Functions of mammalian Polycomb group and trithorax group related genes

OBJECTIVE: Norplant and Norplant-2 have been available for use by Finnish women since 1984 and 1986, respectively. The objective of this study was to explore Norplant users' experiences of insertions, removals and medical treatments. DESIGN: A questionnaire was sent to women who had received Norplant or Norplant-2 implants one to two years earlier (n = 262) in normal clinical settings; the response rate was 79%. RESULTS: At insertion, problems were experienced by 9% and at least some pain by 23% of women. During the first year 20% of all users (14% of Norplant and 33% of Norplant-2 users) had their implants removed. Problems were experienced at removal by 33% of women and pain was experienced by 40%; nevertheless most users were satisfied with the device. Findings were similar for the two types of Norplant. Forty-two percent of the women had received minipills containing levonorgestrel before Norplant insertions in an attempt to assess Norplant's suitability, and 8% had received drugs for adverse effects caused by Norplant. CONCLUSIONS: Studies including perspectives of Norplant users and the whole lifespan of Norplant (including removal) should be conducted in all clinical settings where Norplant is provided.     

Continuation rates with a levonorgestrel-releasing contraceptive implant (Norplant). A prospective study in Belgium

Contraceptive protection offered by a method depends on its duration of use, which reflects costs, side effects, and relatives' opinions. This study investigated in Norplant implants users the continuation rates, some of their determinants, and the motives for removals. Since 1988, 612 Norplant implants sets, designed to protect for 5 years, have been inserted. Observing 13,907 months of use, we determined over time the continuation rates and how age, parity, circumstances at insertion (postpartum, postabortum, others), and patronymic origins (surrogate for sociocultural factors) influenced them. Statistics included Kaplan-Meier's method and log rank tests, and uni- and multivariate Cox models. Continuation increased with age and depended on sociocultural factors. Parity exerted influence only in younger women. Median duration of use was 3 years 11 months. Removals before 5 years related almost equally to irregular bleeding, other side effects, and pregnancy wish. The cumulative 5-year failure rate was 1.5%. Unsatisfied users returned earlier, distorting the first results. A literature search showed that implants yield, in the mean, slightly better continuation figures than do intrauterine devices, and clearly higher than those obtained with pills and injectables. To optimize costs and counseling, warnings about the risk of short duration of use in young nullipara, especially if negative sociocultural influences prevail, are recommended. In no category are the implants absolutely to be avoided. Individual and programmatic contraceptive choice should take into account the expected continuation of use.     

Are fathers helpful, harmful or superfluous for the development of adolescents?

Presented is the first reported case of an anaphylactoid reaction following Norplant contraceptive implant insertion. The 19-year-old UK woman denied any history of allergic reaction to local anesthesia. After subcutaneous infiltration with 50 mg of 1% lidocaine (without adrenalin), 6 Norplant capsules were inserted through use of the standard insertion technique. Shortly after completion of the procedure, the patient collapsed and had 2 short convulsions. Her blood pressure dropped to 80/40 mm Hg and her radial pulse was 60 beats/minute and thready. Recovery was rapid following administration of intramuscular adrenalin and intravenous hydrocortisone. The woman later recalled a similar episode during a visit to her dentist. An estimated 3 in every 100,000 patients receiving lignocaine hydrochloride have an episode of anaphylaxis in the hospital. In type I hypersensitivity reactions, there is often a history of previous exposure to the allergen, as occurred in this patient. Those undertaking Norplant insertion and removal should be aware of the potential for serious allergic reactions and have access to resuscitative equipment.     

Norplant: nursing's responsibility in procreative rights

Trained nurse practitioners can insert the contraceptive implant system Norplant. Courts may call on nurse practitioners to insert Norplant in poor women. Legislative and prosecutorial initiatives to coerce low-income women and female parolees to use contraceptives should not become law. Offering incentives to poor women is another form of involuntary fertility control. Eugenics and the sterilization campaign of the past form the basis for judicial and legislative initiatives to coerce women to accept Norplant. Providers have inserted Norplant in women from other countries without the women knowing the side effects. Often medical personnel do not remove Norplant when women request its removal. Nurses have historically played a public policy role in reproductive rights. They have promoted procreative rights through their roles as educators/counselors, advocators, empowerers, and practitioners. Nursing's power and expertise help protect against punitive government intrusion in reproductive rights and make sure that contraceptive breakthroughs (e.g., Norplant) strengthen procreative choices. They can guide the development of sound public policy. Norplant is not the answer to poverty, child abuse, or drug abuse. Nursing research can help policymakers become more responsive to the contraceptive and reproductive rights of everyone.     

The performance of levonorgestrel rod and Norplant contraceptive implants: a 5 year randomized study

A new contraceptive (LNG rod implants, Jadelle, Leiras Oy's registered trademark for rod implants) was prospectively evaluated in randomized 5 year comparison with Norplant (Population Council's registered trademark for contraceptive implants releasing levonorgestrel) capsule implants. The study involved 1198 women at seven centres. No pregnancies occurred in the first 4 years. At 5 years, the cumulative pregnancy rate was 1 per 100 users or less for each regimen. Annual discontinuation rates averaged 11-12 per 100 users (P > 0.05), corresponding to 5 year continuation rates of 55.1 for rods and 53.0 per 100 for capsules. Mean annual discontinuation rates for menstrual disturbances were 3.5 and 4.2 per 100 for rod and capsule implants respectively (P > 0.05), and mean annual removal rates for medical problems were 3.5 and 3.0 per 100 (P > 0.05) respectively. Apart from menstrual problems, headache, weight gain and acne were the principal medical reasons for removal. In proportional hazard analyses, family formation variables, age, parity and desire/non desire for another child, recorded at admission, significantly affected discontinuation rates for major decrement categories and for all reasons combined. Mean rod removal time was half that of Norplant (P < 0.01); complications of rod removal were at a lower rate. With these contraceptives indistinguishable in performance except for ease and speed of removal, LNG rod implants appear to be preferable to Norplant for use through 5 years by virtue of relative ease of removal.     

Norplant selection and satisfaction among low-income women

OBJECTIVES: This study examined correlates of Norplant selection and satisfaction among low-income women. METHODS: Interviews were completed in family planning clinics in 4 Florida counties with 1152 Norplant users and 1268 nonusers, with follow-up interviews with a subsample up to 1 year later. Logistic regression models estimated the associations of socio-demographic and medical characteristics with Norplant selection and method satisfaction. RESULTS: Odds ratios for Norplant selection were significantly greater among women who planned to have children in 5 or more years, those who were "offered" Norplant, those who lived in Palm Beach County, those who were using drugs, and those who were Medicaid clients. Women younger than 17 and those who learned about Norplant from a friend were twice as likely as others to select Norplant. Ninety-two percent of Norplant users were satisfied with the method; women with side effects and those who felt pressure to select a method were significantly less likely than others to be satisfied. CONCLUSIONS: Norplant provides an acceptable and satisfying method of birth control for many low-income women. Proper counseling about all methods of birth control and about Norplant's side effects remains critical to the appropriate delivery of this method.     

Levonorgestrel subdermal implants. A review of contraceptive efficacy and acceptability

Levonorgestrel 6-capsule subdermal implants (Norplant) are an effective form of reversible contraception. When implanted under the skin of the upper arm, they release drug into the circulation at a relatively constant rate over 5 years. Generally, the cumulative pregnancy rate at the end of 5 years' levonorgestrel implant use is less than 2 per 100 users. The implants provide contraceptive efficacy equivalent to, or better than, that provided by other reversible methods (including oral contraceptives). Younger women are more likely than older women to become pregnant while using levonorgestrel implants. Bodyweight was positively correlated with risk of pregnancy in a number of studies, but may not be a factor with the currently available 6-capsule implant formulation. Limited data suggest that a new 2-rod levonorgestrel subdermal system (Jadelle) is as effective as the more extensively studied 6-capsule system and has a similar tolerability profile. Fertility returns rapidly after the implants are removed. Use of levonorgestrel subdermal implants is compatible with breast-feeding. In several studies, discontinuation rates were 2 to 15% during the first year of use; cumulative 5-year discontinuation rates ranged from 22 to 64 per 100 women. Despite a substantial incidence of adverse events during therapy, levels of user satisfaction are generally high. Menstrual abnormalities (increased or decreased menstrual flow, spotting, irregularity and amenorrhoea) affect most women at some time during therapy and are the most frequent reason for discontinuing levonorgestrel implants before the end of 5 years' treatment (incidence of 4.2 to 30.7 per 100 users). Mood changes and headache also may lead to discontinuation. Other reported adverse events include skin reactions (including acne), dizziness and weight gain. Serious adverse events (such as stroke, thrombotic thrombocytopenia and idiopathic intracranial hypertension) have been reported during levonorgestrel implants therapy, but the population incidence is difficult to calculate and causality is unclear. According to 3 pharmacoeconomic analyses from an institutional or managedcare perspective, all contraceptive interventions result in net cost savings. It is not clear whether levonorgestrel implants provide greater or smaller economic benefits than combined oral contraceptives. CONCLUSION: Levonorgestrel subdermal implants provide effective long term contraception. Despite a high incidence of menstrual adverse events, overall levels of user satisfaction are high, and 1-year continuation rates are better than those for combined oral contraceptives. Levonorgestrel subdermal implants are a good choice of contraceptive method in women who desire effective contraception, but who are unable to, or prefer not to, comply with an oral regimen.     

Behavioral and biomedical research: a partnership for better health

In the last decade, global use of contraceptive methods has increased. About 50% of couples of childbearing age use a modern contraceptive method. This evolution and a positive change in attitude towards male contraception has encouraged research in fertility regulation to enlarge and to improve acceptance of the contraceptive mix. Current injectable contraceptives interfere with the menstrual cycle. Research is exploring ways to minimize such secondary effects by reducing the total hormone dose and by changing the way the active product is delivered (e.g., microspheres). An injectable prototype is an analogue of levonorgestrel (HRP 002). A new IUD is made of leather suspended by a nylon suture which has been inserted into the uterine muscle. RU-486, often used to interrupt early pregnancy, is being tested as an oral contraceptive (OC). It inhibits secretion of gonadotropins and ovulation. It holds promise as an OC with no estrogen component. Since it also inhibits endometrial development and thus prevents implantation, it may someday be used for emergency contraception (i.e., postcoital contraception). New contraceptive implants under study include Norplant RII (2 rods of levonorgestrel lasting for 3 years), Implanon (desogestrel), and Capranor (biodegradable implant lasting 2 years). The female condom consists of a flexible polyurethane sheath with a flexible ring at each end. It has the potential to protect against sexually transmitted diseases since it covers the labial lips and is impermeable to HIV. France and Switzerland have both approved its use. It will enter the UK market at the end of the year. Approval for marketing has been sought in the US.     

Use of subdermal contraceptive implants in a community-based family planning program. Experience after two years

In North Carolina, the Rutherford County Family Planning Council obtained funds from a special grant for levonorgestrel implants for women not eligible for medical assistance benefits. The Council approved the following approaches to promoting responsible sexual behavior and preventing unwanted pregnancy: creation of an interagency council to monitor the program, education in the schools on responsible sexual behavior, establishment of an information-sharing network for social service agencies, and expanded, low-cost or free family planning services. During 1992-1993, clinicians at the county health department and in private practices inserted implants in 287 women aged 13-37 living mainly in Rutherford County but also in McDowell and Polk counties. A survey was also conducted in the public high school to obtain self-assessment and information about family planning from female adolescents. Age distribution of the acceptors of the contraceptive implants was 40% for 13-19 year olds (the initiative's target group), 34% for 21-25 year olds, and 32% for 18-20 year olds (32%). The two-year insertion rate for women aged 10-19 was 17.3/1000 compared to 20.8/1000 for women aged 20-29. The implantation rate was greatest among 18-25 year olds and lowest among women aged 26 and older. The method of payment for implantation was medical assistance in 69% of cases and a philanthropic foundation for women not eligible for medical assistance in 29% of cases. 8% had the implants removed during the study period. The leading reason for removal was psychological distress (25%), followed by headaches (20.8%), desire to conceive (16.7%), bleeding (12.5%), and medical contraindication (12.5%). The interval between implantation and removal ranged from less than 3 months to more than 12 months. 2.3% of the female high school students used implants. Among the 596 students who were sexually active, 4.2% used implants, 1.85% used a diaphragm, 27.5% used condoms, and 15% used oral contraceptives. The implant acceptors attended 65% of scheduled 3-month follow-up visits.     

Levonorgestrel as a postcoital contraceptive

Time-release pellets of levonorgestrel (LNG), the progestogenic hormone contained in the contraceptive system Norplant, were implanted subdermally in mice, after the animals had mated and ovulated but before uterine implantation of embryos would have occurred, to examine whether the hormone could reduce the number of embryos that subsequently implanted and, if so, when it had to be administered in the postcoital period to achieve that effect. Hybrid female mice (C57BL x CBA) were paired with breeder males (CD-1) and LNG pellets were implanted on day 0, the day on which copulation plugs were found, or on day 2 or day 3 in the postcoital period. Mice in some groups were sacrificed on day 14 of the gestation period, and numbers of fetuses and/or resorption sites were counted, while mice in other groups were allowed to go to term. When LNG pellets were implanted subdermally on day 0 of the postcoital period, pellets designed to release 1.5 mg of hormone in 21 days failed to exhibit a contraceptive effect, but pellets designed to release 5 mg of hormone in 90 days were totally effective in preventing uterine implantation of embryos. Although the 5 mg pellets did not prevent embryos from implanting in all cases when administered on day 2, they prevented pregnancies from going to term by causing resorption of those embryos that did implant. When the pellets were implanted as late as day 3 in the postcoital period, uterine implantation of embryos occurred and fetuses were carried to term. Results of the study indicate that subdermal implants of LNG inserted postcoitally can prevent uterine implantation of embryos in mice, and thereby prevent pregnancy, despite fertilization of oocytes having occurred, if the hormone implants are inserted before day 3 of the postcoital period.     

Expression of gonadotropin-releasing hormone (GnRH) gene in human uterine endometrial tissue

OBJECTIVE: To determine if adolescent mothers who request early removal of levonorgestrel implants differ from those who do not in ways that might predispose them to repeated conceptions and in their concerns about adverse effects. We hypothesized that adolescent mothers who request removal of levonorgestrel implants within 2 years of insertion have more risk factors for repeated pregnancy than those who do not. METHODS: We studied the prevalence of 21 characteristics associated with repeated adolescent pregnancy and 16 adverse effects of levonorgestrel implants in 181 postpartum, adolescent levonorgestrel implant recipients, 66 (36%) of whom had the levonorgestrel implants removed within 20 months of insertion (hereafter, removers). RESULTS: Removers (n = 66) had significantly more risk factors for repeated pregnancy and reported significantly more adverse effects than did those who continued to use levonorgestrel implants (hereafter, users) (n = 115). Concerns about adverse effects rose in tandem with risk factors for repeated pregnancy (r = 0.26; P = .001) and were the most important determinant of levonorgestrel implant removal (relative risk, 9.72; 95% confidence interval, 4.62-19.49). However, the number of risk factors for repeated pregnancy was also a significant, independent predictor of levonorgestrel implant removal (relative risk, 2.34; 95% confidence interval, 1.10-4.66). Following removal, contraceptive use was poor and conception occurred rapidly; 24 (37%) of the removers conceived again within 2 years of the index delivery. CONCLUSIONS: The study hypothesis was supported. Our findings that concerns about the adverse effects of levonorgestrel implants rise in tandem with risk factors for repeated pregnancy suggest that the efficacy of counseling before and after levonorgestrel implant insertion could be improved by addressing those aspects of the user's life that undermine the motivation to use contraception.     

Compliance, counseling and satisfaction with oral contraceptives: a prospective evaluation

CONTEXT: Oral contraceptive users' risk of accidental pregnancy may be higher than it should be, because of inconsistent pill-taking. However, few reliable data are available on pill users' everyday experiences with their method, especially characteristics that may affect consistency of use. METHODS: Two months after initiating or resuming oral contraceptive use, a nationwide sample of 943 women completed questionnaires examining their compliance with instructions for proper use, the quality of their interactions with their provider, their satisfaction with the method, and the frequency and costs of visits or calls to their providers because of pill-related side effects. Regression analyses were used to determine the factors associated with compliance difficulties and method dissatisfaction. RESULTS: In all, 47% of users missed one or more pills per cycle, and 22% missed two or more. Women who lacked an established pill-taking routine, who did not read and understand all of the informational material accompanying the pill package, or who experienced spotting or heavy bleeding had increased odds of missing two or more pills per cycle. Method satisfaction was most likely among women who were aware of the pill's noncontraceptive benefits, were satisfied with their relationship with their provider, had used the pill in the past and experienced few side effects. Some 22% of users called their provider at least once about pill-related side effects, and 9% made at least one visit for this reason; these women spent $25 and $62, respectively, to treat side effects. CONCLUSIONS: Improving pill use is a shared responsibility of the provider, the patient and, to a lesser degree, pill manufacturers. Awareness of potential difficulties such as inadequate counseling is a key step in helping women use oral contraceptives effectively.     

Effect of Depo-Provera or Microgynon on the painful crises of sickle cell anemia patients

Forty-three homozygous (SS) female sickle cell anemic patients with a history of at least one painful crisis per month and desiring a reversible contraceptive were administered DMPA/3 months or Microgynon monthly. A third group of 16 surgically sterilized patients served as control. Patients were followed for 1 year to assess possible effects of the contraceptives on the patients' painful crises. No changes were observed in any of the groups in the hematological parameters. At the end of the study, 70% of the patients receiving DMPA were pain-free and only 16% of those still reporting painful crises rated them as intense. Patients receiving Microgynon also had an amelioration of the painful crises, although at a lower rate; after 12 months, 45.5% still experienced some crises. Although less marked than in the other groups, 50.5% of the control patients also reported an improvement of their painful crisis, which may be a result of closer medical care.     

Use and misuse of oral contraceptives: risk indicators for poor pill taking and discontinuation

The contraceptive efficacy of oral contraceptives (OCs) depends on their proper and continued use, particularly with lower estrogen preparations. However, few studies have examined why women miss pills or discontinue OCs, and those that do tend to be small and to focus on adolescents. To address the issues of poor OC compliance and early OC discontinuation, we analyzed OC use in a convenience sample of 6,676 women between the ages of 16 and 30 from Denmark, France, Italy, Portugal, and the United Kingdom. Logistic regression was used to examine the independent effect of each factor. Poor compliance was associated with a lack of established routine for pill-taking (relative risk [RR] = 3.3), failure to read and understand written materials that came with the OC package (RR = 2.2), not receiving adequate information or help about OCs from their health care provider (RR = 1.5), and occurrence of certain side effects, including hirsutism (RR = 2.1), nausea (RR = 1.4), bleeding irregularities (RR = 1.3), and breast tenderness (RR = 1.2). Women who were inconsistent OC users, missing one or more pills per cycle, were almost three times as likely to experience an unintended pregnancy while using OCs than were women who took their OCs consistently. Factors that predicted early discontinuation (women who wished to continue contraceptive protection but discontinued OC use) were primarily side effects, including nausea (RR = 2.1), bleeding (RR = 1.9), breast tenderness (RR = 1.8), mood changes (RR = 1.8), and weight gain (RR = 1.4).(ABSTRACT TRUNCATED AT 250 WORDS)     

The pros and cons of laser dacryocystorhinostomy

Sixty-one patients participated in a longitudinal study designed to compare the psychological effects of osseointegrated implants with those of conventional denture replacements. Thirty-two patients who requested either relining or reconstruction of their dentures were asked to complete questionnaires designed to measure their psychological well-being while they were on a waiting list and then again 6 months after treatment. Their responses were compared with those of 29 patients who had received an osseointegrated implant. While the implant patients had reported significant declines in psychological distress, there was no such change for the denture patients. Although both groups experienced fewer disabling symptoms, the decline was greater for the implant group. Finally, neither group showed evidence of any change in self-esteem. The results suggest that osseointegrated implants can have a more positive effect on well-being than denture replacements.     

A randomized double blind trial of verbal NSAID education compared to verbal and written education

OBJECTIVE: We performed a double blind randomized controlled trial to investigate whether patients taking nonsteroidal antiinflammatory drugs (NSAID) knew more about these drugs at followup depending on whether they were randomized to receiving or not receiving an NSAID information sheet. The patients were unaware they were in a study. METHODS: All patients received verbal education on the side effects of NSAID that was standardized and always given by the same rheumatologist. Thirty patients randomly received an NSAID information sheet and 26 patients did not. At next clinic followup, after reading a letter of explanation about the study and signing a consent form, patients completed a questionnaire asking about their knowledge of NSAID. RESULTS: Outcome variables assessed within the questionnaire included whether NSAID : (1) can decrease inflammation; (2) help with pain; (3) cause stomach upset and bleeding in the bowels. None of these variables were statistically significant. The only variable that was statistically significantly different between the groups was their report of whether they had received an information sheet about NSAID (p<0.00004). A greater proportion of patients who received the NSAID information sheet correctly reported they had received one compared to those who had not received one and who said they had not received one (85% in the former group, 70% in the latter group). The group who received the NSAID information sheet were more apt to say that NSAID can help with their pain (odds ratio 6.1, p<0.05). Education level was positively correlated with knowledge (p<0.04). However, level of education explained only 11% of the variance in overall knowledge scores (r=0.34) among all patients. CONCLUSION: An information sheet may not add educational value over verbal information by a physician in a clinic setting.     

Immunochemical studies of O-specific polysaccharide from Proteus penneri 14 lipopolysaccharide

OBJECTIVE: To assess the safety of Norplant contraceptive implant use by women with mild-moderate homozygous sickle cell disease (HbSS). METHOD: Prospective observation of women pre- and post-insertion of Norplant, with each woman serving as her own control. Participants: 25 women 18-40 years of age who attended a hospital sickle cell clinic; post-insertion data were available for 23 women. Outcome measures: Changes in hematologic parameters including PCV, MCV, reticulocytes, ISCs, HbF and bilirubin; changes in biochemical parameters including HDL cholesterol, aspartate transaminase, alkaline phosphate, serum creatinine and serum albumin. RESULT: With a mean follow-up of 12.4 months (range 1-29 months), there were no clinically or statistically significant group or individual changes in the hematologic or biochemical parameters after Norplant insertion. CONCLUSION: Norplant appears to be a safe and appropriate contraceptive for women with mild-moderate HbSS disease.     

Statistical research needs in mechanistic modelling for carcinogenic risk assessment

This study reports the results of implant therapy involving a sinus membrane lift as well as conventional implant therapy in 24 periodontally compromised patients who were treated during the period between June 1990 and May 1995. Patients were included on the basis of being in need of at least 2 implants, 1 of which was to be placed in the maxillary sinus region, and at least 3 mm bone height was required in the sinus region. Following fenestration of the lateral sinus wall and lifting of the sinus membrane sinus implants were inserted as described for conventional implants. Annual follow-up visits included recording of plaque, probing pocket depth and bleeding on probing, and recording of the radiographic distance from the implant shoulder to the alveolar crest in mm. The Astra, Astra sinus, ITI, and ITI sinus were observed for an average of 30.8, 29.9, 29.4 and 25.3 months, respectively. Of the 80 implants inserted 1 Astra and 2 ITI had failed at 11-12 months and 1 ITI had failed at 42 months. The Kaplan-Meier estimate of the proportion of non-failed implants at 36 months were 100%, 95%, 91%, and 86% for the Astra, Astra sinus, ITI, and ITI sinus implants, respectively. Of the Astra, Astra sinus, and ITI implants, 71-82% remained free from bone-loss > or = 1.5 mm at 36 months, whereas this was the case for only 29% of the ITI sinus implants. About 80-90% of the implants remained free from plaque; 65-86% remained free from bleeding; and 44-80% remained free from pockets > or = 4 mm. These results indicate that the sinus lift technique can be used successfully in periodontally compromised patients.     

Hyperglycemia-induced circulating ICAM-1 increase in diabetes mellitus: the possible role of oxidative stress

Since the introduction of itraconazole in the Netherlands, the Netherlands Pharmacovigilance Foundation LAREB and the Inspectorate for Health Care received 15 reports of pill cycle disturbances and one of pregnancy occurring during simultaneous use of itraconazole and oral contraceptives. Twelve women used oral contraceptives containing ethinylestradiol and desogestrel. In these women, the withdrawal bleeding was either delayed or did not occur at all; one of these women reported a transiently positive pregnancy test after previous breakthrough bleedings. Three women who used a contraceptive containing ethinylestradiol and levonorgestrel had a breakthrough bleeding. One woman who used an oral contraceptive containing ethinylestradiol and cyproterone acetate became pregnant during the concomitant use of itraconazole. The possible mechanism involved remains to be explained. Although an influence of itraconazole on the reliability of oral contraceptives is uncertain, additional contraceptive measurements might be considered.