Zidovudine treatment of the AIDS dementia complex: results of a placebo-controlled trial. AIDS Clinical Trials Group.

The efficacy of two doses of zidovudine was examined for the treatment of the acquired immunodeficiency syndrome (AIDS) dementia complex in a randomized, double-blinded, placebo-controlled trial conducted at nine study centers. For the initial 16 weeks, 40 subjects with mild to moderate AIDS dementia complex were randomized to one of three treatment arms: 400 mg of zidovudine five times daily, 200 mg of zidovudine five times daily, or placebo five times daily. After week 16, patients initially randomized to the placebo group were rerandomized to one of the two zidovudine treatment arms. The primary efficacy end point was improvement in performance on a battery of seven neuropsychological tests; the secondary end point was improvement on a protocol neurological evaluation directed at the cardinal features of the AIDS dementia complex. For the initial 16-week period, average z scores based on the neuropsychological test battery revealed a significant improvement in the combined treatment groups compared to the placebo group; however, when the two treatment groups were compared separately to the placebo group, only the group receiving the higher zidovudine dose exhibited significant improvement. After rerandomization of the placebo patients to one of the two treatment arms at week 16, this group also showed significant improvement in the average neuropsychological z score by week 32. These results extend previous observations that indicate a therapeutic benefit of zidovudine for the treatment of AIDS dementia complex.

Behavioral, health and psychosocial factors and risk for HIV infection among sexually active homosexual men: the Multicenter AIDS Cohort Study.

We examined whether 644 homosexual men who engaged in receptive anal intercourse were at particularly elevated risk for seroconversion if they also possessed specific behavioral, health or psychosocial vulnerability characteristics. Of 11 potential factors examined, heavy drinking, moderate to heavy drug use, and younger age were significantly related to seroconversion. These variables were also associated with an increased number of sexual partners, anonymous sex, and failure to use condoms.

ECT for major depression in four patients infected with human immunodeficiency virus.

The authors describe four individuals infected with the human immunodeficiency virus type I (HIV) whose severe depressions were successfully treated with ECT.

Estrogen modulates neural control of muscle glucose 6-phosphate dehydrogenase.

Exogenously administered estrogens can enhance the rate of increase of glucose 6-phosphate dehydrogenase activity in rat extensor digitorum longus muscles following denervation. In this communication, we report that the effect of denervation on glucose 6-phosphate dehydrogenase activity is modified by variations in endogenous estradiol during the estrous cycle.

Ovarian follicular and luteal physiology.

Follicular maturation and development is a complex process of interrelated intra- and extraovarian events that ultimately lead to ovulation of a mature oocyte and transformation of the ruptured follicle into a corpus luteum. The primordial follicle consists of an immature oocyte arrested in the dictyate stage of meiosis, surrounded by a single layer of relatively undifferentiated granulosa cells. The oocyte remains in the immature state because of many factors, one of which is the oocyte maturation inhibitor (OMI) secreted by granulosa cells. The oocyte subsequently increases in size, and as the antrum forms it becomes surrounded by cumulus cells. The cumulus cells may be intimately involved in the action of O,I to arrest the oocyte in the immature state within the follicle, as well as the resumption of meiosis during the LH surge. The compartments of the follicle that change most dramatically during follicular maturation are the cells lining the follicle--the granulosa and thecal cells. Under the influence of estrogen and FSH, the granulosa cells proliferate and also acquire FSH receptors. At this time, the thecal compartment differentiates and surrounds the granulosa cells, but remains separated from them by a basement membrane. Steroid secretion by the antral follicle involves the interplay of androgens, estrogens, and progestins. Both the granulosa and thecal cell compartments contribute to follicular fluid and serum levels of steroids; the interaction of both cell types may be necessary for estrogen and progesterone secretion in some species. As a consequence of the presence of an elevated number of FSH receptors, the granulosa cells of the small antral follicle are able to respond to FSH in many ways, including increased cyclic AMP accumulation, activation of the aromatase system, and induction of LH receptors, which permits the granulosa cells to later respond to LH. The mechanism by which thecal cells acquire their LH receptors is presently unknown. The granulosa cells of the follicle may indirectly control their own maturation and the number of follicles maturing through the secretion of follicular inhibin, which decreases the pituitary output of FSH. Even though the granulosa cells have acquired large numbers of LH receptors, they are prevented from luteinizing prematurely by factors in follicular fluid, including estrogen and a luteinizing inhibitor (LI). As serum LH levels increase during the preovulatory LH surge, a number of events occur: resumption of oocyte meiosis, transformation of the steroid enzyme complex from estrogen to progesterone secretion, follicular rupture, and formation of the corpus luteum. Granulosa cells form the bulk of the corpus luteum, which secretes elevated amounts of progesterone for a fixed time period depending on the species. Before ovulation the preovulatory follicle must be exposed to and respond to adequate LH and FSH levels in order for the eventual corpus luteum to secrete elevated amounts of progesterone for its normal lifespan...

Effects of follicular development on the ability of cultured porcine granulosa cells to convert androgens to estrogens.

Porcine granulosa cells from different stages of follicular development were examined for their ability to convert androgens to estrogens and their ability to secrete progesterone. Granulosa cells from all stages of follicular development can convert androgens to estrogens, and the addition of exogenous androgen is required for estrogen secretion. Granulosa cells obtained from medium and large follicles have a greater capacity to convert androgens to estrogens than do granulosa cells obtained from small follicles. The addition of FSH brought about an increase in estrogen secretion in the presence of androgen only in granulosa cells from large follicles. LH attenuated estrogen secretion in granulosa cells from medium follicles treated with testosterone. Granulosa cells from medium follicles were unable to secrete estrogen from days two to four irrespective of treatment. Androgens augment FSH stimulated progesterone secretion in granulosa cells from medium follicles from days two to four, and the addition of follicular fluid from small follicles stimulates progesterone secretion in the presence of FSH and androgens.

Hormonal control of oocyte meiosis, ovulation and luteinization in mammals.

The ovulatory process can be regarded as a series of biochemical and morphological changes ultimately leading to the release of a mature oocyte and the transformation of the Graafian follicle into the corpus luteum. This process involves acute changes in steroidogenesis, resumption of oocyte meiosis, and finally rupture of the follicular wall and luteinization of the granulosa cells. Normally, all of these changes are induced synchronously by the pre-ovulatory LH surge. Experimentally, however, these changes in steroidogenesis, oocyte maturation and follicular rupture can be dissociated from each other showing that the LH effect is mediated via different cellular messengers. The gonadotrophins act in an orderly sequence to induce follicular maturation. The granulosa cells increase their number of LH receptors and respond to LH with increased stimulation of cyclic AMP accumulation and progesterone secretion. Concomitantly, they decrease in their FSH receptors and their response to FSH diminishes in terms of ability to stimulate cyclic AMP accumulation. The ovulatory process is associated with increased uptake of LH by the follicle; when granulosa cells are obtained from pre-ovulatory follicles and cultured they luteinize spontaneously. Steroid hormones modulate the actions of gonadotrophins on follicular maturation. In addition, there are non-steroidal factors in follicular fluid which regulate follicular maturation: an oocyte maturation inhibitor keeps the oocyte in meiotic arrest; a luteinizing inhibitor prevents the granulosa cells from luteinizing prior to follicular rupture; a folliculostatin inhibits FSH release from the pituitary gland. The functional activity and the lifespan of the corpus luteum depend on adequate pre-ovulatory as well as post-ovulatory gonadotrophic stimulation. Its lifespan may also be regulated by an LH binding inhibitor.