Fluconazole susceptibility of vaginal isolates obtained from women with complicated Candida vaginitis: clinical implications.

Despite considerable evidence of azole resistance in oral candidiasis due to Candida species, little is known about the azole susceptibilities of the genital tract isolates responsible for vaginitis. The fluconazole susceptibilities of vaginal isolates obtained during a multicenter study of 556 women with complicated Candida vaginitis were determined by evaluating two fluconazole treatment regimens. Of 393 baseline isolates of Candida albicans, 377 (96%) were highly susceptible to fluconazole (MICs, <8 microg/ml) and 14 (3.6%) were resistant (MICs, >or=64 microg/ml). Following fluconazole therapy, one case of in vitro resistance developed during 6 weeks of monitoring. In accordance with the NCCLS definition, in vitro fluconazole resistance correlated poorly with the clinical response, although a trend of a higher mycological failure rate was found (41 versus 19.6% on day 14). By using an alternative breakpoint of 1 micro g/ml, based upon the concentrations of fluconazole achievable in vaginal tissue, no significant differences in the clinical and mycological responses were observed when isolates (n = 250) for which MICs were 1 microg/ml, although a trend toward an improved clinical outcome was noted on day 14 (odds ratio, >2.7; 95% confidence interval, 0.91, 8.30). Although clinical failure was uncommon, symptomatic recurrence or mycological relapse almost invariably occurred with highly sensitive strains (MICs, <1.0 microg/ml). In vitro fluconazole resistance developed in 2 of 18 initially susceptible C. glabrata isolates following fluconazole exposure. Susceptibility testing for women with complicated Candida vaginitis appears to be unjustified.

Treatment of complicated Candida vaginitis: comparison of single and sequential doses of fluconazole.

OBJECTIVE: An attempt was made to validate recent recommendations that women with complicated Candida vaginitis (severe or recurrent, non-albicans Candida spp or abnormal host) require longer-duration antifungal therapy to achieve clinical cure and mycologic eradication. STUDY DESIGN: A prospective, multicenter, randomized, double-blind study was performed comparing a single dose of 150 mg of fluconazole with 2 sequential 150-mg doses of fluconazole given 3 days apart. RESULTS: Five hundred fifty-six women with severe or recurrent Candida vaginitis were enrolled, and 398 had at least one postbaseline evaluation (intent to treat) and of these 309 were fully evaluable (efficacy-valid). At baseline, 92% of vaginal isolates were Candida albicans. The 2-dose fluconazole regimen achieved significantly higher clinical cure rates in women with severe vaginitis when evaluated on day 14 (P =.015) and higher clinical and mycologic responses persisted at day 35. Women with recurrent but not severe vaginitis did not benefit clinically short term by the additional fluconazole dose. Multivariate logistic regression analysis showed that being infected with non-albicans Candida predicted significantly reduced clinical and mycologic response regardless of duration of therapy. Fluconazole therapy was well tolerated and free of serious adverse effects. CONCLUSION: Treatment of Candida vaginitis requires individualization, and women with severe Candida vaginitis achieve superior clinical and mycologic eradication with a 2-dose fluconazole regimen.

Effects of danazol on coagulant activity in the rat.

Coagulation factor activity was evaluated in female rats treated with danazol. Following 30 days of treatment, slight decreases in factor VII and X activities were noted. After 60 days, a prolongation of the prothrombin time, as well as a decrease in factor VII, was noted. The data suggest that in the rodent, danazol has minimal effects on coagulation activity.

A comparison of microsurgery and laser surgery for ovarian wedge resections.

To evaluate the effect of microsurgery and CO2 laser on postoperative adhesion formation after ovarian wedge resection, 30 New Zealand adult female rabbits were randomly divided into three groups of ten animals each. The control group (n = 10) had ovarian wedge resections using a scalpel with closure of the ovary performed using microsurgery technique. The second group had ovarian wedge resections performed using the CO2 laser coupled to an operating microscope. The third group (n = 10) had multiple small areas of vaporization performed on the ovary using the CO2 laser. Four weeks after the initial surgery the animals were killed and evaluated for intraperitoneal adhesions. No significant differences (P greater than .05) were found between the three groups of animals. This study suggests that the use of laser surgery may not offer a significant reduction in postoperative adhesion formation in comparison with standard microsurgery technique when performing ovarian wedge resections.

Orally and parenterally administered ibuprofen for postoperative adhesion prevention.

Adhesion formation was examined in 45 rats that were divided into five groups of 9 animals each: control, oral ibuprofen, intramuscular ibuprofen, intraperitoneal 32% dextran 70, and oral ibuprofen plus intraperitoneal 32% dextran 70. Four weeks after receiving a standard injury, all the animals were killed and the adhesions scored blindly. Both the oral and intramuscular ibuprofen groups had significantly less severe adhesion formation (P less than .01) when compared to the control group. Although 32% dextran 70 alone showed no beneficial effect in reducing adhesions, the combination of oral ibuprofen and 32% dextran 70 had the least adhesion formation (P less than .002) when compared to the control group. Oral and intramuscular ibuprofen seem to be equally efficient in reducing postoperative adhesions. Furthermore, the combination of oral ibuprofen and 32% dextran 70 appears to have a synergistic effect.

Collagen sponge as vaginal contraceptive barrier: critical summary of seven years of research.

Extensive testing of collagen sponge as a vaginal contraceptive (mechanical and chemical) showed that the original expectations regarding the safety, convenience, and efficacy were not met. The collagen sponge was tested both as a cylinder and as a diaphragm and used as such or impregnated with spermicidal detergent or with zinc salt. The collagen sponge must be larger than 6 cm in diameter in order to serve as a mechanical barrier that will not be dislodged during physical activity. This creates problems with the ease of insertion and with the partners' awareness of the barrier. When the collagen sponge containing ejaculate is left in the vagina greater than 48 hours, it develops an offensive odor. The original acidity of the collagen sponge (pH 3.5, 0.1 mol/L) is soon neutralized by the large volume of alkaline vaginal secretions. In vitro studies showed that up to 10 mg of nonoxynol 9 per milliliter of growth medium did not inhibit the growth of Staphylococcus aureus. These effects, as well as the large surface area of the resilient sponge, present a potential risk for growing staphylococci within the collagen sponge. The capacity of the collagen sponge to absorb a large volume of cervical and vaginal fluid produced two symptoms that were annoying to the volunteers: an awareness of either vaginal dryness during intercourse or, conversely, saturation of the sponge from the vagina. Postcoital studies showed viable spermatozoa in the cervical mucus in 25% of the tests with the nonmedicated cylindrical sponge but in only 6% of tests with the sponge containing nonoxynol 9. The results of clinical trials conducted at four centers support the view that collagen sponge as a vaginal contraceptive barrier method is inconvenient to both partners, not effective enough to compete with present methods of vaginal contraception, and possibly might be unsafe because of the capacity to grow bacteria. Despite the negative end result of this goal-oriented research, we believe that our studies have contributed to a better understanding of vaginal physiologic features, the safety and effectiveness of spermicidal detergents, and the mechanisms of vaginal malodor. Although the acceptability study showed some advantages of the collagen sponge over the rubber diaphragm, the overall acceptability of the collagen sponge diaphragm was no better than that of the rubber diaphragm. For all these reasons, including the possible risk of an increased incidence of toxic shock syndrome, we have discontinued further testing of either type of collagen sponge as a vaginal barrier method.

Effects of acute ethanol intoxication combined with secobarbital abuse on hemostasis.

Male Sprague-Dawley rats were treated with 0.5 ml of 46% ETOH, 2.8 mg/kg of secobarbital or 14.3 mg/kg secobarbital or combinations thereof. Twenty-four hours following treatment, blood clotting data was determined. The data indicated that either ethanol or secobarbital alone is just as detrimental to hemostasis as is the combined abuse of both. Likewise, a lesser concentration of alcohol was just as disruptive on hemostasis as was the greater concentration of ethanol.

Interaction between ethanol and contraceptive steroids on clotting activity in the rat.

Female rats were given either ethinyl estradiol or norethindrone in conjunction with water or 5% ethanol. Hematological parameters measured included the prothrombin time (PT), partial thromboplastin time (APTT), fibrinogen (FIB), factors II, V, VII, VIII, X, and XII activity; plus the platelet count (PLT) and hematocrit (HCT). The data indicates that norethindrone together with water produces the greatest number of changes in clotting activity.

Evidence for an ethanol mediated disruption of hemostasis.

Male Sprague-Dawley rats were given 1 ml intraperitoneal (i.p.) injections of saline, 5, 10 or 20% ethanol once daily for 7 days. Clotting times were determined for the PT, APTT, FIB, and factors II, V, VII, VIII, X, and XII. The platelet count (PLT) and the hematocrit (HCT) were also determined. Besides a uniform statistically significant decrease in the platelet count, the clotting times for the coagulation factors were also influenced by the alcohol injected. The data tends to indicate that when the concentration of alcohol was greater, that more clotting times were influenced. Detailed analysis of the data in reference to the total clotting cascade tends to suggest that ethanol principally prolongs the clotting times of the intrinsic pathway, while the extrinsic pathway appears to be unaffected by the treatment, and the common pathway is normal to accelerated in clotting times. This suggests that hemostasis as a whole was not affected by the treatment, but specific portions of the clotting cascade were, and development of abnormal hemostasis due to ethanol might depend on which part of the pathway was activated.

Alcoholism and reproduction.

A brief overview of the reproductive capacities of both men and women in alcoholism is presented. A historical evaluation indicates a resurgence of interest in this area. The effect of chronic alcohol consumption on both male fertility and potency is reported in conjunction with alcohol-mediated effects on the female subject. Emphasis is placed on pharmacokinetics, metabolism and drinking behavior of the alcoholic female. The adverse actions of some therapeutic drugs and chronic alcohol consumption is discussed in relationship to fetal alcohol syndrome and the accompanied mental and somatic abnormalities.

Ratio of amniotic fluid cortisol and maternal serum cortisol (AFC/MSC) as an index of fetal lung maturity.

Fifty-eight samples of amniotic fluid from pregnant women between the gestation period of 34-42 weeks were analyzed for total cortisol levels. Thirty-four simulatneous maternal serum total cortisol levels were also measured. Amniotic fluid cortisol (AFC), maternal serum cortisol (MSC) and the ratio of AFC/MSC were correlated with L/S ratio. AFC alone and AFC/MSC ratios correlate with L/S ratios (r=0.36, p less than 0.01, and r=0.46, p less than 0.01, respectively). MSC and L/S ratios had no correlation. AFC/MSC had less individual variation as compared to AFC alone. The AFC/MSC could be divided by an arbitrary line at 0.1 and values less than 0.1 signify immature fetal lungs. Values of 0.1 and greater signify mature fetal lungs.

Functional endometrial tissue with vaginal agenesis.

Vaginal agenesis in association with an intact and functioning or partially functioning uterus is not a well-described problem. The literature advocates attempting to preserve the uterus and surgically create a neovagina. Two patients are presented who suffered severe mobidity after the latter approach. We believe that there are three possibilities with patients who have functional endometrial tissue with vaginal agenesis: namely, an imperforate hymen, a transverse vaginal septum or complete vaginal agenesis with the absence or malformation of the cervix. If an imperforate hymen and transverse vaginal septum are ruled out, we believe it is the best interest of the patient to remove the Müllerian structures during the initial surgery.

The acceptance of the collagen sponge diaphragm as an intravaginal contraceptive in human volunteers.

Two types of highly resilient and liquid-absorbent collagen sponge contraceptives (CSC) in the shape of cylindrical cups (6 cm wide and 2.5 cm thick) were evaluated for acceptance as an intravaginal contraceptive method for a period of 3 months in 27 volunteers. Parameters such as retention, odor, irritation, itching, discharge, and convenience for the user and her sexual partner were tested. Average retention time was 7 to 9 days (range, 2 to 28 days); still, most sexually active volunteers preferred to remove the CSC every 3 to 4 days, rinse them in tap water, and reinsert them. Odor was noticed by users in 4% of the tested sponges and in 30% of all volunteers by medical personnel at the time of removal of the CSC from the vagina. No irritation, itching, or discharge was reported. The CSC alone did not cause any inconvenience to the user or partner, while the CSC with inserted rubber ring was felt by both partners and was found to be dislocated. This study indicates good acceptance of the CSC in intravaginal use. Studies to evaluate the efficacy of collagen sponges as mechanical contraceptive barriers are in progress.

X-short arm deletion gonadal dysgenesis in two siblings due to unique translocation (Xp-;16p+).

A family demonstrating short arm deletion of the X chromosome as a consequence of X-16 balanced translocation in the mother is reported. The two Xp- sisters exhibit clinical signs of gonadal dysgenesis, while the balanced carriers are phenotypically normal. To our knowledge this represents the only example of both the balanced carrier state for an X translocation and its genetic consequence occurring in the offspring, as well as the involvement of X-16 interchange. Literature data of 37 additional cases of verified X translocations are discussed.