Short onset of action of a serotonin reuptake inhibitor when used to reduce premenstrual irritability.

Several studies suggest that serotonin reuptake inhibitors (SRIs) exert a more rapid effect when used for the treatment of symptoms such as anger and irritability then when used for depression, obsessive-compulsive disorder, or anxiety. In line with this, premenstrual irritability can be effectively dampened by intermittent administration of an SRI, from ovulation to menstruation, indicating an onset of action of 10 days or less. How fast this effect appears, in terms of hours or days, is of considerable theoretical interest, but has previously not been studied in detail. To explore this issue, 22 women with marked premenstrual irritability, who previously had responded to paroxetine, were given this compound during two menstrual cycles and placebo during one cycle in a double-blind, cross-over fashion. The women were asked to start medication in the midst of the luteal phase when irritability had been intense for 2 days. The paroxetine cycles differed significantly from the placebo cycle as early as 14 h after drug intake with respect to the number of subjects experiencing sustained reduction in irritability. When the different cycles were compared with respect to irritability-rating scores for each time of assessment, the difference was significant at day 3. The side effect nausea had an even more rapid onset (4 h), but usually disappeared within 4 days. To summarize, this controlled trial shows that an SRI reduces premenstrual irritability already within a few days after the onset of treatment.

The lower genital tract microbiota in relation to cytokine-, SLPI- and endotoxin levels: application of checkerboard DNA-DNA hybridization (CDH).

In the present study the lower genital tract microbiota in asymptomatic fertile women (n=34) was identified and quantified by culturing vaginal secretions. Also, vaginal and cervical samples were analyzed by a semiquantitative checkerboard DNA-DNA hybridization technique (CDH) based on genomic probes prepared from 13 bacterial species (Bacteroides ureolyticus, Escherichia coli, Fusobacterium nucleatum, Gardnerella vaginalis, Mobiluncus curtisii ss curtisii, Prevotella bivia, Prevotella disiens, Prevotella melaninogenica, Atopobium vaginae, Lactobacillus iners, Staphylococcus aureus ss aureus, Streptococcus anginosus, and Streptococcus agalactiae). The bacterial species found by either culture or CDH were correlated with proinflammatory cytokines (IL-1 alpha, IL-1 beta, IL-6, IL-8), secretory leukocyte protease inhibitor (SLPI), and endotoxin in the cervicovaginal samples. Grading the women into healthy, intermediate, or bacterial vaginosis (BV) as based on Gram staining of vaginal smears, the viable counts of lactobacilli (L. gasseri) and of streptococci-staphylococci combined were highest in the intermediate group. In BV, particularly the high concentrations of Actinomyces urogenitalis, Atopobium vaginae, and Peptoniphilus harei were noted (>or=10(11) per ml). The total viable counts correlated with both cervical IL-1 alpha and IL-1 beta. A strong negative correlation was observed between L. iners and total viable counts, G. vaginalis, or cervical IL-1 alpha, while it correlated positively with SLPI. Analysis of vaginal and cervical samples from 26 out of the 34 women by CDH showed that anaerobic bacteria were more frequently detected by CDH compared to culture. By this method, A. vaginae correlated with G. vaginalis, and L. iners with S. aureus. With regard to cytokines, B. ureolyticus correlated with both cervical and vaginal IL-1 alpha as well as with cervical IL-8, while F. nucleatum, S. agalactiae, S. anginosus, or S. aureus correlated with vaginal IL-1 alpha. Furthermore, all Gram-negative bacteria taken together, as measured by CDH, correlated with vaginal endotoxin and inversely with vaginal SLPI. The significance of the results is discussed. In summary, mapping of the identity and quantity of vaginal bacterial species and their association with locally produced host innate immune factors will help in defining various types of abnormal vaginal microbiota, developing new ways of assessing the risk of ascending subclinical infections, and in treating them. CDH appears to be a suitable tool for future analyses of large numbers of clinical samples with an extended number of bacterial probes.

Outpatient vaginal administration of the nitric oxide donor isosorbide mononitrate for cervical ripening and labor induction postterm: a randomized controlled study.

OBJECTIVE: Our aim was to examine the efficacy, safety, and acceptability of isosorbide mononitrate for cervical ripening and labor induction in women in an outpatient setting. STUDY DESIGN: Two hundred pregnant women of at least 42 weeks' gestation with an unripe cervix were randomly selected to receive vaginally either 40 mg isosorbide mononitrate or placebo tablets. RESULTS: Twenty-two women treated with isosorbide mononitrate went into labor within 24 hours compared to 8 women in the placebo group (P < .05). In women who did not go into labor, cervical status was similar in the 2 groups the next day. Headache was a common side effect. No maternal or fetal side effects of clinical importance were registered. CONCLUSION: Outpatient cervical ripening and labor induction with isosorbide mononitrate seems to be an effective, safe, and well tolerated procedure. The definitive clinical efficacy and safety needs to be evaluated in larger series of patients.

Microbial invasion and cytokine response in amniotic fluid in a Swedish population of women with preterm prelabor rupture of membranes.

BACKGROUND: Previous studies have shown an association between intra-amniotic microbial invasion and/or inflammation and spontaneous preterm birth. The aim of this study was to investigate the occurrence of intra-amniotic microorganisms and cytokines [interleukin (IL)-6 and IL-8] in a Swedish population, with low incidence of preterm birth, of women with preterm prelabor rupture of membranes and their correlation to preterm birth. METHODS: Amniotic fluid was retrieved transabdominally from 58 patients with preterm prelabor rupture of membranes before 34 weeks of gestation. Polymerase chain reaction (PCR) analyses for Ureaplasma urealyticum and Mycoplasma hominis and culture for aerobic and anaerobic bacteria were performed. IL-6 and IL-8 were analyzed with enzyme-linked immunosorbent assay (ELISA). RESULTS: Microorganisms in amniotic fluid were detected in 13 patients (25%). Patients with bacteria detected in the amniotic fluid had significantly higher levels of IL-6 and IL-8. An amniotic fluid concentration of IL-6 >/= 0.80 ng/ml [relative risk 1.93, 95% confidence interval (CI) 1.13-3.29, sensitivity 63%, specificity 75%] was associated with an increased risk of delivery within 7 days. There was also an association between IL-8 and preterm birth (< 34 weeks). CONCLUSIONS: Intra-amniotic microbial invasion and inflammation in this population of Swedish women with preterm prelabor rupture of membranes were similar to data reported from populations with a higher incidence of preterm delivery. Amniotic IL-6 correlated to the presence of microorganisms and delivery within 7 days and IL-8 to delivery before 34 weeks.

Microbial invasion and cytokine response in amniotic fluid in a Swedish population of women in preterm labor.

BACKGROUND: Previous studies indicate an association between intra-amniotic microbial invasion and/or inflammation and spontaneous preterm birth, but there is a limited amount of data available from Europe. The aim of this study was to investigate the occurrence of intra-amniotic microorganisms and cytokines (interleukin-6 and interleukin-8) in a Swedish population of women in preterm labor and their correlation with preterm birth. METHODS: Amniotic fluid was retrieved transabdominally from 61 patients in preterm labor before 34 weeks of gestation. Polymerase chain reaction analyses for Ureaplasma urealyticum and Mycoplasma hominis and culture for aerobic and anaerobic bacteria were performed. Interleukin-6 and interleukin-8 were analyzed with enzyme-linked immunosorbent assay. RESULTS: Microorganisms in amniotic fluid were detected in 10 patients (16%). Patients with detected bacteria in the amniotic fluid had significantly higher levels of interleukin-6 and interleukin-8. There was also an association between interleukin-6/-8, the amniocentesis-delivery interval (or= 1.5 ng/mL or interleukin-8 >or= 1.3 ng/mL was associated with an increased risk of delivery within 7 days (interleukin-6: relative risk 7.3; 95% confidence interval: 2.8-19; sensitivity 83%, specificity 87%; interleukin-8: relative risk 14, 95% confidence interval: 3.6-55, sensitivity 91%, specificity 87%). CONCLUSIONS: The occurrence of intra-amniotic microbial invasion and inflammation in this population of Swedish women in preterm labor was similar to data reported from populations with a higher incidence of preterm delivery. Amniotic interleukin-6 and interleukin-8 correlated with the presence of microorganisms and with preterm birth.

Vaginal administration of the nitric oxide donor isosorbide mononitrate for cervical ripening at term: a randomized controlled study.

OBJECTIVE: Our aim was to examine the effect of the nitric oxide donor isosorbide mononitrate on the uterine cervix at term and to evaluate possible adverse effects of this treatment. STUDY DESIGN: Term pregnant women were randomly selected to receive either 40 mg vaginally administered isosorbide mononitrate or placebo 4 hours before elective cesarean section. Cervical status, maternal blood pressure, maternal pulse rate, fetal heart rate, umbilical arterial Doppler indices, and various side effects were examined. RESULTS: Isosorbide mononitrate induced a significant increase in cervical distensibility. It also caused a significant change in maternal blood pressure and maternal pulse rate. In addition, the frequency of maternal headache and palpitations was significantly higher in the isosorbide mononitrate group versus the placebo group. However, the intensity of these symptoms was moderate. CONCLUSION: Vaginal administration of 40 mg of isosorbide mononitrate induces cervical ripening at term. Although the majority of women experienced side effects, no serious clinical maternal or fetal adverse effects, resulting in specific medication or emergency cesarean section, were diagnosed.

Diagnosis and treatment of premenstrual dysphoria.

Premenstrual dysphoria (PMD) is a severe form of premenstrual syndrome afflicting 5% to 10% of all fertile women. Cardinal symptoms--appearing regularly between ovulation and menstruation and disappearing within a few days after the onset of the bleeding--are depressed mood, tension, affect lability, and irritability. Of these symptoms, irritability is often the most prominent. Serotonin reuptake inhibitors (SRIs), but not nonserotonergic antidepressants, reduce the symptoms of PMD effectively. The onset of action of SRIs is much shorter when used for PMD than when used for depression, enabling women with PMD to restrict medication use to the luteal phase of the cycle (so-called intermittent treatment). The findings that SRIs are effective for PMD--and that sexual dysfunction is the most frequent side effect during long-term treatment--both lend support for the hypothesis that a major role for brain serotonin is to modulate sex steroid-driven behavior.