Managing atypical squamous cells of undetermined significance (ASCUS): human papillomavirus testing, ASCUS subtyping,or follow-up cytology?

OBJECTIVE: This study related morphologic subtype, human papillomavirus status, and a second cytologic examination to the follow-up biopsy-proven high-grade squamous intraepithelial lesion (HSIL; grade II or III cervical intraepithelial neoplasia) after a cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS). STUDY DESIGN: Seven hundred four liquid-based cervical cytology specimens were classified as normal, "ASCUS, favor reactive" (AFR), "ASCUS, not otherwise specified," "ASCUS, favor low-grade squamous intraepithelial lesion," "ASCUS, favor HSIL" (AFHS), low-grade squamous intraepithelial lesion, and HSIL. Human papillomavirus typing used polymerase chain reaction-restriction fragment length polymorphism analysis. A longitudinal review of the cytologic and histologic records of ASCUS cases with > or =1 follow-up test or biopsy ascertained the frequency of a follow-up diagnosis of biopsy-proven HSIL (grade II or III cervical intraepithelial neoplasia). RESULTS: Three hundred eighty-six cases (208 ASCUS, 68 normal, 86 with low-grade squamous intraepithelial lesions, and 24 with HSIL) were evaluated. High-risk human papillomavirus (HRHPV positive) was lowest with normal cytology (13%), highest with HSIL (71%), and was present in 29.8% of ASCUS cases, ranging from 22.2% (AFR) to 75% (AFHS). Most ASCUS tests (64%) were followed by a negative cytologic or histologic examination. Overall, 3.8% and 11% of ASCUS and HRHPV-positive ASCUS had histologic outcomes of HSIL. AFHS had the highest (25%) and AFR had the lowest (1.1%) proportion of HSIL outcomes. Sensitivity, specificity, and positive predictive values of human papillomavirus testing for biopsy-proven HSIL were 87.5%, 72.5%, and 11.3%, respectively. CONCLUSION: HSIL and AFHS are distinguished by the highest frequency of HRHPV types and higher rates of HSIL outcome. The remaining categories of ASCUS are heterogeneous with respect to human papillomavirus type and HSIL risk, and the value of subclassification of these entities is dependent on the practice. A human papillomavirus detection system based on polymerase chain reaction-restriction fragment length polymorphism identifies a smaller percentage of high-risk human papillomaviruses than mixed probe-based methods, probably because of the more precise exclusion of cross-reacting low-risk human papillomavirus. Negative HRHPV findings by either system show a markedly reduced risk of an HSIL outcome. However, the relative advantage of human papillomavirus testing over follow-up cytology will be influenced by the frequency of negative follow-up cytologic examination and sensitivity of liquid-based preparations in a given practice.     

New test to assess pilot's vision following refractive surgery

BACKGROUND: All forms of corneal refractive surgery can sometimes cause an increase in optical aberrations and scattered light, which can affect visual performance. The purpose of this study was to develop a suitable test that was sensitive to retinal image degradation in subjects who have undergone excimer laser refractive surgery and that was also relevant to visual demands in commercial aviation. METHODS: Assessment of the visual environment and the tasks involved in piloting a commercial aircraft formed the basis for the selection of the test parameters. The new contrast acuity assessment (CAA) test covers a functional visual field of +/-5 degrees and is based on minimum spatial vision requirements for commercial pilots. RESULTS: Data measured in 100 normal subjects were used to define the 'standard normal observer' and the range of variation for the parameters of the test. This approach makes it possible to quickly establish whether a given subject's performance falls within the range of the standard normal observer. The test is also administered under low ambient illumination since flying at night involves mesopic levels of light adaptation when the pupil size is large and the effects of aberrations and scattered light are therefore more pronounced. CONCLUSION: The results of the test are simple to interpret and reveal visual performance that falls outside the normal range as a result of either significant degradation of retinal image quality (caused by increased aberrations and scattered light) or abnormal processing of visual information in the retina and/or the visual pathway.     

Prevalence and predictors of chronic lower genital tract discomfort

OBJECTIVE: We sought to determine the prevalence of chronic lower genital tract discomfort in the general population and to identify demographic and reproductive characteristics associated with this disorder. STUDY DESIGN: We surveyed a random sample of 480 women (age range, 20 to 59 years; 60 women for each 5-year age category) from 1 Boston area suburban community. Participants were asked to complete a 1-page self-administered optically scannable questionnaire that pertained to current and previous genital tract discomfort. RESULTS: After 2 mailings and 1 telephone follow-up, as well as the elimination of 42 ineligible women, 303 (70%) questionnaires were returned. Fifty-six women (18.5%) reported a history of lower genital tract discomfort that persisted for >3 months. Approximately 12% reported a history of chronic knife-like or excessive pain on contact to the genital area, whereas 6.6% experienced persistent lower genital tract itching or burning. Women who reported their age at menarche to be 相似文献   

Radiolabeled Sentinel Node Biopsy: Collaborative Trial with the National Cancer Institute

The objective of this study was to maximize the success rate of sentinel node (SN) localization in breast cancer patients with the tracer that demonstrated the highest initial success during a preliminary evaluation. Altogether, 145 patients with operable invasive breast cancer and clinically negative lymph nodes were studied. Technetium 99m (99mTc)-sulfur colloid was injected into the breast parenchyma surrounding the invasive cancer or the biopsy cavity. Variable volumes of tracer, amounts of 99mTc, and duration of time between injection and surgery were evaluated. A hand-held gamma detector was used at surgery to locate and guide resection of all radioactive sentinel nodes (SNs), including those that were extraaxillary. A conventional lymphadenectomy was then performed in all cases. Based on previous studies, unfiltered sulfur colloid provided a higher success rate of SN identification than the other tracer types. Further evaluation with 99mTc-sulfur colloid demonstrated that increased volume increased the success rate of SN identification. An injection volume of 8 ml resulted in a success rate of 98%. SNs were not exclusively located in the axilla: In 8.6% of cases SNs were removed from an internal mammary location. The overall accuracy of patients with SNs resected was 98.4%, and the false-negative rate was 4.4%. It was concluded that (1) unfiltered 99mTc-sulfur colloid at a volume of 8 ml resulted in a high success rate for SN identification; (2) a significant number of the SNs were extraaxillary in location; and (3) the accuracy of the SNs for determining whether regional metastases had occurred was high. The U.S. National Cancer Institute is funding a randomized phase III clinical trial to evaluate SN resection compared to conventional axillary lymphadenectomy in clinical node-negative breast cancer patients. Major endpoints of this trial include long-term regional control and survival.     

Menstrual and reproductive factors in relation to ovarian cancer risk

We assessed menstrual and reproductive factors in relation to ovarian cancer risk in a large, population-based, case-control study. 563 cases in Massachusetts and New Hampshire were ascertained from hospitals and statewide tumour registries; control women (n = 523) were selected through random digit dialing and matched to case women by age and telephone sampling unit. We used multivariate logistic regression to evaluate factors in relation to risk of ovarian cancer and the major tumour histologic subtypes. Ovarian cancer risk was reduced among parous women, relative to nulliparous women (OR = 0.4; 95% CI = 0.3-0.6). Among parous women, higher parity (P = 0.0006), increased age at first (P = 0.03) or last (P = 0.05) birth, and time since last birth (P = 0.04) were associated with reduced risk. Early pregnancy losses, abortions, and stillbirths were unrelated to risk, but preterm, term, and twin births were protective. Risk was lower among women who had breast-fed, relative to those who had not (OR = 0.7; 95% CI = 0.5-1.0), but the average duration of breast-feeding per child was unrelated to risk (P for trend = 0.21). Age at menarche and age at menopause were unrelated to risk overall, although increasing menarcheal age was protective among premenopausal women (P = 0.02). Menstrual cycle characteristics and symptoms were generally unrelated to risk, although cycle-related insomnia was associated with decreased risk (OR = 0.5; 95% CI = 0.3-0.8). We found no association between the type of sanitary product used during menstruation and ovarian cancer risk. In analyses by histologic subtype, reproductive and menstrual factors had most effect on risk of endometrioid/clear cell tumours, and least influential with regard to risk of mucinous tumours. Overall, our findings offer some support to current hypotheses of ovarian pathogenesis, and show aetiologic differences among the tumour subtypes.     

Expected contribution to serum oestradiol from individual ovarian follicles in unstimulated cycles

Data relating serum oestradiol concentration to follicle size in unstimulated cycles are lacking. We provide precise data on serum concentrations expected for any follicle diameter (FD) in the mid- to late follicular phase. Infertile women (n = 35) with apparently normal ovulatory cycles were studied in detail in 128 unstimulated monofollicular cycles leading to IVF. Using mathematical modelling to account for repeated cycles in the same woman, the relationship between serum oestradiol and FD was explored and reference ranges for serum oestradiol at individual FD were calculated. Serum oestradiol concentrations [number of patients, geometric mean, 95% confidence interval (CI)] at the onset of the LH surge were higher in 'fertilized' cycles (73, 1279, 1180-1378 pmol/l) compared with 'unfertilized' cycles (31, 1055, 929-1197 pmol/l, P: = 0.008) and 'no oocyte' cycles (24, 1064, 922-1227 pmol/l, P: = 0.03) respectively. In 'fertilized' cycles, oestradiol concentrations rose exponentially with FD and for each size of follicle the oestradiol distribution was skewed. Functional oocyte competence varied in apparently normal ovulatory cycles and was correlated with pre-ovulatory serum oestradiol but not FD. Serum oestradiol varies within wide limits for maturing follicles of any given diameter prior to the onset of the LH surge.     

Factors associated with early menopause

OBJECTIVE: An understanding of why certain factors contribute to a more rapid decline in ovarian function may, for some women, help prevent premature loss of fecundity and the subsequent impact of health problems secondary to long-term estrogen deficiency such as osteoporosis, cardiovascular disease, and possibly Alzheimer's disease. METHODS: A summary of the evidence regarding factors that have been proposed to contribute to an early onset of natural menopause is presented. These factors include cigarette smoking, race, education, parity, menstrual cycle length, the use of oral contraceptives, age at menarche, major depression, anthropometry, and handedness. RESULTS: Cigarette smoking has been found to hasten the onset of menopause by as much as one year. Lifetime number of ovulatory cycles (indicative of oocyte depletion) is also predictive of the age at natural menopause (ANP). This is consistent with the many studies that have reported early ANP among women with shorter menstrual cycles, and a later ANP among multigravid women or those who used oral contraceptives. The relationship between depressive disorder and ovarian failure is complex, involving consideration of the pharmacological effects of treatment, and is currently unclear. The findings regarding an effect of body mass index on ANP are also mixed. At this time, there is little persuasive evidence that handedness or demographic characteristics (independent of their relationship with behavioral factors like smoking) influence the ANP to any substantial degree. CONCLUSIONS: Some factors that could potentially influence ANP have been identified, but these and other avenues of investigation warrant further study.     

Relationship between midcycle luteinizing hormone surge quality and oocyte fertilization

OBJECTIVE: To determine whether alterations in preovulatory follicular fluid (FF) levels of LH, FSH, and steroids are associated with the probability of fertilization. DESIGN: Retrospective analysis of prospective study results. SETTING: Reproductive medicine clinic of a university teaching hospital. PATIENT(S): Infertile women, with unstimulated, apparently regular cycles in an IVF research program. INTERVENTION(S): Measurement of preovulatory FF levels of LH, FSH, E2, and P and serum LH levels by fluoroimmunometry. MAIN OUTCOME MEASURE: Oocyte fertilization. RESULT(S): There were 84 transferable embryos (rate of normal fertilization and cleavage, 67%), and 41 oocytes (33%) failed to fertilize. Analysis of the matched FF showed that the median concentration of FF LH was significantly higher for cleaving embryos than for unfertilized oocytes (14.6 vs. 10.4 IU/L). Serum LH concentrations were similarly higher in cycles with cleaving embryos. There were no statistically significant differences in FF concentrations of FSH, E2, or P in the two groups. CONCLUSION: Reduced preovulatory FF LH levels are associated with impaired fertilization of oocytes in vitro, despite normal FF FSH and steroid levels.