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WHAT IS THE BLADDER WALL THICKNESS IN NORMAL PRIMARY SCHOOLCHILDREN ?
1121
1122
LOSS OF INTERSTITIAL CELLS OF CAJAL AND GAP JUNCTION PROTEIN CX43 AT THE URETEROVESICAL JUNCTION IN CHILDREN WITH VESICOURETERAL REFLUX
A NEW ORAL MELT FORMULATION OF DESMOPRESSIN IN PRIMARY NOCTURNAL ENURESIS (PNE). A RANDOMISED COMPARISON TO THE TABLET FORMULATION
Schwentner C.1, Oswald J.1, Lunacek A.1, Schlenck B.1, Fritsch H.2, Bartsch G.1, Radmayr C.1
Lottmann H.1, Froeling F.2, Allousi S.3, El-Rhadi A.S.4, Rittig S.5, Riis A.6, Persson B.E.6
Medical University Innsbruck, Paediatric Urology, Innsbruck, Austria, 2Medical University Innsbruck, Anatomy, Innsbruck, Austria
1
INTRODUCTION & OBJECTIVES: Intravesical ureteral endings were investigated by immunohistochemical methods to elucidate the presence of c- kit positive interstitial cells of Cajal (ICC´s) as well as of the gap junction protein connexin 43 in children with vesicoureteral reflux. MATERIAL & METHODS: Samples of the distal intravesical part of the ureter were obtained from 27 ureterorenal units in children (median age 48 months) undergoing anti-reflux surgery. Routine histological paraffin embedded sections were immunostained for smooth muscle alpha- actin to assess general morphology and architecture of the smooth muscle wrap, indirect immunohistochemical methods detecting the c-kit protooncogene were used to study the presence of ICC´s as well as connexin 43 positive cells to determine the gap junction densitx within the ureteral wall. Age matched nonrefluxing ureteral endings (n=11) served as controls. All investigations were done on the basis of high power field magnification for semiquantitative analysis. RESULTS: ICC´s were present in both refluxing and nonrefluxing ureteral endings. Healthy individuals (mean: 14.7; SD +/- 1.87) demonstrated significantly more ICC´s compared to children with vesicoureteral reflux (mean: 4.2/; SD +/- 1.56) p<0.0001. Connexin 43 immunoreactivity was severely reduced in all refluxing ureteral specimens, while it was homogenously distributed in normal controls. CONCLUSIONS: C-kit positive ICC´s are present at the ureterovesical junction in contrast to refluxing ureteral endings. A significant lack of these pacemaker cells indicates an incompetent antireflux mechanism as well as dysmotility. A substantial reduction of gap junctions at the intravesical ureter adverselyaffects intercellular signalling aggravating coordinated ureteral peristalsis which is essential for a competent antireflux mechanism. Severe impairment of the signal transduction by diminished connexin 43 concentrations aggravates the injured ureteral valve action.
1
Service de Chirurgie Viscerale Pédiatrique, Hôpital Necker-Enfants Malades, Paris, France, 2Juliana Pediatric Hospital, Den Haag, The Netherlands, 3Städtisches Klinikum Neunkirchen, Neunkirchen, Germany, 4Queen Mary’s Hospital, Sidcup, United Kingdom, 5Aarhus Universitetshospital, Aarhus, Denmark, 6Ferring International Centre, Ferring Pharmaceuticals, Copenhagen, Denmark INTRODUCTION & OBJECTIVES: Desmopressin (an analogue of vasopressin), has a powerful antidiuretic effect and is widely used to treat PNE in children and adults. Desmopressin is available in drops, spray and conventional tablets. A new convenient, oral, fast-melting formulation that allows lower dosing due to higher bioavailability has now been developed. This study evaluated the preference of children and adolescents with PNE for the new oral lyophilisate (MELT) compared with the tablet formulation of desmopressin. Secondary objectives included compliance, efficacy and safety associated with each formulation during the 6-week treatment period. MATERIAL & METHODS: An open-label, randomised, cross-over study was undertaken at 26 centres across Europe. Eligible subjects were children and adolescents aged 5–15 years with PNE who were already receiving a stable dose of desmopressin tablets (0.2 mg or 0.4 mg). 236 subjects were screened, of which 221 (mean age 9.6±2.4 years) were randomised 1:1 to receive treatment in the order MELT/tablet (110 patients) or tablet/MELT (111 patients). Each formulation was taken for 3 weeks before switching to the alternative formulation. Patients stabilized on 0.2 mg desmopressin tablets received the bioequivalent 120 μg dose of desmopressin MELT, and patients stabilized on 2 x 0.2 mg tablets received the bioequivalent 240 μg dose of MELT. RESULTS: 56% of the patients preferred the MELT formulation compared with 44% who preferred the tablet (P=0.112; 95%CI: 49–63%). The preference for MELT was age-dependent (P=0.006); 62% of patients aged <8 years (n=71) and 60% of patients aged 8–11 years (n=89) preferred the MELT formulation, while 60% of patients aged ≥12 years (n=50) preferred the tablet. Patients < 12 years (n=160) had a statistically significant preference for MELT (P=0.0089; 95% CI: 52.6-68.3%). Efficacy was the same for both formulations (MELT: 1.85±1.89 episodes and tablet: 1.87±1.82 bedwetting episodes/week during treatment). No serious or severe adverse events were reported. 9.5% of patients on the tablet and 4.6% of patients on the MELT formulation had compliance levels of <80%. More patients discontinued the tablet formulation than the MELT (7 vs. 4). CONCLUSIONS: The desmopressin MELT formulation was preferred by the majority of patients with PNE compared with the desmopressin tablet, despite being previously stabilized on a tablet formulation. A statistically significant proportion of patients aged < 12 years had a preference for the MELT, while patients aged ≥12 years preferred the tablet. The MELT formulation supports the recommended initiation of PNE treatment from an age of 5–6 years. The MELT formulation is easy to use, requires no intake of water and is associated with higher compliance than the tablet, while retaining similar levels of efficacy and safety at lower dose levels than the tablet.
1123 PARENTAL AWARENESS OF PAEDIATRIC CONSTIPATION Akyol I., Adayener C., Senkul T., Karademir K., Baykal K., Iseri C. Gulhane Military Medical Faculty Haydarpasa Hospital, Urology, Istanbul, Turkey INTRODUCTION & OBJECTIVES: Constipation is a rather frequent disorder usually occurring with urological problems as well. On the other hand, parents are not aware of their children’s bowel habits. We sought to find out the scale of parental awareness concerning paediatric constipation. MATERIAL & METHODS: Toilet-trained children of ages between 4 and 14 who were referred to paediatrics and urology clinics with or without urinary symptoms have been included in the study. Parents were given questionnaires to find out the symptoms and findings of constipation and urinary complaints. The questionnaire was filled during the first visit and then parents were asked to observe their children’s bowel habits for at least 2 weeks and then return the questionnaires. Patients were diagnosed as constipated if 2 or more symptoms / findings exist and/ or a KUB revealed intestines full of stool. RESULTS: 34 patients, 15 girls and 19 boys of mean age 7.4 (range:4 to 14) were included in the study. 25 patients presented with urinary symptoms and the remaining 9 had irrelevant problems. 27 patients returned the follow-up questionnaires. According to the first questionnaire, 14 patients were constipated and 18 were not, while the parents of two children haven’t got any idea. After a median follow-up of 4 weeks, 13 patients (72%) in no constipation, and an additional 1 patient in no idea group turned out to be constipated. 13 patients with voiding dysfunction in constipation group were treated with laxatives only, and after a 1 to 2 week treatment, 5 of 8 who returned for follow-up were free of urinary symptoms and 3 resolved partially. of those who benefited from the laxative monotherapy, 2 parents had reported normal bowel habits and 1 had no idea at the first interview. CONCLUSIONS: Parents of toilet-trained children are unaware of the bowel habits of their children which suggests that history pertaining to the bowel habits at first interview is inaccurate. When proper treatment is given, constipation and most of the urinary complaints are eliminated with no further diagnostic studies needed. Therefore, parents should be questioned in terms of symptoms of constipation after a close parental observation period.
1124 WHAT IS THE BLADDER WALL THICKNESS IN NORMAL PRIMARY SCHOOLCHILDREN ? Dogan H.S.1, Akpinar B.2, Gurocak S.3, Akata D.2, Bakkaloglu M.1, Tekgul S.1 1
Hacettepe University Faculty of Medicine, Urology, Ankara, Turkey, 2Hacettepe University Faculty of Medicine, Radiology, Ankara, Turkey, 3Gazi University Faculty of Medicine, Urology, Ankara, Turkey INTRODUCTION & OBJECTIVES: This study aims to investigate the bladder wall thickness (BWT) in children with or without voiding dysfunction and relate these findings with voiding characteristics. MATERIAL & METHODS: 212 normal primary school children have been evaluated with ultrasound for bladder wall thickness. The measurements have been taken from anterior, posterior and lateral walls of each bladder at different levels of fullness. The same group has also been investigated for voiding patterns and habits using a validated Voiding Disturbances Symptom Score(VDSS), uroflowmetry and urinalysis. The results were compared with a group of 18 patients who had clinically manifest voiding dysfunction. RESULTS: The average bladder wall thickness from posterior wall at full bladder in normal children was 1.1±0.032 mm. The anterior and posterior bladder wall thickness (BWT) measurements before and after micturition was found to be thicker in boys than girls. As it was expected the DW get thinner as the bladder fullness is increased. The BWT was not different according to the ages of continence achievement. When the patients with normal and abnormal uroflowmetric patterns are compared in terms of BWT, postvoiding measurements of the anterior and posterior BWT were found to be higher in patients with abnormal uroflowmetric pattern. When the normal subjects are compared with those who applied to hospital with voiding dysfunction (VD), it was detected that patients with VD has higher VDSS (2.72 vs. 22.3) and thicker BWT (2.56±0.18 mm) . CONCLUSIONS: In non-symptomatic boys the BWT are thicker. The patients with abnormal uroflowmetric pattern have thicker BWT. Patients with VD have higher VDSS and thicker BWT. These findings reveal that the significant increase in BWT measurements may be a sign of VD and BWT should be used as an objective tool in the evaluation of voiding characteristics. Eur Urol Suppl 2006;5(2):303
1122
LOSS OF INTERSTITIAL CELLS OF CAJAL AND GAP JUNCTION PROTEIN CX43 AT THE URETEROVESICAL JUNCTION IN CHILDREN WITH VESICOURETERAL REFLUX
A NEW ORAL MELT FORMULATION OF DESMOPRESSIN IN PRIMARY NOCTURNAL ENURESIS (PNE). A RANDOMISED COMPARISON TO THE TABLET FORMULATION
Schwentner C.1, Oswald J.1, Lunacek A.1, Schlenck B.1, Fritsch H.2, Bartsch G.1, Radmayr C.1
Lottmann H.1, Froeling F.2, Allousi S.3, El-Rhadi A.S.4, Rittig S.5, Riis A.6, Persson B.E.6
Medical University Innsbruck, Paediatric Urology, Innsbruck, Austria, 2Medical University Innsbruck, Anatomy, Innsbruck, Austria
1
INTRODUCTION & OBJECTIVES: Intravesical ureteral endings were investigated by immunohistochemical methods to elucidate the presence of c- kit positive interstitial cells of Cajal (ICC´s) as well as of the gap junction protein connexin 43 in children with vesicoureteral reflux. MATERIAL & METHODS: Samples of the distal intravesical part of the ureter were obtained from 27 ureterorenal units in children (median age 48 months) undergoing anti-reflux surgery. Routine histological paraffin embedded sections were immunostained for smooth muscle alpha- actin to assess general morphology and architecture of the smooth muscle wrap, indirect immunohistochemical methods detecting the c-kit protooncogene were used to study the presence of ICC´s as well as connexin 43 positive cells to determine the gap junction densitx within the ureteral wall. Age matched nonrefluxing ureteral endings (n=11) served as controls. All investigations were done on the basis of high power field magnification for semiquantitative analysis. RESULTS: ICC´s were present in both refluxing and nonrefluxing ureteral endings. Healthy individuals (mean: 14.7; SD +/- 1.87) demonstrated significantly more ICC´s compared to children with vesicoureteral reflux (mean: 4.2/; SD +/- 1.56) p<0.0001. Connexin 43 immunoreactivity was severely reduced in all refluxing ureteral specimens, while it was homogenously distributed in normal controls. CONCLUSIONS: C-kit positive ICC´s are present at the ureterovesical junction in contrast to refluxing ureteral endings. A significant lack of these pacemaker cells indicates an incompetent antireflux mechanism as well as dysmotility. A substantial reduction of gap junctions at the intravesical ureter adverselyaffects intercellular signalling aggravating coordinated ureteral peristalsis which is essential for a competent antireflux mechanism. Severe impairment of the signal transduction by diminished connexin 43 concentrations aggravates the injured ureteral valve action.
1
Service de Chirurgie Viscerale Pédiatrique, Hôpital Necker-Enfants Malades, Paris, France, 2Juliana Pediatric Hospital, Den Haag, The Netherlands, 3Städtisches Klinikum Neunkirchen, Neunkirchen, Germany, 4Queen Mary’s Hospital, Sidcup, United Kingdom, 5Aarhus Universitetshospital, Aarhus, Denmark, 6Ferring International Centre, Ferring Pharmaceuticals, Copenhagen, Denmark INTRODUCTION & OBJECTIVES: Desmopressin (an analogue of vasopressin), has a powerful antidiuretic effect and is widely used to treat PNE in children and adults. Desmopressin is available in drops, spray and conventional tablets. A new convenient, oral, fast-melting formulation that allows lower dosing due to higher bioavailability has now been developed. This study evaluated the preference of children and adolescents with PNE for the new oral lyophilisate (MELT) compared with the tablet formulation of desmopressin. Secondary objectives included compliance, efficacy and safety associated with each formulation during the 6-week treatment period. MATERIAL & METHODS: An open-label, randomised, cross-over study was undertaken at 26 centres across Europe. Eligible subjects were children and adolescents aged 5–15 years with PNE who were already receiving a stable dose of desmopressin tablets (0.2 mg or 0.4 mg). 236 subjects were screened, of which 221 (mean age 9.6±2.4 years) were randomised 1:1 to receive treatment in the order MELT/tablet (110 patients) or tablet/MELT (111 patients). Each formulation was taken for 3 weeks before switching to the alternative formulation. Patients stabilized on 0.2 mg desmopressin tablets received the bioequivalent 120 μg dose of desmopressin MELT, and patients stabilized on 2 x 0.2 mg tablets received the bioequivalent 240 μg dose of MELT. RESULTS: 56% of the patients preferred the MELT formulation compared with 44% who preferred the tablet (P=0.112; 95%CI: 49–63%). The preference for MELT was age-dependent (P=0.006); 62% of patients aged <8 years (n=71) and 60% of patients aged 8–11 years (n=89) preferred the MELT formulation, while 60% of patients aged ≥12 years (n=50) preferred the tablet. Patients < 12 years (n=160) had a statistically significant preference for MELT (P=0.0089; 95% CI: 52.6-68.3%). Efficacy was the same for both formulations (MELT: 1.85±1.89 episodes and tablet: 1.87±1.82 bedwetting episodes/week during treatment). No serious or severe adverse events were reported. 9.5% of patients on the tablet and 4.6% of patients on the MELT formulation had compliance levels of <80%. More patients discontinued the tablet formulation than the MELT (7 vs. 4). CONCLUSIONS: The desmopressin MELT formulation was preferred by the majority of patients with PNE compared with the desmopressin tablet, despite being previously stabilized on a tablet formulation. A statistically significant proportion of patients aged < 12 years had a preference for the MELT, while patients aged ≥12 years preferred the tablet. The MELT formulation supports the recommended initiation of PNE treatment from an age of 5–6 years. The MELT formulation is easy to use, requires no intake of water and is associated with higher compliance than the tablet, while retaining similar levels of efficacy and safety at lower dose levels than the tablet.
1123 PARENTAL AWARENESS OF PAEDIATRIC CONSTIPATION Akyol I., Adayener C., Senkul T., Karademir K., Baykal K., Iseri C. Gulhane Military Medical Faculty Haydarpasa Hospital, Urology, Istanbul, Turkey INTRODUCTION & OBJECTIVES: Constipation is a rather frequent disorder usually occurring with urological problems as well. On the other hand, parents are not aware of their children’s bowel habits. We sought to find out the scale of parental awareness concerning paediatric constipation. MATERIAL & METHODS: Toilet-trained children of ages between 4 and 14 who were referred to paediatrics and urology clinics with or without urinary symptoms have been included in the study. Parents were given questionnaires to find out the symptoms and findings of constipation and urinary complaints. The questionnaire was filled during the first visit and then parents were asked to observe their children’s bowel habits for at least 2 weeks and then return the questionnaires. Patients were diagnosed as constipated if 2 or more symptoms / findings exist and/ or a KUB revealed intestines full of stool. RESULTS: 34 patients, 15 girls and 19 boys of mean age 7.4 (range:4 to 14) were included in the study. 25 patients presented with urinary symptoms and the remaining 9 had irrelevant problems. 27 patients returned the follow-up questionnaires. According to the first questionnaire, 14 patients were constipated and 18 were not, while the parents of two children haven’t got any idea. After a median follow-up of 4 weeks, 13 patients (72%) in no constipation, and an additional 1 patient in no idea group turned out to be constipated. 13 patients with voiding dysfunction in constipation group were treated with laxatives only, and after a 1 to 2 week treatment, 5 of 8 who returned for follow-up were free of urinary symptoms and 3 resolved partially. of those who benefited from the laxative monotherapy, 2 parents had reported normal bowel habits and 1 had no idea at the first interview. CONCLUSIONS: Parents of toilet-trained children are unaware of the bowel habits of their children which suggests that history pertaining to the bowel habits at first interview is inaccurate. When proper treatment is given, constipation and most of the urinary complaints are eliminated with no further diagnostic studies needed. Therefore, parents should be questioned in terms of symptoms of constipation after a close parental observation period.
1124 WHAT IS THE BLADDER WALL THICKNESS IN NORMAL PRIMARY SCHOOLCHILDREN ? Dogan H.S.1, Akpinar B.2, Gurocak S.3, Akata D.2, Bakkaloglu M.1, Tekgul S.1 1
Hacettepe University Faculty of Medicine, Urology, Ankara, Turkey, 2Hacettepe University Faculty of Medicine, Radiology, Ankara, Turkey, 3Gazi University Faculty of Medicine, Urology, Ankara, Turkey INTRODUCTION & OBJECTIVES: This study aims to investigate the bladder wall thickness (BWT) in children with or without voiding dysfunction and relate these findings with voiding characteristics. MATERIAL & METHODS: 212 normal primary school children have been evaluated with ultrasound for bladder wall thickness. The measurements have been taken from anterior, posterior and lateral walls of each bladder at different levels of fullness. The same group has also been investigated for voiding patterns and habits using a validated Voiding Disturbances Symptom Score(VDSS), uroflowmetry and urinalysis. The results were compared with a group of 18 patients who had clinically manifest voiding dysfunction. RESULTS: The average bladder wall thickness from posterior wall at full bladder in normal children was 1.1±0.032 mm. The anterior and posterior bladder wall thickness (BWT) measurements before and after micturition was found to be thicker in boys than girls. As it was expected the DW get thinner as the bladder fullness is increased. The BWT was not different according to the ages of continence achievement. When the patients with normal and abnormal uroflowmetric patterns are compared in terms of BWT, postvoiding measurements of the anterior and posterior BWT were found to be higher in patients with abnormal uroflowmetric pattern. When the normal subjects are compared with those who applied to hospital with voiding dysfunction (VD), it was detected that patients with VD has higher VDSS (2.72 vs. 22.3) and thicker BWT (2.56±0.18 mm) . CONCLUSIONS: In non-symptomatic boys the BWT are thicker. The patients with abnormal uroflowmetric pattern have thicker BWT. Patients with VD have higher VDSS and thicker BWT. These findings reveal that the significant increase in BWT measurements may be a sign of VD and BWT should be used as an objective tool in the evaluation of voiding characteristics. Eur Urol Suppl 2006;5(2):303