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Biomedical subjects

A Ferenczy

Publications and source records attributed to A Ferenczy.

At least 19 recordsLinked to original sources

Continuous combined hormone replacement therapy with 1 mg 17beta-oestradiol and 5 mg dydrogesterone (Femoston-conti): endometrial safety and bleeding profile.

OBJECTIVES: The aim of the study was to confirm the endometrial safety and describe the bleeding profile of continuous combined 1 mg 17beta-oestradiol and 5 mg dydrogesterone in post-menopausal women. METHODS: An open, multicentre study was carried out in 290 healthy, non-hysterectomised post-menopausal women receiving oral continuous combined 1 mg 17beta-oestradiol and 5 mg dydrogesterone (Femoston-conti) for 1 year. Aspiration endometrial biopsies were performed at baseline and at the end of the study; those classified as hyperplasia or malignancy were considered treatment failures. RESULTS: Only one woman developed simple hyperplasia without atypia at the end of the study; the treatment failure rate was therefore 0.4%. Cross-sectional analysis showed that the percentage of women without bleeding increased from 71% during the first cycle to around 80% by the end of the study. Approximately 50% of the bleeding episodes occurred in the form of spotting; severe bleeding was rare and only seven women withdrew prematurely from the study due to uterine bleeding. Overall, 41% of the women were amenorrhoeic throughout the study. CONCLUSIONS: Continuous combined 1 mg 17beta-oestradiol and 5 mg dydrogesterone provides excellent endometrial safety and is associated with an acceptable bleeding profile.

Aged↗

Endometrial safety and bleeding patterns during a 2-year study of 1 or 2 mg 17 beta-estradiol combined with sequential 5-20 mg dydrogesterone.

OBJECTIVE: To assess the endometrial safety and bleeding patterns of 17 beta-estradiol sequentially combined with dydrogesterone. METHODS: Endometrial safety and bleeding patterns were assessed in 579 postmenopausal women randomized to oral treatment with placebo, 1 mg/day 17 beta-estradiol sequentially combined with 5 or 10 mg/day dydrogesterone for the last 14 days of each 28-day cycle, or 2 mg/day 17 beta-estradiol sequentially combined with 10 or 20 mg/day dydrogesterone for the last 14 days of each 28-day cycle. Treatment was continued for 26 cycles. Proliferative endometrium, endometrial hyperplasia and endometrial malignancy in the end-of-study biopsy were considered as inadequate progestational responses. RESULTS: Biopsies were not available in 137 women mainly because of an insufficient treatment period or non-compliance. An adequate progestational response was seen in more than 98% of the 442 women who underwent biopsy after treatment. Bleeding data were not available in 193 women, most of whom did not remain on treatment for the full 26 cycles. The 1-mg 17 beta-estradiol dose was associated with less cyclic and intermittent bleeding than the 2-mg dose. Higher doses of dydrogesterone were associated with a higher incidence of cyclic bleeds and a later day of onset, while duration, severity and regularity were similar in all groups irrespective of estradiol or dydrogesterone dose. CONCLUSION: Sequential combinations of 1 mg 17 beta-estradiol with 5 or 10 mg dydrogesterone and 2 mg 17 beta-estradiol with 10 or 20 mg dydrogesterone are associated with very good endometrial safety. The incidence of bleeding is lower with the 1-mg dose of 17 beta-estradiol.

Aged↗

Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia.

CONTEXT: Human papillomavirus (HPV) infection is believed to be the central cause of cervical cancer, although most of the epidemiological evidence has come from retrospective, case-control studies, which do not provide information on the dynamics of cumulative or persistent exposure to HPV infection. OBJECTIVE: To assess the risks of cervical neoplasia related to prior persistent HPV infections. DESIGN AND SETTING: Longitudinal study of the natural history of HPV infection and cervical neoplasia in women residing in the city of São Paulo, Brazil, which was conducted between November 1993 and March 1997 and involved repeated measurements of HPV and lesions with follow-up until June 2000. PARTICIPANTS: A total of 1611 women with no cytological lesions at enrollment and HPV test results available from the first 2 visits. MAIN OUTCOME MEASURE: Cervical specimens taken for Papanicolaou cytology and HPV testing every 4 months in the first year and twice yearly thereafter. Incident cervical cancer precursor lesions ascertained by expert review of all cytology smears. RESULTS: The incidence rate of squamous intraepithelial lesions (SILs) was 0.73 per 1000 women-months (95% confidence interval [CI], 0.5-0.9) among women free of HPV at the 2 initial visits and 8.68 (95% CI, 2.3-15.1) among women with HPV type 16 or 18 infections persisting over both visits. Relative to those negative for HPV oncogenic types at both initial visits, the relative risk (RR) of incident SIL was 10.19 (95% CI, 5.9-17.6) for persistent infections with any known oncogenic HPV types. The equivalent RR of incident high-grade SIL was 11.67 (95% CI, 4.1-33.3). The RRs of lesions were considerably higher for persistent infections with HPV type 16 or 18. CONCLUSION: A strong relationship exists between persistent HPV infections and SIL incidence, particularly for HPV types 16 and 18.

Adult↗

Cervical cancer: epidemiology, prevention and the role of human papillomavirus infection.

Organized screening has contributed to a decline in cervical cancer incidence and mortality over the past 50 years. However, women in developing countries are yet to profit extensively from the benefits of screening programs, and recent trends show a resurgence of the disease in developed countries. The past 2 decades have witnessed substantial progress in our understanding of the natural history of cervical cancer and in major treatment advances. Human papillomavirus (HPV) infection is now recognized as the main cause of cervical cancer, the role of coexisting factors is better understood, a new cytology reporting terminology has improved diagnosis and management of precursor lesions, and specific treatment protocols have increased survival among patients with early or advanced disease. Current research has focused on the determinants of infection with oncogenic HPV types, the assessment of prophylactic and therapeutic vaccines and the development of screening strategies incorporating HPV testing and other methods as adjunct to cytology. These are fundamental stepping stones for the implementation of effective public health programs aimed at the control of cervical cancer.

Canada↗

Endometrial safety of continuous combined hormone replacement therapy with 17beta-oestradiol (1 or 2 mg) and dydrogesterone.

OBJECTIVES: To determine the endometrial safety of oral 17beta-oestradiol combined continuously with dydrogesterone in preventing endometrial proliferation. METHODS: The low dose group comprised three 52-week (13 cycles of 28 days) studies (two of which were double blind) using a 17beta-oestradiol dose of 1 mg daily combined with dydrogesterone 2.5, 5, 10 or 20 mg daily. The high dose group comprised two 24-week double-blind studies using a 17beta-oestradiol dose of 2 mg daily combined with dydrogesterone 2.5, 5, 10 or 15 mg daily. Endometrial safety was verified by aspiration endometrial biopsies. Inadequate progestational response was defined as proliferative endometrium, endometrial polyp, hyperplasia and carcinoma. RESULTS: Data was evaluable from 650 healthy postmenopausal women in the low dose group and 310 in the high dose group. Endometrial protection was achieved with dydrogesterone at doses of 5 mg or higher combined with 1 or 2 mg 17beta-oestradiol. The success rate was 97%, 97% and 98% in women receiving 1/5, 1/10 and 1/20 mg, respectively, and 95%, 98% and 91% in women receiving 2/5, 2/10 and 2/15 mg, respectively. A lower success rate was achieved with the 2.5 mg dydrogesterone dosage (93% in the 1/2.5 mg group and 85% in the 2/2.5 mg group) due to more cases of proliferative endometrium. None of the women in the low dose group developed hyperplasia or carcinoma; five (0.7%) had endometrial polyps. In the high dose group, one woman given 2.5 mg dydrogesterone developed hyperplasia; there were no cases of carcinoma. CONCLUSION: 5 mg daily dydrogesterone appears to be the lowest effective dose to ensure endometrial safety in a continuous combined regimen with 1 or 2 mg 17beta-oestradiol.

Adult↗

Cervical-cancer screening beyond the year 2000.

Evidence-based studies have shown that new techniques for cervical cancer screening have a higher diagnostic yield than conventional cervical cytology (Pap test). Automated screening devices that use liquid-based, thin-layer cytology and human papillomavirus DNA testing are likely to become the standard for routine primary screening for cervical cancer and its precursors in the 21st century. The increased initial expense of the new techniques will most certainly be absorbed by instituting longer intervals for safe primary screening, in both low-risk and high-risk populations. To make modern screening programmes even more effective, we must promote extensive public awareness campaigns about cervical cancer, a preventable disease.

Cell Separation↗

Treatment of external genital warts in men using 5% imiquimod cream applied three times a week, once daily, twice daily, or three times a day.

BACKGROUND: Medical therapy for genital warts remains suboptimal. The topical interferon and cytokine inducer, imiquimod, has been proved effective for the treatment of external genital and perianal warts, but there is a substantial difference in the response rates between men and women. When 5% imiquimod cream is applied three times a week up to 16 weeks, approximately two thirds of women treated with imiquimod achieve complete clearance of genital warts, whereas only about one third of men clear completely. GOAL: This study was undertaken to determine whether more frequent application of topical imiquimod cream would improve the rate of genital wart clearance in men. STUDY DESIGN: A randomized treatment trial involving adult men with biopsy-proven genital warts was conducted at nine centers in the United States and Canada using four different application frequencies. RESULTS: Complete clearance rates during the 16-week treatment period were as follows for the different imiquimod treatment frequencies: three times a week (35 %), once daily (28 %), twice daily (24%), and three times a day (27%)(P = 0.88). The four treatment groups all showed comparable reductions in the total lesion area, with a median of more than a 90% reduction in the lesion area by the end of treatment. There was a significant increase in the incidence and severity of local skin reactions including erythema, vesicle formation, ulceration, and excoriation as the dosing frequency increased from three times a week to three times a day. CONCLUSIONS: In this study, the optimal dosage regimen was the approved three times a week regimen. More frequent application (up to three times a day) did not improve clearance and was associated with an increase in local adverse events.

Adult↗

Oncogenic human papillomavirus infection and cervical lesions in aboriginal women of Nunavut, Canada.

BACKGROUND: The high rate of cervical cancer among aboriginal women of northern Canada has prompted the search for more aggressive methods to augment Papanicolaou (Pap) screening in this population. Nearly all cervical cancers result from oncogenic human papillomavirus (HPV) infections. This has generated interest for incorporating HPV testing into the current screening program. GOALS: To determine the prevalence of oncogenic HPVs in Nunavut, and to assess the association between HPV and squamous intraepithelial lesions (SIL). STUDY DESIGN: A cross-sectional study was conducted on the Pap-screened populations in 19 communities of Nunavut, Canada. Liquid-based cytology was used to screen for SIL. HPV testing was performed using the Hybrid Capture II assay. Correlates of HPV infection and SIL were assessed by logistic regression with control for potential confounders. RESULTS: In 1290 women ages 13 to 79 years, the prevalence rate was 26% for oncogenic HPV and 6.9% for SIL. The odds ratio for the association between HPV and SIL was 37.9 (95% CI, 17.7-80.8) after multivariate adjustment. This association increased markedly with increasing viral load. More than 90% of the women with squamous intraepithelial lesions had positive test results for HPV. More than 75% of the women who had positive test results for HPV but negative test results for SIL were younger than 30 years. CONCLUSION: The results of this study form the basis for further evaluation of the role that liquid-based cytology and HPV testing plays and will contribute to the strategy for cervical cancer prevention in Nunavut.

Adolescent↗

Endometrial precancer diagnosis by histopathology, clonal analysis, and computerized morphometry.

Management of endometrial precancers is compromised by longstanding debate over the natural history of endometrial hyperplasias and inconsistencies in their diagnosis. The recent demonstration that some hyperplasias, like cancers, are phenotypically monoclonal is useful in recognizing biological precancers. A clonal analysis has been undertaken of a series of 93 endometrial tissues and their morphology has been evaluated by subjective diagnostic classification and computerized morphometric analysis. A pathologist's diagnosis of atypical endometrial hyperplasia was highly associated with monoclonal growth. Both microsatellite-stable and microsatellite-unstable precancers were classified as atypical hyperplasias, indicating overlapping morphologies for these two groups. Diagnosis of non-atypical endometrial hyperplasias was not reproducible and identified a group of lesions equally likely to be monoclonal as polyclonal. Computerized morphometry resolved these lesions into monoclonal and polyclonal subgroups with a high degree of accuracy and reproducibility. The predictive value of morphometry was dominated by that fraction of the sample which consisted of stroma (volume percentage stroma). This can be measured manually and used to predict monoclonality when below the threshold value of 55%. This study shows that morphometric analysis reproducibly and precisely identifies monoclonal endometrial precancers from histological sections. It may serve, furthermore, to classify accurately lesions judged by pathologists as indeterminate (non-atypical hyperplasias). The material from this study (available at www.endometrium.org from March 1, 2000) and precisely defined architectural diagnostic criteria provide new tools for diagnostic standardization of endometrial precancers.

Cell Lineage↗

Comparison of endocervical curettage and endocervical brushing.

OBJECTIVE: To compare endocervical brushing with endocervical curettage with respect to diagnostic yield by histology and patient discomfort. METHODS: Nonpregnant women referred for colposcopy because of abnormal Papanicolaou test results were randomized to endocervical sampling with either a metal curette (endocervical curettage [ECC]) or an endocervical brush. Extensive endocervical canal brushing was performed. All samples were submitted for histologic study. Results were evaluated against the histologic findings in electroconization specimens in a masked fashion. Pain scores were recorded using Melzack's Present Pain Intensity Scale. RESULTS: During the study period, 315 patients were randomized to the techniques: 157 to ECC and 158 to endocervical brushing. Of the 315 patients, 147 also underwent electroconization. Overall false-positive rates were 28.6% for endocervical brushing and 30.8% for ECC. False positives were due to contamination of the endocervical sample by lesional epithelium near the external os. The proportion of scanty specimens obtained by endocervical brushing (7. 6%) was higher than that obtained by ECC (2.5%) (P =.041). One sample obtained by brushing was insufficient for diagnosis; none obtained by ECC were insufficient. There were no statistically significant differences in the median pain scores between the two groups. CONCLUSION: The techniques were similar in terms of diagnostic yield and patient discomfort. Endocervical brushing had lower false-positive rates than those reported in the literature for cytologic analysis. Although ECC remains the method of choice for evaluation of the endocervical canal, brushing is an acceptable alternative.

Adult↗

Human papillomavirus testing for primary screening of cervical cancer precursors.

Our objective was to determine whether the addition of human papillomavirus (HPV) testing to screening cytology improves the detection of cervical cancer precursors. Women of ages 18-69 years underwent conventional Pap cytology and HPV DNA testing in a multicenter study in Newfoundland, Canada. Those with positive cytology and/or HPV and a random sample of those with dual negative results were referred for colposcopy. The study enrolled 2098 women. The relative sensitivity of HPV testing was significantly higher than cytology for all-grade squamous intraepithelial lesions [SILs; 73%; 95% confidence interval (CI), 62-82] and high grade SILs (HSILs; 90%; 95% CI, 74-97) but had lower relative specificity (62% for all-grade SILs and 51% for HSILs) than most cytological cutpoints. The rate of combined correct results for all-grade lesions was higher for HPV testing (68.8%) than for any cytological cutpoint (equivocal, 52.3%; LSILs, 51.6%; HSILs, 44.5%). The combination of HPV and an LSIL cutpoint had a negative predictive value of 68% (95% CI, 52-80) for all SILs and 100% (95% CI, 91-100) for HSILs, while referring for colposcopy only 12% of the women. We concluded that HPV testing in conjunction with cytology improved the screening efficacy of cytology alone and may allow for a more effective and safe primary screening program with increased screening intervals.

Adolescent↗

Overexpression of anti-apoptotic gene BAG-1 in human cervical cancer.

Apoptosis is a programmed cell death process in which cells commit suicide under certain environmental conditions. Recent studies suggest that apoptosis is controlled by a variety of cellular genes, and dysregulation of these genes plays an important role in the pathogenesis of human diseases, including cancer. BAG-1 is a novel anti-apoptotic protein isolated by its interaction with another anti-apoptotic protein, Bcl-2. It binds to several hormone receptors and growth factor receptors and modulates their function in apoptosis. However, the role of BAG-1 in the oncogenesis of human cervical cancer has yet to be illustrated. In this study, we examined the expression of BAG-1 in cervical normal and carcinoma cultured cells and tissues. BAG-1 was overexpressed in human cervical carcinoma cell lines and tissues. Overexpression was regulated at the transcriptional level. The increased expression of BAG-1 was correlated with enhanced resistance of cervical carcinoma cells to apoptosis induced by a DNA-damaging reagent. In addition, overexpression of BAG-1 enhanced the resistance of cervical cells to apoptosis. This study provided the first evidence that BAG-1 is upregulated in human cervical cancer and may play an important role in apoptosis and human cervical carcinogenesis.

Apoptosis↗

Assessing gains in diagnostic utility when human papillomavirus testing is used as an adjunct to papanicolaou smear in the triage of women with cervical cytologic abnormalities.

OBJECTIVE: We aimed to provide simple methods for calculating expected sensitivity and specificity when an adjunctive test is added to a conventional test. STUDY DESIGN: Use of adjunctive methods for the triage of women with cervical abnormalities produces an apparent gain in sensitivity over Papanicolaou cytologic testing alone. This increase in sensitivity can be misleading, even if deemed significant by results of a statistical test. Combined testing prevents a loss in specificity but sometimes offers no real gain in sensitivity. A nominal increase in sensitivity always occurs by chance whenever an adjunctive test is used in parallel with a conventional one, even if the new test is totally random with respect to the disease being evaluated. RESULTS: Gains in sensitivity and losses in specificity have to be gauged against expected levels of these parameters when a random adjunctive test is coupled with Papanicolaou screening and not gauged against the performance of cytologic testing alone. CONCLUSION: We provide simple formulas for calculating the expected sensitivity and specificity in conditions of combination testing to provide more realistic baselines for assessment of the screening efficacy contributed by the adjunctive test.

Cervix Uteri↗

Design and methods of the Ludwig-McGill longitudinal study of the natural history of human papillomavirus infection and cervical neoplasia in Brazil. Ludwig-McGill Study Group.

This article reports on a large longitudinal study, begun in 1993, of the natural history of human papillomavirus (HPV) infection and cervical neoplasia in a population of low-income women in São Paulo, Brazil, a city with one of the highest risks worldwide for cervical cancer. Known as the Ludwig-McGill cohort study, the epidemiological investigation focuses on persistent infection with oncogenic HPV types as the precursor event leading to cervical neoplasia. The objectives of this study are to: 1) study the epidemiology of persistent cervical HPV infection in asymptomatic women, 2) investigate whether persistent HPV infection increases risk of low-grade and high-grade cervical lesions, 3) search for determinants of persistent HPV infection, 4) search for molecular variants of HPV that may be associated with an increased risk of lesions, 5) investigate whether viral burden is correlated with persistent infections and with lesion risk, 6) study the antibody response to HPV as a predictor of persistence and lesion progression, and 7) examine the role of HLA typing and codon 72 p53 gene polymorphism in mediating HPV persistence and lesion severity. The study accrued 2,528 female subjects through March 1997. Subjects were followed up every 4 months in the first year, with twice-yearly return visits to take place in subsequent years. Participants undergo a questionnaire-based interview, have a cervical specimen taken for Pap cytology and HPV testing, and have a blood sample drawn for HPV antibody testing. A cervicography is performed once in the first year and every two years thereafter. In this article we describe the design and methods of the study, provide baseline cohort characteristics, and present a preliminary assessment of the prognostic value of baseline HPV status.

Adult↗

Self-administered topical 5% imiquimod cream for external anogenital warts. HPV Study Group. Human PapillomaVirus.

OBJECTIVE: To compare the safety and effectiveness of 5% and 1% imiquimod cream with vehicle cream in the treatment of external anogenital warts. DESIGN: Randomized, double-blind, placebo-controlled comparison that evaluated patients for total clearance of their warts. Patients who experienced total clearance were evaluated for recurrence in a 12-week follow-up. SETTING: Eleven ambulatory offices, including both private physician offices and referral medical centers. PATIENTS: Three hundred eleven healthy men and women aged 18 years or older with 2 to 50 external anogenital warts were recruited from the practices of investigators, referring physicians, and advertisements. Eighty-two additional patients were screened but did not qualify. Four patients discontinued use of the medication because of adverse effects. INTERVENTIONS: Five percent imiquimod (Aldara) cream, 1% imiquimod cream, or vehicle cream was applied to all external warts overnight 3 times each week for 16 weeks, or until all treated warts disappeared, whichever occurred first. MAIN OUTCOME MEASUREMENTS: The number of patients experiencing the elimination of all baseline warts and the recurrence rate of these warts. In addition, the reduction in baseline wart area the duration of therapy required to eliminate warts, and the frequency and severity of adverse reactions were principal measurements. RESULTS: In the intent-to-treat analysis, 54 (50%) of 109 patients who received 5% imiquimod cream, 21 (21%) of 102 of those who received 1% imiquimod cream, and 11 (11%) of 100 patients treated with vehicle cream experienced eradication of all treated baseline warts. The difference between the effectiveness of 5% imiquimod cream and the vehicle cream was statistically significant (P < .001). Of those patients whose warts cleared during therapy, 13% of patients who received 5% imiquimod experienced a recurrence of at least 1 wart. Recurrences occurred in none of the patients who used 1% imiquimod cream and in 10% of patients who used the vehicle cream. Local erythema was the most common adverse reaction, but the majority of patients in each group experienced no or only mild local inflammatory reactions. There were no differences in incidences of flulike symptoms among treatment groups. CONCLUSIONS: Five percent imiquimod cream is an effective and safe self-administered therapy for external anogenital warts when applied 3 times a week overnight for up to 16 weeks. The recurrence rate is low.

Adjuvants, Immunologic↗

Clinical significance of histiocytes in the detection of endometrial adenocarcinoma and hyperplasia.

The purpose of this case-control study was to determine the clinical significance of histiocytes and normal endometrial cells as cytologic markers of adenocarcinoma or hyperplasia of the endometrium. Cervical-vaginal smears obtained in 102 patients with mean age 59.7 yr with abnormal uterine bleeding and endometrial pathology, and 101 controls with mean age 56.5 yr with postmenopausal bleeding and whose cytologic smear was negative, were evaluated. Histiocytes alone failed to predict either endometrial adenocarcinoma (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.32-3.22) or hyperplasia (OR, 1.10; 95% CI, 0.37-3.30). The odds of endometrial carcinoma in symptomatic, postmenopausal women was three times greater in the presence of histiocytes with phagocytosis of acute inflammatory cells (PIC) (OR, 3.00; 95% CI, 1.16-7.70). Endometrial hyperplasia was more frequently observed when cervical smears contained normal endometrial cells (OR, 4.09; 95% CI, 1.14-14.67). Only histiocytes with PIC and normal endometrial cells carry a three- and fourfold greater likelihood of coexistent endometrial adenocarcinoma and hyperplasia, respectively. Such strong association may require endometrial biopsy or transvaginal ultrasonography to uncover lesional tissue in the endometrial cavity.

Adenocarcinoma↗

Reflex human papillomavirus deoxyribonucleic acid testing in women with abnormal Papanicolaou smears.

OBJECTIVE: The study examined interrelationships between sensitivity and specificity of "reflex human papillomavirus deoxyribonucleic acid testing" from liquid-based cervical cytologic specimens by means of receiver operator characteristics curves. STUDY DESIGN: A cohort study was performed on 265 women evaluated by colposcopy because of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion found on Papanicolaou smear. RESULTS: At a positive threshold of 0.2 pg/ml (1000 copies of human papillomavirus per test), human papillomavirus deoxyribonucleic acid testing detected 86% of women with cervical intraepithelial neoplasia and 93% of women with high-grade cervical intraepithelial neoplasia with a specificity of 30%. Decreasing the sensitivity of the human papillomavirus test to 1 pg/ml (5000 copies of human papillomavirus per test) improved the specificity of a positive result to 44% but decreased the clinical sensitivity to 78% for cervical intraepithelial neoplasia grade 2 or 3. Relationships between sensitivity and specificity were influenced by patient age and referral diagnosis. For example, limiting the analysis to only women with a referral for atypical squamous cells of undetermined significance found on Papanicolaou smear and a positive human papillomavirus test threshold of 0.5 pg/ml produced a sensitivity of 90% for cervical intraepithelial neoplasia grade 2 or 3 and a test specificity of 55%. CONCLUSION: Human papillomavirus deoxyribonucleic acid testing of residual cellular material from liquid cytologic specimens appears to be more appropriate for older women (>30 years old) and women with atypical squamous cells of undetermined significance, as opposed to low-grade squamous intraepithelial lesion, on their Papanicolaou smears.

Adolescent↗