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Lasioglossins represent a group of peptides with identified antimicrobial activity. We investigated the inhibitory effects of two synthetic lasioglossin derivatives LLIII and D-isomeric variant LLIII-D on the morphological changes of Candida albicans in vitro and the effect of local administration of LLIII during experimental murine candidiasis. C. albicans blastoconidia were grown in the presence of lasioglossin LLIII or LLIII-D at the concentration of 11.5 μM and 21 μM for 1, 2, and 3 days and the viability was determined by flow cytometry using Eosin Y staining. The morphological changes were determined by light and fluorescent microscopy. The Candida-inhibitory effect of daily intravaginal administration of 0.7 or 1.4 μg of LLIII was estimated in experimentally-induced vaginal candidiasis of mice. LLIII and LLIII-D lasioglossins exhibited candidacidal activity in vitro (>76 % after 24 h and > 84% after 48 h of incubation). After 72 h incubation of Candida with low concentration of lasioglossins, increase in the viability was detected, probably due to a Candida antimicrobial peptides evasion strategy. Furthermore, lasioglossins inhibited the temperature-induced morphotype changes toward hyphae and pseudohyphae with a sporadic occurrence of atypical two- or enlarged-nuclei cells supposing interference with mitosis or cytokinesis. Local application of LLIII reduced duration of experimental candidiasis without evidences of side effects. Lasioglossin LLIII seems to be promising candidate for development of antimicrobial drug for the treatment of the vaginal candidiasis.

Problem The capacity of antigen-carrying vaccine nanoparticles (NPs) administered vaginally to stimulate local immune responses may be limited by the relatively low numbers of antigen-presenting cells (APCs) in the genital mucosa. Because inflammation is associated with increased susceptibility to sexually transmitted infections, we sought to increase APC numbers without causing inflammation. Method of Study In this study, we evaluated intravaginal delivery of chemokines, growth factors, or synthetic adjuvants to expand APCs in reproductive tissues. Results We found that granulocyte–macrophage colony-stimulating factor (GM-CSF) stimulated expansion of CD11b+ dendritic cells (DCs) within 24 hr of intravaginal administration, with no effect on Langerhans cells or macrophages. Expansion of the CD11b+ DC population was not associated with increased inflammatory cytokine production, and these cells retained phagocytic function. Conclusion Our data suggest that non-inflammatory expansion of mucosal APCs by intravaginal GM-CSF could be used as an adjuvanting strategy to potentiate the genital immune response to nanoparticulate mucosal vaccines.

Objectives To investigate population-level prevalence of vaginal practices, their frequency and self-reported health consequences in KwaZulu-Natal, South Africa. Methods A household survey using multi-stage cluster sampling was conducted in 2007. Women aged 18-60 (n = 867) were interviewed on demographics, sexual behaviours and vaginal practices, focusing on intravaginal practices. Design-based analysis used multivariate logistic regression to identify factors associated with intravaginal or any practice. Results Most women currently perform vaginal practices (90.2%), with 34.8% reporting two and 16.3%

This study was aimed to evaluate the reproductive performance of rabbit does artificially inseminated (AI) with a GnRH analogue [des-Gly10, D-Ala6]-LHRH. ethylamide to induce ovulation by intravaginal administration, delivered in the seminal dose. In a preliminary experiment, 39 does were divided into three groups (n = 13) that, at the time of AI, received the following ovulation induction treatments: (i) control group: 20 microg of gonadorelin administered intramuscularly; (ii) 25 microg of the GnRH analogue added to the seminal dose; (iii) 30 microg of the GnRH analogue added to the seminal dose. Fertility did not differ between the three groups (control: 80.6%, group 2: 82.8%, group 3: 73.3%). In a second experiment, a large-scale field trial was conducted to test the use of 25 microg of the GnRH analogue [des-Gly10, D-Ala6]-LHRH ethylamide delivered in the seminal dose (n = 270) against 20 microg of gonadorelin administered intramuscularly. Fertility was higher (p < 0.05) when ovulation was induced by intravaginal administration of the GnRH agonist (91.1% vs 85.6%). Prolificacy or mortality at birth was never affected by the ovulation induction treatments. In a third experiment, two groups of does [control group (n = 39): ovulation was induced using 20 microg of gonadorelin administered intramuscularly; treatment group (n = 40): ovulation was induced using 25 microg of [(des-Gly10, D-Ala6)-LHRH ethylamide added to the seminal dose] were inseminated at 42-day intervals for five successive AI cycles, to test the response to the GnRH agonist after repeated intravaginal administration to the same animals. Fertility and prolificacy were not influenced by the ovulation induction treatment neither there was an interaction between treatment and parity. The last experiment was aimed to determine whether it could be possible to add the GnRH agonist to the semen in the AI Center, just after semen collection and dilution, or it would have to be added in the farm, immediately before AI. Kindling rates did not significantly differ when ovulation was induced by intramuscular injection of gonadorelin (84.5%) or when the GnRH agonist was added to the seminal dose just at the moment (93.8 %) or 24 h before AI (90.4 %), but it was significantly lower when the hormone was added to the semen 32 h before AI (76.3 %). Prolificacy, however, was not influenced by the ovulation induction treatment.

Since natural products are considered powerful sources of novel drug discovery, a partially purified extract (meliacine) from the leaves of Melia azedarach L., a plant used in traditional medicine in India for the treatment of several diseases, has been studied. Meliacine exhibits a potent antiviral effect against several viruses without displaying cytotoxicity. The purpose of the present study was to evaluate the therapeutic effect of intravaginal administration of meliacine in a mouse model of genital herpetic infection. BALB/c female mice were infected with MS or G strains of Herpes Simplex Virus type 2 and then treated with meliacine topically. An overall protective effect was observed. Animal survival increased, the severity of the disease was reduced, life span was extended and virus shedding in vagina fluids was diminished. In addition, meliacine reduced the amount of virus that migrated to the brain and vaginal fluids presented higher levels of IFN-γ and TNF-α than untreated infected mice. These results indicate that meliacine could be an alternative therapeutic compound against HSV-2 genital infection.

Summary: After intravaginal application of 2 vaginal tablets each containing 300 mg isoconazole nitrate, isoconazole concentration in vaginal secretion above MBC- and MIC-levels of Candida spec was maintained for at least 72 hours. 7 days after insertion no isoconazole could be detected in the vagina. Obviously the single dose therapy of vaginal mycoses with isoconazole nitrate is as effective and reliable as multi-dose-therapies due to the high long lasting isoconazole levels at the site of infection. Doubts that the high cultural cure rates observed 7 days after application in clinical trials may be caused by still available antimycotic in the vagina are not justified. Zusammenfassung: Nach intravaginaler Applikation von 2 Vaginaltabletten mit jeweils 300 mg Isoconazolnitrat lagen die Isoconazolkonzentrationen im Vaginalsekret mindestens 72 Stunden lang uber den MBK- und MHK-Werten fur Candida-Keime. 7 Tage nach dem Einfuhren konnte kein Isoconazol mehr in der Vagina nachgewiesen werden. Die mehrere Tage anhaltenden hohen Isoconazol-Spiegel am Ort der Infektion sind offensichtlich der Grund dafur, das sich die Ein-Dosis-Therapie von Vaginalmykosen mit Isoconazolnitrat als ebenso wirksam und verlaslich erwies als Mehr-Dosis-Therapien. Zweifel, das die hohen kulturellen Heilungsraten 7 Tage nach der Applikation durch noch vorhandenen antimykotischen Wirkstoff in der Vagina vorgetauscht seien, sind nicht gerechtfertigt.

Summary: 252 patients with symptoms of vaginal candidosis and a positive culture for Candida albicans were treated vaginally with 100 mg miconazole once daily for 7 days, or 400 mg miconazole for 3 days or with one capsule containing 1200 mg miconazole. 14 days after treatment 63–79% of the patients were mycologically cured. The difference between the three regimens was not statistically significant 1200 mg miconazole is usually sufficient. It may be given as a single dose or during three days, especially in acute vaginal candidosis. Zusammenfassung: 252 Patientinnen mit mykologisch gesicherter Candida-Kolpitis wurden an 7 Tagen hintereinander mit 100 mg Miconazol taglich oder an 3 aufeinander folgenden Tagen mit je 400 mg taglich oder einmal mit 1200 mg Miconazol behandelt. Vierzehn Tage nach Behandlungsabschlus waren 63–79% der Frauen mykologisch geheilt. Die Unterschiede im Behandlungser folg zwischen den drei Gruppen waren statistisch nicht signifikant. 1200 mg Miconazol erscheinen fur die Behandlung der akuten Candida-Kolpitis ausreichend. Das Arzneimittel kann als Einzeldosis oder auf 3 Tage verteilt verabreicht werden.

Aim To compare the effectiveness of an acid-buffering formulation gel (ACIDFORM) with metronidazole gel in the treatment of symptomatic bacterial vaginosis (BV). Methods After a confirmed diagnosis of BV according to the criteria established by Nugent and Amsel, 30 nonpregnant women were enrolled in a randomized, double-blind clinical study. The women were randomly assigned to receive either 5 g ACIDFORM gel (n = 13) or 10% metronidazole gel (n = 17) intravaginally once daily for five consecutive days. Participants were evaluated in two follow-up visits (7–12 days and 28–35 days after treatment). Therapeutic success was defined as the presence of less than three of Amsel's criteria. If three or more criteria were present at first or second follow-up visit, the woman was excluded from the study and treated orally with metronidazole. Nugent scores were recorded at each visit but these were not used to define cure. Results At the first follow-up visit, 15 (88%) of the women in the metronidazole group were cured compared with only three (23%) in the ACIDFORM group (P

Objective: To compare the efficacy of oral with vaginal misoprostol for induction of labor at term. Methods: One hundred and fifty-three pregnant women at term with indications for induction of labor and Bishop score ≤6 were randomly assigned to receive misoprostol either 100 µg orally or 50 µg vaginally every 6 h for 48 h. Repeated doses were given until Bishop score ≥8 was achieved or spontaneous rupture of membranes occurred. Those who were not in labor after 48 h had labor induced with amniotomy and oxytocin. The main outcome measure was induction to delivery time. Results: The median induction to vaginal delivery time in the oral group (14.3 h) was not significantly different from that of the vaginal group (15.8 h). The median number of doses was also not significantly different in the oral group compared with the vaginal group. There was a significant higher incidence of uterine tachysystole in the vaginal group compared to the oral group (17.1%vs 5.3%, P = 0.032). There was no hyperstimulation in either group. There were no significant differences between the groups with respect to oxytocin augmentation, cesarean section rate, analgesic requirement, and neonatal outcomes. Conclusion: Oral administration of 100 µg misoprostol has similar efficacy to intravaginal administration of 50 µg misoprostol for labor induction with less frequent abnormal uterine contractility. 100 µg of misoprostol orally can be used as an alternative to the vaginal route for labor induction.

In order to prove the effect of 'fixed time insemination' and insemination at standing oestrus after post-weaning application of GnRH, in a Croatian large breeding unit, 502 sows were assigned to three groups and were artificially inseminated (AI) at their first post-weaning oestrus as many times as they stand, in 24-h intervals. The groups were treated as follows: group 1 (control, n = 160) were AI during their standing reflex; group 2 ['GnRH-fixed time insemination' (GnRH-FT-AI), n = 175] were AI, independent of detection of oestrus and following administration of GnRH-agonist at 96 h post-weaning; group 3 [GnRH insemination at standing oestrus (GnRH-OE-AI), n = 167] the animals were GnRH-agonist treated as group 2 and were AI at their standing reflex. Pre-trial daily average lactational feed intake, average daily feed intake from weaning to oestrus, oestrus within 6 days post-weaning (%), ovulation within 6 days post-weaning (%), weaning-to-oestrus interval (h), duration of oestrus (h), follicle size (mm), interval from oestrus to ovulation (h), subsequent day 24 pregnancy rate (%), farrowing rate (%) and total pigs born were evaluated. Pre-trial average daily lactational voluntary feed intake was 7.1 +/- 0.08 kg in group 1, 7.0 +/- 0.07 kg in group 2 and 7.1 +/- 0.17 kg in group 3 (p > 0.05). Average voluntary daily feed intake from weaning to oestrus was 5.1 +/- 0.3 kg in group 1, 5.2 +/- 0.5 kg in group 2 and 5.2 +/- 0.19 kg in group 3 (p > 0.05). Oestrus was detected within 6 days post-weaning in 134 (83.8%) in control, 164 (93.7%) in GnRH-FT-AI and 155 (92.8%) animals in GnRH-OE-AI groups (p = 0.05). Follicle size did not differ (p > 0.05) among the groups. In control 82.8%, in GnRH-FT-AI 91.5% and in GnRH-OE-AI 91.0% of the sows ovulated within 6 days post-weaning (p = 0.04), and had 80.6, 90.9 and 89.7% 24-day pregnancy rates (p = 0.16), respectively. In GnRH-FT-AI group 90.2%, in GnRH-OE-AI sows 89.7%, in control animals 79.9% farrowing rates were recorded (p = 0.17). Weaning to oestrus interval was 113.1 h in control, 114.1 h in GnRH-FT-AI and 112.6 h GnRH-OE-AI (p > 0.05). Duration of oestrus was significantly shorter in GnRH-FT-AI (44.9 h) and GnRH-OE-AI (48.1 h) animals, compared with the control (62.9 h) sows (p = 0.001). Similarly, the interval from oestrus to ovulation revealed significant (p = 0.004) differences between the groups (control 44.1 h, GnRH-OE-AI 34.1 h and GnRH-FT-AI 32.9 h). GnRH-FT-AI (12.5) and GnRH-OE-AI (12.6) sows had significantly higher (p = 0.01) number of total pigs born (n = 10.4) compared with control sows. GnRH-agonist-gel treatment to the sow shortens duration of oestrus, the interval from oestrus to ovulation, and may eliminate the need for oestrus detection in the hands of skilled personnel.

A 59-year-old woman who had had several episodes of contact urticaria after hair treatment, developed anaphylaxis after vaginal application of povidone-iodine solution for disinfection. Prick tests showed wheal-and-flare responses to both povidone-iodine (0.1% aqueous) and polyvinylpyrrolidone (povidone, PVP) (0.001% aq.), but not to iodine or polyoxy-ethyrenenonylphenyl ether, both of which are also contained in povidone-iodine solution. We confirmed that basophils from her peripheral blood released considerable amounts of histamine on stimulation by PVPs. It appeared that both the shampoo and the permanent-wave solution contained polyvinylpyrrolidone N, N-dimethyl aminoethyl methacrylic acid copolymer diethyl sulphate solution and polyvinylpyrrolidone styrene-copolymer emulsion. Both these agents in the hair care products provoked an immediate skin response on prick testing. We speculate that sensitization to PVP had been established by these hair care products at a beauty parlor. She was recommended to avoid PVP-containing products and remained free from symptoms thereafter.

Background. Multiparous patients have a higher risk of hyperstimulation and uterine rupture than nulliparous patients. The minimum possible dose of uterotonic drug should be used in induction of labor for multiparous patients to avoid excessive uterine activity, which could increase both maternal and fetal risks. Methods. One hundred and four women were randomized to either a single dose of 50 µg of intravaginal misoprostol in 24 h, or two consecutive doses of intravaginal 50 µg misoprostol 6 h apart. Results. The mean induction to delivery interval (789 min [95% CI: 637-941] vs. 576 min [95% CI: 484-667], p = 0.018) and delivery rate within 12 h (63% vs. 83%, p = 0.035) were higher in the two-dose group. The oxytocin augmentation rate (14% vs. 2%, p = 0.03) was higher in the single-dose group. There was a higher rate of clinician input related to suspicious cardiotocographic readings in the single-dose arm ( p = 0.04). There was no statistical difference ( p > 0.05) between the one- and two-dose regimens...

Background. The objectives of the study were to compare the efficacy and safety of intravaginal misoprostol and intravaginal dinoprostone for induction of labor and to quantify the clinical response to suspicious cardiotocographic (CTG) readings. Methods. One hundred and ninety-one patients were randomized to receive either 50 µg misoprostol initially then a further identical dose 6 h later or 2 mg dinoprostone initially followed by 1 mg 6 h later, over a period of 24 h. If not in labor after 24 h, then both arms of the study would thereafter receive dinoprostone alone as per hospital protocol. Results. The induction to delivery interval (1047 vs. 1355 min, p = 0.01), delivery within 12 h (35.4% vs. 18.9%, p = 0.02) and delivery within 24 h (83.3% vs. 63.3%, p = 0.01) were all shorter in the misoprostol arm. There were no differences in rates of oxytocin augmentation ( p = 0.47), tachysystole ( p = 0.32) and hyperstimulation syndrome ( p = 0.82). There was an increase in the median number of times a docto...

This study was undertaken to determine the bioavailabilityof a 1200 mg miconazole nitrate vaginal ovule in 20 healthy premenopausal females following a single application (Day 1, Group 1) and two applications, 48 hours apart (Day 1 and Day 3, Group 2). In Dose Group 1 (n = 10), the mean Cmax of 10.7 ng/ml occurred at 18.4 hours. The average plasma miconazole concentration was calculated to be 5.7 ng/ml during the 4- to 96-hour time interval. In Dose Group 2 (n = 10), mean Cmax values were 10.8 ng/ml and 12.0 ng/ml and occurred at 18.4 hours (Day 1) and 16.0 hours (Day 3), respectively. Comparing AUC0-48 on Days 1 and 3 (338 vs. 408 ng x h/ml) indicated small accumulation of plasma miconazole, while AUC0-48 obtained from Dose Group 2, Day 1 was similar to that of Dose Group 1 (338 vs. 329 ng x h/ml, respectively). Plasma miconazole profiles were best described by a monoexponential equation with zero-order input. Pharmacokinetic simulations performed on the pooled data from two dose groups (n = 20) suggest a steady-state accumulation after five doses administered daily or three doses taken once every other day. Drug exposure was similar to that of the marketed formulation (MONISTAT 7 vaginal cream), applied once daily for 7 days and more than 100-fold less than that reported when given intravenously or orally.

5-bromo-6-methoxy-5,6-dihydro-3(')-azidothymidine-5(')-(p-bromophenyl) methoxyalaninyl phosphate (WHI-07), a novel bromo-methoxy-substituted aryl phosphate derivative of zidovudine (ZDV), is a potent dual-function contraceptive agent with anti-HIV activity. Its potential for reproductive toxicity was assessed in a series of experiments using CD-1 mice under the conditions of its intended use as an intravaginal microbicide. Female CD-1 mice were exposed intravaginally to a gel-microemulsion formulation containing 0%, 0.5%, 1.0% or 2.0% WHI-07 for up to 13 weeks. On a molar basis, these concentrations represent 1400-5700 times its in vitro spermicidal IC(50) and 1.4-5.7(x10(6)) times its in vitro anti-HIV IC(50). We examined the effects of intravaginally administered WHI-07 on: ovulation efficiency; in vivo fertilization and early embryonic, fetal development; and reproductive outcome, including neonatal survival and pup development. Compound WHI-07 was administered intravaginally during superovulation, organogenesis and prior to mating for 5 and 10 consecutive days and for 13 weeks, respectively. Mice were evaluated for ovulation efficiency and fertilization rate and cleavage 14 and 40 h after human chorionic gonadotropin (hCG) injection, respectively. Pregnant mice were administered 2% WHI-07 intravaginally during gestation days (GD) 6-15 and measures of teratogenicity were evaluated on GD 17. For short-term toxicity study, mice were given intravaginal treatment of gel-microemulsion containing 0%, 0.5%, 1.0% and 2.0% WHI-07 for 13 weeks and then mated with untreated males to evaluate potential reproductive and developmental effects. Repeated intravaginal exposure of mice to 2% WHI-07 had no adverse effects on ovulation response, mean number of eggs recovered or the percentage of eggs fertilized or cleaved. No evidence of reproductive toxicity, fetal toxicity or teratogenicity was found following repetitive intravaginal application of 2% WHI-07 during the period of organogenesis. Furthermore, repeated intravaginal exposure of mice to 0.5-2.0% WHI-07 for 13 weeks had no adverse effect on the subsequent reproductive capability, perinatal outcome or growth and development of the offspring. Compound WHI-07 shows unique clinical potential as a safe, dual-function vaginal contraceptive for curbing mucosal and perinatal HIV transmission.

Background. Atrophic vaginitis is a common condition. This study compared the usefulness of estradiol vaginal tablets (EVT) and estriol vagitories (EV) in treatment of atrophic vaginitis. Methods. Ninety-six postmenopausal women with symptoms of atrophic vaginitis were treated for 24 weeks with either EVT or with EV. Patients used the medication daily for the first 2 weeks of the study, and twice-weekly thereafter. Results. Both EVT and EV were effective in treating vaginal atrophy and patients in both treatment groups experienced a significant improvement in vaginal symptoms such as itching, irritation, dryness, and dyspareunia. At the end of the study three (6%) EVT treated women reported leakage and none needed to use sanitary towels. Among the EV treated women 31 (65%) reported leakage and 14 (29%) required sanitary protection. Furthermore, 90% in the EVT group perceived the medication as hygienic compared to 79% in the EV group, and 49% in the EVT group indicated that the product was easy to use comp...

Topical delivery systems can provide prolonged delivery of antibodies to the vaginal mucosal surface for long-term protection against infectious diseases. We examined the biodistribution of antibodies during 30 days of vaginal antibody delivery in mice. Different antibody preparations (including monoclonal IgG and IgM, as well as several different 125I-labeled IgGs) were administered by polymer vaginal rings, which were designed to provide continuous antibody delivery. Antibody concentrations remained high in the vaginal secretions for up to 30 days after disk insertion; radiolabeled antibody was also found, at ∼100 times lower concentration, in the blood and other tissues. The measured concentrations agreed reasonably well with a simple pharmacokinetic model, which was used to calculate mucosal and systemic concentrations as a function of antibody delivery and elimination rates. Results from the model were consistent with previously reported antibody pharmacokinetic measurements: the half-life for antibody elimination for the vagina was ∼3 h; the half-life for IgG1 clearance from the blood was >1 day; and the overall permeability constant for vaginal uptake of IgG was ∼0.01 to 0.03 h−1. These results provide important information for the design of controlled antibody delivery devices for vaginal use, and suggest that high-dose, long-term vaginal administration of antibodies may be a reasonable approach for achieving sustained mucosal and systemic antibody levels. © 2000 John Wiley & Sons, Inc. Biotechnol Bioeng 67: 253–264, 2000.

Heterosexual transmission of human immunodeficiency virus (HIV) accounts for 90% of all new infections worldwide and significantly contributes to new acquired immunodeficiency syndrome (AIDS) cases in the USA. In a systematic effort to develop a microbicidal contraceptive capable of preventing HIV transmission as well as providing fertility control, we previously identified novel phenyl phosphate derivatives of 3′-azido-3′-deoxythymidine (zidovudine) that exhibit potent anti-HIV and spermicidal activities. This study reports the preclinical studies of our lead compound WHI-07, 5-bromo-6-methoxy-5,6-dihydro-3′-azidothymidine-5′-(p-bromophenyl) methoxyalaninyl phosphate, for use as a dual-function topical microbicide. In vivo toxicity studies in non-human primates and rodents given WHI-07 (20 mg kg−1) intravenously and intraperitonealy, respectively, had no detectable adverse effects on hematological and clinical chemistry profiles. The 13-week subchronic and reproductive toxicity potential of an intravaginal gel–microemulsion formulation of WHI-07 was studied in mice to support its further development as a dual-function microbicide. Groups of ten female B6C3F1 mice were exposed intravaginally to a gel–microemulsion formulation containing 0, 0.5, 1.0 or 2.0% WHI-07, 5 days a week, for 13 consecutive weeks. On a molar basis, these concentrations represent 1400–5700 times their in vitro spermicidal potency EC50) and 1.4 × 106–5.7 × 106 times their in vitro anti-HIV activity50). After 13 weeks of intravaginal treatment, half of the treated mice were evaluated for toxicity and the other half were mated with untreated males to evaluate potential reproductive and developmental effects. The endpoints that were evaluated included survival, body weight gain, hematological and clinical chemistries, absolute and relative organ weights and histopathology. The WHI-07 applications did not cause weight loss, morbidity, mortality or specific tissue lesions detectable by histopathology. Repeated intravaginal exposure of mice to WHI-05 for 13 weeks had no adverse effects on subsequent reproductive performance (100% fertile), neonatal survival (>95%) or pup development. These findings collectively show that the experimental dual-function anti-HIV and contraceptive agent WHI-07 did not cause significant acute or subchronic toxicity. Copyright © 2000 John Wiley & Sons, Ltd.

Contents Fifty-nine female yearlings of local Awassi sheep were randomly divided into two groups. Animals in group T (treated) were fitted with intravaginal sponges containing 60 mg of medroxyprogesterone acetate for 14 days followed by 400 IU of pregnant mare’s serum gonadotrophin (PMSG) at sponge withdrawal, whereas group C (control) received no treatment. Oestrus rate was 92.7 and 11.2% for groups T and C, respectively. Lambing rate was 78 and 5.6% for groups T and C, respectively. Twinning rate was 31.3% in group T compared to zero in group C. Average birth weight for single born lambs (4.7 ± 0.6 kg) was significantly (p

For seminal plasma-allergic patients to achieve pregnancy, immunotherapy or artificial insemination is recommended. However, these modalities require complicated procedures. We recently treated a patient with human seminal plasma anaphylaxis who was successfully desensitized after intravaginal rush desensitization and became spontaneously pregnant. She had a healthy full-term infant. With immunoblotting, we identified multiple allergens in her husband's seminal plasma, with molecular masses such as 100, 75, 65, 50, 40, 38, 33, 20, and 18 kDa, and the pattern of immunoblotting did not change after desensitization. We found not only specific antibodies to the seminal plasma of the patient's partner, but also common antibodies to both the partner's and the control specimen. Our results suggest that intravaginal desensitization might be an effective and convenient initial approach for patients who want to achieve pregnancy, and also confirm the presence of both the specific and shared common allergens in the seminal plasmas of the patient's partner and the control subject.

The efficacy and safety of administration of intravaginal misoprostol for labor induction were investigated in 110 Portuguese women with singleton pregnancies with a Bishop score of 6 or under. The primary indicators for labor induction were gestation of 41 weeks or more (54%) and rupture of the membranes (27%). Fractionated doses (50-100 mcg) of misoprostol were applied every 6 hours until a maximum of three doses or the beginning of labor. The average interval from vaginal application to active labor was 9.5 +or- 5.7 hours while that from misoprostol administration to delivery was 14.8 +or- 9.5 hours. 15 women (14%) required cesarean section primarily due to arrest of dilatation. Although the incidences of tachysystole and hypersystole were 18% and 4% respectively abnormal heart rate patterns occurred in only 3%. There were no significant adverse effects on fetal well-being even in cases with diminished amniotic fluid. These findings confirm that misoprostol is a safe effective drug for cervical ripening and labor induction with or without rupture of the membranes.

The efficacy and side effects of 3 doses of intravaginal misoprostol were investigated in 151 women admitted to Ramathibodi Hospital (Bangkok Thailand) in 1995-97 for termination of a second trimester pregnancy. 200 mcg of misoprostol was inserted in the posterior vaginal fornix at 12-hour intervals for up to 48 hours in 51 women. Another 50 were allocated to receive 400 mcg of misoprostol while the final 50 were administered 600 mcg. If abortion did not occur in 48 hours treatment was considered a failure. The cumulative rate of abortion at 48 hours was 70.6% in the 200 mcg group 82% in the 400 mcg group and 96% in the 600 mcg group. The mean abortion-to-induction intervals were 45.0 33.4 and 22.3 hours respectively. The mean total dosages used were 416.7 772.8 and 1296 mcg respectively. Side effects (temperature nausea/vomiting diarrhea) increased with greater misoprostol dosage but there were no serious complications. Although the induction interval in misoprostol-induced second trimester termination is longer than that reported for gemeprost alone or the combination of mifepristone and gemeprost the significantly lower cost of misoprostol alone justifies use of this agent in developing countries such as Thailand. The cost can be reduced further by teaching women to self-administer misoprostol every 12 hours at home and to present to the hospital for assessment at 24-hour intervals.

Comparison of two different methods of vaginal disinfection was made with regard to prevention of neonatal infections. In method I, an antepartum vaginal douche with a chlorhexidine solution was used; method II involved the use of chlorhexidine gluconate obstetrical gel during vaginal exploration. We studied 2853 normal deliveries from a total number of 3236 deliveries: 1467 deliveries were allocated randomly to receive a vaginal douche whereas 1386 underwent vaginal exploration using chlorhexidine gel. A total of 203 neonates were transferred to the neonatal unit (120 males and 83 females): 101 belonged to the group where the mothers were subjected to method I, whereas in 102 method II had been used. Within 48 h postpartum 30 neonates from the method I group and 34 neonates from the method II group received systemic antibiotics. There was a tendency towards a higher proportion of full-term neonates with verified septicaemia in the method II group (6 versus 2), whereas the numbers of probable infections were 8 versus 12. The corresponding total numbers in preterm infants were 3 and 2, respectively. These differences were not statistically significant. We conclude that the use of chlorhexidine douche compared with vaginal exploration with chlorhexidine gel provides no additional advantages.

Objective. To determine whether performance of endovaginal sonography for the measurement of cervical length results in a statistically significant change in endocervical culture results. Methods. Women attending a routine prenatal clinic were offered enrollment in the study. Exclusion criteria included the presence of a cervical cerclage, vaginal examination or coitus within the preceding 24 hours, antibiotic therapy within the preceding 7 days, or the presence of ruptured membranes. A sterile speculum examination and collection of cervical cultures were performed before (initial) and immediately after (final) endovaginal sonographic measurement of cervical length. Quantitative cultures were completed and evaluated for differences in growth by a standardized 4-quadrant technique. Results. A total of 25 women enrolled and completed the study protocol. Quantitative assessment of colony growth showed that the mean growth in the initial samples ± SD was 3.48 ± 1.74, with 1+ indicating growth in 1 quadrant; 2+, growth in the first and second quadrants; 3+, growth in the first, second, and third quadrants; and 4+, growth in all quadrants. The mean growth cultured in the final sample was 3.79 ± 2.26 (P = .364; 95% confidence interval of the difference, ‐1.00 to +.381). Conclusions. The results of this study do not show a statistically significant inoculation effect associated with performance of endovaginal sonography for the measurement of cervical length. Key words: cervical cultures; cervical length; endovaginal sonography; preterm premature rupture of

OBJECTIVE: To determine the effectiveness of intravesical formalin instillation in hemorrhagic cystitis following irradiation of cancer of the cervix. METHOD: Records were reviewed for 35 patients with hemorrhagic radiation cystitis who underwent treatment with 1% (n = 22), 2% (n = 10), and 4% formalin (n = 4), using Fair's technique. RESULT: Complete response was seen in 31 patients (89%) and partial response in 3 patients (8%) after a single instillation. Minor complications were seen in 19 patients (54%). Major complications occurred in 11 patients (31%), with 5 cases requiring subsequent urinary diversion. One patient died of persistent bleeding and probable formalin toxicity. Hematuria recurred in 7 patients achieving complete response at a mean period of 8 months after treatment. A 1% solution was as effective in controlling hematuria as higher concentrations and was associated with significantly less morbidity. CONCLUSION: Intravesical instillation of 1% formalin is an effective treatment for intractable hematuria secondary to radiation cystitis.

Successful intravaginal desensitization in a woman who developed generalized urticaria and dyspnea to seminal fluid.

OBJECTIVE To compare the safety and efficacy of intravaginal misoprostol versus intravenous (IV) oxytocin infusion for labor induction. METHODS One hundred thirty patients were randomly assigned to one of two induction groups: 1) intravaginal misoprostol or 2) IV oxytocin by continuous infusion, with prior cervical ripening using prostaglandin (PG) E2 gel if necessary. RESULTS Among 129 patients evaluated, 64 were allocated to the misoprostol group and 65 to the oxytocin group. Prostaglandin E2 gel was administered to 29 patients (45%) in the oxytocin group with unripe cervices. Uterine tachysystole occurred more frequently in patients in the misoprostol group (34.4%) than in the oxytocin group (13.8%) (P < .05). Nevertheless, no statistically significant differences were noted between the groups in intrapartum complications including uterine hyperstimulation syndrome, mode of delivery, and neonatal or maternal adverse outcomes. The interval from induction to vaginal delivery was significantly shorter in the misoprostol group (11 versus 18 hours; P = .004). In 74% of patients in the misoprostol group, only one intravaginal dose was required for successful labor induction. CONCLUSIONS Intravaginal administration of misoprostol safely and effectively induces labor while minimizing the expense associated with IV oxytocin infusion. The higher frequency of uterine tachysystole associated with the use of misoprostol did not increase the risk of adverse intrapartum or perinatal outcomes. The use of PGE2 gel for cervical ripening contributed to the longer induction-to-vaginal delivery interval noted in the oxytocin group. Clinical trials appear warranted to detail misoprostol's optimal route, dose, and schedule for labor induction and its safety.

Octoxynol-9, a nonionic surfactant used as a spermicidal agent in ORTHO-GYNOL (registered trademark) Contraceptive Jelly (Ortho Pharmaceutical Corporation, Raritan, NJ), was administered intravaginally to pregnant Sprague Dawley COBS CD rats at dosages of 0.5 mg/kg/day and 5 mg/kg/day (two-thirds and six times the clinical dosage) on days 6-15 of gestation in order to assess its teratogenic potential. Untreated, sham, and vehicle control groups were also incorporated into the study protocol. No meaningful differences were observed between the treated and control groups in maternal toxicity, maternal reproductive parameters, fetal toxicity, and the incidence of external, visceral, and skeletal malformations or developmental variations. It is concluded that octoxynol-9 is not embryotoxic or teratogenic when administered intravaginally to rats during organogenesis.

During the 27-year period from 1956 to 1982, transvaginal parametrial needle biopsies were performed on 76 patients clinically suspected of harboring postirradiation recurrent cervical cancer without mucosal lesions suitable for biopsy under direct vision. Needle biopsies indicated cancer in 41 patients, resulting in 20 abdominal explorations. Eleven of these patients underwent total pelvic exenteration. Three patients survived longer than 5 years. Among 35 patients whose biopsies did not suggest cancer, eight proved to be false-negative as demonstrated by later progression of local and systemic disease. The remaining 27 patients in whom biopsies showed negative results were cured by radiation therapy. Bleeding, easily controlled by vaginal packing, occurred in one patient; in another, a pelvic abscess was drained 7 days after the biopsy. The authors conclude that when judiciously performed, transvaginal parametrial needle biopsy has a high diagnostic yield (89%) with minimal morbidity (2.6%). Its application during the careful observation of patients suspected to harbor recurrence may increase the operability rate and may offer selected patients a chance for cure by radical pelvic surgery.

A randomized doubleblind investigation of prostaglandin vaginal suppositories prior to hysteroscopy was undertaken in 30 non-pregnant women. PGE2 in 14 of 15 treated patients we found a softening and a dilatation of the cervical canal, but with a relatively high frequency of side effects-nausea, vomiting and diarrhea. No serious bleeding or side effects were observed.

The effects of the spermicide benzalkonium chloride (BKC) were studied on the conceptus of rat. Single doses (0, 25, 50, 100 or 200 mg kg-1) of aqueous solutions of BKC were administered intravaginally (1 ml kg-1) on gestational day 1. The vulval metallic clips, used to prevent leakage of the solution, were removed 24 h post-treatment. Fetuses were obtained and examined for malformations on day 21 of gestation. slight to copious amounts of vaginal discharge and vaginitis were noticed in rats treated with the two largest doses of BKC. A dose-related increase in resorptions and fetal death, reduction in litter size and weight were observed in BKC-treated dams. The conceptus loss seemed to occur both before and after implantation. BKC did not cause any discernible visceral malformations, although minor sternal defects occurred in fetuses exposed to 100 and 200 mg kg-1 of the spermicide. These results suggest that single vaginal application of BKC is embryo- and fetocidal in the rat at a dose about 143 times higher than that recommended for controlling conception in women.

Daily doses of 0.625 mg of conjugated estrogens were administered intravaginally for 14 days to 12 postmenopausal women (six with highly atrophic and six with slightly atrophic vaginal mucosa), resulting in vaginal mucosae similar to those found in premenopausal women in all 12 subjects. In a second experiment, serum estrogens, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined before and hourly for six hours after a single intravaginal dose of 0.625 mg of conjugated estrogens was given to five postmenopausal women and to five premenopausal women on cycle days 6-8. Serum levels of unconjugated immunoreactive estrogens and total estrone increased rapidly in four of five postmenopausal women. Luteal phase values were found after only two hours, but there were no effects on serum FSH and LH. One of the postmenopausal women who had an unatrophied vaginal mucosa, showed a considerable lower resorption of estrogens. There were no significant changes in the serum estrogen levels of the premenopausal women. Thus, we conclude that daily vaginal administration of 0.625 mg of conjugated estrogens for 14 days is sufficient to restore an atrophic vaginal mucosa to a premenopausal condition. Furthermore, the condition of the vaginal mucosa seems to influence the resorption, thus indicating an inbuilt mechanism of protection against overdosage of intravaginally applied estrogens.

The absorption of trimethoprim-sulfonamide combination into serum and transfer to the amniotic fluid after oral and intravaginal administration was studied on 134 patients undergoing legal abortion. The combination given orally as a single dose was absorbed rapidly: the peak levels of both trimethoprim and sulfamethoxazole in serum were reached within 4 hours. In amniotic fluid, the peak level of trimethoprim appeared within 14 hours and that of sulfamethoxazole within 10 hours. After a single intravaginal application of cream, the absorption of trimethoprim into serum and transfer to the amniotic fluid was smaller although measurable amounts could be demonstrated. After repeated intravaginal application during several days no accumulation of trimethoprim in serum or amniotic fluid could be detected.