[Efficacy of toxin-A Botulinum for treating intractable bladder hyperactivity in children affected by neuropathic bladder secondary to myelomeningocele: an alternative to enterocystoplasty]. / La Tossina A-Botulinica in bambini con vescica neurogena iperattiva secondaria a mielomeningocele refrattaria agli urofarmaci: una alternativa all'enterocistoplastica.

AIM: To verify the efficacy of botulinus toxin A (TB-A) in treating children with neuropathic bladder secondary to myelomeningocele (MMC) with detrusor hyperactivity/low compliance, resistance to pharmacological therapy, and candidates for enterocystoplasty. METHODS: From January 2002 to June 2003, a group of 7 patients was selected (4 females, 3 males, mean age, 9.8 years, age range, 5-17 years) with detrusor hyperactivity, clean intermittent catheterization and resistance to pharmacological therapy. Two patients presented with grade 2-3 monolateral vesicoureteral reflux (VUR). All patients were incontinent despite catheterization. Botulinus toxin A was administered under general or local anesthesia by the injection of 200 IU of toxin diluted in 10 cc of physiologic solution with a metal or a flexible needle (3.7 F/21 GA). The needle was fully inserted into the detrusor muscle in about 20 sites, and 0.5 cc of solution were injected in each site, except the trigonum vesicae. Follow-up included ultrasound examination of the urinary tract and urodynamic studies performed at 6, 12 and 24 weeks and biannually thereafter. Micturition cystography was performed 3 months after the intervention. Urodynamic parameters were leak point pressure (LPP), leak point volume (LPV) and specific volume at 20 cm H2O pressure. The results were analyzed using the Wilcoxon test. RESULTS: A significant increase in LPV (range, 30-108%, mean, 77.6%) and in specific volume at 20 cm H2O pressure (CS 20) was observed in all patients. No significant change in LPP was found. One patient previously treated with the Cohen reimplantation technique experienced transient VUR which resolved spontaneously within 1 month. No major side effects from the injection of TB-A occurred. All patients were hospitalized for 24 hours with catheterization. CONCLUSIONS: The preliminary results in this small sample of patients suggest that the use of TB-A is efficacious in significantly improving urodynamic parameters and urine storage volume at low pressures in patients with neuropathic bladder resistant to pharmacological therapy.

Desmopressin for the treatment of nocturnal bedwetting in patients with neural tube closure defects.

PURPOSE: We evaluated desmopressin (DDAVP) treatment in patients with neuropathic bladder secondary to neural tube closure defects (NTDs) and nocturnal incontinence. MATERIALS AND METHODS: We selected 25 patients, that is 10 males (40%) and 15 females (60%), between ages 7 and 16 years (mean 9.8) with neuropathic bladder secondary to NTDs without a ventricular-peritoneal shunt. All had a low pressure bladder and presented with daytime continence between catheterizations but had persistent nocturnal urine loss 7 nights weekly. They underwent treatment with oral DDAVP according to a certain design, namely an initial dose of 0.2 mg for 3 weeks, which was increased to 0.3 or 0.4 mg for another 3 weeks in nonresponders. The average dose was 0.2 mg. At the effective minimal dose (bedwetting decrease greater than 50%) patients continued for 6 months and then decreased by intervals of 0.05 mg every 2 weeks. In the event of recurrence treatment continued for 1 year. RESULTS: All patients responded to treatment during the nighttime hours except 1 who suspended treatment after 4 weeks. There were no adverse effects from DDAVP. CONCLUSIONS: Treating nocturnal bedwetting with DDAVP in patients with NTDs was effective and safe. Nevertheless, to our knowledge treatment duration has not yet been determined.

Renal size and function in patients with neuropathic bladder due to myelomeningocele: the role of growth hormone.

PURPOSE: Patients with spina bifida have smaller kidneys than healthy individuals. We evaluated the correlation between small size and decreased renal function, and the possible role of growth hormone deficiency. MATERIALS AND METHODS: A total of 54 patients (mean age 11.5 years, median 11, standard deviation +/- 4.52) were healthy except for neuropathic bladder due to spina bifida. Renal function was evaluated with mercaptoacetyltriglycine renal scintigraphy and creatinine clearance. Renal anatomy was evaluated with renal ultrasound and voiding cystourethrography. Serum insulin-like growth factor-1 (IGF-1) levels were measured in all patients with immunoradiometric assay. Renal measurements in our patients were compared using the Sutherland nomogram. RESULTS: A total of 22 patients (41%) had smaller kidneys than normal subjects and 31 appeared to have creatinine clearance values lower than 120 ml per minute per 1.73 m2. The statistical comparison between kidney size and creatinine clearance was significant (p <0.05, r = 0.381). Scintigraphic data showed total effective renal plasma flow less than 568 ml per minute per 1.73 m2 body surface area (normal mean value for age). Comparison between effective renal plasma flow and creatinine clearance was significant (p <0.05, r = 0.31). Serum levels of IGF-1 were normal for age in all patients (mean 332.06 ng/ml, median 303.4, range 39.4 to 732.3). CONCLUSIONS: The kidneys are smaller in patients with spina bifida than in healthy subjects when compared using the Sutherland nomogram. There is a significant correlation between smaller renal length and decreased renal function in all patients, even in those who are healthy except for neurogenic bladder secondary to spina bifida. IGF-1 levels were normal for age, and, therefore, these patients had no growth hormone deficiency. These findings call into question the hypothesis that growth hormone deficiency contributes to smaller kidney size. Other hypotheses can be suggested, such as a defect of embryological growth secondary to malformation, or the result of a defect in homocysteine-methionine metabolism.

Nocturnal enuresis in the adolescent: a neglected problem.

OBJECTIVE: To assess the features of adolescent bedwetters, as few data are available on enuresis in this age group. PATIENTS AND METHODS: A specific database for adolescents and young adults was created with the collaboration of various specialists (paediatricians, urologists, gynaecologists, psychiatrists). Questions focused on family and personal history, stressful events, age of attaining urinary and fecal control, characteristics of enuresis (primary vs secondary, monosymptomatic vs enuresis associated with daytime urinary symptoms), school performance, diagnostic examination and physical examinations, and treatment and its response. RESULTS: Data were collected from 107 enuretic adolescents (mean age 15.3 years, median 14, range 13-23; 63 males and 44 females). A positive family history for enuresis was recorded in 82%. Enuresis was primary in 79 patients (74%), secondary in 28 (26%), monosymptomatic in 76 (71%) and associated with daytime urinary symptoms in 31 (29%). In males monosymptomatic enuresis was significantly more frequent than in females (P < 0.01). Urinary tract infections were reported by 13 patients, all females; eating disorders (anorexia, polyphagia) were present in six. In 85 patients (80%) enuresis was considered severe (> or = three nights/week). Of the 107 patients, 27 (20%) had never consulted a doctor about their problem and 43 (40%) had received no therapy; 66 received desmopressin monotherapy, with a good response (half the number of wet nights) in 44 (79%). There was no relation between response to desmopressin and gender, age, type and severity of enuresis or positive family history of enuresis. Eight patients were provided with a nocturnal alarm but this was not tolerated by two. Altogether, 25 patients refused any therapy or did not comply with the given therapy. CONCLUSIONS: Enuresis can persist into adolescence and be a significant problem; 80% of these patients had severe enuresis and 31% also had associated daytime urinary symptoms, with 40% receiving no previous therapy. The treatment of enuresis can be particularly difficult at this age; 22% of patients did not respond to desmopressin and 23% had low compliance with the given therapy. Enuresis in adolescents requires further study; hopefully more enuretic children will receive adequate treatment before reaching adolescence.

Italian multicentre open trial on DDAVP spray in nocturnal enuresis.

OBJECTIVE: The aim of the study was to compare the efficacy and safety of different doses of DDAVP spray treatment (20 to 40 mcg/day) in patients with primary monosymptomatic nocturnal enuresis (defined as three or more wet nights per week). MATERIAL AND METHODS: 237 patients (152 males, 75 females; age range 5-17 years), with no infections or organic abnormalities of the urinary apparatus and no neurological disorders, were admitted into the trial. The experimental design was planned as an "open study" with five different treatments schedules (5 groups). The daily doses of DDAVP at bedtime in groups 1 and 2 were 20 and 30 mcg, respectively, for 6 weeks. In groups 3 and 4 the daily doses for the first 2 weeks were 20 and 30 mcg, respectively, and then, after a washout period of 2 weeks, the daily doses for the two groups were 30 and 20 mcg, respectively. A dose-response study (20 to 40 mcg/day) was carried out in group 5. RESULTS: DDAVP spray therapy in primary monosymptomatic nocturnal enuresis was found to be resolutive in 70-75% of treated patients. No difference in response was found between the patients treated with the daily dose of 20 and those on 30 mcg. No important reactions were observed in patients treated with DDAVP spray at the different daily dose (20 to 40 mcg) or for different periods of time (up to 6 weeks). CONCLUSIONS: DDAVP spray therapy at a dose of 20 mcg/day was effective in 70-75% of primary monosymptomatic nocturnal enuretics. In non-responders the daily dose of DDAVP should be increased to 30 to 40 mcg.

The C677T mutation of the 5,10-methylenetetrahydrofolate reductase gene is a moderate risk factor for spina bifida in Italy.

OBJECTIVE: To estimate the risk for spina bifida associated with the common mutation C677T of the MTHFR gene in a country with a relatively low prevalence of NTDs. DESIGN: Case-control study. CASES: 203 living patients affected with spina bifida (173 myelomeningocele and 30 lipomeningocele); controls: 583 subjects (306 young adults and 277 unselected newborns) from northern and central-southern Italy. CASES: three spina bifida centres; young adult controls: DNA banks; newborn controls: regional neonatal screening centres. MAIN OUTCOME MEASURES: Prevalence of the C677T genotypes in cases and controls by place of birth; odds ratios for spina bifida and estimated attributable fraction. RESULTS: The prevalence of T/T, T/C, and C/C genotype was 16.6%, 53.7%, and 29.7% in controls and 25.6%, 43.8%, and 30.6% in cases, respectively. We found no differences between type of defect or place of birth. The odds ratio for spina bifida associated with the T/T genotype v C/C plus T/C was 1.73 (95% CI 1.15, 2.59) and the corresponding attributable fraction was 10.8%. No increased risk was found for heterozygous patients (OR=0.79, 95% CI 0.53-1.18). CONCLUSION: This study, as well as the meta-analysis we updated, shows that homozygosity for the MTHFR C677T mutation is a moderate risk factor in Europe, and even in Italy where there is a relatively low prevalence of spina bifida. The estimated attributable fraction associated with this risk factor explains only a small proportion of cases preventable by periconceptional folic acid supplementation. Thus, other genes involved in folate-homocysteine metabolism, their interaction, and the interaction between genetic and environmental factors should be investigated further.

An Italian epidemiological multicentre study of nocturnal enuresis.

OBJECTIVE: To estimate the prevalence of enuresis in schoolchildren in Italy. SUBJECTS AND METHODS: The Italian Club of Nocturnal Enuresis promoted a prevalence study of nocturnal enuresis using a self-administered questionnaire in seven cities in Northern, Central and Southern Italy. The association between enuresis and potential risk factors, e.g. a family history of enuresis, stress, socio-economic status and abnormal diurnal voiding habits, was investigated. The perceived impact on the child and on the family was also evaluated. A random-cluster sampling scheme was used to obtain a sample of primary and secondary schoolchildren from each city. One primary school and one secondary school for each socio-economic level was sampled in each city, giving a total of 42 schools surveyed; 9086 children were covered by the survey. In a cluster sampling method, the variance of prevalence is divided into two components, binomial and extra-binomial variability. Both the DSM III and DSM IV definitions of enuresis were used because at present, there is no consensus on the diagnostic criteria. RESULTS: Completed questionnaires were received from 7012 children, an overall response rate of 77.2%. Those aged 6-14 years were analysed, restricting the sample to 6892 children. There were 250 enuretic children using the DSM III definition of enuresis and 112 using the DSM IV definition. The overall prevalence was 3.88% and showed a decreasing trend with increasing age. Bedwetting was more frequent in boys than in girls. The prevalence of enuresis was higher when the child was from a family of low socio-economic status despite the child's age group. The logistic analysis showed that familiality, stress, birthweight, age of attaining diurnal continence, soiling and, for girls, menstruation, were statistically significant variables and thus contributed to predicting the probability of bedwetting, confirming the findings of previous studies. There was a large difference in prevalence using the two DSM definitions; a high percentage of DSM III enuretic children had more than two wet nights per week. CONCLUSION: It is important that a consensus about the 'working definitions' of enuresis is reached to avoid bias in the recruitment step, to carry out comparable epidemiological studies and to obtain adequate therapeutic responses.

Height and weight in children with vesicoureteric reflux and renal scarring.

Height standard deviation scores (HSDS) and weight-for-height index (WHI) at diagnosis were evaluated in 156 children aged 2 months to 10.8 years (mean 3.7 years) with vesicoureteric reflux (VUR) and normal creatinine clearance, and in 156 age- and sex-matched healthy controls. Forty-three patients had bilateral VUR with scintigraphic signs of renal scarring (B SCAR+), 25 had bilateral VUR without renal scarring (B SCAR-); 40 had unilateral VUR with (U SCAR+) and 48 unilateral VUR without (U SCAR-) renal scarring. B SCAR+ patients had an average HSDS of -0.5 +/- 1.4 (SD) which was significantly (P = 0.02) below that of controls (0.05 +/- 1 HSDS) and an average WHI of 100.6% +/- 16% which was significantly (P = 0.007) below that of controls (108% +/- 12%); 14% of B SCAR+ patients had a height below -2 HSDS. B SCAR-, U SCAR+, and U SCAR- patients had heights near to O HSDS which was not different from that of controls, as well as WHI between 104% and 107.9%, which was not different from that of controls. HSDS and WHI were significantly (P = 0.00001) correlated in patients but not in controls. B SCAR-, U SCAR+, and U SCAR- patients are similar to healthy controls in weight and in height growth and have, on average, some excess weight as do the latter. In contrast, B SCAR+ subjects have a significant decrease of the relative height and normal WHI.

Endocrine studies in children with myelomeningocele.

Pituitary-hypothalamic abnormalities due to impaired cerebrospinal fluid circulation have long been recognized. The aim of this study was to assess pituitary, thyroid, adrenal, and gonadal function in 46 prepubertal (22 M and 24 F) and 10 pubertal (4 M and 6 F) subjects with myelomeningocele (MMC). Basal serum levels of FT3, FT4, TSH, PRL, LH, FSH, T or E2, cortisol, 17-OH-P and DHEA-S were measured by routine radio-immunoassay methods. Twenty-two prepubertal patients had a TRH test for TSH and PRL evaluation, and eight underwent a GnRH test. Three patients presented with precocious puberty. Six subjects had modest elevations of serum TSH together with normal free thyroid hormone levels. In three cases, TSH responses to TRH were significantly exaggerated and prolonged: in two patients, TSH responses were delayed. The mean basal plasma FSH level in females with ventriculo-peritoneal shunt was significantly higher than in controls. In six cases FSH responses to GnRH were significantly higher than in controls. Both basal and stimulated PRL levels were elevated in patients with shunts; in patients without shunts, basal PRL was normal, but peak PRL levels following TRH stimulation were elevated. Our data show an abnormal hypothalamic-pituitary function in MMC subjects. These findings reinforce the importance of physical examination, hormonal evaluation and follow-up of pubertal development in patients with myelomeningocele.

Reduced response to hepatitis B virus vaccination in boys with steroid-sensitive nephrotic syndrome.

Vaccination against hepatitis B virus (HBV) was performed in 18 boys (aged 5.7 +/- 2.4 years) suffering from steroid-sensitive nephrotic syndrome (SSNS) and in a control group of 21 healthy boys (aged 5.6 +/- 3.8 years). The percentage of patients who responded to vaccination was significantly lower than the control group 1, 6, 8, 12, 18 and 24 months after the start of vaccination. The titre of antibodies to HBV surface antigen produced by responders at 6 and 24 months was significantly lower in patients than in the control group. Boys with SSNS have an impaired response to HBV vaccination.

Progression of chronic renal failure.

The deterioration rate of creatinine clearance (CCr) was studied in 40 children with chronic renal failure (CRF) on conservative treatment followed up for at least 1 year (range 1-12). The deterioration rate of CCr was significantly (p less than 0.01) higher in glomerulopathies (G) than in hypoplasias (H) and in vascular nephropathies (VN) and significantly (p less than 0.01) higher in hereditary nephropathies (HN) than in VN. The differences in the deterioration rate of CCr between H and HN and between H and VN were not explainable on the basis of the different age at diagnosis or of the different prevalence of hypertension. These data indicate that the primary renal disease is important in determining the progression of CRF.

Plasma and urinary growth hormone and insulin-like growth factor I in children with chronic renal insufficiency.

We investigated the plasma and urinary growth hormone (GH) levels, and plasma insulin-like growth factor (IGF-I) in 15 (8 prepubertal and 7 pubertal) subjects with chronic renal insufficiency. Four of our 7 pubertal patients had a short stature (standard deviation score from -2.7 to -4.0). Significantly increased plasma GH and IGF-I levels were found in pubertal subjects alone (p less than 0.05). The urinary GH levels was significantly increased in prepubertal and pubertal subjects (p less than 0.001 and 0.05, respectively). A significantly inverse correlation between urinary GH excretion and creatinine clearance was found (r = -0.55; p less than 0.05). Increased plasma GH, IGF-I and urinary GH levels seem to suggest a complex alteration of GH and somatomedin metabolism in central and peripheral (receptor) cells.

Levamisole in children's idiopathic nephrotic syndrome.

13 children with frequently relapsing and/or steroid-dependent idiopathic nephrotic syndrome (INS) were treated with levamisole. 2.5 mg of levamisole per kilogram body weight twice a week (cycle A) were administered to all patients during 2-16 months (mean 5.8). A daily administration of the same dose of levamisole was given during 2-9 months (mean 4.9) to 8 patients who did not respond to cycle A (cycle B). A beneficial effect was observed in 6 cases: 4 with cycle A and 2 with cycle B. These patients suffered no relapse despite a significant decrease in the amount of prednisone administered or its discontinuation and they experienced a remission period of 7-29 months without prednisone administration. The side effects of the therapy turned out to be minimal both with cycle A and B. Levamisole may be effective in frequently relapsing and/or steroid-dependent INS with minimal side effects.

Hepatitis B surface antigenaemia and glomerulopathies in children.

Serum HBsAg positivity prevalence was studied on 98 children affected by various nephropathies or obstructive uropathies and on a control group of 71 children, consecutively admitted into the same clinical ward, suffering from other than hepatic or renal diseases. No significant difference was found between the group of children with non-glomerular nephropathies or obstructive uropathies and the control group. The prevalence of HBsAg positivity was significantly higher in male children with membranous glomerulopathy and in those with lipoid nephrosis than in the control group. All HBsAg positive children with glomerulopathies were chronic carriers of the hepatitis B virus. However, though left undemonstrated, there still lies a probable pathogenetic relationship between the hepatitis B virus infection and membranous glomerulopathy. The authors hypothesize that an impaired immune response in male children with lipoid nephrosis may account for both the hepatitis B virus infection and the development of the glomerular disease.

Membranous glomerulopathy and hepatitis B virus (HBV) infection in children.

Histological examination of renal biopsies in 64 Neapolitan children aged 13 months to 14 years who presented with nephrotic syndrome or persistent hematuria and/or proteinuria revealed membranous glomerulopathy (M.G.) in 14. Hepatitis B surface antigen (HBsAg) was found in the serum of 9/14 children with M.G. and in 1/14 children in an age and sex matched control group. The prevalence of HBsAg positivity in the M.G. children suggests a relationship between HBV infection and the disease. The high prevalence of males in HBsAg positive M.G. children suggests that males have an increased risk of contracting M.G. The absence of chronic liver disease in 8/9 HBsAg positive M.G. patients, and the lack of correlation between the clinical manifestations of kidney disease and the rate of HBV replication indicate that different mechanisms underlie the hepatic and renal pathologies.

[Glomerulonephritis caused by a shunt: description of a case]. / Glomerulonefrite da shunt: descrizione di un caso.

The authors report a case of shunt-nephritis due to bacteremia from Stafilococcus albus. Kidney biopsy, comprehensive of IF study allowed to assess the diagnosis of a disease from immunocomplexes. The Authors stress the importance of a close follow-up of patients who carry liquoral shunt for an early recognition of symptoms of glomerulopathy.