[Puerperal inhibition of lactation with metergoline or bromocriptine]. Lactation suppression with bromocriptine. Lactation inhibition by the dopamine agonist CV 205-502. Lactation inhibition by a single injection of a new depot-bromocriptine. Serum prolactin and the suppression of lactation. Inhibition of lactation by cyclofenil and bromocriptine. Inhibition of puerperal lactation. A double blind study of bromocriptine and placebo. Study of the suppression of lactation and the influence on blood clotting with bromocriptine (CB 154) (Parlodel): a double blind comparison with diethylstilboestrol. The combined oral contraceptive pill versus bromocriptine to suppress lactation in puerperium: a randomized double blind study. Suppression of lactation. A comparison of bromocriptine and prostaglandin E2. Inhibition of puerperal lactation: evaluation of bromocriptine and placebo. Puerperal lactation suppression and prolactin. Inhibition of puerperal lactation: A comparative study of bromocriptine and pyridoxine. Bromocriptine in an injectable retard form for puerperal lactation suppression: comparison with Estandron prolongatum. Cabergoline versus bromocriptine in suppression of lactation after cesarean delivery. Effects of bromocriptine mesylate on the composition of the mammary secretion in non-breast-feeding women. Metergoline versus bromocriptine in the prevention of puerperal lactation. A double-blind clinical trial. Effect of bromocriptine and chlorotrianisene on inhibition of lactation and serum prolactin. A comparative double-blind study. Suppression of puerperal lactation using jasmine flowers (Jasminum sambac). Prevention of breast pain and milk secretion with bromocriptine after second-trimester abortion. Controlled trial of bromocriptine, quinoestrol, and placebo in suppression of puerperal lactation. [Cabergoline for inhibition of lactation]. Bromocriptine, methyl testosterone and placebo for inhibition of physiological lactation: a controlled study. [Treatment of pain due to unwanted lactation with a homeopathic preparation given in the immediate post-partum period]. Effects of hormonal contraceptives on milk volume and infant growth. WHO Special Programme of Research, Development and Research Training in Human Reproduction Task force on oral contraceptives. French multicenter randomized double-blind placebo-controlled trial on nebulized amiloride in cystic fibrosis patients. The Amiloride-AFLM Collaborative Study Group. Effects of lisuride and bromocriptine on inhibition of lactation and on serum prolactin levels: comparative double-blind study. Combined behavioral and individualized drug therapy versus individualized drug therapy alone for urge urinary incontinence in women. Prevention of puerperal lactation by a single oral administration of the new prolactin-inhibiting drug, cabergoline. The suppression of puerperal lactation with bromocriptine. A prospective, double-blind, randomized, placebo-controlled clinical trial of bromocriptine in clomiphene-resistant patients with polycystic ovary syndrome and normal prolactin level. Effect of hyoscine-N-butyl bromide rectal suppository on labor progress in primigravid women: randomized double-blind placebo-controlled clinical trial. Randomised trial of one versus two doses of prostaglandin E2 for induction of labour: 1. Clinical outcome. Hormonal suppression treatment or dietary therapy versus placebo in the control of painful symptoms after conservative surgery for endometriosis stage III-IV. A randomized comparative trial. Effectiveness of lactational amenorrhoea in prevention of pregnancy in Manila, the Philippines: non-comparative prospective trail. Effects of a dietary and environmental prevention programme on the incidence of allergic symptoms in high atopic risk infants: three years' follow-up. Prospective, randomized, double-blind study of the efficacy and tolerability of the extended-release formulations of oxybutynin and tolterodine for overactive bladder: results of the OPERA trial. Effects of moderate-dose treatment with varenicline on neurobiological and cognitive biomarkers in smokers and nonsmokers with schizophrenia or schizoaffective disorder. Prospective, randomized, parallel-group trial to evaluate the effects of lactulose and polyethylene glycol-4000 on colonic flora in chronic idiopathic constipation. Suppression of lactation with high doses of pyridoxine. Cluster randomised trial of an active, multifaceted educational intervention based on the WHO Reproductive Health Library to improve obstetric practices. A short-term, multicenter, randomized double-blind dose titration study of the efficacy and anticholinergic side effects of transdermal compared to immediate release oral oxybutynin treatment of patients with urge urinary incontinence. Behavioral therapy to enable women with urge incontinence to discontinue drug treatment: a randomized trial. Efficacy of bromocriptine and chlorotrianisene in preventing postpartum lactation. Intracervical versus intravaginal PGE2 for induction of labor at term in patients with an unfavorable cervix. Urodynamic changes associated with behavioral and drug treatment of urge incontinence in older women. Double-blind comparison of bromocriptine and placebo in cocaine withdrawal. PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial. Bromocriptine for cocaine dependence. A controlled clinical trial. A prospective randomised trial to compare the efficacy and safety of hemabate and syntometrine for the prevention of primary postpartum haemorrhage. A prospective study on the effects on hemostasis of two oral contraceptives containing drospirenone in combination with either 30 or 20 microg ethinyl estradiol and a reference containing desogestrel and 30 microg ethinyl estradiol. The efficiency of prostaglandin E2 vaginal suppositories versus intracervical prostaglandin gel for induction of labor in patients with unfavorable inducibility prospects. Randomized, placebo-controlled trial of Lactobacillus rhamnosus GG as treatment of atopic dermatitis in infancy. Oral nicardipine versus intravenous magnesium sulfate for the treatment of preterm labor. No effects of probiotics on atopic dermatitis in infancy: a randomized placebo-controlled trial. Dry mouth with conventional and controlled-release oxybutynin in urinary incontinence. The Ditropan XL Study Group.
In a controlled, randomised, prospective, clinical study, the effect of prolactin suppression and clinical course of the lactation suppressors Bromocriptine and Metergoline were investigated. During 7 months 150 patients were studied. 81 of those patients, who did not nurse, were treated by Bromocriptine (primary lactation suppression: n = 62, secondary suppression: n = 19) and 69 of the patients were treated by Metergoline (primary suppression: n = 54, secondary suppression: n = 15). The drugs were administrated orally to all subjects, dosed 2 x 2.5 mg/d of Bromocriptine for 14 days and 3 x 4 mg/d of Metergoline for 10 days, starting in average after 13 hours. Puerperal suppression of prolactine were compared with randomised breast feeding subjects (n = 30). In Bromocriptine treated women the average plasma prolactin level decreased from 78.4 +/- 22 ng/ml to 17.0 +/- 3.3 ng/ml during five days of treatment. In Metergoline treated women the plasma prolactin level decreased from 129.7 +/- 15.1 ng/ml to 56.9 +/- 10.0 ng/ml during the first days of treatment. Prolactin level of breast feeding subjects decreased from 233.6 +/- 21.4 ng/ml to 185.8 +/- 23.7 ng/ml during the same period (p < 0.05). There is no statistical significancy of clinical difference of both drugs, but a statistical trend was seen. With Bromocriptine treated women were suppressed efficiently in 71 of 81 cases, 10 refused. Refusals were divided in two quality levels, level I with subjects with moderate complaints and little puerperal lactation, level II with subjects with considerable complaints including strong puerperal lactation. With Metergoline suppressed women, treatment was efficiently in 51 of 69 cases, but refusals of level I were observed in 11 cases and refusals of level II were observed in 7 cases. The results show that Bromocriptine and Metergoline are effective on suppression of lactation. Under the current drug dose of Metergoline an advantage of Bromocriptine were observed. Only further studies could investigate, whether an adaptation of drug dose would improve the clinical efficiency of Metergoline. The efficacy and acceptability of bromocriptine in suppressing postpartum lactation was determined in a double blind study in which bromocriptine 2.5 mg twice daily for 14 days was compared with a placebo. Forty women who decide during the antenatal period not to breast feed entered the study. The bromocriptine treated group had significantly less mammary secretion and breast engorgement than the control group and also required less analgesia. The most noticeable side effects during the trial were dizziness, headache and abdominal pain. The only statistical difference between the two groups was a higher incidence of dizziness in the bromocriptine treated group. In an open pilot study with a parallel group design 30 bottle feeding women were randomly assigned in a two to one ratio to receive either the new dopamine agonist CV 205-502 or bromocriptine for lactation inhibition. Ten women who intended to breast feed served as normal controls. All treated women reached prepregnant prolactin levels within 72 h with once-daily 0.075 mg of CV 205-502 or twice-daily 2.5 mg of bromocriptine, at starting doses of 0.05 mg and 2.5 mg respectively. Fifteen of the 20 women treated with CV 205-502 reported breast symptoms, 50% occurring on days 3 and 4 of treatment. Three of the 10 women treated with bromocriptine had breast symptoms between days 2 and 28. Overall efficacy and tolerance in the two groups was very good. Side effects did not differ between the groups, with the exception of pulse rate in the standing position, which was significantly higher in the bromocriptine treated group than in either the CV 205-502 group (P = 0.02) or the breast feeding group (P less than 0.01). The coagulation tests (fibrinogen, AT III, PTT and APTT) showed no significant differences between the three groups. Recently, long-acting injectable forms of bromocriptine have become available for the prevention of lactation. The first developed depot-form was very effective, but had the disadvantage of a slowly metabolized carrier. we investigated the pharmacokinetics, efficacy, tolerance and safety of 40 and 50 mg of a new rapidly eliminated depot-form in 61 postpartum women. Bromocriptine rapidly increased after injection and prolactin was effectively suppressed during the study-period of 60 days. Overall efficacy was very good or good in 98% and no rebound lactation occurred. Sixteen women experienced side effects. Tolerance at the injection site was good and safety tests did not show abnormalities. There were no differences between the two dosages. We conclude that this new depot-bromocriptine is a safe, well tolerated and effective drug in the suppression of prolactin and the prevention of post-partum lactation. Bromocriptine (2 bromo-alpha-ergocryptine), stilboestrol, clomiphene citrate, testosterone propionate and a placebo were given to 75 postpartum women for the suppression of puerperal lactation. An additional 15 women who breast-fed their babies served as a control group. Blood samples were taken for the determination of serum prolactin levels by a specific homologous double antibody radioimmunoassay. Concurrently, the clinical effectiveness of the various treatments was assessed. High levels of prolactin were found at the time of delivery. Bromocriptine effectively reduced serum prolactin and prevented lactation; stilboestrol increased serum prolactin and partially suppressed lactation; clomiphene citrate and testosterone propionate both lowered serum prolactin levels and partially suppressed lactation. The placebo showed almost no effect on serum prolactin. It appeared that bromocriptine was the drug of choice in the suppression of puerperal lactation. In a double blind controlled study of the inhibition of lactation 13 women received 300 mg of cyclofenil and 11 women 2.5 mg of bromocriptine twice daily for 14 days. Lactation was effectively inhibited by both drugs, but with bromocriptine there was a significantly higher frequency of relapse. The plasma concentration of prolactin, which decreased rapidly with bromocriptine, returned to the pretreatment level the day after drug treatment stopped, but with cyclofenil it remained low. Plasma oestradiol followed a similar pattern. Plasma FSH increased more rapidly with bromocriptine than with cyclofenil. There was no significant difference between the treatment groups at any stage for haematology, coagulation or liver function tests. The more sustained effect of cyclofenil on prolactin secretion with a reduced frequency of relapse, and the lower oestradiol level, which might indicate a reduced risk of thromboembolism, suggest that this drug has some advantage over bromocriptine in the inhibition of postpartum lactation. Bromocriptine and placebo were randomly allocated for three weeks to 52 postpartum patients requiring lactation suppression. Bromocriptine significantly lowered plasma prolactin levels and suppressed breast milk, breast pain and engorgement quicker than placebo. No side-effects were noted and rebound lactation did not occur. Menstruation appeared to re-start sooner when Bromocriptine was given. Inhibition of lactation was studied in 38 puerperal women in a double blind trial to assess the effect of bromocriptine in comparison with diethylstilboestrol (DS). Simultaneously the influence of both compounds on blood clotting was studied, along with a control group of 20 women not receiving any medication. Bromocriptine was given in a daily dose of 5 mg for 14 days and DS in a daily dose of 20 mg for 7 days followed by a placebo for a further 7 days. The first doses were not later than 8 hours after delivery. Both compounds showed an inhibitory effect on the onset of lactation and mammary congestion. This inhibitory effect on both parameters was significantly in favour of bromocriptine during the last days of the treatment due to rebound in the DS group. The bromocriptine doses used (5 mg daily for 2 weeks) caused no objective side effects and no subjective restraint. Treatment with bromocriptine caused no untoward effect on the blood clotting, while in the DS group a slower return to normal antithrombin III could be observed. Also in this group one case of thrombophlebitis occurred. Bromocriptine can be administered to puerperal women for the suppression of lactation. A randomised double blind comparative study of 230 HIV infected mothers who had a normal delivery at 37-42 weeks' gestation were divided into two groups; 116 combined pill users and 114 bromocriptine users to suppress lactation. There were 33 cases (28.5%) of combined pills users and 29 cases (25.4%) of bromocriptine users who had breast engorgement without statistical difference. All of them had mild breast engorgement without any treatment except one case (0.9%) in the bromocriptine group had severe breast engorgement with puerperal fever and needed an analgesic drug. There were no side effects of the drugs. This study showed that combined pills were beneficial to suppress lactation in HIV infected mothers to prevent postnatal mother-to-child transmission because of low risk and low cost. Women in the puerperium who requested lactation suppression were randomly allocated to receive bromocriptine from puerperal day 1 to 14 or prostaglandin E2 from day 3 or 4 for 24 hours. Subjectively, lactation suppression was satisfactory in all cases. Objective measurements showed a trend toward more-effective early suppression with bromocriptine. After discharge from the hospital, 3 of the 21 women who received prostaglandin E2 complained of mild breast tenderness, whereas 10 of the 22 who received bromocriptine reported severe "rebound" breast tenderness. Bromocriptine and placebo were randomly allocated to 50 patients who wished to suppress lactation. Patients on bromocriptine suffered no subjective symptoms such as breast pain and engorgement, and lactation was significantly reduced compared with patients on the placebo with or without breast binding. No side-effects were noted, and rebound lactation was seen in only 3 patients. In most patients contraceptives were commenced once the drug therapy ceased on the fourteenth day. Five methods for puerperal lactation inhibition were assessed in a randomized fashion. The 90 women were divided into five groups. Four of these received a pharmacologic treatment: oral stilbestrol (15 mg dd for 5 days), a diuretic compound (bendroflumethazide 15 mg dd for 5 days) by mouth, oral bromocriptine (5 mg dd for 14 days), or an intramuscular injection containing estradiol (10 mg and testosterone (200 mg) esters administered immediately after delivery. To the women in the remaining group only physical methods were applied (breast support and local infra-red waves) and they served as controls. Prolactin plasma concentrations were determined daily for five consecutive days and showed a correlation with the clinical effectiveness of the various treatment schedules. While bromocriptine reduced and stilbestrol augmented prolactin levels, both types of treatment were equally effective in preventing lactation during the observation period. Treatment with a diuretic compound or with an injection of steroids, though less effective than the first two regimens, was nevertheless significantly more efficacious than physical treatment. Ninety-seven patients requiring suppression of lactation in the postpartum period were treated on a double-blind basis with bromocriptine and pyridoxine--49 patients received bromocriptine and 48 pyridoxine. A statistically significant difference between the two groups was noted, beginning after 1 day of treatment. Bromocriptine was superior to pyridoxine in the parameters measured. At the end of therapy the clinician, the midwife and the patient assessed the therapeutic efficacy of the trial drug. There was a statistically significant difference in favour of bromocriptine. Two patients treated with bromocriptine reported mild side-effects, but medication was not discontinued. In 1 patient receiving pyridoxine side-effects were so severe that medication was discontinued--however, the patient was already receiving the inactive tablets at this stage. Intramuscular injection of a single 50-mg dose of long-acting bromocriptine microspheres was compared with a single intramuscular dose of an estradiol/testosterone ester combination in a single-blind, randomized study of 54 subjects. Bromocriptine was significantly more effective than the steroid drug in preventing milk flow, and rebound lactation was not observed in any bromocriptine-treated patients. Neither group showed deleterious side effects or significant biologic changes in coagulation parameters. There were no blood pressure or electrocardiographic alterations. Postpartum prolactin suppression was more intense after bromocriptine administration than after steroid therapy. We evaluated the efficacy of cabergoline, a new ergoline derivative, in blocking puerperal lactation in a group of women delivered by cesarean section. In a single-blind controlled trial 36 women were randomly allocated to treatment with cabergoline 1 mg in a single dose p.o. (n = 18) or bromocriptine 5 mg/day p.o. for 14 days (n = 18). Treatment was started about 50 h after delivery. Clinical assessment of breast signs and determination of serum prolactin were performed just before treatment and at 3, 5, 7 and 14 days. In the cabergoline-treated group milk secretion was inhibited in 17 women (94.4%). Maximum decrease of serum prolactin was -89.7% at 5 days, and the prolactin-lowering effect of cabergoline was still present at 14 days. In the bromocriptine group milk secretion was inhibited in 16 women (88.9%). Maximum prolactin decrease (-86.9%) was reached at 3 days. Persistent side effects were comparable in the two groups. This study demonstrates that a single oral dose of 1 mg cabergoline is as effective in suppressing puerperal lactation as a full treatment with bromocriptine, even in women delivered by cesarean section. A double-blind trial was performed on 26 women, who had elected not to breast-feed their infants, to determine the effect of bromocriptine mesylate (2.5 mg twice daily for 14 days postpartum) on the composition of the mammary secretion during lactogenesis. Mammary secretion (less than 5.0 ml) was collected from each breast of each woman at daily intervals during the 14-day treatment period and the progressive changes in the concentration of the milk constituents, lactose, alpha-lactalbumin, serum albumin, total protein, lactoferin, IgA, IgG, sodium and potassium were determined. The degree of milk leakage and breast engorgement were also assessed. Both the subjective assessments and the changes in the concentration of the milk constituents demonstrated that lactogenesis occurred between about Day 2 and Day 5 postpartum in the placebo group (in the absence of the suckling stimulus) but was suppressed in the bromocriptine-treated group. In a double blind study of the prevention of puerperal lactation, the clinical efficacy of two antiprolactin drugs was compared: metergoline 4 mg tid and bromocriptine 2.5 mg bid were both given for 7 days. An additional 7 days of treatment was administered to 16 patients in whom mammary activity was still present or appeared in the following 3 days. The first 7 day period of treatment was effective in 16/20 women receiving metergoline and in 7/20 on bromocriptine (p less than 0.02); the second period of treatment was effective in all remaining patients. These data indicate that metergoline acts rapidly to arrest puerperal lactation, possibly by a mechanism different from that of bromocriptine. A double-blind study to compare the effect of 2-Br-alpha-ergocryptine (bromocriptine, CB 154, Sandoz) an ergot alkaloid with chlorotrianisene (Tace, Mer-National) on the inhibition of postpartum lactation was carried out in 38 women. At the dosages selected bromocriptine was more effective than chlorotrianisene in inhibiting lactation. Furthermore, bromocriptine significantly reduced serum prolactin levels to low normal values by the seventh day of treatment, whereas chlorotrianisene did not alter the normal progressive reduction in prolactin post-partum. Neither drug had significant toxic effects. The efficacy of jasmine flowers (Jasminum Sambac) applied to the breasts to suppress puerperal lactation was compared that of Bromocriptine. Effectiveness of both regimens was monitored by serum prolactin levels, clinical evaluation of the degree of breast engorgement and milk production and the analgesic intake. While both bromocriptine and jasmine flowers brought about a significant reduction in serum prolactin, the decrease was significantly greater with bromocriptine. However, clinical parameters such as breast engorgement, milk production and analgesic intake showed the 2 modes of therapy to be equally effective. The failure rates of the 2 regimens to suppress lactation were similar; however, rebound lactation occurred in a small proportion of women treated with bromocriptine. Jasmine flowers seem to be an effective and inexpensive method of suppressing puerperal lactation and can be used as an alternative in situations where cost and nonavailability restrict the use of bromocriptine. Within 24 hours after abortion, 62 patients with a mean gestational age of 19 weeks, who had either induced (n = 50) or spontaneous (n = 12) abortions were randomly allocated to three groups: Group 1, bromocriptine 2.5 mg twice daily for 2 weeks; Group 2, placebo tablets 1 tablet twice daily for 2 weeks; Group 3, no treatment. Fifty-two patients completed the study (bromocriptine n = 18, placebo n = 18 and no treatment n = 16). Placebo had no apparent influence on breast symptoms. In both the placebo group and the untreated group, breast pain and milk secretion peaked on days 3 to 7, and milk secretion often continued for 3 weeks. Only 3/34 (9%) of untreated and placebo treated patients were free of breast symptoms. Compared with placebo, bromocriptine caused a significant reduction in the objective assessment score of breast tenderness (p less than 0.05) and milk secretion (p less than 0.01), in serum prolactin (PRL) (p less than 0.001) and in the subjective assessment score of breast pain (p less than 0.01) and milk secretion (p less than 0.01). Alleviation of breast pain and prevention of milk secretion appears to be indicated after second-trimester abortion, and treatment with bromocriptine is efficacious. 2-bromo-alpha-ergocryptine (bromocriptine) in a dosage of 2-5 mg twice daily caused a rapid fall in plasma prolactin. It was more effective than either a single dose of 4 mg quinoestrol or a placebo in suppressing puerperal lactation, as judged by milk flow and the relief of breast pain and congestion. Patients who received quinoestrol were more comfortable than those who received placebo. Despite advances in prevention inhibition of lactation, only administration of estrogens or these combined with androgens show variable effectiveness and are indirectly associated with high percentage for lactation rebound, thrombosis, or pulmonary embolism or both of the later during puerperium; in addition, bromocriptine, also used indirectly for inhibition of lactation, is associated with lactation, rebound in 18-40%. Cabergolin is a new ergoline with efficient and durable prolactin reducer effect with fewer adverse effects.
                Which will the smallest cabergolin dosage be to inhibit lactation?
                To demonstrate clinical effectiveness with smallest cabergolina dosage in lactation inhibition.
                We carried on a the Service Clinical test on patients hospitalization with an indication to inhibit lactation as the Hospital of Gynecology and Obstetrics, Infantil Maternal Institute of the State of Mexico (IMIEM). The study was done 80 patients to who we administered oral 0.5 mg cabergoline to 40 patients and another group of 40 whom we administered 1.0 mg of cabergoline orally at random and blinded by means of out-patient consultation. We studied correlation between dose and inhibition of lactation as well as presence of adverse effects.
                In the group of patients to whom administered 0.5 mg, we found 65% (n = 26) with lactation inhibition; adverse effects in this group appeared in 32.5% (n = 13) the second group with a dose of 1.0 mg; 95% with adverse effects in 25% P < 0.001.
                Inhibition of lactation with unique dose of 1.0 has satisfactory clinical effectiveness, this being the smaller dose to inhibit lactation at a suitable percentage. Lactation occurs when the fully developed breast is released from the inhibitory influence which oestrogen and progesterone exert upon the action of prolactin. The use of oestrogens to suppress lactation depends on a continuation of the peripheral, that is, mammary, inhibition of prolactin. Androgens are also believed to act by inhibition of the action of prolactin on the mammary gland epithelium. Bromocriptine, when compared in a double-blind trial with orally administered methyl testosterone and placebo, gave almost complete relief of breast discomfort and congestion, though a small amount of milk production was seen. Methyl testosterone, in the dosage used in this study, was quite ineffective in suppressing lactation or breast symptoms. Dopaminergic agonists, such as Parlodel((R)), are now widely used to inhibit lactation. However, some countries, such as the United States, no longer use these drugs in this indication because of their sometimes serious adverse effects. In this context, the authors tested a homeopathic treatment designed for parturients unable or not wanting to breastfeed. The APIS MELLIFICA 9 CH and BRYONIA 9 CH combination was chosen for its anti-inflammatory and analgesic effects. 71 patients were included in this double-blind placebo-controlled study. All received basic treatment comprising naproxen and fluid restriction. A significant improvement of lactation pain (main criterion of the study) was observed in parturients treated with homeopathy (p<0.02 on D2 and p<0.01 on D4). A similar effect (p<0.05 on D4) was observed for breast tension and spontaneous milk flow. No significant difference was observed for the other criteria of the study. The homeopathic combination studied was therefore effective on the pain of lactation and should be integrated into the therapeutic armamentarium. WHO conducted a three-centre study in Hungary and Thailand to evaluate the effects of hormonal contraception on lactation and infant growth. Women choosing oral contraceptives were randomly assigned to a combined oral contraceptive containing 30 micrograms ethinyl estradiol and 150 micrograms levonorgestrel (N = 86) or a progestin-only preparation containing 75 micrograms dl-norgestrel (N = 85). Identical packaging and treatment schedules allowed double-blind observation. One-hundred-and-eleven women using no contraception or non-hormonal methods acted as controls. In the two Thai centres 59 women using depot-medroxyprogesterone acetate formed an additional comparison group. All subjects were healthy women with normal deliveries, whose infants had normal birth weights and satisfactory growth in the neonatal period. Breast milk volume was determined by pump expression using standardized procedures. Information was obtained on nursing frequency and supplementation, infant growth and morbidity. Pretreatment observations at 6 weeks post-partum were used as a baseline, and subjects were followed-up at 9, 12, 16, 20 and 24 weeks post-partum. Women using combined oral contraceptives had a decline in milk volume within 6 weeks of initiating treatment, whereas no significant decrease was observed in the other treatment groups. After 18 weeks of treatment, combined oral contraceptive users experienced a 41.9% decline in milk volume, compared to 12.0% with progestin-only minipills and 6.1% in the non-hormonal controls. The prevalence of complementary feeding and withdrawals due to inadequate milk supply were comparable in the four treatment groups. However, data were not available on the daily amounts of complementary feeds. There were no significant differences in growth of infants between treatment groups. Thus, women may have compensated for declines in milk volume by more supplementary feeding or by more prolonged and intense suckling episodes. We conclude that 30 micrograms estrogen-containing combined oral contraceptives impair milk secretion, but in the selected healthy group of mothers and children studied with the prevailing level of supplementary feeding, this did not adversely affect infant growth. The effect of amiloride, a sodium channel blocker, has been evaluated in a multicenter randomized double-blind placebo-controlled trial in cystic fibrosis patients more than 5-years-old (n = 137) whose forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV(1)), and forced mid-expiratory flow (FEF(25-75)) were not below 50%, 50%, and 30% of reference values, respectively. Patients were randomly allocated to two parallel groups. Sixty-four patients were chronically colonized with Pseudomonas aeruginosa; they received either amiloride or placebo as a nebulized solution three times daily for 6 months. Routine treatments were continued. Patients chronically colonized with Pseudomonas received nebulized colimycine twice a day for a month during the third and sixth months of treatment. Bronchopulmonary exacerbations were treated in the usual way. The effects of the amiloride treatment were assessed at the end of the 6-month treatment period. The effects on FVC and secondarily on FEV(1), FEF(25-75), the number of days on antibiotic therapy, the Shwachman score, a nutritional index (weight/height(2)), the change in sputum bacterial flora, and nocturnal cough were assessed. For the patients not chronically colonized with Pseudomonas, the effect of the treatment was also evaluated by counting chronic colonizations with pathogens appearing during the trial period. The present study failed to demonstrate any significant benefit of amiloride over placebo on FVC, FEV(1), and the other secondary endpoints in the studied population. Neither the chronically colonized, nor the noncolonized patients benefited. The confidence intervals of the differences between treatment groups indicated small differences that were most likely of no clinical significance. Complementary analyses taking into account the gender, the type of mutation, the subpopulations whose FVC and FEV(1) were below 80% of normal values at the beginning of the study, and also patients less than 10 years old, did not show any statistically or clinically significant improvements following amiloride therapy.
                Copyright 2000 Wiley-Liss, Inc. The effects of lisuride (Schering) and bromocriptine (Parlodel, Sandoz), two dopaminergic drugs, on the inhibition of puerperal lactation were compared in a double-blind study. At the dosages selected, lisuride was as effective as bromocriptine for the inhibition of lactation but bromocriptine was more effective in lowering serum prolactin levels. We tested whether individualized drug therapy enhanced with behavioral training would result in better outcomes than individualized drug therapy alone.
                Participants were community dwelling women with urge predominant incontinence. Using a randomized clinical trial design women were randomized to 8 weeks (4 visits) of drug therapy alone (32) or drug therapy plus behavioral training (32). Drug therapy was individually titrated, extended release oxybutynin with proactive management of side effects. Behavioral training included pelvic floor muscle training and urge suppression techniques. The primary outcome measure was reduction in frequency of incontinence episodes on bladder diary at 8 weeks (with followup at 6 and 12 months). Secondary outcomes included patient satisfaction, global perception of improvement, Urogenital Distress Inventory and Incontinence Impact Questionnaire.
                In intent to treat analysis frequency of incontinence was reduced a mean of 88.5% in the drug alone group and 78.3% in the combined therapy group (p = 0.16). Outcomes were not significantly different between the groups in the analysis of completers (91.5% vs 86.2%, p = 0.34), or in either analysis at 6 or 12 months. The groups also did not differ significantly on secondary outcomes at any point. Participants in the drug alone group tended to be taking higher doses of oxybutynin at 8 weeks but the final dose did not differ significantly between the groups. Based on a conditional power calculation the trial was stopped early for futility.
                When drug therapy is implemented with frequent individualized dose titration, daily bladder diaries and careful management of side effects, initiating concurrent behavioral training does not enhance outcomes for urge incontinence in women.
                Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved. To evaluate the efficacy of a single oral administration of the new ergot derivative Cabergoline in the prevention of post-partum lactation, we compared the effects of three different doses of the drug with those of placebo in 32 puerperal women. In a controlled, double-blind trial, the subjects were randomly allocated to four treatment groups receiving either placebo or 400, 600, or 800 micrograms Cabergoline (N = 8 in each group) within 24 hours after delivery. Treatment efficacy was assessed clinically by physical examination before (day 0) and at one, two, three, four, and 14 days after treatment. Plasma prolactin (PRL) concentrations were measured in blood samples collected before and at one, two, three, and four days after treatment. Lactation was prevented in four of the eight subjects (50%) who received 400 micrograms Cabergoline and in all subjects who received 600 or 800 micrograms Cabergoline. By contrast, only one of the eight subjects (12.5%) receiving placebo showed no signs of spontaneous lactation within the 14 days after delivery. No effects of placebo administration on plasma PRL levels were observed. Plasma PRL concentrations were significantly reduced starting from one day after Cabergoline administration, however, and the amount of inhibition of PRL secretion induced by different doses of the drug was not statistically different. These preliminary data demonstrate that Cabergoline has a dose-related effect in the prevention of postpartum lactation, and milk secretion can be prevented completely by a single oral administration of 600 or 800 micrograms of the drug. nan To evaluate the effects of administration of bromocriptine combined with clomiphene citrate (CC) in CC-resistant patients with polycystic ovary syndrome (PCOS) and normal prolactin (PRL) level.
                Prospective double-blind, placebo-controlled, randomized.
                Referral university hospitals.
                One hundred women with PCOS and normal PRL who failed to ovulate with a routine protocol of CC.
                Treatment group received 150 mg of CC from day 5 to 9 and 7.5 mg bromocriptine continuously, with hCG 10,000 units on day 16 or 17. Control group received the same protocol of CC combined with placebo.
                Follicular development, hormonal changes, ovulation rate, pregnancy rate.
                Follicular development (follicular size greater than 15 mm) was observed in 12 (25.5%) and 8 (15.1%) women in the treatment and placebo group, respectively (p = 0.29). The serum prolactin level was within normal limits in all patients before treatment. After 3 and 6 months of treatment with bromocriptine, there was a significant decrease in serum level of prolactin (p = 0.000001). No significant differences were seen in ovulation, pregnancy rate, or serum levels of FSH, LH, DHEAS, and progesterone between treatment and placebo groups after treatment.
                The only significant effect of long-term bromocriptine therapy in CC-resistant women with PCOS was to lower the serum PRL concentration. It is also concluded that 10%-15% of patients with PCOS experienced occasional ovulatory cycles and pregnancy whether or not they were on treatment. To determine the effects of hyoscine-N-butyl bromide (HBB) rectal suppository on labor progress in primigravid women.
                A randomized double-blind placebo-controlled clinical trial was carried out on 130 primigravid women admitted for spontaneous labor. The women were recruited based on the inclusion and exclusion criteria and randomized into the experimental (n=65) and control group (n=65). In the beginning of the active phase of labor, 20 mg of HBB rectal suppository was administered to the experimental group, while a placebo suppository was administered to the control group. Cervical dilatation and duration of active phase and second stage of labor were recorded.
                The rate of cervical dilatation was 2.6 cm/h in the experimental and 1.5 cm/h in the control group (P<0.001). The active phase and the second stage of labor were significantly shorter in the experimental group (P=0.001 and P<0.001, respectively). There was no significant difference between the two groups in the fetal heart rate, maternal pulse rate, blood pressure, and the APGAR score 1 and 5 minutes after birth.
                Use of HBB rectal suppository in the active management of labor can shorten both the active phase and second stage of labor without significant side-effects. To compare the outcome of induction of labour using a single versus two doses of prostaglandin E2 vaginal gel.
                Prospective randomised trial comparing a single dose of prostaglandin E2 2 mg vaginal gel in the evening with two doses of prostaglandin E2 (2 mg), the second being given after six hours if labour had not started or the cervix was still unripe. Amniotomy and oxytocin titration were performed when necessary for both protocols. Nulliparae and multiparae were analysed separately by treatment intention.
                A maternity unit in a district general hospital annually delivering > 6000 women.
                Nine-hundred and ninety-five women with viable singleton pregnancies and cephalic presentation at term without previous history of caesarean section who were advised to have labour induced with prostaglandins.
                Need for formal amniotomy and oxytocin augmentation, use of epidural analgesia, rate of intrapartum interventions, mode of delivery and neonatal condition at birth.
                For multiparae two prostaglandin doses resulted in a significant reduction in the need for formal amniotomy (15% vs 30%) and oxytocin augmentation (28% vs 38%) compared with those receiving a single dose; there was no significant difference for nulliparae. Other interventions during labour, length of labour, and mode of delivery were similar in both protocols. Failed induction occurred only in nulliparae and was similar in both protocols (1%). There was no discernible difference in fetal or neonatal outcome although passage of meconium was more common in labour if two doses had been given, as was neonatal admission to the special care baby unit.
                There was little clinical benefit from inducing labour with two doses of prostaglandin E2 at a six-hour interval, compared with a single dose. There may be financial advantages with a two-dose regimen. To evaluate the effectiveness for the outcomes of endometriosis-related pain and quality of life of conservative surgery plus placebo compared with conservative surgery plus hormonal suppression treatment or dietary therapy.
                Randomized comparative trial.
                University hospital.
                Two hundred twenty-two consecutive women who underwent conservative pelvic surgery for symptomatic endometriosis stage III-IV (r-AFS).
                Six months of placebo (n = 110) versus GnRH-a (tryptorelin or leuprorelin, 3.75 mg every 28 days) (n = 39) or continuous estroprogestin (ethynilestradiol, 0.03 mg plus gestoden, 0.75 mg) (n = 38) versus dietary therapy (vitamins, minerals salts, lactic ferments, fish oil) (n = 35).
                Painful symptoms (visual analogue scale score) and quality-of-life endometriosis-related symptoms (SF-36 score) at 12 months' follow-up.
                Patients treated with postoperative hormonal suppression therapy showed less visual analogue scale scores for dysmenorrhoea than patients of the other groups. Hormonal suppression therapy and dietary supplementation were equally effective in reducing nonmenstrual pelvic pain. Surgery plus placebo showed significative decrease in dyspareunia scores. Postoperative medical and dietary therapy allowed a better quality of life than placebo.
                Postoperative hormonal suppression treatment or dietary therapy are more effective than surgery plus placebo to obtain relief of pain associated with endometriosis stage III-IV and improvement of quality of life. To determine the contraceptive efficacy of the lactational amenorrhoea method.
                Non-comparative prospective trial.
                Urban Manila, the Philippines.
                485 lower income, educated women with extensive experience of breast feeding.
                Women were offered all available contraceptives for use after birth. Those who chose the lactational amenorrhoea method were taught the method, screened for the study, and followed for 12 months to determine the risk of pregnancy when the method was used.
                Life table pregnancy rates during correct and incorrect use of the method, censored monthly in the event of sexual abstinence or the use of another contraceptive method.
                The lactational amenorrhoea method was 99% effective when used correctly (that is, during lactational amenorrhoea and full or nearly full breast feeding for up to six months). At 12 months the effectiveness during amenorrhoea dropped to 97%.
                The lactational amenorrhoea method provided as much protection from pregnancy as non-breast feeding women experience with non-medicated intrauterine devices and barrier methods. The contraceptive effect of lactation cannot be attributed to lactational or postpartum abstinence. A prospective case-control study is presented to assess an allergy prevention programme in children up to 36 months of age. Infants born at three maternity hospitals were followed from birth: 279 infants with high atopic risk (intervention group) were compared with 80 infants with similar atopic risk but no intervention (non-intervention group). The intervention programme included dietary measures (exclusive and prolonged milk feeding diet followed by a hypoantigenic weaning diet) and environmental measures (avoidance of parental smoking in the presence of the babies, day care > 2 years of life). Mothers in this group who had insufficient breast milk were randomly assigned to one of two coded formulas: either a hydrolysed milk formula (Nidina HA, Nestlé) or a conventional adapted formula (Nan, Nestlé). Other environmental measures remained the same as for the breastfeeding mothers. The non-intervention group were either breastfed or received the usual Italian milk feeding and weaning diet, without environmental advice. The main outcome measures were anthropometric measurements and allergic disease manifestations. Normal anthropometric data were observed both in the intervention group and in the non-intervention group. The incidence of allergic manifestations was much lower in the intervention group than in the non-intervention group at 1 year (11.5 versus 54.4%, respectively) and at 2 years (14.9 versus 65.6%) and 3 years (20.6 versus 74.1%). Atopic dermatitis and recurrent wheezing were found in both the intervention group and the non-intervention group from birth up to the second year of life, while urticaria and gastrointestinal disorders were only present in the non-intervention group in the first year of life. Conjunctivitis and rhinitis were present after the second year in both the intervention group and the non-intervention group. Relapse of the same allergic symptom was less in the intervention group (13.0%) than in the non-intervention group (36.9%). In comparison to the non-intervention group, there were fewer intervention group cases with two or more different allergic symptoms (8.7 versus 32.6%), and they were more likely to avoid steroid treatment (0 versus 10.8%) and hospital admission (0 versus 6.5%). Babies in the non-intervention group fed with adapted formula were more likely to develop allergies than breastfed babies in the same group. In the intervention group the breastfed infants had the lowest incidence of allergic symptoms, followed by the infants fed the hydrolysed formula (ns). Infants in the intervention group fed the adapted formula had significantly more allergies than the breastfed and hydrolysed milk fed infants, although less than their counterparts in the non-intervention group. Of the affected subjects in the intervention group, 80.4% were RAST and/or Prick positive to food or inhalant allergens. Total serum IgE values detected at birth in the intervention group were not predictive, but at 1 and 2 years of age, IgE values more than 2 SD above the mean in asymptomatic babies were found to predictive for later allergy. In breastfed babies the total IgE level at 1 and 2 years of age was lower than in the other two feeding groups. Of the various factors tested in the non-intervention group, the following were the most important in the pathogenesis of allergic symptoms: (i) formula implementation begun in the first week of life; (ii) early weaning (< 4 months); (iii) feeding beef (< 6 months); (iv) early introduction of cow's milk (< 6 months); and (v) parental smoking in the presence of the babies and early day care admission (< 2 years of life). All the preventive measures used in this study (exclusive breastfeeding and/or hydrolysed milk feeding, delayed and selective introduction of solid foods, and environmental advice) were effective at the third year of follow-up, greatly reducing allergic manifestations in high atopic risk babies in comparison with those not receiving these interventions To compare the efficacy and tolerability of extended-release formulations of oxybutynin chloride and tolterodine tartrate in women with overactive bladder.
                The OPERA (Overactive bladder: Performance of Extended Release Agents) trial was a randomized, double-blind, active-control study performed at 71 US study centers from November 21, 2000, to October 18,2001. Extended-release formulations of oxybutynin at 10 mg/d or tolterodine at 4 mg/d were given for 12 weeks to women with 21 to 60 urge urinary incontinence (UUI) episodes per week and an average of 10 or more voids per 24 hours. Episodes of UUI (primary end point), total (urge and nonurge) incontinence, and micturition were recorded in 24-hour urinary diaries at baseline and at weeks 2, 4, 8, and 12 and compared. Adverse events were also evaluated.
                Improvements in weekly UUI episodes were similar for the 790 women who received extended-release formulations of oxybutynin (n = 391) or tolterodine (n = 399). Oxybutynin was significantly more effective than tolterodine in reducing micturition frequency (P = .003), and 23.0% of women taking oxybutynin reported no episodes of urinary incontinence compared with 16.8% of women taking tolterodine (P = .03). Dry mouth, usually mild, was more common with oxybutynin (P = .02). Adverse events were generally mild and occurred at low rates, with both groups having similar discontinuation of treatment due to adverse events.
                Reductions in weekly UUI and total incontinence episodes were similar with extended-release formulations of oxybutynin and tolterodine. In the oxybutynin group, micturition frequency was significantly lower, and the percentage of women reporting no urinary incontinence episodes was significantly higher compared with the tolterodine group. Dry mouth was more common with oxybutynin, but tolerability was otherwise comparable, including adverse events involving the central nervous system. The administration of nicotine transiently improves many neurobiological and cognitive functions in schizophrenia and schizoaffective disorder. It is not yet clear which nicotinic acetylcholine receptor (nAChR) subtype or subtypes are responsible for these seemingly pervasive nicotinic effects in schizophrenia and schizoaffective disorder.
                Because α4β2 is a key nAChR subtype for nicotinic actions, we investigated the effect of varenicline tartrate, a relatively specific α4β2 partial agonist and antagonist, on key biomarkers that are associated with schizophrenia and are previously shown to be responsive to nicotinic challenge in humans.
                A double-blind, parallel, randomized, placebo-controlled trial of patients with schizophrenia or schizoaffective disorder to examine the effects of varenicline on biomarkers at 2 weeks (short-term treatment) and 8 weeks (long-term treatment), using a slow titration and moderate dosing strategy for retaining α4β2-specific effects while minimizing adverse effects.
                Outpatient clinics.
                A total of 69 smoking and nonsmoking patients; 64 patients completed week 2, and 59 patients completed week 8. Intervention Varenicline.
                Prepulse inhibition, sensory gating, antisaccade, spatial working memory, eye tracking, processing speed, and sustained attention.
                A moderate dose of varenicline (1) significantly reduced the P50 sensory gating deficit in nonsmokers after long-term treatment (P = .006), (2) reduced startle reactivity (P = .02) regardless of baseline smoking status, and (3) improved executive function by reducing the antisaccadic error rate (P = .03) regardless of smoking status. A moderate dose of varenicline had no significant effect on spatial working memory, predictive and maintenance pursuit measures, processing speed, or sustained attention by Conners' Continuous Performance Test. Clinically, there was no evidence of exacerbation of psychiatric symptoms, psychosis, depression, or suicidality using a gradual titration (1-mg daily dose).
                Moderate-dose treatment with varenicline has a unique treatment profile on core schizophrenia-related biomarkers. Further development is warranted for specific nAChR compounds and dosing and duration strategies to target subgroups of schizophrenic patients with specific biological deficits. Although lactulose and polyethylene glycol are osmotic laxatives widely used in the treatment of chronic constipation, no study has been conducted to compare their actions on the colonic bacterial ecosystem, which has an important influence on host health.
                To assess the effects of lactulose and polyethylene glycol on the composition and metabolic indices of the faecal flora in patients with chronic idiopathic constipation.
                Sixty-five patients with chronic idiopathic constipation were included in this controlled, multi-centre, randomized, parallel-group study. Participants received lactulose (Duphalac) or polyethylene glycol-4000 (Forlax) powders for the first week at a fixed dosage at night (20 g/day); in the second week, patients were given the option to vary the dose according to efficacy and tolerance (10-30 g/day); for the last 2 weeks, treatment was administered at a fixed dosage based on the results of the second week (10-30 g/day). Stools were recovered for bacteriological analysis at days -1, 21 and 28.
                Clinical efficacy and tolerance were similar with both treatments. In the lactulose group, an increase in faecal bifidobacteria counts (P = 0.04) and beta-galactosidase activity (P < 0.001) was observed from day -1 to day 28, whereas, in the polyethylene glycol group, there was a decrease in total short-chain fatty acids (P = 0.02), butyrate (P = 0.04), acetate (P = 0.02) and faecal bacterial mass (P = 0.001). No differences were observed in stools with regard to the following parameters: counts of Lactobacillus, clostridial spores, Bacteroides and enterobacteria, pH, biliary acids and neutral sterol concentrations.
                Both lactulose and polyethylene glycol are efficacious and well tolerated. However, although lactulose can be considered as a pre-biotic in constipated patients, polyethylene glycol produces signs of decreased colonic fermentation in the stool. Administration of high doses of vitamins B6, B1 and B12 successfully inhibited lactation without any untoward side-effects or discomfort in 96% of patients who had not yet established lactation, compared with 76,5% of control patients who received placebo. We conducted a trial to evaluate the effect of an active, multifaceted educational strategy to promote the use of the WHO Reproductive Health Library (RHL) on obstetric practices.
                Cluster randomised trial. The trial was assigned the International Standardised Randomised Controlled Trial Number ISRCTN14055385.
                Twenty-two hospitals in Mexico City and 18 in the Northeast region of Thailand.
                The intervention consisted primarily of three interactive workshops using RHL over a period of 6 months. The focus of the workshops was to provide access to knowledge and enable its use. A computer and support for using both the computer and RHL were provided at each hospital. The control hospitals did not receive any intervention.
                The main outcome measures were changes in ten selected clinical practices as recommended in RHL starting approximately four to six months after the third workshop. Clinical practice data were collected at each hospital from 1000 consecutively delivered women or for a 6-month period whichever was reached sooner.
                The active, multifaceted educational intervention we employed did not affect the ten targeted practices in a consistent and substantive way. Iron/folate supplementation, uterotonic use after birth and breastfeeding on demand were already frequently practiced, and we were unable to measure external cephalic version. Of the remaining six practices, selective, as opposed to routine episiotomy policy increased in the intervention group (difference in adjusted mean rate = 5.3%; 95% CI -0.1 to 10.7%) in Thailand, and there was a trend towards an increased use of antibiotics at caesarean section in Mexico (difference in adjusted mean rate = 19.0%; 95% CI: -8.0 to 46.0%). There were no differences in the use of labour companionship, magnesium sulphate use for eclampsia, corticosteroids for women delivering before 34 weeks and vacuum extraction. RHL awareness (24.8-65.5% in Mexico and 33.9-83.3% in Thailand) and use (4.8-34.9% in Mexico and 15.5-76.4% in Thailand) increased substantially after the intervention in both countries.
                The multifaceted, active strategy to provide health workers with the knowledge and skills to use RHL to improve their practice led to increased access to and use of RHL, however, no consistent or substantive changes in clinical practices were detected within 4-6 months after the third workshop. We compared the short-term efficacy, safety and tolerability of transdermal versus oral oxybutynin in adults with urge urinary incontinence.
                Volunteers with detrusor instability currently responding to oral immediate release oxybutynin were enrolled in our study. Those patients presenting with recurrence of incontinent symptoms after a 2-week washout underwent confirmatory cystometrogram with subsequent randomization to transdermal or oral treatment. Matching active and placebo medications included matrix patches applied twice weekly and capsules taken 2 or 3 times daily. Dose titration was based on anticholinergic symptoms. Outcome measures included comparison of baseline to 6 week changes in incontinence episodes on a 3 day urinary diary, a visual analog scale for efficacy and anticholinergic symptoms reported on a questionnaire. Safety monitoring included adverse events and skin tolerability of the transdermal system.
                A total of 76 patients were enrolled and 74 completed at least 4 weeks of treatment. Mean age in the transdermal and oral groups was 64 and 63 years, and 87% and 97% were female, respectively. Daily incontinent episodes decreased in the transdermal and oral groups (7.3 to 2.4 [66%] and 7.4 to 2.6 [72%], respectively, p = 0.39). The visual analog scale reduction in urinary leakage improved from washout in both groups (p <0.0001) with no difference between them (p = 0.9). Dry mouth occurred in significantly fewer patients in the transdermal (38%) compared with those in the oral group (94%, p <0.001). Of the patients in the transdermal group 67% noticed a reduction in dry mouth severity compared with previous oral treatment, and 90% had none or mild skin erythema.
                Transdermal delivery of oxybutynin resulted in comparable efficacy and a significantly improved anticholinergic side effect profile compared with oral administration in adults with urge urinary incontinence. Women with urge urinary incontinence are commonly treated with antimuscarinic medications, but many discontinue therapy.
                To determine whether combining antimuscarinic drug therapy with supervised behavioral training, compared with drug therapy alone, improves the ability of women with urge incontinence to achieve clinically important reductions in incontinence episodes and to sustain these improvements after discontinuing drug therapy.
                2-stage, multicenter, randomized clinical trial conducted from July 2004 to January 2006.
                9 university-affiliated outpatient clinics.
                307 women with urge-predominant incontinence.
                10 weeks of open-label, extended-release tolterodine alone (n = 153) or combined with behavioral training (n = 154), followed by discontinuation of therapy and follow-up at 8 months.
                The primary outcome, measured at 8 months, was no receipt of drugs or other therapy for urge incontinence and a 70% or greater reduction in frequency of incontinence episodes. Secondary outcomes were reduction in incontinence, self-reported satisfaction and improvement, and scores on validated questionnaires measuring symptom distress and bother and health-related quality of life. Study staff who performed outcome evaluations, but not participants and interventionists, were blinded to group assignment.
                237 participants completed the trial. According to life-table estimates, the rate of successful discontinuation of therapy at 8 months was the same in the combination therapy and drug therapy alone groups (41% in both groups; difference, 0 percentage points [95% CI, -12 to 12 percentage points]). A higher proportion of participants who received combination therapy than drug therapy alone achieved a 70% or greater reduction in incontinence at 10 weeks (69% vs. 58%; difference, 11 percentage points [CI, -0.3 to 22.1 percentage points]). Combination therapy yielded better outcomes over time on the Urogenital Distress Inventory and the Overactive Bladder Questionnaire (both P <0.001) at both time points for patient satisfaction and perceived improvement but not health-related quality of life. Adverse events were uncommon (12 events in 6 participants [3 in each group]).
                Behavioral therapy components (daily bladder diary and recommendations for fluid management) in the group receiving drug therapy alone may have attenuated between-group differences. Assigned treatment was completed by 68% of participants, whereas 8-month outcome status was assessed on 77%.
                The addition of behavioral training to drug therapy may reduce incontinence frequency during active treatment but does not improve the ability to discontinue drug therapy and maintain improvement in urinary incontinence. Combination therapy has a beneficial effect on patient satisfaction, perceived improvement, and reduction of other bladder symptoms. nan In a randomized double-blind study we evaluated the effects on cervical ripening and labor induction of 0.5 mg PGE2 in gel given intracervically and 2.0 mg PGE2 given as a vaginal suppository. All patients were at term with unfavorable cervical scores. The indications for induction were toxemia, diabetes mellitus, Rh-immunization, or intrauterine growth retardation. Significantly better results for both cervical priming and labor induction were obtained after intracervical PGE2-gel application than after treatment with placebo or vaginal suppositories. Eleven out of 19 patients (58%) were delivered within 24 h after intracervical PGE2-gel compared to two out of 19 patients given placebo (p less than 0.01). In patients not delivered 24 h after the start of treatment, the mean cervical score had changed from 3.7 to 6.0 (p less than 0.05) after PGE2-gel application compared to a change from 3.9 to 4.3 after placebo treatment (n.s.). The outcome after treatment with PGE2 suppositories did not differ significantly from that with placebo treatment. In a subsequent study 25 patients were given 0.5 mg PGE2-gel intracervically. The results were consistent with those obtained in patients receiving PGE2-gel intracervically in the double-blind study. Few side effects were noted. No patient complained of gastro-intestinal discomfort but increased myometrial activity was observed in two patients; one after placebo and the other after active intracervical PGE2-gel treatment. The hyperactivity was readily countered with the beta 2-agonist, terbutaline. All infants were born in good condition with Apgar scores of 7 or more within 5 min. At pediatric examinations at 1 week and at 6 months of age all children seemed healthy. To describe changes in bladder function and voiding frequency associated with behavioral and drug treatment for urge incontinence and to examine whether these variables mediate the positive effects of treatment on the frequency of incontinence.
                Randomized, double-blinded, placebo-controlled, clinical trial. Eligible patients were stratified according to type of incontinence (urge only vs mixed urge and stress) and severity of incontinence (frequency of accidents as documented in bladder diary).
                University-based outpatient geriatric medicine clinic.
                One hundred five ambulatory, nondemented, community-dwelling women; mean age 67.0 (range 55-91); 98% white, 2% African American.
                Four sessions (over 8 weeks) of biofeedback-assisted behavioral training, drug treatment with individually-titrated oxybutynin chloride, or a placebo control condition.
                Two-channel cystometry was performed to determine threshold volumes for first desire to void (FDV), strong desire to void (SDV), bladder capacity, and the volume at which detrusor instability (DI) or leakage occurred, before randomization and after completion of treatment. Two-week bladder diaries were used before and after treatment to document episodes of incontinence and voiding frequency.
                Bladder capacity increased by 68.9 mL in the oxybutynin group (P <.001) and 17.3 mL in the behavior group and decreased 6.0 mL in the control group. SDV increased 69.9 mL in the oxybutynin group (P <.001), 40.5 in the behavior group (P <.05), and 7.8 mL in the control group. FDV increased by 44.4 mL in the oxybutynin group (P <.001), 18.8 mL in the behavior group, and 8.9 mL in the control group. One of seven patients who presented with DI (12.0%) resolved in the behavior group, seven of eight (87.5%) resolved in the oxybutynin group, and seven of 12 (58.3%) resolved in the control group. These differences were not statistically significant. Voiding frequency was significantly reduced after treatment in both the behavior and the oxybutynin group. Behavioral training resulted in a mean 82.3% reduction in frequency of accidents, oxybutynin (final doses 2.5 mg daily to 5 mg three times a day) resulted in a mean 78.3% reduction, and the control condition resulted in a mean 51.5% reduction (P =.002). Although oxybutynin and behavioral treatment were both effective, and oxybutynin increased SDV and bladder capacity, the structural equation modeling did not demonstrate that the clinical improvement was mediated through the effects of these treatments on urodynamic or voiding frequency measures.
                Studies using more-complex urodynamics and studies with larger sample sizes are needed to better characterize changes in bladder function and explore other urodynamic changes that may accompany treatment. In addition, other factors, both physiological and behavioral, need to be explored as mechanisms by which conservative therapies improve urge incontinence. Twenty-nine cocaine-dependent male veterans without other drug dependence completed a double-blind controlled, randomly-assigned study examining the efficacy of bromocriptine versus placebo in the management of cocaine abstinence symptomatology. Serum prolactin (PL) and growth hormone (GH) levels were obtained prior to and after the study was completed. Patients were seen daily and completed several self-report questionnaires, including the Symptom Checklist-90-Revised, the Beck Depression Inventory, and a Cocaine Craving Report. The patients were also asked to rate a variety of cocaine withdrawal symptoms. Overall, there did not appear to be any advantage to receiving bromocriptine versus placebo during the first 3 weeks following cocaine use cessation with the possible exception of changes in activity and appetite level. The placebo group showed a statistically significant increase in activity level during the first week in treatment and a significant increase in appetite throughout the study. Patients in both groups showed significant improvement in the other areas assessed, with improvement appearing to progress according to length of treatment. Hyperprolactinemia or abnormal GH levels were not found in this patient sample as a group. Thirty-four of the original 63 patients dropped out of the study. Seventeen received bromocriptine, and 17 received placebo. There was no significant difference between drug groups in incidence of retaining patients in treatment. The high dropout rate may reflect the difficulty incurred in retaining cocaine-dependent patients in treatment. Recently, polyethylene glycol (PEG 3350) has been suggested as a good alternative laxative to lactulose as a treatment option in paediatric constipation. However, no large randomised controlled trials exist evaluating the efficacy of either laxative.
                To compare PEG 3350 (Transipeg: polyethylene glycol with electrolytes) with lactulose in paediatric constipation and evaluate clinical efficacy/side effects.
                One hundred patients (aged 6 months-15 years) with paediatric constipation were included in an eight week double blinded, randomised, controlled trial.
                After faecal disimpaction, patients <6 years of age received PEG 3350 (2.95 g/sachet) or lactulose (6 g/sachet) while children > or =6 years started with 2 sachets/day. Primary outcome measures were: defecation and encopresis frequency/week and successful treatment after eight weeks. Success was defined as a defecation frequency > or =3/week and encopresis < or =1 every two weeks. Secondary outcome measures were side effects after eight weeks of treatment.
                A total of 91 patients (49 male) completed the study. A significant increase in defecation frequency (PEG 3350: 3 pre v 7 post treatment/week; lactulose: 3 pre v 6 post/week) and a significant decrease in encopresis frequency (PEG 3350: 10 pre v 3 post/week; lactulose: 8 pre v 3 post/week) was found in both groups (NS). However, success was significantly higher in the PEG group (56%) compared with the lactulose group (29%). PEG 3350 patients reported less abdominal pain, straining, and pain at defecation than children using lactulose. However, bad taste was reported significantly more often in the PEG group.
                PEG 3350 (0.26 (0.11) g/kg), compared with lactulose (0.66 (0.32) g/kg), provided a higher success rate with fewer side effects. PEG 3350 should be the laxative of first choice in childhood constipation. On the basis of the dopamine depletion theory, bromocriptine has been tested to treat cocaine withdrawal and dependence. The authors conducted a 6-week study with 1 week of pretreatment observation and 5 weeks of a randomized, double-blind, placebo-controlled clinical trial of bromocriptine for DSM-III-R-defined cocaine dependence in methadone-maintained male patients. The bromocriptine group (n = 24) did not differ from the placebo group (n = 26) in self-reported cocaine use, proportion of positive urine toxicology samples, craving for cocaine, resistance to cocaine use, or mood symptoms between the pretreatment baseline and the last week of the clinical trial. Both groups showed significant reduction in self-reported frequency of cocaine use, resistance to craving, and mood symptoms during participation in the protocol. The results of this study are consistent with recent clinical and laboratory findings in primary cocaine users. Despite initially promising pilot studies, recent evidence does not support the efficacy of bromocriptine to reduce cocaine use or craving. In a prospective, open-label, assessor-blind, randomised parallel group study the efficacy and safety of Hemabate (Pharmacia-Upjohn Pharmaceuticals, Milton Keynes, Buckinghamshire) an analogue of 15-methyl-prostaglandin (PGF2alpha) analogue was compared with Syntometrine (Alliance Pharmaceuticals, Chippenham, Wilts) the standard combination of ergometrine and syntocinon used for the active management of the third stage of labour and the prevention of primary postpartum haemorrhage (PPH). The study was set in a district general hospital with approximately 4,000 deliveries annually. The study was discontinued at the time of the interim analysis because of unacceptable gastrointestinal side effects. At the time of the interim analysis, a total of 529 women had completed the study with 263 randomised to receive PGF2alpha and 266 to receive ergometrine and syntocinon. In a pre-specified subgroup analysis, women delivered vaginally were further subdivided into those considered to be at high or low risk of primary PPH. The measured blood loss and incidence of PPH was similar in both treatment groups whether delivered by caesarean section or vaginally independent of whether women were considered to be at high or low risk. Adverse gastrointestinal events were recorded more often in the Hemabate group. The most common symptom was diarrhoea which occurred in 21% of women who received Hemabate compared to only 0.8% of Syntometrine users. PGF2alpha is as effective as Syntometrine in the prophylaxis of primary PPH in all groups studied but there was a statistically significantly increased risk of diarrhoea among users of PGF2alpha. In this open-label, randomized study, we assessed the effects on hemostasis of two combined oral contraceptives containing drospirenone (DRSP) as progestogen component.
                Three milligrams of DRSP, a progestogen with antimineralocorticoid activity, was combined with either 30 or 20 microg ethinyl estradiol (EE) (DRSP/30EE; DRSP/20EE) and compared with a preparation containing 150 microg desogestrel (DSG) and 30 microg ethinyl estradiol (DSG/30EE). A total of 75 healthy female volunteers aged 18-35 years were enrolled. The hemostasis variables were measured in the medication-free precycle (baseline); in the first, third and sixth treatment cycle; and in the follow-up phase. The target variables for comparison were the relative changes from baseline to Cycle 6.
                Data of 25 volunteers in each group were valid for the per-protocol evaluation. Most changes in hemostasis variables were similar in the three treatment groups. All procoagulatory variables and the anticoagulatory variable protein C antigen increased slightly, while protein S antigen and activity decreased. For fibrinogen and protein S activity, the changes were statistically significant: less pronounced with DRSP/20EE compared to DSG/30EE at Cycle 6. There were no statistically significant differences in the changes of antifibrinolytic variables, the global clotting tests and D-dimer. All pairwise comparisons of DRSP/30EE vs. DSG/30EE yielded nonsignificant results; however, there was a trend of a lower impact of DRSP/20EE on nearly all hemostatic parameters compared to the 30EE products. All three study treatments were safe and well tolerated by the volunteers and provided adequate contraceptive reliability.
                The changes in the hemostatic variables for DRSP/20EE were less pronounced compared to DSG/30EE and DRSP/30EE. The results were in accordance with previous reports on effects of similar OCs. Two different applications of prostaglandin E2 for induction of labor were randomly used in 113 women with an unripe cervix; 57 women were given prostaglandin suppositories each containing 2.5 mg PGE2 in a basis of Witepsol S55 (Dynamit Nobel), another 56 women were treated with intracervical gel containing 1 mg PGE2 in 5 g hydroxypropylmethyl cellulose. The treatment was repeated after 4 h if the cervix was still unripe, and the procedure was repeated the following day if the cervix was still unfavorable. Cesarean sections was performed within 48 h after the start of induction and before the second stage of labor in 8 women in the suppository group and 7 women in the intracervical gel group. Of the remaining 98 women, 73% (34/48 women) in the suppository group and 36% (18/50 women) in the cervical gel group had delivered within 24 h (p less than 0.01). After 48 h, 88% (42/48 women) in the suppository group and 74% of the women (37/50 women) in the cervical gel group had delivered (p greater than 0.05). The induction-delivery interval in the suppository group was half that found in the cervical gel group. There was no significant difference between the two groups in the use of instrumental vaginal deliveries and cesarean sections nor was there any difference with regard to fetal distress. The post-delivery condition of the newborn was similar in the two groups. No side-effects were reported in either of the two groups. Some studies have suggested that supplementation of food with lactobacilli may prevent or improve atopic dermatitis in children. This study was designed to investigate the therapeutic effect of Lactobacillus rhamnosus GG (LGG) as a food supplement in infants suffering from atopic dermatitis.
                Infants aged 3-12 months suffering from mild-to-moderate atopic dermatitis (severity scoring of atopic dermatitis or SCORAD index of 15-40) without current antiinflammatory treatment were randomized to receive LGG (5 x 10(9) colony forming units b.i.d.) or placebo as a food supplement for 12 weeks. Severity scoring of atopic dermatitis index and use of hydrocortisone 1% ointment as rescue medication (2 points per application) were recorded at 4, 8, and 12 weeks of treatment and combined as symptom load (SL).
                Fifty-four infants (LGG group, mean +/- SD SCORAD index 24.6 +/- 8.8) and 48 infants (placebo group, SCORAD index 23.6 +/- 7.8) were randomized and completed the treatment period (intention-to-treat analysis). Symptom load generally improved over time at 4 weeks (LGG vs placebo, 23.8 +/- 12.4 vs 20.6 +/- 9.9), 8 weeks (22.5 +/- 14.6 vs 17.9 +/- 13.1), and 12 weeks (19.6 +/- 15.4 vs 15.1 +/- 12.1), without statistically significant group differences. When stratified for age, eczema severity or use of rescue medication, no statistically significant group differences, in improvement, were found. No significant group differences were found for the use of rescue medication (0.8 +/- 45.0 g vs 3.5 +/- 29.8 g), increase in mean logarithmic total serum IgE (0.17 +/- 0.30 kU/l vs 0.26 +/- 0.45 kU/l), and newly developed allergic sensitization against hen's egg or cow's milk (18.8%vs 10.0%).
                This placebo-controlled trial showed no therapeutic effect of LGG against mild-to-moderate atopic dermatitis in infancy. The aim of this study was to compare the efficacy and safety of oral nicardipine in acute therapy for preterm labor with those of parenteral magnesium sulfate.
                Patients between 24 and 34 weeks' gestation with documented preterm labor were randomly assigned to receive oral nicardipine (n = 57) or intravenous magnesium sulfate (n = 65) as initial tocolytic therapy. Patients in the nicardipine group received a 40-mg loading dose and then 20 mg every 2 hours as needed to stop contractions (total 80 mg). Patients in the magnesium sulfate group received a 6-g bolus followed by 2 to 4 g/h to provide uterine quiescence. Patients could be switched to another tocolytic regimen if they continued to have contractions after 6 hours of therapy. The main outcome variables examined were time to uterine quiescence, time gained in utero, recurrence of preterm labor, failure of tocolysis, and pertinent maternal and neonatal outcomes.
                There were no significant differences in maternal demographic characteristics between the groups. Among patients who responded with uterine quiescence within 6 hours, there was a significant decrease in the time to uterine quiescence in the nicardipine group (P <.01). Patients in the magnesium sulfate group were more likely to have recurrence of preterm labor necessitating further tocolytic attempts (P =.048). The patients in the magnesium sulfate group had more adverse side effects, mainly nausea and vomiting (P =.004). There were no differences in birth weight, estimated gestational age at delivery, or neonatal complications between the 2 groups.
                Oral nicardipine is an effective, safe, and well-tolerated tocolytic agent. In this prospective clinical trial patients randomly assigned to receive oral nicardipine had arrest of preterm labor more rapidly than did those randomly assigned to receive parenteral magnesium sulfate. Patients who received magnesium sulfate were more likely to have adverse medication effects and recurrent preterm labor. Studies have been performed suggesting that administration of probiotics may have therapeutic and/or preventive benefits in the development of sensitization and atopic disease, particularly in infants with atopic dermatitis (AD).
                The purpose of this study was to evaluate the clinical and immunological effects of supplementation of a hydrolysed formula with two probiotic strains of bacteria on symptoms of AD in infancy.
                We conducted a randomized, double-blind, placebo-controlled study. After 4-6 weeks of baseline and double-blind, placebo-controlled challenges for diagnosis of cow's milk allergy (CMA), infants less than 5 months old with AD received a hydrolysed whey-based formula as placebo (n = 17), or supplemented with either Lactobacillus rhamnosus (n = 17) or Lactobacillus GG (n = 16) for 3 months. Before, during and after intervention, the clinical severity of AD was evaluated using SCORing index Atopic Dermatitis (SCORAD). Allergic sensitization was evaluated by measurement of total IgE and a panel of food-specific IgEs as well as skin prick testing for cow's milk. Inflammatory parameters were blood eosinophils, eosinophil protein X in urine, fecal alpha-1-antitrypsin and production of IL-4, IL-5 and IFN-gamma by peripheral blood mononuclear cells after polyclonal stimulation.
                No statistically significant effects of probiotic supplementation on SCORAD, sensitization, inflammatory parameters or cytokine production between groups were found. Only four infants were diagnosed with CMA.
                We found no clinical or immunological effect of the probiotic bacteria used in infants with AD. Our results indicate that oral supplementation with these probiotic bacterial strains will not have a significant impact on the symptoms of infantile AD. To compare the efficacy and safety of controlled-release oxybutynin with conventional, immediate-release oxybutynin and determine rates of dry mouth.
                Patients (n = 226) who were known to be responsive to anticholinergic therapy and who had seven or more urge incontinence episodes per week were randomized to receive controlled-release oxybutynin or immediate-release oxybutynin. After an initial placebo run-in period, dosing in each began at 5 mg per day and increased weekly by 5 mg per day to a maximum of 20 mg per day or when a balance between improvement of incontinence symptoms and tolerability of side effects was achieved. Rates of urge incontinence and dry mouth were compared. Post hoc Kaplan-Meier survival analysis was used to describe elimination of incontinence episodes by dose and to analyze dry mouth risk by dose.
                Reductions in urge urinary incontinence episodes from baseline to the end of treatment were 18.6 to 2.9 per week (83% mean decrease) and 19.8 to 4.4 per week (76% mean decrease) in the controlled- and immediate-release oxybutynin groups (P =.36), respectively. At equal doses, comparable proportions of patients in both groups reported the absence of urge incontinence (P =.85). The incidence of dry mouth increased with dose in both groups, but there was no difference in dry mouth rates between the groups: 47.7% and 59.1% for the controlled- and immediate-release oxybutynin (P =.09), respectively. However, Kaplan-Meier analysis to examine first report of dry mouth at a given dose revealed that a significantly lower proportion of patients taking controlled-release oxybutynin had moderate to severe dry mouth (P =.007) or any dry mouth (P =.003) compared with those taking immediate-release oxybutynin.
                At the same daily dose, controlled- and immediate-release oxybutynin demonstrated comparable efficacy in reduction of urge incontinence episodes. The incidence of dry mouth was dose dependent but equal in both groups; first report of moderate to severe dry mouth was significantly lower in the controlled-release group.
There is weak evidence that some pharmacologic treatments (most of which are currently unavailable to the public) are better than no treatment for suppressing lactation symptoms in the first postpartum week. No evidence currently exists to indicate whether non-pharmacologic approaches are more effective than no treatment. Presently, there is insufficient evidence to address the side effects of methods employed for suppressing lactation. When women desire treatment, bromocriptine may be considered where it is registered for lactation suppression in those without predisposition to its major side effects of public concerns. Many trials did not contribute data that could be included in analyses. Large randomised trials are needed to compare the effectiveness of pharmacologic (especially bromocriptine) and non-pharmacologic methods with no treatment. Such trials should consider the acceptability of the intervention and lactation symptoms of concern to women and be large enough to detect clinically important differences in major side effects between comparison groups.