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Clinical experience with the GYNE-T 380 postpartum intrauterine device.

OBJECTIVE: The insertion of conventional intrauterine devices (IUDs) during the 1st 10 days after delivery is associated with a high rate of expulsions. DESIGN: The GYNE-T 380 (Ortho Pharmaceutical [Canada] Ltd., Toronto, Ontario, Canada) IUD was modified by the addition of a loose loop of knotted biodegradable no. 2 catgut to the top of the IUD (GYNE-T 380 postpartum IUD). After delivery, a special inserter was used to imbed the knotted portion of the loop into the myometrium of the uterine fundus. PATIENTS, PARTICIPANTS: This modified IUD was evaluated in a phase II trial involving 190 women at four clinical sites. MAIN OUTCOME MEASURES: There were no pregnancies during the 1st year of the study. The continuation rate was 74 per 100 women and a life table expulsion rate of 9.6 and 13.3 per 100 women was observed at 6 and 12 months, respectively. RESULTS: Complications associated with the insertion and the use of this IUD were minimal. Large scale trials evaluating this IUD are in progress.

Equipment Design↗

Nonpregnant women with a history of habitual abortion have normal and luteal function independent production of prostacyclin and thromboxane A2.

OBJECTIVE: To see if changes in prostacyclin and thromboxane A2 (TXA2) production during early pregnancy in women with habitual abortion is a pregnancy-induced change, we compared the production of these prostanoids in habitual aborters and in healthy controls in nonpregnant state and related it to luteal function. DESIGN: Comparison between patients (n = 16) with a history of at least three consecutive miscarriages and healthy controls without a history of abortions (n = 11). SETTING: Departments I and II of Obstetrics and Gynecology, University Central Hospital of Helsinki, Helsinki, Finland. RESULTS: Habitual aborters and control women exhibited no change in the urinary output of the stable degradation products of prostacyclin and TXA2 when studied between 0 and 2 and 5 and 8 days after the luteinizing hormone peak. Habitual aborters as a whole, or when subgrouped to those with normal (10 cycles) or defective luteal function (12 cycles) did not differ from the control series with regard to prostacyclin and TXA2 production. CONCLUSIONS: Productions of prostacyclin and TXA2 are not relative to the luteal function and are normal in nonpregnant women with a history of habitual abortion.

Abortion, Habitual↗

Sequential regimen of the antiprogesterone RU486 and synthetic progestin for contraception.

OBJECTIVE: To examine the effect of sequential use of the antiprogesterone RU486 and synthetic progestin on ovarian function of healthy women. DESIGN: Healthy women were given a sequential antiprogesterone-progestin treatment. Blood samples were taken twice a week during one control cycle and one to three treatment cycles; prospective analysis. SETTING: The outpatient clinic of the Helsinki City Maternity Hospital, Helsinki, Finland, and Steroid Research Laboratory, Department of Medical Chemistry, University of Helsinki, Helsinki, Finland. PATIENTS: Eleven healthy women, volunteers, 20 to 34 years of age. INTERVENTIONS: A dose of 25 mg/d of RU486 was given during cycle days 1 to 21, and synthetic progestin (5 mg of norethisterone to six and 5 mg of medroxyprogesterone acetate to five women) during cycle days 22 to 31. MAIN OUTCOME MEASURES: Serum P, E2, FSH, and LH were measured from serum samples. RESULTS: In 20 of the 24 treatment cycles analyzed the serum concentrations of P were anovulatory. In the remaining 4 cycles, P levels rose above 3 ng/mL, suggestive of ovulation. Folliculogenesis was not completely inhibited, but serum E2 profiles were subnormal and delayed. Bleeding control was satisfactory. CONCLUSIONS: Antiprogesterone RU486 hampers or delays follicular development, suggesting a possible use as an estrogen-free oral contraceptive. However, the synthetic progestins used in this regimen induced serum P rises in some cycles. The synthetic progestin provides the cycle control, but its possible effect on the reliability of the method remains to be evaluated.

Adult↗

Effects of a single contraceptive Silastic implant containing nomegestrol acetate on ovarian function and cervical mucus production during 2 years.

OBJECTIVE: To study the mechanism of action of Uniplant (South to South Corporation in Reproductive Health, Salvador, Brazil), a single Silastic capsule containing nomegestrol acetate (Lutenyl, Theramex, France) in women during 2 years. DESIGN: Comparison between the hormonal levels, follicular development, cervical mucus (CM) production, and endometrial thickness in the menstrual cycle before implant insertion and at 1, 6, 12, 18, and 24 months after implant insertion. PARTICIPANTS: A total of 15 women of reproductive age were enrolled for the 1st year of use. Twelve of these women continued for a 2nd year of Uniplant use. MAIN OUTCOME MEASURES: Hormonal plasma levels were measured in control cycles and at 1, 6, 12, 18, and 24 months of Uniplant use. Cervical mucus, follicular development, and endometrial thickness also were evaluated. RESULTS: In this study, Uniplant blocks ovulation in 86 percent of cycles studied. Disturbances in follicular growth were observed also. Cervical mucus was scanty and viscous in all women during this study. Endometrial thickness was <8 mm in all cycles studied. CONCLUSION: This study shows that Uniplant is a long-acting contraceptive that probably acts at the hypothalamic-pituitary levels, on the ovary, on CM production, and on the endometrium. These properties suggest the use of Uniplant as a contraceptive agent, especially if one considers the lack of androgenic and metabolic effects and the maintenance of periodic bleeding similar to menstruation.

Adolescent↗

Early pregnancy termination with antiprogestins: a comparative clinical study of RU 486 given in two dose regimens and Epostane.

Mifepristone, (RU 486, Roussel Uclaf, Romainville, France), a progesterone (P) receptor blocking agent, and Epostane, (WIN 32,729, Sterling-Winthrop, Guildford, United Kingdom), a P synthesis inhibitor, were compared for their ability to terminate early human pregnancy. Seventy-eight healthy women, with a gestational length of less than 49 days from the last menstrual period and who requested termination of pregnancy, were recruited to the study. The patients were randomly allocated to three treatment regimens: (1) Mifepristone 25 mg bid for 7 days; (2) Mifepristone 50 mg bid for 7 days; and (3) Epostane 200 mg qid for 7 days. The results of the study confirmed that both compounds are potent abortifacients in early human pregnancy. No difference in efficacy was seen between the two dose regimens of Mifepristone, which both resulted in 61% complete abortions. Seventy-three percent aborted completely in the Epostane group. Subjective side effects, especially nausea, were more common in the women treated with Epostane, but no serious side effects were seen.

Abortion, Induced↗

Male or female sterilization: a comparative study.

The study compares 709 males and 546 females recruited from a well-defined geographic area and sterilized during a 5-year period at the same hospital. Medical records were reviewed and questionnaires sent out. Widespread satisfaction with the sterilization was found. The sterilized women had experienced contraceptive side effects and failures more often than the men. Only 70% of the laparoscopic sterilizations could be carried out during a 1-day admission, 25% of the women complained about long-term sequelae, and there were 1% failures. The vasectomies were carried out on an outpatient basis, there were few postoperative symptoms, and 0.5% failures were recorded. Female sterilization was at least four times as expensive as vasectomy. It is concluded that vasectomy is generally to be preferred to female sterilization, and that the preoperative guidance should involve both man and wife.

Adult↗

Intracervical and fundal administration of levonorgestrel for contraception: endometrial thickness, patterns of bleeding, and persisting ovarian follicles.

OBJECTIVE(S): To study the prevalence of persisting ovarian follicles and to assess the endometrial changes and patterns of vaginal bleeding over 1 year of use of a 20 micrograms/24 h levonorgestrel-releasing intracervical contraceptive device. DESIGN: Prospective, randomized study. SETTING: Two family planning clinics in Helsinki, Finland. PATIENT(S): Women requesting intrauterine hormonal contraception. INTERVENTION(S): Insertion of a levonorgestrel-releasing intracervical contraceptive device into the cervical canal (group 1, n = 151) or fundally into the uterine cavity (group 2, n = 147) for contraception. MAIN OUTCOME MEASURE(S): Transvaginal ultrasonography of the ovaries and endometrium at insertion and 3, 6, and 12 months after insertion. Data on bleeding were collected using menstrual diary cards. RESULTS: Persisting ovarian follicles were found in < 8% of women. In both groups, the amount of endometrial tissue decreased significantly in 3 months. The incidence of amenorrhea during the 1st year was higher in the fundal insertion group. CONCLUSION(S): The number of persisting follicles was low. Follicles resolved within 6 to 8 weeks. No association was found between persisting follicles and problems of bleeding. Compared with intracervical insertion, fundal insertion resulted in more uniform endometrial suppression and fewer days of bleeding and spotting.

Adult↗

Contraceptive efficacy of low doses of mifepristone.

OBJECTIVE: To determine whether a 5-mg dose of mifepristone is sufficient to prevent pregnancy. DESIGN: Clinical study. SETTING: Academic research center. SUBJECT(S): Healthy, fertile, sexually active female volunteers. INTERVENTION: Volunteers received a 5-mg dose of mifepristone once weekly, starting on cycle day 2, for up to 6 months. This was their only contraceptive method. MAIN OUTCOME MEASURE(S): Number of pregnancies. RESULT(S): The treatment resulted in a significant decrease in pregnancy rate without affecting the menstrual cycle or causing disturbing side effects. CONCLUSION(S): A low dose of mifepristone, which does not inhibit ovulation, reduces fertility significantly by affecting the endometrium. However, the contraceptive effect needs to be improved for the drug to compete with other contraceptive methods.

Adult↗

Topical anesthesia with eutetic mixture of local anesthetics cream in vasectomy: 2 randomized trials.

Two paired randomized trials testing topical anesthesia with a eutetic mixture of local anesthetics (EMLA cream*) in vasectomy were performed. In 1 trial EMLA cream was applied on 1 side of the scrotum, while infiltration anesthesia into the skin and subcutaneous tissue with mepivacaine was used on the contralateral side. All but 1 of the 13 patients (p less than 0.05) preferred infiltration anesthesia because of pain as the incision reached the subcutaneous tissue. In the other trial 29 patients received EMLA cream on 1 side of the scrotum before bilateral mepivacaine infiltration. There was significantly less pain on the sides with the anesthetic cream (p less than 0.001). Many patients would pay the price of the cream. In conclusion, EMLA cream cannot replace but it can supplement infiltration anesthesia during vasectomy.

Adult↗

Epidemiology of inflammatory bowel disease.

Epidemiologic studies of inflammatory bowel disease indicate that these disorders occur in susceptible individuals, possibly due to genetic abnormalities, resulting in disturbance of bowel wall function. Environmental factor(s) exerting a primary effect at an early age, in most patients, cause the disease to manifest usually in teenagers or young adults. Secondary environmental factors may alter disease expression, severity, or influence relapse. Studies in identical twins provide the best evidence for the role of genetic factors in the cause of Crohn's disease. Changing trends in disease incidence (seen in many countries) provide strong support for environmental factors as playing a major influence in disease expression. We now require further laboratory and epidemiologic studies in family members at risk of disease, in migrants who move from low incidence areas to high incidence areas, and in area where Crohn's disease particularly is starting to appear. The clinician can play an important role by performing careful observations in patients with a view to uncovering new clues to disease etiology.

Contraceptives, Oral↗

No influence of proinsulin and insulin on plasma levels of plasminogen activator inhibitor type 1 and tissue plasminogen activator in young women before and during intake of contraceptive steroids.

Clinical observations in patients predisposed to cardiovascular disorders and recent experimental observations suggest that proinsulin and insulin participate in the regulation of fibrinolysis in vivo. In the present study, we examined if proinsulin and insulin affect the constitutive (fasting) secretion of plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (t-PA) in young healthy women (N = 17). We also measured the antigen concentrations of PAI-1 and t-PA during slow and fast changes in proinsulin and insulin levels induced by oral (OGTT) and intravenous (IVGTT) glucose tolerance tests. The assessments were performed before and after 6 months of treatment with contraceptive steroids, which have a well-defined influence on the fibrinolytic variables. We observed no consistent correlations between fasting values of proinsulin, insulin, PAI-1, and t-PA either before or during hormonal treatment. Before hormonal treatment, PAI-1 and t-PA antigen levels decreased (P < .05) during the hyperproinsulinemia and hyperinsulinemia induced by the OGTT and IVGTT. After hormonal intake for 6 months, a decrease only in t-PA concentrations during the OGTT was observed despite similar proinsulin and insulin responses to the glucose loads. Our findings suggest that proinsulin and insulin have no influence on the regulation of plasma levels of PAI-1 and t-PA in young healthy women, irrespective of intake of contraceptive steroids.

Adult↗

Higher proportion of CD8+ T cells in the blood in healthy adults from Ethiopia and Bangladesh compared with Sweden.

The phenotypic composition of peripheral blood lymphocytes in 45 healthy adults (15 each from Bangladesh, Ethiopia and Sweden) was analysed as an indicator of the influence of environment and/or ethnic background on the human immune response. The possible interference of technical factors was minimized by highly standardized handling of samples and by use of a similar simultaneous 3-colour flow cytometry analysis technique for all samples. The percentage of CD4+ cells was lower, and the percentage of CD8+ cells was higher, in Bangladeshi and Ethiopian subjects than in those from Sweden. A higher percentage of CD57+/CD8+ T cells was also found in these 2 groups than in Swedish subjects. The percentage of gamma delta T cells was higher in Bangladeshi subjects and a difference in T cell receptor V beta expression was also noted between Bangladeshi and Swedish subjects. The data suggest that environmental or genetic factors are important bias factors to be considered in immunophenotyping studies. Possibly differences in the pattern or level of microbial challenge, as well as nutritional factors, may lead to different adaptive changes in the immune response. The potential influence of such immune adaptation on the response to vaccination or pharmaceutical therapy may be important in the development of new strategies of medical intervention in different geographical regions or ethnic groups.

Adult↗

Diversity of clinical spectrum of HTLV-III infection.

In a prospective follow-up volunteer study lasting 4 to 16 months, 17 of 200 homosexual men living in Finland had antibodies to human T-lymphotrophic virus type III (HTLV-III). 1 man who initially had a low titre of HTLV-III antibodies became seronegative within 6 months without any symptoms developing, and a seronegative man became seropositive. 14 men had high titres of HTLV-III antibodies when they first joined the study and during the study titres rose in all other HTLV-III-positive men except those with AIDS. Initially 9 men were symptom-free, 3 had lymphadenopathy syndrome (LAS), 3 had AIDS-related complex (ARC), and 2 had AIDS. During follow-up LAS developed in 3 symptom-free HTLV-III positive men but none of those with LAS or ARC progressed to AIDS. Most HTLV-III-positive men, including those who were otherwise symptom-free, had mucocutaneous lesions generally associated with immune deficiency. Regardless of the symptoms, those with increasing HTLV-III antibody titres showed lowered T helper/T suppressor ratios, decreased numbers of T helper cells, and/or diminished responses to tuberculin antigen (PPD). These results suggest that the clinical spectrum of HTLV-III infection ranges from transient infection through chronic provirus state, asymptomatic virus producer state, LAS or ARC, and rarely full-blown AIDS. Cofactors probably determine the final outcome of infection in the individual.

Acquired Immunodeficiency Syndrome↗

Oral contraceptive use and breast cancer in young women. A joint national case-control study in Sweden and Norway.

The possible association between oral contraceptive (OC) use and the risk of breast cancer developing before the age of 45 was investigated by means of a population based case-control study in Sweden and Norway. Information was obtained by personal interview from 422 (89.2%) of all eligible patients with a newly diagnosed breast cancer from May, 1984, to May, 1985, and from 722 (80.6%) of all contacted age-matched controls. A multivariate analysis, which accounted for several possible confounding factors, revealed a significant (p = 0.03) association between total duration of OC use and breast cancer risk. The relative risk (RR) of breast cancer after 12 or more years of OC use was 2.2 (1.2-4.0). OC use for more than 7 years before first full-term pregnancy entailed an increased breast cancer risk (RR = 2.0 [1.0-4.2]) which was of borderline significance. When total duration of use was considered, the risk of breast cancer was virtually unrelated to age at first OC use and latency from first use. The results suggest that long-term use of OCs may increase the risk of breast cancer in young women.

Adult↗

Maternal smoking during pregnancy and risk of childhood cancer.

In a case-control study of childhood cancer a dose-response relationship was found between the number of cigarettes smoked per day by the mother during pregnancy and cancer risk in the offspring. When all tumour sites were considered the cancer risk was 50% higher for the most exposed group than for the controls. The risk was doubled for non-Hodgkin lymphoma, acute lymphoblastic leukaemia, and Wilms' tumour. These findings provide further evidence for the harmful effects of cigarette smoke on the growing fetus.

Adolescent↗