search and quality appraisal of benefits and harms of the therapeutic alternatives for symptomatic fibroids, dysfunctional bleeding and adenomyosis was done through MEDLINE up to 6/2014 focusing on systematic reviews and meta-analysis. Results: All types of hysterectomy led in studies to high rates of patient satisfaction. If possible, vaginal instead of abdominal hysterectomy should preferably be done. If a vaginal hysterectomy is not feasible, the possibility of a laparoscopic hysterectomy should be considered. An abdominal hysterectomy should only be done with a special indication. Organ-sparing interventions also led to high patient satisfaction rates, but contain the risk of symptom recurrence. Conclusion: As an aim, patients should be enabled to choose that therapeutic intervention for their benign disease of the uterus that convenes best to them and their personal life situation.
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Neurobiological models of obesity postulate that obese individuals have difficulty regulating food intake partly because they attribute excessive salience to stimuli signaling food availability. Typically, human studies that investigate the relationship between brain responses to food-related stimuli and obesity present food cues without subsequent delivery of food. However, in order to identify the brain correlates of cue reactivity, we must record brain responses to food-related cues signaling food availability. Therefore, we have developed a dispensing apparatus for use in a cued-food delivery task in which event-related potentials (ERPs) to food-related images predicting food delivery and images not predicting food delivery can be recorded. Here, we describe a method where:â¢The experimental apparatus dispenses an edible item (i.e., a chocolate candy) which may or may not be eaten, or a non-edible control item (e.g., a plastic bead).â¢Deposit boxes are available to store uneaten candies and the non-edible control items.â¢The dispensing mechanism is capable of recording the exact timestamp when each delivery event occurs (e.g., release from the dispenser, arrival in the receptacle, storage in the deposit box).
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The objective of this paper is a valuation of colposcopy as a screening tool. As database, 392 patients with histologically confirmed intraepithelial neoplasia were used. Colposcopic and cytologic findings were compared with the final histologic diagnosis. The following results were obtained: (1)The colposcopic findings correlated with the histologic diagnosis to a significantly higher degree than the cytologic findings. Depending upon the rate of dysplasia, the colposcopic findings predicted the diagnosis in 84-97%. (2) The false-negative rate of cytology in condylomatous lesions and mild dysplasia was high (39 and 26%, respectively), in particular in comparison with the false-negative rate of colposcopy of 5% for both lesions. Thus, a negative smear does not exclude consistently a dysplasia of the cervix. (3) The false-negative rate of cytology for the high grade lesions (CIN II and CIN III) was 13 and 1% respectively and, thus, lower than in the low grade lesions. There were, however, considerable discrepancies in comparison with the histologic rating of the lesion. In CIN III cytology correlated with histology in only 61%, colposcopy, however, 85% (P < 0.001). Our results demonstrate that colposcopy is an excellent tool for detecting HPV caused lesions especially subclinical lesions and CIN I. Colposcopy is also a corrective for the false-negative cyto-smear rate (about 20-40%). Thus, colposcopy may be used as an effective quality assurance method and an excellent screening method in that colposcopy is superior in grading dysplastic lesions of the cervix. The application of the European terminology was advantageous.
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Colposcopia , Programas de Rastreamento/métodos , Displasia do Colo do Útero/diagnóstico , Feminino , Humanos , Papillomaviridae , Infecções por Papillomavirus/diagnóstico , Infecções Tumorais por Vírus/diagnóstico , Esfregaço Vaginal , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaAssuntos
Transtornos Mentais/epidemiologia , Adolescente , Feminino , Humanos , Irlanda , Masculino , Transtornos Mentais/genéticaRESUMO
AIMS: The oncogenic potential of the high-risk human papillomavirus (HR-HPV) genotypes depends on the expression of the viral oncogenes E6 and E7. Thus, the detection of these transcripts could serve as a factor in the evaluation of a woman's risk of development of cervical intraepithelial neoplasia (CIN). METHODS: A nested RT-PCR assay for the detection of E6/E7 oncogene transcripts of all known HR-HPV genotypes was established. Cervical scrapes of 779 HR-HPV-DNA-positive women exhibiting all grades of CIN were examined. RESULTS: Spliced E6/E7 oncogene transcripts of all the HR-HPVs were detected in numerous samples. In 459 cases with agreement between the cytologic and histologic findings, the prevalence increased with lesion severity: CIN 0, 18%; CIN I, 58%; CIN II, 77%; CIN III, 84%. While sensitivity and negative predictive value of HR-HPV DNA-positivity for the detection of a CIN lesion were significantly (p < 0.0001) higher than those of E6/E7 mRNA positivity (90.3% vs. 65.5% and 93% vs. 83.1%), the opposite was true for the specificity and positive predictive value (72.8 % vs. 95.2%) and 65.1% vs. 88.5%, p < 0.0001). Preliminary follow-up data in 120 initially HPV-16 DNA-positive women revealed the development, persistence or progression of a CIN lesion in 33% (8/24) of HR-HPV DNA-positive and E6/E7 mRNA-negative women, compared to 93% (66/71, p < 0.0001) in women in whom transcriptional activity of the E6/E7 oncogenes was detectable. CONCLUSIONS: Besides the identification of HPV DNA, the detection of HR-HPV E6/E7 oncogene transcripts may serve as a valuable tool in increasing the specificity of HPV testing.
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Carcinoma in Situ/genética , Carcinoma/genética , Proteínas Oncogênicas Virais/análise , Papillomaviridae/genética , Proteínas E7 de Papillomavirus/análise , Transcrição Gênica , Neoplasias do Colo do Útero/genética , Carcinoma/epidemiologia , Carcinoma/virologia , Carcinoma in Situ/virologia , Feminino , Humanos , Proteínas Oncogênicas Virais/genética , Papillomaviridae/isolamento & purificação , Proteínas E7 de Papillomavirus/genética , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologiaRESUMO
In order to evaluate the cervical flora in patients with histologically confirmed cervical intraepithelial neoplasia (grades I to III) the microbiologic results of 216 patients with CIN were compared with those of 100 symptom free controls. Gardnerella vaginalis combined with Mykoplasma spp. and Bacteroides spp. were found in 22% of the patients with dysplasia and in 5% of the control group. The difference was significant (p < 0.004). Microorganisms causing sexually transmitted diseases like Neisseria gonoroheae and Trichomonas vaginalis were not found. Chlamydia trachomatis was detected in 5% of all CIN groups. Comparing patients with CIN I, CIN II and CIN III, we did not notice any difference in their bacterial flora, wet smear or smell test. However the results of this study indicate that women with cervical dysplasia may have a higher prevalence of an altered cervical flora in comparison to controls.