Breaking the vicious circle: Onabotulinum toxin A in children with therapy-refractory dysfunctional voiding.

INTRODUCTION: An increased activity of the external urethral sphincter or pelvic floor muscles during voluntary voiding leads to dysfunctional voiding. Frequently reported symptoms are urinary incontinence, urinary tract infections and high post-void residuals. Dysfunctional voiding is a common problem in school-aged children and despite various treatment options, 10-40% of the children remain therapy-refractory. OBJECTIVE: The aim of this study is to evaluate the effectiveness of Onabotulinum toxin-A (BTX-A) injections in the external urethral sphincter in children with therapy-refractory dysfunctional voiding. PATIENTS AND METHODS: Patients with therapy-refractory dysfunctional voiding who have received BTX-A injections in the external urethral sphincter from 2010 to 2013 were analysed. Children with known neuropsychiatric disorders were excluded. All children had abnormal flow patterns and increased pelvic floor tone during uroflowmetry/EMG studies. They had received at least five sessions of urotherapy and two sessions of pelvic floor physical therapy prior to treatment. A total of 100 IU of BTX-A was injected in the external urethral sphincter at the 3, 9 and 12 o'clock positions. Our main outcome measures were urinary incontinence, recurrent urinary tract infections and post-void residual. RESULTS: A total of twenty patients, of whom 16 girls, with a median age of 9 years (range 5-14) were treated with BTX-A. The median follow-up was 13 months (range 5-34). Post-void residual decreased by 75% after BTX-A, from a median of 47.5 ml (16.3-88.5 ml) to 0 ml (0.0-28.0 ml) (p = 0.001) Six patients had a post-void residual < 20 ml prior to treatment. After BTX-A sixteen patients had a post-void residual <20 ml (Figure). No significant changes in uroflowmetry results was seen. Sixteen children are no longer daily incontinent, of whom 9 became completely dry (p = 0.0001). Eleven patients suffered from recurrent urinary tract infections prior to treatment. After BTX-A five children remained infection free, while the other six experienced only one urinary tract infection during follow-up (p = 0.003). Fourteen patients received additional urotherapy after BTX-A. Repeat injections were necessary in four patients after initial satisfactory results, with repeated good clinical responses. Two children showed no improvement after first BTX-A injection. No serious adverse events were reported. DISCUSSION: The results in this homogenous group of patients confirm the conclusions of previous studies in opting BTX-A in the external urethral sphincter to be a viable treatment option for the therapy-refractory group of patients with dysfunctional voiding. What is new, is that in most of our patients post-injection urotherapy was used to amplify the BTX-A effect. During our long-term follow-up the satisfactory results were sustained, similar to the results of the long-term follow-up presented by Vricella et al. [1]. The retrospective character and relative small sample size are limitations of this study. CONCLUSIONS: This study shows safe and persistent satisfactory results during our average 13-month follow-up in 90% of our patients with therapy-refractory dysfunctional voiding. A prospective study using validated and standardized measurements will be performed to affirm our results and evaluate the exact role of post-injection urotherapy.

Systemic ghrelin levels in subjects with growth hormone deficiency are not modified by one year of growth hormone replacement therapy.

OBJECTIVE: Ghrelin stimulates growth hormone (GH) secretion both in vivo and in vitro. Ghrelin is mainly produced in and released from the stomach but it is probably also produced in the hypothalamic arcuate nucleus. Whether pituitary GH release is under the control of ghrelin from the stomach and/or from the arcuate nucleus is not known. Moreover, no data on the feedback of GH on systemic ghrelin concentrations are available. It has recently been suggested that ghrelin may induce obesity. DESIGN: In this study, we addressed the following two questions: a) are circulating ghrelin levels increased in human GH deficiency (GHD), and b) does GH treatment modify ghrelin levels in human GHD? METHODS: The study group consisted of 23 patients with GHD. Eighteen had developed adult-onset GHD and five had developed GHD in their childhood (childhood-onset GHD). Ghrelin was measured with a commercially available radioimmunoassay. All measurements were performed twice, first at baseline, before the start of GH replacement therapy, and then again after one year of therapy. GH doses were adjusted every 3 months, targeting serum total IGF-I levels within the normal gender- and age-related reference values for the healthy population. Maintenance doses were continued once the target serum total IGF-I levels were reached. RESULTS: The sum of skinfolds and body water increased significantly, body fat mass and percentage body fat decreased significantly and body mass index and waist-hip ratio were not significantly changed by one year of GH replacement therapy. Before the start of GH replacement therapy, mean value and range for fasting ghrelin in the studied GHD subjects tended to be lower in comparison with healthy subjects in the control group although the difference did not reach significance (GHD ghrelin mean 67.8 pmol/l, range 37.6-116.3 pmol/l; control mean 83.8 pmol/l, range 35.4-132 pmol/l; P=0.11). One year of GH replacement therapy did not modify circulating ghrelin levels (ghrelin before GH therapy: 67.8 pmol/l, range 37.6-116.3 pmol/l; after GH therapy: 65.3 pmol/l, range 35.8-112.6; P=0.56). CONCLUSIONS: We did not observe elevated ghrelin levels in adult GHD subjects and GH replacement therapy did not modify circulating ghrelin levels, despite significant decreases in body fat mass and percentage body fat. It is conceivable that the lack of ghrelin modifications after long-term GH therapy was due to the reduction of adiposity and insulin on one hand, and increased GH secretion on the other. However, it is still possible that systemic ghrelin is involved in the development of obesity, both in normal and GHD subjects.

[Streptococcus gallolyticus infections in racing pigeons, a literature review]. / Streptococcus gallolyticus-infecties bij de postduif, een literatuuroverzicht.

S. gallolyticus, formerly known as S. bovis is known since 1988 as a facultative pathogen of racing pigeons. Important clinical signs include acute mortality, inability to fly, lameness, weight loss and slimy green diarrhea. A pathognomonic sign at post mortem examination is the presence of well circumscribed areas of necrosis in the pectoral muscle. Furthermore tenosynovitis of the supracoracoid muscle and arthritis of the knee, shoulder and hock can be observed. In one study S. gallolyticus septicaemia was diagnosed in 10% of necropsied pigeons. Since S. gallolyticus was also isolated from nearly 40% of clinical healthy pigeons it is regarded as a facultative pathogen. Various biotypes, serotypes and culture supernatant phenotypes can be distinguished. Supernatant phenotypes are identified on the basis of the presence of either a T1, T2 or T3 protein triplet and the presence or absence of an extracellular A protein. S. gallolyticus strains with A protein are highly virulent, while strains with only T3 or T2 protein are of moderately or low virulence respectively. Fimbriae are only seen in highly virulent and some of the moderately virulent strains. Possible virulence factors include survival in macrophages, adhesion to cells and toxin production. Infection with serotype 1 and 2 induces some degree of protection against re-infection with serotype 1, which offers perspectives for the development of a vaccine. Experimentally ampicillin, doxycycline and erythromycin have shown therapeutic effects. For the treatment of clinical cases the use of ampicillin is advocated, together with hygienic measures, such as the use of grid floors and avoiding overcrowding.