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PubMed1998

Hypomethylation in cervical tissue: is there a correlation with folate status?

We have shown previously that DNA hypomethylation is significantly associated with grade of cervical intraepithelial neoplasia (CIN; Y.I. Kim et al., Cancer, 74: 893-899, 1994). The objective of this study was to further describe this relationship and to investigate the role of folate in the observed association of DNA hypomethylation and CIN. Eighty-three patients with abnormal PAP smear results were referred to the Cervical Dysplasia Clinic at the University of Arizona for colposcopic examination and biopsy. Patients completed a short questionnaire and provided a nonfasting serum sample. DNA hypomethylation was assessed by incubating DNA extracted from biopsy samples with [3H]methyl-S-adenosylmethionine and Sss 1 methylase. Cervical tissue and serum folate concentrations were assessed using a microbiological assay. All folate levels were log transformed prior to statistical analysis. The histological distribution of the samples was: 7 adjacent normal, 30 CIN I, 18 CIN II, 13 CIN III, and 11 carcinoma in situ (CIS). The mean age of participants was 29.8 +/- 9.6 years. DNA hypomethylation was significantly different between select histological levels. Both cervical tissue folate and serum folate levels were significantly correlated to methylation level (P = 0.0211 and P = 0.0569, respectively). Smoking, hormonal contraceptive use, parity, and human papillomavirus infection were not associated with DNA hypomethylation or folate status. The current use of vitamins was significantly associated with serum folate level but not with methylation or cervical folate levels. These data extend our earlier findings that DNA hypomethylation is an early event in cervical carcinogenesis. To conclude that the folate level is significantly related to DNA hypomethylation, further investigation of DNA hypomethylation of specific genes is required.

Adolescent↗
PubMed1988

Disease and pregnancy in adolescent girls.

The frequency of visits to the outpatient clinic, chief complaints, and pregnancies of adolescent girls were analyzed. The age distribution of adolescent girls who visited the clinic showed that the higher the age, the higher the frequency of menstrual cycle abnormalities. Recently, increased sexual activity has been seen in teenagers and has caused problems, especially the increase in teenage pregnancies, contributing to increases in induced abortion. To avoid unwanted pregnancy of unmarried teenagers, intensive sex education is essential, as well as provision of contraceptives.

Adolescent↗
PubMed2006

Feasibility and use of school-based condom availability programs in Tijuana, Mexico.

Condom availability programs (CAPs) may increase access to condoms and contribute to increased condom use among youth. This study describes the characteristics, degree of satisfaction, and gender differences among users of a CAP implemented in two high schools in Tijuana (Baja California, Mexico). A kiosk distributing free male condoms was set up in two high schools in Tijuana. Kiosk users (N=570) were more likely to be male, young, and/or enrolled in a lower SES school. Most kiosk users were either sexually active or planning to have sex. Females were less likely to request condoms and to continue using the kiosk, but more likely to request information on other contraceptive methods. Results demonstrate the feasibility of implementing CAPs in Mexican schools and suggest that these programs can improve adolescents' condom access.

Adolescent↗
PubMed2001

Female control of sexuality: illusion or reality? Use of vaginal products in south west Uganda.

This paper reports on a trial of vaginal products that were distributed and used by 131 women and 21 men in south west Uganda. It focuses specifically upon the issue of female control in heterosexual relationships and examines whether methods which are ostensibly under women's control, will in practice give women greater control of their sexual health. Participants were invited to select two from a range of vaginal products that included the female condom, contraceptive sponge, film, tablets, foam and gel, and use each for five weeks and their favourite product for a further three months. They were interviewed up to seven times over a five-month period. Although the women perceived that a major advantage of the products (with the exception of the female condom) was that they could be used secretly, less than 40% were using the products without their partner's knowledge after one week and this proportion declined over time with only 22% using the products secretly after ten weeks. In the main male partners were told as women felt it their duty to inform them. In general the women were very much more positive about the products than they were about the male condom, as were the men. A contributory factor to their popularity among women was the greater control they gave them. Even though, use of these products in practice often involved negotiation with male partners, the fact that use was contingent on women's action was empowering and increased somewhat their ability to control their sexual health.

Adolescent↗
PubMed2005

Do Indonesian medical practitioners approve the availability of emergency contraception over-the-counter? A survey of general practitioners and obstetricians in Jakarta.

BACKGROUND: Few studies have examined the attitude of medical practitioners towards the availability of emergency contraception (EC) without prescription. In Indonesia, EC (either Yuzpe regimen or Postinor-2) is available by prescription only. We aimed to examine the level of knowledge, attitudes and practices of medical practitioners in Indonesia about EC, in particular their attitudes to the availability of EC over-the-counter (OTC), using a questionnaire. METHODS: Data were collected by an anonymous structured questionnaire. Questionnaires were distributed to general practitioners in 36 Community Health Centres and 25 private clinics using stratified random sampling according to area in Jakarta, and to obstetricians practicising in 24 government and private hospitals and eight private clinics in Jakarta. Two hundred and five general practitioners and 142 obstetricians and gynaecologists participated; overall response rate was 75%. RESULTS: Although most participants were familiar with EC, only 22% received a very good knowledge score (4 or 5/5 answers correct), while 52% received a poor score (0-2/5 correct). Most participants did not support the OTC availability of EC (70%). Logistic regression identified that participants who prescribed EC had an Odds of 3.8 (95% CI 1.90, 7.73) of approving OTC EC, after adjustment for age and speciality. CONCLUSION: Although many organisations are working towards OTC availability of EC, it needs to be recognized and addressed that doctors who do not prescribe EC are unlikely to support the increased availability of EC.

Journal Article↗
PubMed1995

Gestodene. A review of its pharmacology, efficacy and tolerability in combined contraceptive preparations.

The newer progestogens gestodene, desogestrel and norgestimate were developed in an attempt to produce agents with more selective progestational activity that would improve cycle control and minimise metabolic changes and adverse events while effectively preventing pregnancy. In clinical practice, gestodene is combined with ethinylestradiol in monophasic or triphasic combined oral contraceptive preparations. The drug has pharmacokinetic advantages over the other new progestogens in that it is active per se (the others are prodrugs) and has high bioavailability (approximately 100%). The ability of gestodene-containing oral contraceptives to inhibit ovulation is similar to that of preparations containing other progestogens although the required dosage is lower. In common with oral contraceptives containing desogestrel or norgestimate, and in contrast with those containing levonorgestrel, gestodene-containing preparations are associated with neutral or positive changes in lipid and carbohydrate metabolism. The effects of gestodene preparations on coagulation parameters, like those of desogestrel and levonorgestrel, are balanced by changes in the fibrinolytic system. Although the impact of these changes on clinical cardiovascular end-points has not been determined, the altered lipid profile is not likely to have significant clinical relevance because of the predominantly thrombogenic nature of cardiovascular disease in oral contraceptive users. Pregnancy rates and Pearl Indices with gestodene-containing preparations are low and similar to those with preparations containing other progestogens. Most pregnancies are attributable to user failure. Cycle control appears to be better with gestodene preparations than with levonorgestrel preparations, and available data suggest that cycle control may also be better with monophasic gestodene/ethinylestradiol than with monophasic desogestrel- or norgestimate-containing preparations, and better with triphasic gestodene- than with triphasic levonorgestrel- or norgestimate-containing preparations. However, differences between the new progestogen-containing preparations need to be confirmed in further large-scale trials. The most common adverse events with gestodene/ethinylestradiol are headaches and breast tension; the incidence of short term adverse events, including acne, is similar to that with preparations containing other progestogens. Changes in blood pressure and bodyweight are negligible. There are no comparative data on the incidence of cardiovascular events with gestodene-containing and other combined preparations. While the risk of breast cancer appears to be increased with long term combined oral contraceptive use in certain patient subgroups, this risk needs to be balanced against the noncontraceptive benefits of these preparations.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗
PubMed1994

Lack of pantoprazole drug interactions in man.

This review summarizes the results of pharmacokinetic and pharmacodynamic drug interaction studies in man with pantoprazole, a new, selective proton pump inhibitor. Different mechanisms have to be considered as causes for potential drug-drug interactions. Proton pump inhibitors (PPIs) in general may alter the absorption of drugs by increasing the intragastric pH. Due to the presence of an imidazole ring, the PPIs of the class of substituted benzimidazole sulfoxides may interfere with the metabolism of other drugs by altering the activity of drug metabolizing enzymes of the cytochrome P450 system, via either induction or inhibition. With the increasing use of PPIs, their interaction potential gains therapeutic importance as was the case with the first and second generation of H2-blockers (cimetidine and ranitidine, respectively). The enhanced selectivity of pantoprazole to the gastric H+/K(+)-ATPase characterizes the new PPI generation. In comparison to omeprazole and lansoprazole, pantoprazole showed a much lower affinity to cytochrome P450 in vitro and a markedly lower potency in the in vivo rat model for interaction with diazepam. In contrast to omeprazole, pantoprazole does not interact with the cytochrome P450 system in man. In the drug interaction studies conducted so far, pantoprazole did not affect the pharmacokinetics or pharmacodynamics of antipyrine, diazepam, digoxin, a hormonal contraceptive, nifedipine, phenytoin, theophylline and warfarin in man. Also pantoprazole neither induced the drug metabolism of antipyrine nor increased urinary excretion of the induction markers D-glucaric acid and 6 beta-hydroxycortisol. Vice versa, the investigated drugs had no relevant influence on the pharmacokinetics of pantoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Gabapentin: pharmacokinetics, efficacy, and safety.

Gabapentin is a new antiepileptic drug (AED) with an attractive pharmacokinetic profile. It is absorbed by an active and saturable transport system, and has a high volume of distribution. Gabapentin is not bound to plasma proteins, does not induce hepatic enzymes and is not metabolized. At steady state, it has a half-life of 6-8 h, and is eliminated unchanged by renal route with a plasma clearance proportional to the creatinine clearance. It is devoid of significant drug-drug interactions when administered with the established AEDs or with oral contraceptives. Gabapentin used as an add-on AED significantly reduced the frequency of partial seizures and secondarily generalized tonic-clonic seizures in three large double-blind, placebo-controlled, parallel-group clinical trails. It is well tolerated, with transient somnolence and dizziness being the most frequent adverse effects. Although the mechanism of action of gabapentin is not fully established, there is strong evidence to suggest a novel mechanism of action. Gabapentin is a unique and promising drug that could improve the quality of life of patients with epilepsy and is a welcome addition to the armamentarium of currently available AEDs for the treatment of patients with seizures of partial onset.

Acetates↗
PubMed1995

Effects of storage and temperature upon soft jelly capsules containing nonoxynol as spermicide.

Recently, adverse effects of long periods of storage and high temperature on physical characteristics of the soft jelly capsule wall were observed. In the present study, the effects of both parameters upon the mean rupture time of the capsule, and the release of the active compound were evaluated in vivo in 40 women. The results disclosed that the storage for long time and the exposure of the capsules to high temperatures, delays significantly the mean rupture time and the release of the active compound. A rapid distribution, adequate storage, as well as a delay of intercourse after vaginal insertion of the device are suggested.

Adult↗
PubMed1999

Trends in United States ovarian cancer mortality, 1979-1995.

OBJECTIVE: To describe the epidemiology of ovarian cancer mortality in the United States from 1979 to 1995. METHODS: The mortality data of the Centers for Disease Control and Prevention were accessed using the Wide-ranging Online Data for Epidemiologic Research (WONDER). We selected all deaths among women with International Classification of Diseases, Ninth Revision (ICD-9) code 183.0 (ovarian malignant neoplasm). Mortality data for the years 1979-1995 were age-adjusted to the United States 1990 female population, and mortality rates for each year were calculated for females of all ages by age category, by race, and by geographic location. Trends were obtained for the periods 1979-1983 to 1991-1995, and the impact on the number of ovarian cancer deaths was calculated. RESULTS: Age-adjusted ovarian cancer mortality rates have changed little in the United States from 1979 to 1995, but rates are increasing in older women (65 years and older) and decreasing in younger women. Age-adjusted mortality rates are higher among whites than in blacks. Ovarian cancer mortality rates are higher in northern compared with southern states. CONCLUSION: The trends in ovarian cancer mortality among younger and older women parallel published changes in incidence and may be due to changes in risk factors, such as the use of oral contraceptives. The reasons for the higher ovarian cancer death rates in northern states are unknown. Better understanding of how modifiable risk factors and treatment methods affect ovarian cancer mortality trends is needed.

Adult↗
PubMed2001

Immunoneutralisation of GnRH-I, without cross-reactivity to GnRH-II, in the development of a highly specific anti-fertility vaccine for clinical and veterinary use.

In recent years, several forms of gonadotrophin releasing hormone (GnRH) molecules have been isolated from primate brain. These molecules are very similar in sequence and this raises the question of whether previously developed neutralisation vaccines based on GnRH (now termed GnRH-I) would remove other forms of GnRH (namely GnRH-II) as well. As the function of these other molecules has not yet been clearly defined, potential health risks could exist by their ablation. In view of the high sequence homology between the molecules, this paper describes the production of highly specific polyclonal antibodies against GnRH-I and GnRH-II, with negligible cross-reactivity. The ultimate aim of this is to develop an anti-fertility vaccine which does not present any inappropriate side-effects, caused by neutralisation of a GnRH molecule which may or may not be directly involved in reproduction. Several formulations were investigated, based on analogues of the following molecules, conjugated to tetanus toxoid: 1. GnRH-I pGlu-His-Trp-Ser-Try-Gly-Leu-Arg-Pro-Gly-NH2 and 2. GnRH-II pGlu-His-Trp-Ser-His-Gly-Trp-Tyr-Pro-Gly-NH2. The specificity of the antibodies produced was examined, together with effects on fertility and any inappropriate side-effects. Immunostaining of hypothalamic sections was carried out, using the generated antisera, to determine the regional distribution of GnRH-I and GnRH-II neurones, as well as to further evaluate the specificity of the antibodies.

Animals↗
PubMed2001

Reproductive risk factors for epithelial ovarian cancer according to histologic type and invasiveness.

PURPOSE: Differences in histology among the subtypes of epithelial ovarian tumors suggest possible differences in their etiologies. We examined reproductive risk factors for epithelial ovarian cancer according to histologic subtype and tumor invasiveness. METHODS: We conducted a population-based, case-control study of associations between reproductive risk factors and epithelial ovarian cancer in the Delaware Valley from 1994 to 1998. Cases age 20 to 69 years with a recent diagnosis of epithelial ovarian cancer (n = 767) were compared to community controls (n = 1367) frequency matched by age. RESULTS: With few exceptions, we found significant risk reduction for each histologic subtype of epithelial ovarian cancer by using oral contraceptive, bearing children, and having a tubal ligation; for each subtype, there was significant increased risk associated with a family history of the disease. There were no significant differences among histologic subtypes in the magnitude of the odds ratios for OC use, parity, breastfeeding, tubal ligation, hysterectomy, family history of breast or ovarian cancer, use of noncontraceptive estrogens, age at menarche, and age at menopause. There were also few differences between invasive and borderline tumors, except that women with borderline tumors were significantly younger than women with invasive disease (44.7 years vs. 52.0 years, p < 0.001). Among serous tumors only, women with borderline tumors were more likely to use oral contraceptives than women with invasive tumors (OR = 2.28 95% CI 1.20-4.35). CONCLUSION: The results of this study suggest that reproductive risk factors do not differ among histologic subtypes of epithelial ovarian cancers.

Adult↗
PubMed2002

The effect of perioperative distal vasal lavage on subsequent semen analysis after vasectomy: a prospective randomized controlled trial.

OBJECTIVE: To determine the effect of perioperative distal vasal lavage with 50 mL of normal saline on subsequent time to azoospermia after vasectomy. PATIENTS AND METHODS: Seventy-two patients were prospectively enrolled and randomized to undergo vasectomy with or without vasal lavage. Infertility rates at 8, 10 and 12 weeks were compared for both groups and for those undergoing the procedure under local or general anaesthesia. Patient compliance for returning postoperative semen for analysis was also assessed. RESULTS: There was no statistically significant difference in infertility rates at 8, 10 or 12 weeks after vasectomy with or without vasal lavage. Vasectomies performed under local and general anaesthesia had comparable rates of infertility at 12 weeks after surgery. Compliance in providing semen for analysis was poor. CONCLUSION: The routine adoption of distal vasal lavage during vasectomy for contraception cannot be recommended. As compliance in providing semen for analysis was poor, the clinician has a responsibility to remind the patient of the consequences of such action.

Adult↗
PubMed1984

Genetic aspects of the polymodally distributed sulphoxidation of S-carboxymethyl-L-cysteine in man.

Interindividual variation in the sulphoxidation of S-carboxymethyl-L-cysteine (750 mg p.o.) was investigated in 200 healthy volunteers. Nearly a 100-fold difference was observed between individuals with respect to the amount of sulphoxide metabolites detected in their 0-8 h urine (0.6 to 59.1% recovery). Such a difference was shown to be reproducible over several months in 40 subjects who spanned the entire range of capacities. Cumulative plots and maximum likelihood analysis of the distribution indicated that a bimodal model was most probable. Analysis of pedigree data obtained from 12 families suggested a genetic effect with overlying environmental influences.

Adolescent↗