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

Flexible and mobile doctors as a strategy for capacity problems.

Background: Medical specialists in the Netherlands are coping with a high workload and long waiting lists of patients. Most doctors are selfemployed and working in a partnership with colleagues. This system of small companies of doctors is restrictive to mobility and flexibility in careers, because every change within the partnership will cause income consequences for all members. Restrictions towards flexibility and mobility can have a negative effect on satisfaction and career challenge. In earlier research a loss of capacity is detected, caused by early retirement, turnover to other occupations and under-capacity (part-time) caused by inflexible work conditions. Aim: This study is focussed on the preferences and types of flexibility and mobility among doctors. Furthermore, insight in the relationship between preferred flexibility and satisfaction will be given and finally, the gain of capacity under flexible conditions can be traced. Methods: A questionnaire (online and a written version) was sent to all doctors in different (28) medical specialisms in almost all Dutch hospitals. Most doctors answered the online questionnaire. The response was 31% (N=2.746) which is moderate but acceptable for this population- wide survey. The response analysis showed comparable figures with earlier research. Results: Flexibility in time is preferred by 80% of all respondents. Most doctors wish part time participation. Others want flexible schedules or a sabbatical. Especially part-time, young female doctors, who are not self-employed and who experience dissatisfaction with their workload and have work family conflicts, prefer flexibility in time. Flexibility in tasks is preferred by 60% of all respondents. Partly they wish to specialise on a part of their domain and prefer to drop all management tasks. Night, and weekend shifts and several additional duties are also not favourable tasks. Doctors, who are dissatisfied with their work and the time they can spend on the main task, prefer flexibility in tasks. Mobility is preferred by almost 50% of all respondents. Partly a permanent change to another location/hospital is preferred. Others would prefer a temporary change: stationed to another location. A combination of both options was often mentioned. Especially young self-employed doctors, who are dissatisfied with their work, would prefer more mobility. If flexible conditions as preferred would be facilitated respondents mentioned how much years extra they would work and also how much time (Fte) per year. 54% of all respondents intend to work more years as planned if the work conditions will be more flexible. Most of them would work 2 to 5 years longer. Only 18% of the respondents would work less. Conclusions: Conclusion is that most doctors are positive towards flexible work conditions. Self-employed doctors especially prefer mobility, and doctors who are contracted prefer flexibility in time. Flexibility in tasks is not influenced by the type of work relation. Finally, if flexible conditions are facilitated a lot of extra capacity would be activated. (aut. ref.

Flexibel werken: medisch specialisten willen geen fulltime baan.

Ruim 2700 medisch specialisten reageerden op een enquête over flexibilisering van de werkomstandigehden. De meesten van hen staan daar positief tegenover. Relatief veel medisch specialisten hebben behoefte aan een andere taakinvulling dan het traditionele fulltime werken en het complete takenpakket. Het maatschaps- en samenwerkingsverband en de vakgroepstructuur bieden mogelijkheden tot flexibiliteit. 'Interim-specialisten' kunnen worden ingezet op plaatsen waar sprake is van een acuut capaciteitsgebrek. Flexibiliteit draagt bij aan het terugdringen van voortijdige praktijkbeëindiging, uitval door arbeidsongeschiktheid en uitstroom naar andere beroepen. Flinke capaciteitswinst is hiervan het gevolg. (aut.ref.

Epidemiologic and mucosal immunologic aspects of HPV infection and HPV-related cervical neoplasia in the lower female genital tract: A review

Human papillomavirus (HPV) infections are known to play an important role in the pathogenesis of cervical neoplasia. Considering the morbidity and mortality of cervical cancer, infection with HPV can be regarded as a worldwide problem, especially in developing countries. Currently, many studies focus on the development of both prophylactic and therapeutic HPV vaccines. Crucial for these vaccination protocols to be successful is that they will result in a long-lasting ability to generate an immune response that will eliminate the virus. HPV transmission and subsequent infection is a local event in the lower female genital tract and therefore the efficacy of vaccines against this locally transmitted infection can be best assessed by parameters of local immunity. In this review we describe both the epidemiology of HPV-related cervical neoplasia and the general aspects of mucosal immunity in the female genital tract while focusing on the local humoral immunity in HPV-related cervical neoplasia

The prognosis of cervical cancer associated with pregnancy: a matched cohort study

To assess the effect of pregnancy on the prognosis of cervical cancer and the morbidity of standard treatment. We analyzed 44 women with cervical carcinoma associated with pregnancy, who were matched with 44 controls. Matching criteria were age, stage of disease (according to the International Federation of Gynecology and Obstetrics classification), tumor type, treatment modality, and period of treatment. In 23 cases, cervical cancer was diagnosed during pregnancy and in the other 21 cases, within 6 months after delivery. Thirty-nine women had early-stage disease (eight IA, 25 IB, and six IIA), and five had advanced stages (four IIB and one IIIB). The overall 5-year survival rate was 80% among subjects and 82% among controls, whereas the relative risk (RR) of dying within 5 years was 1.12 (95% confidence interval [CI] 0.48-2.65). With regard to the 5-year survival rate (85% for both subjects and controls, the RR of dying was 1.00 [95% CI 0.35-2.83]); no differences were found between subjects and controls for early-stage cervical carcinoma. The size of the group with advanced-stage cervical carcinoma was too small to allow any statistical analysis. No statistically significant differences in survival were observed between cases diagnosed during pregnancy and cases diagnosed after delivery. In addition, the mode of delivery had no effect on survival. Early complications within 6 weeks after treatment were seen 33 times in 25 subjects and 29 times in 23 controls. No differences were observed in the prevalence and type of early complications in subjects versus controls. Late complications after 6 weeks of treatment were seen nine times in nine subjects and 11 times in ten controls. No significant differences were observed in the prevalence and type of late complications in subjects versus controls. The prognosis of early-stage cervical cancer is similar in pregnant and nonpregnant patients when standard treatment is given. Because of the limited number of patients, no conclusions can be drawn about advanced-stage cervical cancer. The goal should be standard oncologic treatment, which does not lead to increased morbidity in pregnant patient

Antibodies against human papillomavirus type 16 and 18 E6 and E7 proteins in cervicovaginal washings and serum of patients with cervical neoplasia

Serum antibodies against the E6 and E7 proteins of human papillomavirus (HPV) 16 and 18 are associated with cervical cancer. The aim of this study was to investigate the presence of local antibodies against HPV in cervicovaginal washings (CWs). In this study antibodies against the native HPV16 and HPV18 E6/E7 proteins were detectable in CWs (48%) and sera (29%) from patients with cervical cancer (n = 21) utilizing a sandwich protein enzyme-linked immunosorbent assay (ELISA). In paired CWs and sera from patients with cervical intraepithelial neoplasia (n = 38) and from healthy women (n = 22) no antibodies against these proteins were found. In 10 of 11 patients, the antibody response corresponded with the HPV type in the cervical smear and/or tumor tissue, which indicates the HPV type specificity of the assay. In 7 of 11 patients with antibody reactivity against HPV16 or HPV18 E6 and/or E7 proteins a higher level of antibody reactivity in the CWs than in the paired serum samples was found at similar inputs of total IgG. This suggests that the antibodies in the CWs against the investigated HPV proteins in these patients were locally produced

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