Repeated botulinum-A toxin injections in treatment of children with neurogenic detrusor overactivity.

OBJECTIVES: To assess the long-term success of treatment with repeated botulinum-A toxin (BTX-A; Botox) injections into the detrusor muscle for neurogenic detrusor overactivity in children. METHODS: We reviewed the charts of 10 children (average age at first injection 11.2 years) with neurogenic detrusor overactivity who had received at least three BTX-A detrusor injections; four had received five or more injections. The total dose of BTX-A was 85 to 300 U. We measured the urodynamic outcomes 6 months after each injection and compared the results after the first injection with the results after the third and fifth injections (in the children who had five or more injections). RESULTS: The relative changes--each in comparison with the value before injection therapy--after the first versus the fifth injection were as follows: the reflex volume increased by 81% versus 88%, maximal detrusor pressure decreased by 7% versus 39%, maximal cystometric bladder capacity increased by 88% versus 72%, and bladder compliance showed no change at the 6-month follow-up visit after the first injection and an increase of 109% after the fifth injection. The results after the third injection were generally similar to those after the fifth injection. No major side effects occurred. CONCLUSIONS: Although we surveyed only a few patients, the efficacy seems clear in all the urodynamic measures after repeated BTX-A detrusor injections in children with neurogenic bladder. Also, we found no evidence of drug tolerance. Thus, BTX-A detrusor injection has gained additional importance in the treatment of these difficult-to-treat patients.

Botulinum-A toxin detrusor and sphincter injection in treatment of overactive bladder syndrome: objective outcome and patient satisfaction.

OBJECTIVE: We investigated the effect of botulinum-a toxin injections into the detrusor and external sphincter muscle in patients with overactive bladder (OAB) symptoms. METHODS: We included 44 patients - 41 women and three men with a mean age of 66.1 years - who were suffering from OAB symptoms that were refractory to anticholinergic treatment. We injected 200-300 U of BTX-A (Botox) into the detrusor muscle; 22 patients also received external sphincter injections. For outcome analysis, we used a bladder diary, a urodynamic examination, and a questionnaire that consisted of 27 validated questions. RESULTS: Changes in the bladder diary 4 weeks and 3, 6, and 9 months after BTX-A injection were as follows: Micturition frequency was reduced by 12%, 16%, 13% and 9%, respectively. Average pad use decreased from 4.2 pads per day to at most 2.4 pads per day after 6 months. Urodynamic changes were most distinct after 4 weeks: the volume when the first uninhibited detrusor contraction occurred increased from 149+/-18.2 mL to 263 +/- 24.2 mL, and maximum cystometric bladder capacity increased from 228 +/- 19.2 mL to 305 +/- 19.0 mL. Subjectively, 86% of the patients would choose this procedure for their bladder condition again. Residua 4 weeks after additional injection into the sphincter muscle were distinctly smaller than in the "only detrusor" group. CONCLUSIONS: BTX-A detrusor and sphincter injection is very effective in treating OAB symptoms. For patients who might be expected to have residual urine after injection only into the detrusor, additional injection of low doses of BTX-A into the external sphincter muscle could be one option to reduce that risk.

Botulinum-A toxin for treatment of overactive bladder without detrusor overactivity: urodynamic outcome and patient satisfaction.

OBJECTIVES: To investigate the effect of botulinum toxin type A bladder injections in the treatment of overactive bladder syndrome in the absence of detrusor overactivity. METHODS: The subjects were 7 women (average age 61.1 years, range 51 to 79) who presented with overactive bladder symptoms. Their disorder had been refractory to several classic treatment options. Urodynamic examination excluded detrusor overactivity. A total of 300 U BTX-A (Botox) was injected, of which 50 to 75 U was injected as quadrant injections into the external sphincter muscle to avoid the postoperative need for catheterization in the case of high postvoid residual urine volume. For follow-up, complete urodynamic studies were performed, and a bladder diary and validated incontinence questionnaires were given to patients at all visits at 1, 3, and 6 months. RESULTS: The bladder diaries indicated a clear reduction in daytime frequency and nocturia and a reduction in pad use. The maximal voiding volume increased significantly. The urodynamic examinations showed a significant increase in volume when the first and the strong desire to void were expressed. The maximal bladder capacity increased by 20% in 3 months. In the questionnaires, 5 of the 7 patients reported better urine control after therapy, and 6 would have chosen this therapy again for their condition. The overall satisfaction score (on a scale of 0 to 10) averaged 6.8. No side effects, such as urine retention, occurred. CONCLUSIONS: Botulinum-A toxin injection has positive effects in treating overactive bladder symptoms without detrusor overactivity. The effects were seen not only in urodynamic measures but also in patient satisfaction.

Endothelin system in normal and hypertensive pregnancy.

Pre-eclampsia complicates approximately 5-7% of pregnancies and it may be deleterious to both maternal and fetal health. In a prospective study, we investigated plasma endothelin (ET)-1 concentration within the 24th and 36th gestational week in non-smoking pregnant women. Thirty women fulfilled the criteria for the diagnosis of pre-eclampsia according to the American College of Obstetricians and Gynaecologists: de novo arterial hypertension after the 20th gestational week in at least two separate measurements and proteinuria of more than 300 mg/l in a random specimen. For comparison, we analysed blood samples from 125 non-pre-eclamptic pregnant women. ET-1 concentrations were higher in pre-eclamptic pregnancies at both time points (mean+/-S.D.: 1.07+/-2.00 versus 0.54+/-0.56 pg/ml, P=0.045 at 24th week; 0.75+/-1.20 versus 0.44+/-0.45 pg/ml, P=0.023 at 36th week). Receiver operating characteristic (ROC) curves revealed a significant interaction between ET-1 plasma concentrations at the 36th week and the diagnosis of pre-eclampsia [area under the curve (AUC)+/-S.E.M.: 0.657+/-0.049, P=0.008] and a cut-off value at 0.30 pg/ml. Multivariate analysis showed a 4.6-fold higher chance (95% confidence interval: 1.7-12.1, P=0.002) for the diagnosis of pre-eclampsia in pregnant women with ET-1 plasma concentration higher than 0.30 pg/ml at the 36th week. Interaction between ET-1 plasma concentration at the 24th week and diagnosis of pre-eclampsia was not significant in ROC curve analysis (AUC+/-S.E.M.: 0.594+/-0.071, P=0.278). Interestingly, we found a strong positive correlation between ET-1 concentration in the 24th and 36th week in linear regression analysis in pre-eclamptic (r=0.99, P<0.001) and non-pre-eclamptic pregnancies (r=0.61, P<0.001) with a slightly, non-significant decrease from the 24th to 36th week (for group means see above), indicating individual plasma ET-1 levels even in non-pre-eclamptic pregnancies. Linear regression analysis showed no correlation between blood pressure or urine protein excretion and ET-1 plasma concentration in non-pre-eclamptic pregnant women. In conclusion, our prospective study indicates that the ET system is, in contrast to most other forms of human hypertension, activated in pre-eclamptic pregnant women.