State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS)

PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy

Cytokines in cervicovaginal washing fluid from patients with cervical neoplasia

Human papillomavirus (HPV) infections play an important role in the development of cervical neoplasia. To get to a better understanding of the role of cytokines in the development of these neoplasias, we analysed the presence of various cytokines in cervicovaginal washings of healthy volunteers (n = 22), cervical intraepithelial neoplasia (CIN) patients (n = 63) and cervical cancer patients (n = 33). IL-12p40, IL-10, TGF-β1, TNF-α and IL-1β levels were significantly higher in patients with cervical cancer than in controls and CIN patients. The levels of IFN-γ were not different. Our data demonstrate alterations in the local cervical immune environment in cervical cancer patients. This could have important consequences for the further development of immune modulating therapies and vaccination strategies

IgG antibodies against human papillomavirus type 16 E7 proteins in cervicovaginal washing fluid from patients with cervical neoplasia

Little information is available about the cervicovaginal mucosal antibodies against human papillomavirus (HPV) proteins. In this study specific IgG antibodies against HPV 16 E7 protein were determined in paired samples of cervicovaginal washing fluid and serum from patients with cervical cancer (n = 22), cervical intraepithelial neoplasia (CIN) (n = 38), healthy individuals (n = 22), and serum from children (n = 41) by a radioactive immunoprecipitation assay (RIPA). HPV 16 E7 specific IgG antibodies were found in cervicovaginal washings (n = 8) and in sera (n = 8) of the patients with cervical cancer. About 60% of the patients with HPV 16 positive cervical cancer had HPV 16 E7 specific IgG antibodies. Titration studies showed that the IgG antibody reactivity in cervicovaginal washings was higher than in the paired serum samples of six patients with cervical cancer (P < 0.001). In the CIN group we found no IgG reactivity in the serum, but in five patients we found a low IgG reactivity in the cervicovaginal washings. No IgG reactivity was found in cervicovaginal washings and sera from healthy individuals and sera from children. HPV 16 E7 specific IgG antibodies seem to be locally produced in a number of patients with HPV 16 positive (pre)malignant cervical lesions. For more definitive evidence for the local production of these antibodies immunostaining should be performed to demonstrate the presence of specific anti-HPV 16 E7 IgG producing plasma cells in the cervical epithelium

Normal findings in vulvar examination and vulvoscopy

To determine the normal vulvar findings by naked eye examination and by vulvoscopy in healthy women without vulvar complaints. Observational study. Forty healthy volunteers without vulvar complaints recruited via a newspaper advertisement. Vulvar examination, human papillomavirus (HPV) polymerase chain reaction of vulvar and cervical swabs, saline and KOH smears and vulvoscopy before and after the application of 5% acetic acid. Prevalence of vestibular erythema, vestibular papillomatosis, HPV infection on the vulva and in the cervix and vulvoscopic findings. The mean age of the women was 37.8 years (median 38.0, range 21-56). Nine women were current smokers and 21 had previously smoked. Naked eye vulvar examination showed vestibular papillomatosis in 13 women (33%) and vestibular erythema in 17 women (43%). The touch test was positive in 9 of the 17 women (53%) with vestibular erythema. Vulvoscopy after the application of acetic acid 5% showed an acetowhite vestibule in all women. Twelve women (30%) had acetowhite lesions outside the vestibule. Six women (15%) were positive for HPV DNA. The presence of HPV DNA did not correlate with vestibular erythema or vestibular papillomatosis. There was a weak association between HPV DNA and acetowhite lesions outside the vestibule (P = 0.055, Fisher's exact test). In this group the younger women significantly more often had vestibular papillomatosis (t-statistic = 3.07; P = 0.003) and women who smoke more often had a genital HPV infection (P = 0.016, Fisher's exact test). Vestibular erythema, vestibular papillomatosis, and acetowhite lesions are common in this group of healthy women without vulvar complaint

Human papillomavirus DNA in multicentric vulvar intraepithelial neoplasia

Human papillomavirus (HPV) DNA in vulvar intraepithelial neoplasia (VIN) is associated with multifocality of VIN III and with multicentricity of other neoplastic squamous lesions in the cervix and vagina. The aim of this study was to establish the prevalence and type of HPV DNA in the lesions of vaginal intraepithelial neoplasia (VaIN) and cervical intraepithelial neoplasia (CIN) in patients with VIN III using the polymerase chain reaction (PCR). HPV DNA detection and histologic analysis were performed on alternating sections of paraffin-embedded biopsies of concomitant CIN and VaIN in 27 patients with VIN III. PCR was performed with consensus primers and HPV typing was performed by direct sequencing of the PCR amplimers. HPV DNA was detected in all VIN III lesions (93% contained HPV-16 DNA); in 96% of the CIN lesions (73% contained HPV-16 DNA); and in all VaIN lesions (75% contained HPV-16 DNA). The HPV type was not the same in 22% of the different lesions of VIN, CIN, and VaIN, even if the biopsies were taken at the same tim

D-TRP-6-LHRH (Triptorelin) is not effective in ovarian carcinoma: an EORTC gynaecological cancer co-operative group study

Between March and September 1988, 74 patients with progressive ovarian cancer after prior platinum-based therapy were treated with the luteinizing hormone-releasing hormone (LHRH) agonist Triptorelin (Decapeptyl(R)). Treatment consisted of i.m. injection of 3.75 mg of microencapsulated Triptorelin on days 1, 8 and 28 followed by 4-weekly injections until tumor progression. No objective responses were observed. Eleven out of 68 evaluable patients (16%) had stable disease. The median progression-free survival was 5 months in patients with disease stabilization and 2 months for all evaluable patients. The median survival for patients with disease stabilization was 17 months, whereas for all patients it was 4 months. The treatment was well tolerated; the only reported adverse events were incidental hot flushes. This study showed that the LHRH agonist Triptorelin has only modest efficacy in patients pretreated with platinum-containing chemotherapy. [(C) 2001 Lippincott Williams & Wilkins.]

Choice or necessity? A review of the role of DIY in tackling housing repair and maintenance

Do-it-yourself (DIY) is a staple element of the spare time activities of many households, but little is known about the extent to which basic repair work is carried out through DIY and about the quality of this work. Through secondary analyses of UK government data (English House Condition Survey and Family Expenditure Survey), this paper examines the scale of DIY work by owner-occupiers, how work is organized, the interrelationship of DIY work, the use of unpaid help, and the use of contractors. It considers the types of work carried out, the characteristics of those who tackle DIY or use unpaid help, the dwelling types most likely to experience DIY work, and the motivations of and constraints on those home-owners who do it. The paper concludes with a discussion on the policy implications of these findings for government and the building industry. Although most DIY work is cosmetic and does not deal with basic repair and maintenance, the sheer scale of DIY ensures that it makes a contribution to improving housing conditions. The provision of more advice, information and education by government, local authorities and the private sector could ensure that more DIY work is of better quality and that home owners give priority to essential repairs whether or not they tackle these themselves.Building Do-IT-YOURSELF Housing Maintenance Repair,