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Tolterodine: Selectivity for the bladder over effects on visual accomodation
MONDAY,
SEPTEMBER 4
After 16 weeks of treatment, significant improvements(p
41
correlated with the ICS measurements and those made in the upright position (P
FC1.15 VIRAL INFECTIONS FC1.14.08 TOLTERODINE: SELECTIVITY FOR THE BLADDER OVER EFFECTS ON VISUAL ACCOMODATION M.B. Chancellor, Dept. of Urology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. Objectives: The selectivity of tolterodine for the bladder compared with the salivary gland has been shown both in vitro and in viva. This finding has been repeated in humans, where tolterodine (2 mg, twice daily [BID]), causes significantly less dry mouth (frequency and severity) vs. oxybutynin at equivalent dosages (5 mg three times daily FID]). The objective of this study was to evaluate the tissue selectivity profile of these antimuscarinic agents by comparing dose-response effects in the bladder vs. effects on visual accommodation. Study Methods: In a double-blind, randomized, 4-way cross-over study, 16 healthy volunteers (mean age 31 years) received single oral doses of tolterodine 5 mg and oxybutynin 2.5, 5 and 7.5 mg. Each study period was 2 days in duration. On Day l(baseline), subjects drank fluid hourly for 12 hours. On Day 2, patients drank fluid hourly for 2 hours and were then dosed. Hourly fluid consumption continued after dosing. Voiding parameters were assessed for 12 hours post-dose, along with visual accommodation (near point of vision; convergence meter) at regular intervals. Results: A linear response in bladder effect (maximum bladder capacity) was noted for the 3 doses of oxybutynin compared with baseline (2.5 mg +35%; 5 mg, +45%; 7.5 mg, +57%). The bladder effect of tolterodine (+93%) was approximately double that of oxybutynin (maximum changes in near point of vision of 13%, 20% and 29%) while maximum change for tolterodine 5 mg was the same as for oxybutynin 5 mg (i.e. 20%). Conclusions: The bladder selectivity of tolterodine extends beyond the salivary gland, as effects on the bladder occur to a greater extent than effects on visual accommodation. On the basis of these findings, it can be expected that the normal dosage of tolterodine (2 mg BID) will have less clinically relevant effects on visual accommodation than the equivalent dosage of oxybutynin (5 mg TID).
FC1.14.09 VAGINAL PROLAPSE: DO SYMPTOMS CORRELATE WITH EXAMINATION FINDINGS? VKhullar, G.A.Digesu, L.Cardozo, S.Athanasiou Department of Urogynaecology, King’s College Hospital, London, UK Objectives: Vaginal prolapse is a common problem affecting up to 30% of women attending gynaecology outpatients. The aim of this study was to correlate the severity of prolapse with its effects on quality of life (QOL). Study Methods: Two experienced clinicians digitally examined women with vaginal prolapse in the conventional manner in Sims’ position and using the ICS prolapse score (POP-Q). A second group of women were examined in the same manner in the supine and standing positions. A quality of life questionnaire (PQOL) was developed to assess symptoms of prolapse and quantify their severity. Results: 43 women were examined in the Sims’ position digitally and using the POP-Q. Digital examination only showed poor inter-observer reliability with a Kappa value of 0.54. The POP-Q showed a high degree of reliability with the 95% confidence interval for the difference between examiners being 0.9 cm at most. 183 women were examined lying supine and standing. The inter-observer reliability of the supine examinations was poor with a Kappa value between 0.29 0.52. However when the women were examined standing the Kappa value was 0.76 to 0.91 showing that this method was reliable. The PQOL form was validated in 125 women who completed the form twice one week apart. The questions had a good inter-rater reliability with a Cronbach alpha of (0.80-0.96). The severity of PQOL scores
IN PREGNANCY
FCl.lS.01 CLINICAL, ENCEPHALOGRAPHIC AND IMMUNOLOGICAL ASPECTS OF THE INTRAUTERINE INFLUENZAL INFECTION D. Sinus, M. Devdariani, B. Korsantia, M. Kokhia, Scientific Research Institute of Perinatal Medicine Obstetrics and Gynecology, M.Costava 38, Tbilisi, Georgia, 380009. The Influence of the influenza infection during pregnancy on the state of the newborn has been studied. The indices of the immune system in the maternal and umbilical blood have been studied. The value of the clinical and neurological conditions of the neonates and their electrical and encephalographic characteristics has been carried out. In the main group (150 patients) preterm labor were in 15,5%. The hypoxic damage of CNS (central nervous system) was in 9,4%. EEG (electroencephalograph) in 68,2% of newborns were normal, and in 31,8% we registered pathology of the diffusive type which manifested as a high amplitude slow activity, separate sharp waves occurred in the different regions of the brain and spike-waved complexes and only in some cases as a flat cmve during non-deep sleep. Clinical and neurological study proves the pathologic state of the CNS. In 17,4% of cases pathological alterations on EEG were revealed in clinically healthy neonates. The immune homeostasis in all neonates was characterized by the disbalance typical for the depression: the suppression of phagocytosis and endogenous interferon activity, reduction of T-cell percentage and also the appearance of Ig A and Ig M in the umbilical blood. Severe immunodepression is revealed in mothers too. We concluded necessity of the inclusion in high-risk group of both newborns with hypoxic brain damage of the CNS and healthy ones whose mother suffered from the flu during pregnancy
FCl.lS.02 PRENATAL DIAGNOSIS OF CYTOMEGALOVIRAL INFECTION H.N.Kirubamani, Government RSRM Hospital, Cemetry Road, Chennai, Tamil Nadu, India, 600 013. Objectives : The aim of the study is to diagnose Prenatal Cytomegaloviral Infection among pregnant women with primary Cytomegaloviral Infection. Study Methods: Prosepective study was conducted at RSRM hospital in 50 sero positive women for CMV infection Results : These cases were evaluvated from lo-26 wks ,USG, cordocentesis,and post natally placental and skin biopsy were carried out.Fetal blood was analysed for specific IgM, Hb%,Platelet count,LFT & Karyotyping.USG demonstrated Microcephaly 16%, Hydrops 24%,Hydrocephalous 12%,Hydranencephalous S%,Anencephalous 2%, Limb deformity 4%,IUGR with oligohydramnios 12%, Normal 12%.Seventy Eight percent of the pregnant women were asymptomatic and screened in view of bad obstetric history and 22% had symptomscordocentesis showed IgM positive in76%, it is because fetal response to infection is less below 20 wks of gestation.Placental and Skin Biopsy showed inclusion bodies on histologic sectionsNewborn were normal both clinically & immunologically when USG was normal. Conclusion : Though USG Observation were conclusive, skin and placental biopsy provides additional information in sero positive and conclusive in sero negative cases
FCl.lS.03 CONGENITAL CYTOMEGALOVIRUS INFECTION IN JAPAN T. Hoshiba Y. Yabuki, Dept. OBIGYN, Ishikawa Prefectural Central -> Hospital, Kanazawa, Ishikawa, Japan. Objectives: The aim of this study was to investigate intrauterine transmission of cytomegalovirus (CMV) in Japan using cord blood.
SEPTEMBER 4
After 16 weeks of treatment, significant improvements(p
41
correlated with the ICS measurements and those made in the upright position (P
FC1.15 VIRAL INFECTIONS FC1.14.08 TOLTERODINE: SELECTIVITY FOR THE BLADDER OVER EFFECTS ON VISUAL ACCOMODATION M.B. Chancellor, Dept. of Urology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. Objectives: The selectivity of tolterodine for the bladder compared with the salivary gland has been shown both in vitro and in viva. This finding has been repeated in humans, where tolterodine (2 mg, twice daily [BID]), causes significantly less dry mouth (frequency and severity) vs. oxybutynin at equivalent dosages (5 mg three times daily FID]). The objective of this study was to evaluate the tissue selectivity profile of these antimuscarinic agents by comparing dose-response effects in the bladder vs. effects on visual accommodation. Study Methods: In a double-blind, randomized, 4-way cross-over study, 16 healthy volunteers (mean age 31 years) received single oral doses of tolterodine 5 mg and oxybutynin 2.5, 5 and 7.5 mg. Each study period was 2 days in duration. On Day l(baseline), subjects drank fluid hourly for 12 hours. On Day 2, patients drank fluid hourly for 2 hours and were then dosed. Hourly fluid consumption continued after dosing. Voiding parameters were assessed for 12 hours post-dose, along with visual accommodation (near point of vision; convergence meter) at regular intervals. Results: A linear response in bladder effect (maximum bladder capacity) was noted for the 3 doses of oxybutynin compared with baseline (2.5 mg +35%; 5 mg, +45%; 7.5 mg, +57%). The bladder effect of tolterodine (+93%) was approximately double that of oxybutynin (maximum changes in near point of vision of 13%, 20% and 29%) while maximum change for tolterodine 5 mg was the same as for oxybutynin 5 mg (i.e. 20%). Conclusions: The bladder selectivity of tolterodine extends beyond the salivary gland, as effects on the bladder occur to a greater extent than effects on visual accommodation. On the basis of these findings, it can be expected that the normal dosage of tolterodine (2 mg BID) will have less clinically relevant effects on visual accommodation than the equivalent dosage of oxybutynin (5 mg TID).
FC1.14.09 VAGINAL PROLAPSE: DO SYMPTOMS CORRELATE WITH EXAMINATION FINDINGS? VKhullar, G.A.Digesu, L.Cardozo, S.Athanasiou Department of Urogynaecology, King’s College Hospital, London, UK Objectives: Vaginal prolapse is a common problem affecting up to 30% of women attending gynaecology outpatients. The aim of this study was to correlate the severity of prolapse with its effects on quality of life (QOL). Study Methods: Two experienced clinicians digitally examined women with vaginal prolapse in the conventional manner in Sims’ position and using the ICS prolapse score (POP-Q). A second group of women were examined in the same manner in the supine and standing positions. A quality of life questionnaire (PQOL) was developed to assess symptoms of prolapse and quantify their severity. Results: 43 women were examined in the Sims’ position digitally and using the POP-Q. Digital examination only showed poor inter-observer reliability with a Kappa value of 0.54. The POP-Q showed a high degree of reliability with the 95% confidence interval for the difference between examiners being 0.9 cm at most. 183 women were examined lying supine and standing. The inter-observer reliability of the supine examinations was poor with a Kappa value between 0.29 0.52. However when the women were examined standing the Kappa value was 0.76 to 0.91 showing that this method was reliable. The PQOL form was validated in 125 women who completed the form twice one week apart. The questions had a good inter-rater reliability with a Cronbach alpha of (0.80-0.96). The severity of PQOL scores
IN PREGNANCY
FCl.lS.01 CLINICAL, ENCEPHALOGRAPHIC AND IMMUNOLOGICAL ASPECTS OF THE INTRAUTERINE INFLUENZAL INFECTION D. Sinus, M. Devdariani, B. Korsantia, M. Kokhia, Scientific Research Institute of Perinatal Medicine Obstetrics and Gynecology, M.Costava 38, Tbilisi, Georgia, 380009. The Influence of the influenza infection during pregnancy on the state of the newborn has been studied. The indices of the immune system in the maternal and umbilical blood have been studied. The value of the clinical and neurological conditions of the neonates and their electrical and encephalographic characteristics has been carried out. In the main group (150 patients) preterm labor were in 15,5%. The hypoxic damage of CNS (central nervous system) was in 9,4%. EEG (electroencephalograph) in 68,2% of newborns were normal, and in 31,8% we registered pathology of the diffusive type which manifested as a high amplitude slow activity, separate sharp waves occurred in the different regions of the brain and spike-waved complexes and only in some cases as a flat cmve during non-deep sleep. Clinical and neurological study proves the pathologic state of the CNS. In 17,4% of cases pathological alterations on EEG were revealed in clinically healthy neonates. The immune homeostasis in all neonates was characterized by the disbalance typical for the depression: the suppression of phagocytosis and endogenous interferon activity, reduction of T-cell percentage and also the appearance of Ig A and Ig M in the umbilical blood. Severe immunodepression is revealed in mothers too. We concluded necessity of the inclusion in high-risk group of both newborns with hypoxic brain damage of the CNS and healthy ones whose mother suffered from the flu during pregnancy
FCl.lS.02 PRENATAL DIAGNOSIS OF CYTOMEGALOVIRAL INFECTION H.N.Kirubamani, Government RSRM Hospital, Cemetry Road, Chennai, Tamil Nadu, India, 600 013. Objectives : The aim of the study is to diagnose Prenatal Cytomegaloviral Infection among pregnant women with primary Cytomegaloviral Infection. Study Methods: Prosepective study was conducted at RSRM hospital in 50 sero positive women for CMV infection Results : These cases were evaluvated from lo-26 wks ,USG, cordocentesis,and post natally placental and skin biopsy were carried out.Fetal blood was analysed for specific IgM, Hb%,Platelet count,LFT & Karyotyping.USG demonstrated Microcephaly 16%, Hydrops 24%,Hydrocephalous 12%,Hydranencephalous S%,Anencephalous 2%, Limb deformity 4%,IUGR with oligohydramnios 12%, Normal 12%.Seventy Eight percent of the pregnant women were asymptomatic and screened in view of bad obstetric history and 22% had symptomscordocentesis showed IgM positive in76%, it is because fetal response to infection is less below 20 wks of gestation.Placental and Skin Biopsy showed inclusion bodies on histologic sectionsNewborn were normal both clinically & immunologically when USG was normal. Conclusion : Though USG Observation were conclusive, skin and placental biopsy provides additional information in sero positive and conclusive in sero negative cases
FCl.lS.03 CONGENITAL CYTOMEGALOVIRUS INFECTION IN JAPAN T. Hoshiba Y. Yabuki, Dept. OBIGYN, Ishikawa Prefectural Central -> Hospital, Kanazawa, Ishikawa, Japan. Objectives: The aim of this study was to investigate intrauterine transmission of cytomegalovirus (CMV) in Japan using cord blood.