- Email: [email protected]
Meta-analysis of safety and tolerability of once-daily oxybutynin chloride
ZEARALENONE CONCENTRATION
hyperplastic endometrium; therefore, this substance might be of importance in carcinogenesis.
AND APOPTOSIS IN HUMAN ENDOMETRIAL HYPERPLASIA Ali Farid M. Ali, MD,* Alaa El-Tobgy, MD, Hoda Abd El-A&, MD, Sanaa El-Shayeb, MD, Magd El Din, MD, and Abd El-Azeem Sarhan, MD *Ain Shams University Hospital, Cairo, Egypt
META-ANALYSIS
OF SAFETY AND
TOLERABILITY OF ONCE-DAILY OXYBUTYNIN CHLORIDE Eboo Versi, MD
Introduction: Disorders of the apoptotic processes are considered to play a notable role in pathogenesis of proliferative disease. Oligonucleosome fragments are used now as one of biologic markers of the apoptotic processes. Zearalenone (ZEA), a nonsteroidal mycotoxin with estrogen-like activity, is synthesized by molds of the Fusarium genus commonly contaminating poorly stored agriculture products and foodstuffs. Zearalenone has been observed to possess tumor-promoting activity similar to that of estradiol and hypothetically can induce proliferation and carcinogenesis in estrogendependent tissues. Aim of the work: 1) To assess the apoptotic processes in endometrial hyperplasia based on the study of CME activity. 2) To determine if ZEA is present in human endometrium and whether concentrate of this mycoestrogen is associated with endometrial cell proliferation. Material: Thirty-five patients with pathologically proved endometrial hyperplasia (EH): 20 patients (mean age 36.5 2 4.5) with cystic EH, 15 patients (mean age 38.5 ? 3.9) with adenomatous EH; and 20 patients as control (mean age 30.2 2 1.3) without any endometrial pathology. Method: 1) Evaluating Ca+‘/Mg+’ -dependent endonuclease CME, according to the results of DNA electrophoresis in nonnuclear cells of peripheral blood and in nuclei of endometrial cells. 2) Tissue ZEA concentration was estimated in endometrial homogenates, using competitive ELISA. The sensitivity of the method was 31.3 ng/mL (range 31.3-4,000.0
Harvard Medical School,Boston,MA
Objective: Immediate-release (IR) oxybutynin has been the mainstay of medical treatment for urge incontinence (UI) despite low patient compliance due to dry mouth. We studied a controlled-release (CR) form of oxybutynin in a metaanalysis of all studies of similar design to compare safety and tolerability to IR-oxybutynin. Methods: Only double-blind, adjustable-dose trials were included in this analysis. Patients (n = 331; mean age 59) with UI were randomly assigned 1:l to CR-oxybutynin taken once daily or IR-oxybutynin taken once daily to four times a day. Patients adjusted their dose starting with 5 mg up to 20 mg (IR-oxybutynin) or 30 mg (CR-oxybutynin) for a balance of efficacy and tolerability. A Kaplan-Meier survival analysis compared doses up to 20 mg. Results: Significantly fewer patients first reported moderatesevere dry mouth on each dose of CR-oxybutynin versus IR-oxybutynin (see Figure). Comparable effectiveness was seen at each dose of CR-oxybutynin and IR-oxybutynin with regard to complete continence (P = 0.75).
80
ng/mL).
Resulfs: 1) There were no marked statistically difference found in the mean value of CME activity indexes in mononuclear in patients with EH, regardless of its type and the normal endometrium. 2) CME activity in endometrial tissues revealed statistically significant decrease in adenomatous hyperplasia, followed by cystic hyperplasia in comparison to normal endometrium. 3) Mean tissue ZEA concentration in adenomatous hyperplasia was 52.5 i 1.2 ng/mL, followed by 41.3 2 2.3 ng/mL in cystic hyperplasia (statistically significant P < 0.05). 4) No detection of ZEA in normal endometrium was found. Conclusion: 1) Endometrial hyperplasia, especially adenomatous, is followed by disorders of apoptotic processes that is shown by a marked decrease of DNA fragmentation of CME activity. 2) Our findings confirm the presence of ZEA in
56s
Tuesday Posters
0
5
10 15 20 Daily Dose, mg
ConcIusion: In these studies, once-daily CR-oxybutynin was better tolerated than IR-oxybutynin and comparably effective in the treatment of UI.
Obstetrics 6 Gynecology
hyperplastic endometrium; therefore, this substance might be of importance in carcinogenesis.
AND APOPTOSIS IN HUMAN ENDOMETRIAL HYPERPLASIA Ali Farid M. Ali, MD,* Alaa El-Tobgy, MD, Hoda Abd El-A&, MD, Sanaa El-Shayeb, MD, Magd El Din, MD, and Abd El-Azeem Sarhan, MD *Ain Shams University Hospital, Cairo, Egypt
META-ANALYSIS
OF SAFETY AND
TOLERABILITY OF ONCE-DAILY OXYBUTYNIN CHLORIDE Eboo Versi, MD
Introduction: Disorders of the apoptotic processes are considered to play a notable role in pathogenesis of proliferative disease. Oligonucleosome fragments are used now as one of biologic markers of the apoptotic processes. Zearalenone (ZEA), a nonsteroidal mycotoxin with estrogen-like activity, is synthesized by molds of the Fusarium genus commonly contaminating poorly stored agriculture products and foodstuffs. Zearalenone has been observed to possess tumor-promoting activity similar to that of estradiol and hypothetically can induce proliferation and carcinogenesis in estrogendependent tissues. Aim of the work: 1) To assess the apoptotic processes in endometrial hyperplasia based on the study of CME activity. 2) To determine if ZEA is present in human endometrium and whether concentrate of this mycoestrogen is associated with endometrial cell proliferation. Material: Thirty-five patients with pathologically proved endometrial hyperplasia (EH): 20 patients (mean age 36.5 2 4.5) with cystic EH, 15 patients (mean age 38.5 ? 3.9) with adenomatous EH; and 20 patients as control (mean age 30.2 2 1.3) without any endometrial pathology. Method: 1) Evaluating Ca+‘/Mg+’ -dependent endonuclease CME, according to the results of DNA electrophoresis in nonnuclear cells of peripheral blood and in nuclei of endometrial cells. 2) Tissue ZEA concentration was estimated in endometrial homogenates, using competitive ELISA. The sensitivity of the method was 31.3 ng/mL (range 31.3-4,000.0
Harvard Medical School,Boston,MA
Objective: Immediate-release (IR) oxybutynin has been the mainstay of medical treatment for urge incontinence (UI) despite low patient compliance due to dry mouth. We studied a controlled-release (CR) form of oxybutynin in a metaanalysis of all studies of similar design to compare safety and tolerability to IR-oxybutynin. Methods: Only double-blind, adjustable-dose trials were included in this analysis. Patients (n = 331; mean age 59) with UI were randomly assigned 1:l to CR-oxybutynin taken once daily or IR-oxybutynin taken once daily to four times a day. Patients adjusted their dose starting with 5 mg up to 20 mg (IR-oxybutynin) or 30 mg (CR-oxybutynin) for a balance of efficacy and tolerability. A Kaplan-Meier survival analysis compared doses up to 20 mg. Results: Significantly fewer patients first reported moderatesevere dry mouth on each dose of CR-oxybutynin versus IR-oxybutynin (see Figure). Comparable effectiveness was seen at each dose of CR-oxybutynin and IR-oxybutynin with regard to complete continence (P = 0.75).
80
ng/mL).
Resulfs: 1) There were no marked statistically difference found in the mean value of CME activity indexes in mononuclear in patients with EH, regardless of its type and the normal endometrium. 2) CME activity in endometrial tissues revealed statistically significant decrease in adenomatous hyperplasia, followed by cystic hyperplasia in comparison to normal endometrium. 3) Mean tissue ZEA concentration in adenomatous hyperplasia was 52.5 i 1.2 ng/mL, followed by 41.3 2 2.3 ng/mL in cystic hyperplasia (statistically significant P < 0.05). 4) No detection of ZEA in normal endometrium was found. Conclusion: 1) Endometrial hyperplasia, especially adenomatous, is followed by disorders of apoptotic processes that is shown by a marked decrease of DNA fragmentation of CME activity. 2) Our findings confirm the presence of ZEA in
56s
Tuesday Posters
0
5
10 15 20 Daily Dose, mg
ConcIusion: In these studies, once-daily CR-oxybutynin was better tolerated than IR-oxybutynin and comparably effective in the treatment of UI.
Obstetrics 6 Gynecology