Social selection favours offspring prone to the development of androgenetic alopecia.

In recent years, dermatologists have observed an increase in the incidence of male androgenetic alopecia (AGA). In a survey of 41 dermatologists, 88% reported an increase in incidence of AGA in men younger than 30 years. This phenomenon has no apparent explanation. However, due to the strong genetic inheritance component of AGA, a social or environmental factor which favours the inheritance of genes that increase the risk of developing AGA is suspected. To date, the strongest predictor of AGA in men has been the length of the CAG repeat located in the androgen receptor gene (AR gene) on the X chromosome. The same genetic variant in women is associated with ovulation at a later age, higher antral follicle count, and lower risk for premature ovarian failure. This led us to theorize that, due to social pressure to conceive later in life, women carriers of the short CAG repeat in the AR gene would have a selective advantage to conceive later in life and would thus favour male offspring exhibiting AGA.

Potential risk of developing herpes simplex encephalitis in patients treated with sildenafil following primary exposure to genital herpes.

Herpes simplex encephalitis (HSE) is associated with significant mortality and morbidity. As a consequence of HSE, up to 75% of infected individuals die or experience irreversible neurological damage. While the pathogenesis of the disease is unknown, it is traditionally hypothesized that the viral infection occurs by neuronal transmission directly from peripheral sites. Non-neuronal modes of infection have generally been overlooked as the brain is protected by the blood-brain-barrier (BBB). The BBB poses an effective barrier to pathogens as well as to drugs such as chemotherapies. In the pursuit to deliver chemotherapeutic agents to the brain, several studies demonstrated that phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, may increase the permeability of the BBB enabling successful delivery of chemotherapeutic agents to the brain. In this communication, we report a case of HSE infection in a 62-year-old man, which we suspect was facilitated by the use of sildenafil during a primary genital herpes simple virus (HSV) infection. Due to large number of patients treated with PDE5 inhibitors for erectile dysfunction and the high incidence of genital HSV infection in the general population, a larger study should examine the potential risk of developing HSE in patients treated with PDE5 inhibitors.

ASCCP Practice Guidelines Management Guidelines for the Follow-up of Atypical Squamous Cells of Undetermined Significance (ASCUS).

: Editor's Note: This guideline was first published in The Colposcopist in January 1996 and reflected the peer-reviewed literature available on the management of ASCUS at that time. The decision to republish this guideline in The Journal of Lower Genital Tract Disease, to accompany guidelines on the management of low-grade squamous intraepithelial lesion (LGSIL) and benign cellular changes (BCC) was made to complete the set of guidelines in the Journal pertaining to management of the cytology screening system. (See also previous guidelines on Management Issues Related to the Quality of the Smear, Management of Atypical Glandular Cells of Undetermined Significance (AGUS), and the Abnormal Pap Follow-up System.) Our original intention was to update the ASCUS guideline for this publication in the expectation that the data from the enrollment phase of the National Cancer Institute's ASCUS LGSIL Triage Study (ALTS) would be available to provide relevant evidence-based recommendations. The unavailability of this data at this time has ensured a later update of the ASCUS guideline. However, an accumulating body of new literature, particularly on the clinical utility of HPV testing with Hybrid Capture II (Digene Corp., Gaithersburg, MD), will be incorporated within the next year with the enrollment ALTS data in a new ASCUS guideline. Until that time, the guideline presented here remains the recommendation of the ASCCP, based on the review of the literature at that time, and on the collective experience and knowledge of the ASCCP Practice Committee and the Board of Directors.The cost analysis in this guideline is based upon a set of cost assumptions which will vary from setting to setting. This analysis is intended to serve as a reference for average costs in a fee-for-service setting. The individual practitioner will need to analyze cost differentials for his/her own setting.This guideline reflects emerging clinical and scientific advances as of February 1996, and is subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed.

The clinical significance of the poor correlation of cervical dysplasia and cervical malignancy with referral cytologic results.

OBJECTIVE: We prospectively studied the diagnostic utility of our Bethesda system-based cervical cytology screening program with colposcopy and biopsy as the criterion standard. STUDY DESIGN: We prospectively collected and studied the correlation of cytologic, colposcopic, and histologic data in women referred for colposcopic examination because of "nonnormal" cytologic results or other risk factors. RESULTS: We found that 771 of 5585 initial colposcopic visits yielded high-grade (cervical intraepithelial neoplasia II or worse) biopsies (13.8% prevalence); 13 showed invasive cancer (0.23% prevalence). Only 132 of 771 cases of high-grade dysplasia (17%) and 5 of 13 cases of invasive cancer (38%) followed Papanicolaou smears suggesting high-grade intraepithelial lesions or cancer, with 77% being discovered after "minor" Papanicolaou smear abnormalities. High-grade disease or cancer was confirmed in 1 of 2 high-grade or cancer Papanicolaou referrals and in 1 of 11 referrals with atypical squamous cells of undetermined significance. CONCLUSION: Papanicolaou smears, especially those that are low grade, should not be equated with histologic sampling in association with poor cytohistopathologic correlation. Most high-grade dysplasias and cancers occur in women with either minor Papanicolaou smear abnormalities or visible lower genital tract lesions or both. Colposcopy for women with any "nonnormal" screening result is feasible.

Perspectives in cervical cancer prevention and health services management.

Preventive screening, management, and treatment of patients at risk for cervical cancer reduces the incidence of cervical cancer in the United States but not without significant costs. The costs can be measured both in dollars and in "opportunity costs" (access to care for one patient affecting another patient visit) associated with providing care to an overburdened colposcopy infrastructure. To provide colposcopic services, sometimes access to other needed care may be neglected in clinical practices that are already overburdened by high demand and limited access to care. Colposcopy services in the fee-for-service, managed-care, health maintenance organizations, and academic health service delivery settings are delivered not solely on the basis of quality (expertise and technological advances) of care. Delivery of colposcopy services should be balanced by economic and service-related issues as well. This study aids clinicians in assessing the value of interventions based on the value equation for health care: quality, service, and cost impact.

Ability of visual tests to predict underlying cervical neoplasia. Colposcopy and speculoscopy.

OBJECTIVE: To describe the attributes of colposcopy and a low-power, magnified examination that utilizes chemiluminescent illumination (speculoscopy) in the visualization of cervical epithelium in a predefined, high-risk population and to compare how the two tests predict cervical histology. STUDY DESIGN: During this multicenter, prospective study, 395 women who were referred to our colposcopy clinic underwent a repeat cervical smear and speculoscopy followed immediately by colposcopy. Abnormal colposcopic lesions were biopsied and endocervical curettage performed when indicated. Histologic diagnoses were compared with cytology, speculoscopy and colposcopy results. RESULTS: Colposcopy was more sensitive than speculoscopy in the detection of cervical neoplasia (97% vs. 82%) (P < .001) and was superior in visualizing focal lesions and vascular patterns. An antecedent acetowhite abnormality detected during speculoscopy was highly predictive of subsequent abnormal colposcopy (97% positive predictive value). The "overall" rate of acetowhite lesions during speculoscopy was nearly half the rate during colposcopy (P < .001). CONCLUSION: Colposcopy is better suited than speculoscopy to the follow-up of patients with abnormal cervical cytology because it facilitates lesion grading and assists in directing biopsies. Speculoscopy is best utilized as a dichotomous screening test based on the presence or absence of at least one well-demarcated acetowhite lesion and may be more suitable than colposcopy as an adjunct to cervical cancer screening due to its lower overcall rate. The biophysical properties of blue-white chemiluminescent light as it relates to the diagnosis of cervical neoplasia are discussed.

Low-grade Papanicolaou smears and the Bethesda system: a prospective cytohistopathologic analysis.

OBJECTIVE: To examine the clinical usefulness of the Bethesda classification system of low-grade cervicovaginal cytology as it relates to predicting underlying histology and aiding in triage to colposcopy. METHODS: We evaluated 1454 women with abnormal cytologic screening results: 782 with atypical squamous cells of uncertain significance (atypia), 355 with low-grade squamous intraepithelial lesions (SIL) determined by the presence of human papillomavirus (HPV) alone, and 317 with low-grade SIL determined by the presence of cytologic evidence of mild dysplasia (cervical intraepithelial neoplasia [CIN] I) devoid of HPV cytopathologic features. All women underwent colposcopy, directed-punch biopsy or loop electrosurgical excision, and/or endocervical curettage (ECC), as indicated. RESULTS: Women from the low-grade SIL-CIN I referral cytology group were significantly more likely to harbor all grades of biopsy-proven dysplasia than were those from the atypical squamous cells of uncertain significance and low-grade SIL-HPV groups, which showed no statistical differences. CONCLUSIONS: Contrary to the Bethesda system, which combines CIN I and HPV changes because of cytomorphologic similarities, this study suggests that patients with HPV cytologic smears are similar to patients with atypical smears and are less likely to harbor any biopsy-proven CIN lesions than are patients with CIN I cervicovaginal smears. If excluded from colposcopic triage, approximately 5% of patients with atypical cytologic smears from a well-screened population similar to ours will harbor high-grade lesions that may progress during any waiting period. Triage of low-grade cervicovaginal smears based on histopathologic correlation is encouraged.

Papanicolaou smear screening augmented by a magnified chemiluminescent exam.

OBJECTIVES: Since the adequacy of screening for cervical cancer and pre-cancer with Papanicolaou smear alone has been questioned, a number of adjunctive tests have been evaluated. This study evaluated whether a magnified chemiluminescent visual screening exam can improve cervical screening when performed coincident with cytologic sampling. METHODS: Patients were evaluated using the Papanicolaou smear, magnified chemiluminescent visual exam (MCE) and colposcopy at 10 study centers. Screening with either Papanicolaou smear alone or in combination with MCE (Pap and MCE), was evaluated using colposcopy directed biopsy as the highest diagnostic standard. RESULTS: The Papanicolaou smear alone detected 9/29 (31%) of women with significant pathology (cervical neoplasia) on biopsy, whereas the combination of the Pap and MCE detected 24/29 (83%) of the women (P < 0.001). Patients in whom both tests results were negative (negative Pap and MCE) were extremely unlikely to harbor significant pathology (1% of those screened). Pap and MCE was especially helpful in the detection of low grade cervical lesions when compared with the Papanicolaou smear alone. CONCLUSIONS: These data indicate that MCE enhances the sensitivity of cervical screening. MCE appears to be particularly useful as a triage instrument in women with otherwise negative Papanicolaou smears. Further studies of cost effectiveness of this combined screening protocol using non-colposcopists is warranted.

Use of speculoscopy in the evaluation of women with atypical Papanicolaou smears. Improved cost effectiveness by selective colposcopy.

Since up to 45% of patients with atypical Papanicolaou smears have been shown to have significant pathology, women with persistent atypia are usually referred for colposcopy. This study evaluated the use of a new adjunctive screening test, speculoscopy, in selecting women with atypical Papanicolaou smears who would most benefit from referral for colposcopy. Both screening and referral patients were evaluated with the Papanicolaou smear, speculoscopy and colposcopy at 10 study centers. Biopsies were obtained from most women with positive colposcopy. The results in patients with atypical smears were used to perform a cost-benefit analysis of each of three management protocols. Using the results of speculoscopy to select women with atypical Papanicolaou smears for colposcopy provided a cost-effective alternative to performing colposcopy either on all women or on those with persistent atypia following treatment. Even when all women undergo speculoscopy at the time of screening, this protocol provides a cost savings of up to 24% and no significant loss of diagnostic accuracy. These data suggest that speculoscopy performed at the time of initial screening can accurately select women with atypical Papanicolaou smears who require colposcopy for diagnostic biopsy in a cost-effective manner.

External cephalic version after previous cesarean section.

Approximately 100,000 cesarean sections are performed each year in the United States because of breech presentation. Numerous studies have shown that external cephalic version can eliminate the need for many of these operations. However, because of the fear of uterine rupture, these studies have generally excluded patients who have undergone previous cesarean section. To evaluate the validity of this exclusion policy, we studied patients with one or more previous cesarean sections and breach presentations near term. Version attempts were successful in 82% of 56 patients who had undergone a previous cesarean section. Sixty-five percent of the successful version patients went on to have vaginal birth after cesarean section. There were no serious maternal or fetal complications associated with the version attempts. We conclude that external cephalic version is a reasonable option in patients with prior low transverse cesarean section.

Diagnosing human papillomavirus of the female lower genital tract: failure of the Pap smear as a sole screening test.

Of 197 patients referred for colposcopy who underwent repeat Pap smears and colposcopic biopsies (when indicated), histologic evidence of human papillomavirus (HPV) infection involving the endocervix, cervix, or vagina or all three sites was documented in 109 biopsies. Sixty-six (61%) had normal Pap smears at the time of colposcopy. Despite a specificity of 92% for detecting HPV, the Pap smear demonstrated a low sensitivity (39%), with a positive and negative predictive test value of 88% and 50%, respectively. In patients with biopsies revealing HPV infection without associated dysplasia, false negative Pap smears were found most often in women with strictly vaginal HPV (74%) (P less than 0.05), followed by those with coexistent cervical and vaginal HPV (65%), and then by those with solely cervical HPV (51%). We question the use of the Pap smear for the detection of lower genital tract HPV, particularly in patients with only vaginal involvement, especially when the smear is repeated at the time of colposcopy. Benefits and disadvantages of other screening tests for HPV are discussed.

Prediction of cesarean section scars with ultrasound imaging during pregnancy.

We sought to determine whether a sonographic examination could identify uterine scars in patients with a history of previous cesarean section and further distinguish patients having previous low transverse from vertical uterine incisions. Forty-six antenatal obstetrical patients with a history of prior cesarean section(s) and 30 control patients without prior uterine surgery underwent sonogram examinations to identify the scar. The researcher who later reviewed the sonogram was blinded as to the presence or type of uterine scar. Of the 47 scars examined, uterine scars were visualized in 13 (27.7%). All scars seen were low transverse; no vertical scars were identified by sonography (p less than .05). No scars were visualized with sonography in the control group and cesarean section scars were seen more easily prior to the third trimester. No information concerning the scar condition (dehiscence) could be obtained with sonography. We conclude it is of benefit to perform sonogram exams in patients with prior cesarean sections of unknown incision to better counsel them as to their risk to rupture. Although vertical cesarean section scars could not be visualized, those patients who had low transverse scars identified could be included in a low-risk vaginal birth population.

Ectopic pregnancy with shock and undetectable beta-human chorionic gonadotropin. A case report.

A patient with an ectopic pregnancy presented with intraabdominal hemorrhage, hypotension and a beta-human chorionic gonadotropin (beta-hCG) less than 5 mIU/mL. Although rare, a negative beta-hCG does not rule out the diagnosis of ectopic pregnancy.