Two mifepristone doses and two intervals of misoprostol administration for termination of early pregnancy: a randomised factorial controlled equivalence trial.

OBJECTIVE: To compare the efficacy of 100 mg and 200 mg of mifepristone and 24- and 48-hour intervals to administration of 800 microg vaginal misoprostol for termination of early pregnancy. DESIGN: Placebo-controlled, randomized, equivalence trial, stratified by centre. SETTING: 13 departments of obstetrics and gynecology in nine countries. POPULATION: 2,181 women with 63 days or less gestation requesting medical abortion. METHODS: Two-sided 95% CI for the risk differences of failure to complete abortion were calculated and compared with 5% equivalence margin between two doses of mifepristone and two intervals to misoprostol administration. Proportions of women with adverse effects were compared between the regimens using standard testes for proportions. OUTCOME MEASURES: Rates of complete abortion without surgical intervention and adverse effects associated with the regimens. RESULTS: Efficacy outcome was analysed for 2,126 women (97.5%) excluding 55 lost to follow up. Both mifepristone doses were found to be similar in efficacy. The rate of complete abortion was 92.0% for women assigned 100 mg of mifepristone and 93.2% for women assigned 200 mg of mifepristone (difference 1.2%, 95% CI: -1.0 to 3.5). Equivalence was also evident for the two intervals of administration: the rate of complete abortion was 93.5% for 24-hour interval and 91.7% for the 48-hour interval (difference -1.8%, 95% CI: -4.0 to 0.5). Interaction between doses and interval to misoprostol administration was not significant (P = 0.92). Adverse effects related to treatments did not differ between the groups. CONCLUSIONS: Both the 100 and 200 mg doses of mifepristone and the 24- and 48-hour intervals have a similar efficacy to achieve complete abortion in early pregnancy when mifepristone is followed by 800 micrograms of vaginally administered misoprostol.

"Giant" blastoconidia of Candida albicans: morphologic presentation and concepts regarding their production.

Candida albicans normally produces blastoconidia measuring 2 to 8 microns in diameter. Markedly enlarged "giant" (approximately 30 microns) blastoconidia of a C. albicans isolate (designated BH) were observed after growth on commercially prepared chocolate agar already supplemented with IsoVitalex (BBL-Microbiology Systems, Cockeysville, MD, USA). Morphologically, "giant" blastoconidia presented a spectrum of forms such as blastoconidia with linear creases, with a single broad-based bud resembling Blastomyces dermatididis, with multiple buds resembling Paracoccidioides brasiliensis, or elliptical in shape. "Giant" blastoconidia contained a large oval clear vacuole occupying greater than 50% of the blastoconidium. Pseudohyphae emanating from these blastoconidia were also enlarged and contained a similar oval inclusion. Rarely observed were "giant" blastoconidia with either adherent or internalized blastoconidia uniformly arranged within the blastoconidium. "Giant" or enlarged blastoconidia production was constant, usually approaching 10 to 20% of the blastoconidial units comprising a single colony, irrespective of the number of subcultures. IsoVitalex supplementation of Remel (Lexana, KS, USA) chocolate agar but not a variety of other media also resulted in "giant" blastoconidia production. It is, therefore, theorized that a component(s) of IsoVitalex activates/blocks a gene present in select clones of C. albicans blastoconidia resulting in "giant" or enlarged blastoconidiogenesis.

Women's perspectives on abortion in Romania.

Romanian women have commonly used abortion (both legal and clandestine) to prevent unwanted births. We introduce this paper with a brief summary of the recent history of abortion in Romania, then we combine quantitative data from a previous report ([1] Johnson et al., Lancet 341, 875, 1993) of the research with women's own words about the following issues: their decisions to have an abortion, the impact of abortion restrictions under the Ceausescu government, and their needs and desires for improved reproductive health services. We also present gynaecologists' views of abortion restrictions and needs for improved family-planning services to make a compelling case for the need for safe, legal, comprehensive abortion care in Romania and elsewhere.

Safe abortion: WHO technical and policy guidance.

In 2003, the World Health Organization published its well referenced handbook Safe Abortion: Technical and Policy Guidance for Health Systems to address the estimated almost 20 million induced abortions each year that are unsafe, imposing a burden of approximately 67 thousand deaths annually. It is a global injustice that 95% of unsafe abortions occur in developing countries. The focus of guidance is on abortion procedures that are lawful within the countries in which they occur, noting that in almost all countries, the law permits abortion to save a woman's life. The guidance treats unsafe abortion as a public health challenge, and responds to the problem through strategies concerning improved clinical care for women undergoing procedures, and the appropriate placement of necessary services. Legal and policy considerations are explored, and annexes present guidance to further reading, international consensus documents on safe abortion, and on manual vacuum aspiration and post-abortion contraception.

Reproductive health in eastern Europe: a collaborative training project in Romania.

Since the fall of the Berlin Wall, fundamental political changes in eastern Europe have affected the Soviet-style health care systems that formerly provided basic care for everyone. Many of these systems have collapsed, and the new systems of social insurance that have replaced them often are inadequate. Advanced Training in Reproductive Health in Romania aimed to create an authority in family planning and reproductive health in selected Romanian university centers and to improve training and research capabilities. Initially, the project had 2 main goals: to provide advanced training in reproductive health and family planning to Romanian obstetrics-gynecology specialists from the main university centers-which would allow them to train other physicians (obstetricians, gynecologists, and general practitioners) and medical students-and to develop, test, and finalize specific training materials in Romanian to be used by the new trainers.

Contraception and abortion in Romania.

After the downfall of the Ceausescu regime in December, 1989, the new Government of Romania abolished the law that prohibited abortions on request. Subsequently, the rate of legally induced abortions increased significantly while the rate of maternal mortality declined dramatically. Despite the large number of women who request induced abortions, most women and gynaecologists say that they would prefer to prevent unwanted pregnancies through the use of modern contraception. In this paper we examine factors that contribute to the disparity between women's desire to use modern contraception to prevent unwanted pregnancies and their practice of having induced abortions to prevent unwanted births. The results show that women (and suggest that men) need a wide choice of dependably available high-quality contraceptives; they need to be able to obtain information, counselling, and methods from a wide range of sources/health-care providers; both women's and men's perceptions about, and use of, modern contraception could be positively affected through sexual education started in secondary school; and, to reduce repeat abortions, women's post-abortion family-planning needs must not be neglected.

PIP: The factors that contribute to the disparity between women's desire to use modern contraception and the practice of induced abortions to prevent unwanted births are examined. Structured interviews of 1000 women were conducted in 5 hospitals located in 3 culturally different regions of Romania--Bucharest, Moldova (2 sites), and Transylvania (2 sites). All data were collected between November 1991 and April 1992. At each site structured interviews were conducted over 4-6 weeks with a random sample of 200 women who were either waiting for or recovering from an induced abortion, and 80 semi-structured client interviews were conducted among the 5 sites. There were 35 semi-structured provider interviews in the 5 sites, and one group interview was conducted with clients and one with providers of abortion services in each location. In 1991 there were 789,096 reported legal abortions compared with about 275,000 live births. 47% of the women said that they had had a previous legally induced abortion and 25% reported a previous illegal abortion. 31% of the women said that they would have an illegal abortion if they were unable to have one legally. The choice of contraceptive methods was often limited to 1 type available (condoms or Depo Provera). Women and gynecologists reported that modern contraceptive methods are rarely available from pharmacies. Some contraceptive services were available in most hospitals, but women had to take the initiative. 69% of gynecologists responded that women who want information about contraception wait for the gynecologist to offer it. 72% of the women thought that other women gave gifts to the gynecologist who performed their abortion; 39% did not think a gift would ensure better treatment and enthusiasm to counsel women about contraception. Many women and most gynecologists believed that sexual and contraceptive educations should begin early in the schools involving both sexes. 52% of clients and 75% of providers said that sexual and contraceptive education should begin in secondary schools.

Mechanism of interference mediated by human parainfluenza virus type 3 infection.

Viral interference is characterized by the resistance of infected cells to infection by a challenge virus. Mechanisms of viral interference have not been characterized for human parainfluenza virus type 3 (HPF3), and the possible role of the neuraminidase (receptor-destroying) enzyme of the hemagglutinin-neuraminidase (HN) glycoprotein has not been assessed. To determine whether continual HN expression results in depletion of the viral receptors and thus prevents entry and cell fusion, we tested whether cells expressing wild-type HPF3 HN are resistant to viral infection. Stable expression of wild-type HN-green fluorescent protein (GFP) on cell membranes in different amounts allowed us to establish a correlation between the level of HN expression, the level of neuraminidase activity, and the level of protection from HPF3 infection. Cells with the highest levels of HN expression and neuraminidase activity on the cell surface were most resistant to infection by HPF3. To determine whether this resistance is attributable to the viral neuraminidase, we used a cloned variant HPF3 HN that has two amino acid alterations in HN leading to the loss of detectable neuraminidase activity. Cells expressing the neuraminidase-deficient variant HN-GFP were not protected from infection, despite expressing HN on their surface at levels even higher than the wild-type cell clones. Our results demonstrate that the HPF3 HN-mediated interference effect can be attributed to the presence of an active neuraminidase enzyme activity and provide the first definitive evidence that the mechanism for attachment interference by a paramyxovirus is attributable to the viral neuraminidase.

Do women want a once-a-month pill?

The attitudes of women of reproductive age in Scotland, Romania and Slovenia to the idea of a contraceptive pill which is taken only once each month or only when menses are delayed was investigated. In all three centres, the great majority of women felt positive towards the idea of a once-a-month pill which inhibited ovulation and greater than 50% found a pill which inhibited or interfered with implantation an acceptable idea. Only 24% of women in Scotland were attracted to the idea of a pill which was taken only if menstruation was delayed by 1 or 2 days, that is a pill which would cause an abortion, while in contrast 58% of women in Slovenia and 80% in Romania thought that such a method of controlling fertility would be acceptable. Attitudes were not related to age, social class or marital status but were influenced by religious belief and in Scotland by a history of abortion. In countries where the availability of contraception is limited and abortion is common, women would seem to welcome another method of fertility regulation--even one which disrupts the very early stages of pregnancy.

PIP: In 1990-91, 400 women attending clinics at the Family Planning Centre Dean Terrace, Edinburgh, Scotland; 400 women attending a gynecology clinic in Tirgu-Mures, Romania; and 100 women attending a family planning clinic in Ljubljana, Slovenia, completed a questionnaire as part of a study to determine attitudes about taking a once-a-month contraceptive (OC) or using an OC to induce menstruation (missed-period OC). The highest abortion rate was in Ljubljana (55%)even though the rate in Romania was more than 2 times as high as the rate in Yugoslavia. Ljubljana had the most Roman Catholics (54%), but the lowest percentage espousing strong religious beliefs (2%). Women with weak religious beliefs were more positive about a once-a-month OC than those with strong religious beliefs in Scotland and Romania (p .005). This same relationship existed about the missed-period OC among only Scottish women. Most women in all 3 centers liked the idea of a once-a-month OC (71.8% in Edinburgh, 81.3% in Tirgu-Mures, and 94% in Ljubljana). Women in Edinburgh were less likely to accept a missed-period OC than women from the other centers (24.2% vs. 80% and 58%, respectively). The women from all 3 centers found ovulation inhibition to be the most acceptable mode of action (77.3-90.4% vs. 54.2-68% for prevention of implantation and 15.7-33.4% for implantation suppression). Overall, most women found any method which acts after implantation unacceptable. Scottish women who did not use an IUD or postcoital emergency contraception in the past tended to have a negative attitude about a once-a-month OC (p .01) and a missed-period OC (p .001). Women who had a induced abortion tended to have a positive attitude about a missed-period OC (p .01 in Edinburgh and p .05 in Ljubljana). Abortion history did not influence attitudes towards either OC in Romania. Childless women in Edinburgh were more likely to be positive about the once-a-month OC than women with children (p .05).

Human parainfluenza virus type 3 HN-receptor interaction: effect of 4-guanidino-Neu5Ac2en on a neuraminidase-deficient variant.

The envelope of human parainfluenza virus type 3 (HPF3) contains two viral glycoproteins, the hemagglutinin-neuraminidase (HN) and the fusion protein (F). HN, which is responsible for receptor attachment and for promoting F-mediated fusion, also possesses neuraminidase (receptor-destroying) activity. We reported previously that 4-guanidino-neu5Ac2en (4-GU-DANA) and related sialic acid-based inhibitors of HPF3 neuraminidase activity also inhibit HN-mediated receptor binding and fusion processes not involving neuraminidase activity. We have now examined this mechanism, as well as neuraminidase's role in the viral life cycle, using a neuraminidase-deficient HPF3 variant (C28a) and stable cell lines expressing C28a or wild-type (wt) HN. C28a, which has a wt F sequence and two point mutations in the HN gene corresponding to two amino acid changes in the HN protein, is the first HPF3 variant with insignificant neuraminidase activity. Cells expressing C28a HN did not bind erythrocytes at 4 degrees C unless pretreated with neuraminidase, but no such pretreatment was required for hemadsorption activity (HAD) at 22 or 37 degrees C. HAD was blocked by 4-GU-DANA, attesting to the ability of this compound to inhibit HN's receptor-binding activity. C28a or wt plaque enlargement, a process that involves cell-cell fusion and does not depend on virion release, is diminished by the presence of 4-GU-DANA, confirming the inhibitory effect of 4-GU-DANA on the fusogenic function of C28a HN. In C28a-infected cell monolayers, virion release and thus multicycle replication are severely restricted. This defect was corrected by supplementation of exogenous neuraminidase and also by the addition of 4-GU-DANA; neuraminidase destroys the receptors whereby newly formed C28a virions would remain attached to the cell surface, whereas 4-GU-DANA prevents the attachment itself, obviating the need for receptor cleavage. In accord with the ability of 4-GU-DANA to prevent attachment, the neuraminidase inhibitory effect of 4-GU-DANA on wt HPF3 did not diminish virion release into the medium. Thus, it is by inhibition of viral entry and syncytium formation that sialic acid analogs like 4-GU-DANA may counteract wt HPF3 infection.

Prevalence of endemic goiter in Mures County.

A number of 20,000 children representing 91.19% of all the enlisted children aged 6-14 years were examined. The clinical status of each child was assessed according to the WHO criteria. Goiter was found in 3,363 (16.81%) children. Of these, 1504 (44.72%) were boys and the zero degree, 2,137 (63.54%) to the 1 degree and 84 (2.49%) to the 2nd degree. As related to the total number of children examined, the zero degree goiter was found in 5.71%, the ist degree in 10.68% and the 2nd degree in 0.42% of the cases. The incidence of goiter in rural and urban areas was in the range of 6.80%-38.46%. Only in 2 areas the incidence was higher: 42.33% and 60%. A predominantly increased incidence was found in those areas which were not screened in 1951 and consequently prophylaxis was not constantly applied.