Change to atazanavir/ritonavir treatment improves lipids but not endothelial function in patients on stable antiretroviral therapy.

Objective: Protease inhibitors and other antiretroviral drugs have been associated with dyslipidemia, endothelial dysfunction, and increased cardiovascular disease risk. The protease inhibitor atazanavir has an advantageous lipid profile; we studied its effects on arterial function and other metabolic and inflammatory cardiovascular disease risk factors.

Design: Prospective, randomized, multinational trial in HIV-infected patients receiving stable protease inhibitor-based therapy with plasma HIV RNA less than 500 copies/ml and fasting low-density lipoprotein cholesterol more than 130 mg/dl, or triglycerides more than 200 mg/dl.

Mitochondrial function, morphology and metabolic parameters improve after switching from stavudine to a tenofovir-containing regimen.

Objectives: HIV-associated lipoatrophy has been associated with mitochondrial dysfunction induced by nucleoside reverse transcriptase inhibitor therapy. We hypothesize that lipid profiles and markers of mitochondrial function will improve in HIV-lipoatrophic patients switched to the nucleotide analogue tenofovir.

Methods: Ten patients receiving stavudine, lamivudine and lopinavir/ritonavir (Kaletra(R)) for over 6 years were switched from stavudine to tenofovir for 48 weeks.

Consumption of tall oil-derived phytosterols in a chocolate matrix significantly decreases plasma total and low-density lipoprotein-cholesterol levels.

In a randomized, double-blind, placebo-controlled trial we evaluated the effect of dietary chocolates enriched with a wood-based phytosterol-phytostanol mixture, containing 18 % (w/w) sitostanol, compared with placebo dietary chocolates in seventy subjects with primary hypercholesterolaemia (total cholesterol levels below 8 mmol/l). For 4 weeks, participants consumed three servings of the phytosterol-enriched chocolate/d that provided 1.8 g unesterified phytosterols/d or a placebo chocolate in conjunction with a low-fat, low-cholesterol diet.

Lack of efficacy of low dose oral interferon alfa in symptomatic HIV-1 infection: a randomised, double blind, placebo controlled trial.

Background: Interferon alfa (IFN-alpha) exhibits dose related in vitro activity against human immunodeficiency virus (HIV), with complete inhibition of HIV replication at IFN-alpha concentrations > or = 256 IU/ml. In mid-1990, Kenyan investigators reported that oral administration of an extremely low dose (150 IU/day) of natural human (nHu) IFN-alpha resulted in complete alleviation of AIDS related complex and AIDS symptoms and resolution of opportunistic infections without additional treatment. Moreover, loss of HIV antibody seropositivity was reported in approximately 10% of treated patients.

Menstrual bleeding patterns in untreated women. Task Force on Long-Acting Systemic Agents for Fertility Regulation.

Menstrual histories recorded by more than 1000 healthy, untreated women have been analyzed using the reference period method. Results were obtained for each year of age from 15 to 49. Between menarche and age 19, the most important feature of menstrual patterns is their variability.

Clinical evaluation of the therapeutic effectiveness of ethinyl oestradiol and oestrone sulphate on prolonged bleeding in women using depot medroxyprogesterone acetate for contraception. World Health Organization, Special Programme of Research, Development and Research Training in Human Reproduction, Task Force on Long-acting Systemic Agents for Fertility Regulation.

A placebo-controlled randomized clinical trial was conducted in six centres to compare the effects of a 14 day treatment with either 50 micrograms ethinyl oestradiol daily or 2.5 mg oestrone sulphate daily, on depot medroxyprogesterone acetate (DMPA)-induced prolonged bleeding. Out of 1035 women admitted to the study, 278 requested treatment and were given ethinyl oestradiol (n = 90), oestrone sulphate (n = 91) or placebo (n = 97).

Frequent use of menfegol spermicidal vaginal foaming tablets associated with a high incidence of genital lesions.

Menfegol is a spermicide with in vitro activity against human immunodeficiency virus (HIV). A randomized placebo-controlled safety study covered the use of menfegol foaming tablets for 14 days at increasing frequencies of insertion by 125 prostitutes in Dakar, Senegal. The frequencies of colposcopically diagnosed genital lesions were 5.

Sensitivity of HIV-antibody assays determined by seroconversion panels.

Objectives: To determine the sensitivity of HIV-antibody assays for detecting low levels of HIV antibody using seroconversion and other panels containing plasma of varying titres.

Methods: Eight HIV-antibody assays, available under the World Health Organization bulk-procurement agreement, were evaluated on sets of sequential plasma samples derived from 11 individuals who had recently become HIV-infected (seroconversion panels). In addition, two non-seroconversion panels, consisting of low performance (titre) and mixed titre samples were used to further define the sensitivity of the assays.

Preparation for phase III HIV vaccine efficacy trials: methods for the determination of HIV incidence.

Objective: Accurate estimates of HIV incidence that reflect the effect of non-vaccine interventions (education, counselling, condom promotion, and possibly sexually transmitted disease treatment) and that may be provided in a Phase III vaccine efficacy trial, are needed so that vaccine trial population sample sizes can be accurately determined. In order to avoid delays in the implementation of efficacy trials, well characterized cohorts must also be developed and available to participate in such trials. We reviewed the potential study populations, the epidemiologic methods for the determination of HIV incidence (using open cohort, closed cohort, and seroprevalence data methods), and the need for the development of population cohorts in preparation for Phase III HIV vaccine efficacy trials.

Menstrual bleeding patterns in untreated women and with long-acting methods of contraception. Task Force on Long-Acting Systemic Agents for Fertility Regulation.

The bleeding patterns recorded by women using one of two new types of long-acting hormonal contraception, a levonorgestrel-releasing vaginal ring or a monthly injectable, have been compared with those in an untreated group and those experienced by women using either a combined oral contraceptive (OC) or depot-medroxyprogesterone acetate (DMPA). The frequency of bleeding was very similar between the combined pill users, the ring users and the untreated women, who all recorded an average of 3.2-3.

Lysosomal enzymes in the human endometrium: a biochemical study in untreated and levonorgestrel-treated women.

The activities of four lysosomal enzymes, i.e. N-acetyl-beta-hexosaminidase, acid phosphatase, alpha-D-mannosidase and alpha-L-fucosidase have been measured in extracts of endometrial biopsies from untreated and levonorgestrel-treated women of fertile age.

Endometrial vascular features prior to and following exposure to levonorgestrel.

A study of endometrial vasculature, mast cell numbers and tissue levels of tissue plasminogen activator (tPA) prior to and following exposure to levonorgestrel (20 micrograms/day) administered via a vaginal ring was undertaken. Following exposure to levonorgestrel, significantly fewer arterioles were present in the endometrium. During the early secretory phase of the control cycle, a positive correlation was found between mast cell numbers and progesterone levels.

Morphometric study of the human endometrium following continuous exposure to levonorgestrel released from vaginal rings during 90 days.

The effects of vaginal devices releasing levonorgestrel (LNG) at a constant rate of approximately 20 micrograms/24 hrs on the human endometrium were studied in a group of 69 normally menstruating women during a period of 90 days of continuous use. Peripheral blood samples were withdrawn three times weekly starting at day 10 of a pretreatment (control) cycle and then three times weekly from day 60 to 90 of the treatment period. The levels of LNG, estradiol, progesterone and sex hormone binding globulin (SHBG) were analyzed by radioimmunoassay techniques.

Prostaglandin production in human endometrium following continuous exposure to low-dose levonorgestrel released from a vaginal ring.

Arachidonic acid metabolites produced by primary cultures of human endometrial cells derived from biopsies obtained before and after exposure to 20 micrograms/day levonorgestrel for 84 +/- 1 days were analysed by reverse phase HPLC. This revealed a significant increase in PGF1 alpha and an epoxide metabolite upon levonorgestrel stimulation. The proportion of epoxide metabolite, PGF1 alpha and PGE2 were positively correlated with serum levonorgestrel levels while HETES, PGE2 and epoxide were similarly correlated with serum oestradiol.

Menstrual blood loss and body iron stores in Brazilian women.

Menstrual blood loss (MBL) studies are relevant for developing world women as this could be an important cause of anemia. Whenever a contraceptive method is to be used by such women, consideration should be given to the method which least affects the volume of MBL. In 309 women considered as clinically healthy, MBL, serum ferritin, serum iron and hemoglobin levels were measured: a mean MBL of 23 ml was found.

The description of menstrual bleeding patterns: towards fewer measures.

The disturbance in menstrual bleeding induced by many methods of contraception is an important factor in their acceptability, and women participating in clinical trials of new methods are usually asked to keep a calendar record of the occurrence of bleeding. A recent WHO report recommends that, for analysis and presentation, each menstrual diary should be divided into successive periods, and the woman's bleeding pattern in each period summarized in ten indices. These indices are simple to calculate and easily understood by clinicians, but comparison of several groups is problematic because of the large number of summary statistics generated.

Termination of early human pregnancy with RU 486 (mifepristone) and the prostaglandin analogue sulprostone: a multi-centre, randomized comparison between two treatment regimens.

A multi-centre, randomized trial was conducted to compare the efficacy and side-effects of two combination regimens of the antiprogestin RU 486 and the intramuscular PGE2 analogue sulprostone for termination of early pregnancy (amenorrhoea up to 49 days). Women in the 3-day group (n = 125) received 25 mg RU 486 twice daily for 3 days plus a single injection of 0.25 mg sulprostone in the morning of the third day of antiprogestin treatment.

Effect of oral prostaglandin E2 on uterine contractility and outcome of treatment in women receiving RU 486 (mifepristone) for termination of early pregnancy.

It has been shown that the antiprogestin RU 486 (mifepristone) increases the sensitivity of the early pregnant human uterus to the stimulatory action of synthetic prostaglandin E (PGE) analogues. To examine if RU 486 also increases uterine sensitivity to the naturally occurring PGE2 given orally, two investigative approaches were used in the present studies: (i) direct registration of uterine contractions before and after PGE2 administration in untreated and RU 486-treated early pregnant women; and (ii) a double-blind, randomized, controlled efficacy trial involving treatment of pregnant women (amenorrhoea of less than or equal to 49 days) with RU 486 (25 mg twice daily for 4 days) and PGE2 (1 mg once or twice) or placebo on the last day of RU 486 treatment. The results indicate that oral PGE2 at the doses employed had little or no stimulatory effect on uterine contractility and that it did not improve the rate of complete abortion achieved with RU 486 alone.

The analysis of menstrual bleeding patterns: a review.

Patterns of vaginal bleeding are an important factor in the acceptability of contraceptive methods. The analysis of data obtained from daily menstrual diary records is a major methodological problem to which no satisfactory solution exists. This review describes approaches to the analysis of bleeding patterns among contracepting and non-contracepting women and reviews the difficulties involved.

Determinants of menstrual bleeding patterns among women using natural and hormonal methods of contraception. II. The influence of individual characteristics.

Menstrual diary records were obtained from women using either a natural method of contraception, a combined or progestogen-only oral contraceptive, a vaginal ring, or a long-acting injectable (DMPA). Within each method group, multiple regression analysis was used to examine the relationships between the subjects' bleeding patterns and their age, age at menarche, ponderal index, obstetric and contraceptive history and ethnic origin. The influence of ethnic origin was described in the preceding paper.

Determinants of menstrual bleeding patterns among women using natural and hormonal methods of contraception. I. Regional variations.

Records of the occurrence of vaginal bleeding were obtained from women using either a natural method of contraception or one of four types of hormonal contraceptive. The relationships between their bleeding patterns and a number of demographic variables were examined, with the aim of identifying subgroups of women who, if they used a particular hormonal method of contraception, would be likely to suffer more or less disruption to their bleeding pattern than the 'norm'. Within contraceptive method, bleeding patterns were more closely related to the women's geographical region of residence than to any other factor.

The association between vaginal bleeding patterns and reasons for discontinuation of contraceptive use.

This paper describes the relationship between menstrual bleeding patterns recorded and reasons for discontinuing method use given by women using one of four types of hormonal contraception: combined oral pills, progestogen-only oral pills, a vaginal ring or depot-medroxyprogesterone acetate (DMPA). The women were recruited to five clinical trials, each of which lasted at least 48 weeks. The subject's reason for discontinuation was recorded if she stopped contraceptive use before the scheduled time.