Human fear acquisition deficits in relation to genetic variants of the corticotropin-releasing hormone receptor 1 and the serotonin transporter--revisited.

We recently showed that a genetic polymorphism (rs878886) in the human corticotropin-releasing hormone receptor 1 (CRHR1) is associated with reduced fear-conditioned responses to a threat cue. This is a potentially important finding considering that the failure to acquire fear contingencies can leave an individual in a maladaptive state of more generalized anxiety. Consistent with that idea, the CRHR1-dependent fear acquisition deficit translated into heightened contextual anxiety when taking genetic variability within the serotonin transporter long polymorphic region (5-HTTLPR) into account. To replicate our previous findings, we conducted a replication study in 224 healthy medication-free human subjects using the exact same cue and context virtual reality fear-conditioning procedure as in study by Heitland et al. (2013). In the replication study, consistent with the original findings, CRHR1 rs878886 G-allele carriers showed reduced acquisition of cue-specific fear-conditioned responses compared with C/C homozygotes. Also, in this larger sample the cue acquisition deficit of G-allele carriers translated into heightened contextual anxiety, even independent of 5-HTT gene variation. In contrast to our earlier findings, there was an additional interaction effect of CRHR1 rs878886 and the triallelic 5-HTTLPR/rs25531 variant on cued fear acquisition. In summary, this study replicated the initially reported association of the CRHR1 rs878886 G-allele with cued fear acquisition deficits, albeit with a different pattern of results regarding the interaction with 5-HTT variation. This further supports the notion that the human corticotropin-releasing hormone plays a role in the acquisition of fears.

Melatonin treatment in children with therapy-resistant monosymptomatic nocturnal enuresis.

OBJECTIVE: To evaluate the effects of exogenous melatonin on the frequency of wet nights, on the sleep-wake cycle, and on the melatonin profile in children with therapy-resistant MNE. PATIENTS AND METHODS: 24 patients were included. Patients had to maintain a diary including time of sleep and arousal, and whether they had a dry or a wet bed in the morning. We measured baseline melatonin profiles in saliva. Hereafter, patients were randomized to synthetic melatonin or placebo. After 3 and 6 months we evaluated the frequency of enuresis and the melatonin profiles. RESULTS: 11 patients were randomized to melatonin, 13 to placebo. We evaluated melatonin profiles of 7 patients in the melatonin group and of 8 in the placebo group. We observed a change in profile in the melatonin group, but we did not observe a difference in the sleep-wake cycle or the frequency of wet nights in either group. CONCLUSION: This is the first time exogenous melatonin has been evaluated in the treatment of MNE. Although we observed a change in melatonin profile after the use of exogenous melatonin, we did not observe a change in enuresis frequency or in the sleep-wake cycle of this select group of patients.

[Non-neurogenic bladder dysfunction and vesicoureteral reflux in children]. / Nicht neurogene Blasenfunktionsstörungen und vesikoureteraler Reflux bei Kindern.

Various types of bladder dysfunction are associated with urinary tract infection, renal damage and vesicoureteral reflux (VUR). In this article the influence of functional bladder disturbances such as detrusor instability (overactive bladder, OAB) and bladder sphincter dyssynergia (dysfunctional voiding), on the resolution of vesicoureteral reflux are reviewed. In summary, it is important to distinguish between children with dysfunctional voiding (increased activity of the pelvic floor during voiding) and those with OAB (detrusor overactivity during filling) because the latter has less effects on VUR.

[Imaging studies in infants and children with dilatation of the upper urinary tract]. / Bildgebung bei Hohlsystemdilationen des oberen Harntraktes im Neugeborenen- und Kindesalter.

Prenatally or postnatally diagnosed dilatation of the upper urinary tract initiates postnatal investigations, including sonography, dynamic renography (MAG 3) and optional voiding cystourethrography. The first ultrasound examination should be performed 3-5 days after birth and in urgent cases 10-12 h after delivery of the baby. Dynamic renography (MAG 3) is the standard diagnostic investigation and permits simultaneous assessment of renal perfusion and drainage. MRI combines excellent anatomical detail with functional information, without exposure to radiation but needs general anaesthesia in infants and younger children. Intravenous urography is no longer performed routinely in children with a dilated upper urinary tract. The combination of ultrasound and MAG 3 produces the necessary anatomical and functional information to follow the degree of obstruction and to decide between surgical intervention or a conservative follow-up.

Voiding habits and wetting in a population of 4,332 Belgian schoolchildren aged between 10 and 14 years.

OBJECTIVE: To determine the prevalence of daytime- with/without night-time wetting, in Belgium, in a group of 10 to 14 year old schoolchildren, and to study the voiding habits. SUBJECTS AND METHODS: A questionnaire of 41 questions was developed and completed by 4,332 parents at home. RESULTS: Wetting or soiling episodes were reported by a total of 528 (12%) of the children: monosymptomatic nocturnal enuresis by 62 (1%), daytime wetting with/without night-time wetting by 343 (8%), and faecal soiling by 123 (3%). We found significantly more girls in the wetting group, and the capacity to regularly postpone the voiding was significantly lower in this group. Significantly more children had nocturia in the group with wetting. CONCLUSIONS: Children with daytime wetting with/without night-time wetting have very often bladder-sphincter dysfunctions, which is in turn correlated with recurrent urinary tract infections. Eight percent of the 10 to 12 year old schoolchildren report daytime wetting with/without night-time wetting with some frequency. Surprisingly few parents, especially in the daytime wetting group, searched for medical help. Physicians and paediatricians should be encouraged to be more attentive to wetting in children and initiate discussion about urinary en faecal problems with parents and children.

Results of a questionnaire evaluating the effects of different methods of toilet training on achieving bladder control.

OBJECTIVE: To analyse if family situation, personal habits and toilet training methods can influence the achievement of bladder control. SUBJECTS AND METHODS: A questionnaire with 41 questions was distributed to 4332 parents of children completing the last 2 years of normal primary school. The questionnaire had been tested for reproducibility of the answers in a random subgroup of 80 parents. The aims of the investigation were explained in an accompanying letter and the response rate was 76.7%. The result were analysed using the chi-square test (Yates corrected). RESULTS: Two groups of children were identified, one with no lower urinary tract symptoms (3404) and one with complaints of daytime and night-time wetting, and urinary tract infections (928). The groups were termed the 'control' and 'symptom' groups, respectively. There were no differences in the family situation between the groups. The symptom group reported more 'below average' school results and less independence in homework and hygiene. The age at which toilet training started was significantly higher in the symptom group and scheduled voiding was used significantly less. The reaction of the parents when the attempt at voiding was unsuccessful was significantly different; in the control group most parents just postponed the effort and had the child try again later, whereas in the symptom group more parents asked the child to push, made special noises or opened the water tap. CONCLUSIONS: These data show significant differences in toilet training between children with and with no lasting problems of bladder control. Postponing the onset of the training after 18 months of age and using certain methods to provoke voiding (asking to push, opening the water tap) probably increases the risk of later problems with bladder control.

Morphometry of human superficial dorsal and dorsolateral column fibres: significance to spinal cord stimulation.

In spinal cord stimulation (SCS) large diameter cutaneous (Abeta) fibres in the dorsal columns (DCs) are activated and have an inhibiting effect on the transmission of pain signals by Adelta and C fibres from the corresponding dermatome(s). The largest Abeta fibres can be activated up to a maximum depth of about 0.25 mm in the DCs. No data are available on the distribution of the large fibres in this superficial human DC layer at the common SCS levels Th(10-11). Such data are indispensable to improve the predictive capability of a computer model of SCS. The whole myelinated fibre population in the superficial 300 microm of the dorsal column (DC(0-300)) at Th(10-11 )of two human subjects was morphometrically analysed. Some data was obtained from a third subject. The superficial dorsolateral column (DLC(0-300)) was included in this analysis because it was hypothesized that large dorsal spinocerebellar tract fibres could also be activated by SCS. Only very few fibres larger than 10.7 microm were found: a mean of 68 (0.5%) in DC(0-300) and 114 (2%) in DLC(0-300). Considering that the effect of SCS is primarily attributed to activation of these largest fibres, it is concluded that a surprisingly small average amount of 2.4 fibres per running 0.1 mm width and 6 fibres per segmental division of the DC is involved. Distinct mediolateral heterogeneity in fibre composition was found in both DC(0-300) and DLC(0-300). In the DC(0-300), the mean diameter of fibres > or =7.1 microm increases significantly by 5% from medial to lateral. Density (i.e. number of fibres per 1000 microm(2)) and frequency (i.e. percentage of a fibre size group compared to its parent population) of the large fibres increase significantly from medial to lateral in the DC(0-300). For fibres > or =10.7 microm, these parameters increase by 200 and 269%, respectively. It is concluded that the difference in stimulation threshold of large Abeta fibres in the median and lateral DC can be mainly attributed to the absence and presence, respectively, of collaterals at the stimulation site. Marked differences were found between DC(0-300) and DLC(0-300). The largest DLC(0-300) fibres (> or =10.7 microm) have a 320% higher frequency and a 473% higher density. Their mean diameter is, however, only 2% larger. The largest DLC(0-300) fibres are not likely to be recruited by SCS, since they are not larger than their DC(0-300) counterparts, they lack collaterals (which would reduce the threshold stimulus substantially) and they are more remote from the stimulation electrode.

Angiotensin II type 2 receptors and cardiac hypertrophy in women with hypertrophic cardiomyopathy.

The development of left ventricular hypertrophy in subjects with hypertrophic cardiomyopathy (HCM) is variable, suggesting a role for modifying factors such as angiotensin II. Angiotensin II mediates both trophic and antitrophic effects, via angiotensin II type 1 (AT(1)-R) and angiotensin II type 2 (AT(2)-R) receptors, respectively. Here we investigated the effect of the AT(2)-R gene A/C(3123) polymorphism, located in the 3' untranslated region of exon 3, on left ventricular mass index (LVMI) in 103 genetically independent subjects with HCM (age, 12 to 81 years). LVMI and interventricular septum thickness were determined by 2D echocardiography. Extent of hypertrophy was quantified by a point score (Wigle score). Plasma prorenin, renin, and ACE were determined by immunoradiometric or fluorometric assays, and genotyping was performed by polymerase chain reaction. In men, no associations between AT(2)-R genotype and any of the measured parameters were observed, whereas in women, LVMI decreased with the number of C alleles (211+/-19, 201+/-18, and 152+/-10 g/m(2) in women with the AA, AC, and CC genotype, respectively; P=0.015). Similar C allele-related decreases in women were observed for interventricular septum thickness (P=0.13), Wigle score (P=0.05), plasma renin (P=0.03), and plasma prorenin (P=0.26). Multiple regression analysis revealed that the AT(2)-R C allele-related effect on LVMI (beta=-30.7+/-11.1, P=0.010) occurred independently of plasma renin, the AT(1)-R gene A/C(1166) polymorphism, or the ACE gene I/D polymorphism. In conclusion, AT(2)-Rs modulate cardiac hypertrophy in women with HCM, independently of the circulating renin-angiotensin system. These data support the contention that AT(2)-Rs mediate antitrophic effects in humans.

Measuring the sacral inclination angle in clinical practice: is there an alternative to radiographs?

BACKGROUND: In patients with low back pain (LBP) the position of the pelvis is often a focus of physical or manual therapy. The "gold standard" to determine sacral inclination is by radiograph, but methods to measure sacral inclination externally with an inclinometer have also been introduced. OBJECTIVE: To determine the validity of the inclinometer in measuring the sacral inclination in patients with LBP. SUBJECTS: Adult patients with LBP who were referred by the general practitioner to the hospital for radiograph examination of the lumbosacral spine were included. METHODS: Measurement of sacral inclination acquired with the inclinometer, simultaneous with the x-ray exposure, was compared with the "gold standard" measurement of sacral inclination on the radiograph. Regression analysis was used to define the measurement error. RESULTS: Of 50 consecutive patients with LBP, radiographs of 41 patients were useful for the required measurements on the radiograph. The mean difference between the radiographic and inclinometer method was 23.12 degrees. The measurement error was 8.26 degrees. Regression analyses showed poor correlation between both methods (r = 0.28). CONCLUSIONS: The method we used to measure sacral inclination with an inclinometer proved to be invalid.

Bladder-sphincter dysfunction in myelomeningocele.

Pediatric urodynamics taught us that detrusor-sphincter dyssynergia creates a bladder outlet obstruction in about 50% of any population of children with myelomeningocele. This functional obstruction causes renal damage due to obstructive uropathy, exactly the same way as a congenital anatomical urethral obstruction does. Pediatric urodynamics also taught us that in children with myelomeningocele pelvic floor activity and detrusor activity can be abnormal (hyperactive or inactive) completely independent from each other. These insights have changed the management of myelomeningocele. Children with overactivity of the pelvic floor can be singled out at infant age, and started on clean intermittent catherization, to prevent obstructive uropathy and preserve renal function. Children with detrusor overactivity can be singled out too at very early age, and treated with anticholinergics, to prevent irreversible structural damage to the detrusor and preserve normal bladder capacity and compliance.

The treatment of post-urethrotomy incontinence in pediatric and adolescent females.

PURPOSE: Until 1986 many urologists performed currently outdated, redundant internal urethrotomy as standard therapy for recurrent urinary tract infection in girls. We describe the results of therapy in patients who became incontinent due to previous internal urethrotomy. MATERIALS AND METHODS: Between 1986 and 1995, 21 female patients with post-Otis urethrotomy incontinence have presented at our department with combined dysfunctional voiding, recurrent urinary tract infection and various types of urinary incontinence partially based on bladder instability and often provoked by abdominal straining. All cases were diagnosed by repeat video urodynamics and ultrasound of the open bladder neck. Endoscopy provided proof of scarring in the bladder neck and urethra. All patients except 1 underwent conservative treatment for at least 2 years, consisting of pharmacological therapy, physical therapy and biofeedback training. Surgical therapy to cure incontinence was performed in 14 cases, including a conventional Burch-type colposuspension in 5, modified needle colposuspension in 4 and complete endoscopic excision of the urethral scars followed by open reconstruction of the bladder neck and urethra in an abdominoperineal procedure in 5. RESULTS: Conservative treatment has been completely successful in 7 patients. Primary open or needle colposuspension was unsuccessful in 6 of 9 cases, including several requiring further surgery to achieve dryness. The results of excising urethral scars with bladder neck and urethral reconstruction were good in 4 of 5 patients at a followup of at least 4 years. CONCLUSIONS: When previous internal urethrotomy appears to be an important factor in the evaluation of incontinence, conservative therapy is the treatment of choice. Conservative therapy should consist of biofeedback reeducation of the voiding pattern and physical therapy. When surgery is needed, excision of the urethral scars with reconstruction of the bladder neck and urethra plus colposuspension is superior to colposuspension only.

The effect of rectosigmoidectomy and Duhamel-type pull-through procedure on lower urinary tract function in children with Hirschsprung's disease.

BACKGROUND/PURPOSE: The aim of this study was to investigate the effect of rectosigmoidectomy and Duhamel-type pull-through procedure on lower urinary tract function in children with Hirschsprungs disease. METHODS: During a 3-year period the authors assessed 11 consecutive children with Hirschsprung's disease prospectively by standard urodynamic investigations, before and after surgery. Urodynamics included simultaneous measurement of abdominal pressure, bladder pressure, detrusor pressure, and pelvic floor electromyography during filling and voiding. All children were submitted to laparoscopic resection of the aganglionic bowel segment below the cul de sac and a Duhamel-type pull-through procedure. Postoperatively, the children were assessed urodynamically and evaluated every 3 months for urologic problems. RESULTS: Mean age at first urodynamic study was 5 months (range, 2 to 10). Postoperative urodynamics were performed at a mean age of 10 months (range, 5 to 159). The mean interval between operation and postoperative urodynamic study was 6 months (range, 2 to 10). No child had structural urologic anomalies or urologic problems before surgery, and all had normal preoperative urodynamic findings. After surgery, urodynamics were considered normal in 3 children. In 7 children cystometric bladder capacity (CBC) was abnormally large, and 6 of these children had significant residuals. However, all had detrusor contractility and were able to void spontaneously. One child had low bladder compliance postoperatively. Despite the urodynamic changes, no child had clinical urologic problems at further follow-up. Mean follow-up after surgery was 24 months. CONCLUSIONS: This study found that after rectosigmoidectomy below the cul de sac alterations of bladder function can be observed. In 7 of the 11 patients studied, mean cystometric bladder capacity was 87% higher than capacity estimated for age. Moreover, postoperative residuals were 156% higher than the preoperative values. These findings suggest that partial detrusor denervation is likely in these patients. However, because detrusor contractility was present, and none of the children had retention or any urologic problems, the findings must be interpreted carefully. Because children with Hirschsprung's disease generally do not have preexisting urologic problems, routine preoperative urodynamic screening is not necessary. However, children with voiding problems after operation should be investigated urodynamically. For legal reasons parents should be informed of possible urologic problems, especially if subtotal resection of the aganglionic bowel segment is planned.

Results of a questionnaire evaluating different aspects of personal and familial situation, and the methods of potty-training in two groups of children with a different outcome of bladder control.

OBJECTIVE: This study aimed to investigate the family situation, personal behaviour and current micturition habits, the time of beginning and the method of potty-training in two groups of children with different outcomes of bladder control. MATERIAL AND METHODS: Parents of 140 children, between 7 and 15 years old, filled in a questionnaire comprising 43 questions. They were divided into a symptom group (n = 73) and a symptom-free group (n = 67) according to the outcome of bladder control. RESULTS: Parents remembered clearly the method of training and the time of starting the potty-training to achieve continence in their child, and the exact age at which these objectives were achieved. There was some confusion regarding the term incontinence: the majority of the parents (70%) considered their child to be continent in spite of day-wetting several times a week. All children with urge syndrome who had undergone a urodynamic investigation (n = 50) had an objective functional bladder disorder. CONCLUSIONS: Methods of training differed between the groups with and without lasting problems. The symptom group started training at a later age, had more tendency to punish and were more demanding when micturition did not start readily. The findings from the questionnaire strengthen the hypothesis that urge syndrome can be due to poor methods of potty-training. Very few parents searched spontaneously for help, which should prompt practitioners and paediatricians to be more alert to this problem.

Ectopic ureterocele: results of open surgical therapy in 40 patients.

PURPOSE: The treatment of ectopic ureterocele is controversial. In addition to debate on optimal therapy, discussion exists on whether there is further risk of deteriorating bladder function after extensive bladder surgery during the first year of life, which is a reason to postpone surgery. In a prospective nonrandomized trial we treated 40 patients regardless of age who had ectopic ureterocele with complete surgical reconstruction of the lower urinary tract and upper pole resection of poorly functioning upper pole moieties at referral. Excluded from study were 3 patients with only 1 affected renal moiety initially. MATERIALS AND METHODS: We treated 31 female and 9 male patients 0 to 8.8 years old (mean age 2.17) at surgery for ectopic ureterocele extending into the bladder neck and urethra, including 19 younger than 1 year. Primary ureterocele excision was performed in 37 cases with reconstruction of the urethra, bladder neck and trigone, and ureteral reimplantation. Because of small ureterocele size, the ureterocele was left in situ in 3 patients, leading to secondary ureterocele removal due to obstructive voiding and urinary incontinence in 1 each. A staged procedure in 5 neonates involved primary lower urinary tract reconstruction with upper pole cutaneous ureterostomies followed by upper pole resection or ureteral reimplantation a few months later. After bladder neck reconstruction in 16 cases colposuspension was also done to create a normal vesicourethral angle. All patients underwent clinical and urodynamic evaluation at least 1.25 years after surgery (mean followup 5.59). Patients who were too young for the clinical assessment of continence by January 1999 were excluded from study. RESULTS: All patients are continent. A secondary endoscopic procedure was required in 13 cases, including cystoscopy only in 2, scar incision near the ureteral orifice in 3, endoscopic reflux treatment in 4, ureterocele remnant resection in 2 and bladder neck incision for obstructive voiding in 2. Secondary open bladder reconstruction was performed in another case due to a diverticulum. Postoperatively only 1 or 2 uncomplicated episodes of urinary tract infection developed in 11 patients, while there were recurrent urinary tract infections in 4. In a patient with a preexisting loss of renal function a severe infection led to renal scarring. The voiding pattern was normal in 29 patients but 11 had dysfunctional voiding, including 5 with recurrent urinary tract infection. Urodynamic followup confirmed these clinical findings. Bladder capacity in these patients was relatively high at an average of 124% of expected capacity for age. We noted no statistically significant difference in followup parameters in patients who underwent surgery before and after age 1 year. Additional colposuspension in 16 patients did not result in any significant change in outcome compared with that in patients without this procedure. CONCLUSIONS: When compared with results in the literature, complete primary lower urinary tract reconstruction in patients with ectopic ureterocele appears to have better results than a staged approach with initial endoscopic treatment. Moreover, our study provides no proof that extensive reconstructive bladder surgery in neonates and infants leads to bladder function deterioration at a later age.

Pediatric renal transplantation in the Netherlands.

In the Netherlands, pediatric kidney transplantation programs are available in four centers. We retrospectively analyzed the results obtained over the past decade. Between 1985 and 1995, 231 patients (139 boys) received 269 transplants, including 61 repeat. The recipients were aged 1.9-21.8 yrs (mean 10.9), the donors 0.3-63.3 yrs (median 11.4, mean 19.7). Immunosuppression consisted of corticosteroids, cyclosporin A and azathioprine, in various combinations and dosages. The patient survival during follow-up was 97%. The overall graft survival was 73% at 1 yr and 60% at 5 yrs after transplantation. Major causes of graft loss were acute rejection (21%), thrombosis (12%) and chronic rejection (28%). Acute rejection episodes were noted in 74% of all grafts. First acute rejection episodes had a moderate predictive value for graft loss (relative risk (RR), compared to rejection-free grafts, 5.9). First rejection episodes occurring later than 3 months after transplantation were considerably more predictive (RR 18.3) than early ones. Grafts from living related donors (n = 35) yielded a superior 5-yr graft survival (77%) and remained free of rejection more often than grafts from adult cadaveric donors(43% vs. 25%). The results of pre-emptive transplants were excellent (n = 13, 5-yr survival 100%). Repeat transplants had the same results as primary transplants. Recipients younger than 4 yrs showed a poor 5-yr graft survival of 38% (n = 13). Single kidney grafts from donors younger than 4 yrs (n = 35) had a 5-yr graft survival of 44%. In contrast, kidneys from these young donors did well if transplanted en bloc (n = 10, 5-yr graft survival 89%). These overall results are in line with those of others. The results may be improved by expansion of immunosuppressive therapy in the first year and by thrombosis prophylaxis in high-risk patient-donor combinations. Better results may be expected from more extensive use of living related donations, pre-emptive transplantation and en bloc transplantation instead of single kidneys of young donors.

Subtypes in monosymptomatic nocturnal enuresis. II.

Lasting cure rates in monosymptomatic nocturnal enuresis (MNE), using the alarm, imipramine or desmopressin, have been quoted as 43%, 17% and 22%, respectively. The low cure rates in addition to the number of different treatments indicate insufficient knowledge of MNE. Only research on arginine vasopressin (AVP) levels and nocturnal enuresis is unique in attempting to find a group within the MNE population that could benefit from substitution therapy with desmopressin. AVP levels are restored or amplified during desmopressin treatment. However, low nocturnal AVP production with high nocturnal urine output may be indicative of a disturbance in circadian rhythm. Pre-clinical data suggest a role for melatonin in the regulation of endogenous AVP and in the regulation of the sleep/wake cycle.

Plasma renin and prorenin and renin gene variation in patients with insulin-dependent diabetes mellitus and nephropathy.

BACKGROUND: The most striking abnormality in the renin angiotensin system in diabetic nephropathy (DN) is increased plasma prorenin. Renin is thought to be low or normal in DN. In spite of altered (pro)renin regulation the renin gene has not been studied for contribution to the development of DN. METHODS: We studied plasma renin, prorenin, and four polymorphic markers of the renin gene in 199 patients with IDDM and DN, and in 192 normoalbuminuric IDDM controls matched for age, sex, and duration of diabetes. Plasma renin and total renin were measured by immunoradiometric assays. Genotyping was PCR-based. RESULTS: Plasma renin was increased in patients with nephropathy (median (range), 26.3 (5.2-243.3) vs 18.3 (4.2-373.5) microU/ml in the normoalbuminuric group, P<0.0001). Prorenin levels were elevated out of proportion to renin levels in nephropathic patients (789 (88-5481) vs 302 (36-2226) microU/ml, P<0.0001). Proliferative retinopathy had an additive effect on plasma prorenin, but not on renin. DN was associated with a BglI RFLP in the first intron of the renin gene (bb-genotype: n=106 vs 82 in DN and normoalbuminuric patients respectively, P=0.037), but not with three other polymorphisms in the renin gene. A trend for association of higher prorenin levels with the DN-associated allele of this renin polymorphism was observed in a subgroup of patients with DN (bb vs Bb+BB, P=0.07). CONCLUSIONS: The results indicate that in DN there is an increase in both renin and prorenin levels. A renin gene polymorphism may contribute weakly to DN. Although speculative, one of the renin gene alleles could lead to increased renin gene expression, leading to higher renin and prorenin levels. These may play a role in the pathogenesis of DN.

Nocturnal enuresis: a suggestion for a European treatment strategy.

The objective of this study was to review the published literature on aetiology and treatment of nocturnal enuresis, with the aim of providing a treatment strategy which is easy for the patient and their family to follow. Results from European studies conducted over the last 15 y were included in this review. It can be concluded from the results of these studies that enuresis is the cause and not the result of a psychiatric disorder. However, there is still considerable variation in success rates, from 28 to 90%. It is of vital importance that a caring approach from the doctor and a positive family and patient attitude are present for successful treatment. The first choice of treatment should be the one most acceptable to the family, e.g. alarm, desmopressin and combination treatment.

Urinary continence and erectile function after bladder neck sling suspension in male patients with spinal dysraphism.

OBJECTIVE: To assess the outcome of using sling suspensions combined with clean intermittent catheterization (CIC) in patients with spina bifida, of whom a third are incontinent through pelvic floor paralysis. PATIENTS AND METHODS: Between March 1992 and April 1997, 14 male patients (mean age at surgery 11.7 years, range 6.5-15.2) with spina bifida and neurogenic sphincter incontinence underwent a puboprostatic sling suspension as a primary treatment. The procedure, via an abdominoperineal approach, consists of suspending the bladder neck by placing a simple U-shaped rectus abdominus fascial sling. The perineal approach is used to develop the plane between the rectum and Denonvillier's fascia, and to prepare the passage of the sling alongside the prostate. Apart from the sling procedure, eight of the 14 patients underwent autoaugmentation of the bladder and two underwent ileocystoplasty during the same operation. All patients used CIC daily. Erectile function was assessed by reports from the patients and their parents, and continence by report and urodynamic studies. RESULTS: Of the 14 patients, 13 achieved urinary continence with no additional procedures; one required a subsequent submucosal injection at the suspension site with silicone particles in povidone (Macroplastique(R)) to become continent. Two patients reported slight leakage at night. Before surgery, all but one patient reported having spontaneous or mechanically manipulated erections; none had erections on psychological stimulation. After surgery, erectile function was preserved in 13 of the 14 patients; in one there were problems establishing the right dissection plane between the rectum and prostate, but spontaneous erections returned a year after surgery. CONCLUSION: In males, the abdominoperineal puboprostatic sling suspension using rectus abdominis fascia appears to be a successful treatment for sphincter incontinence in patients with spina bifida, and safely maintains erectile function.

Anomalies of the external urethral meatus in girls with non-neurogenic bladder sphincter dysfunction.

OBJECTIVE: To investigate in a prospective study the clinical and urodynamic characteristics associated with the correlation previously reported between non-neuropathic bladder sphincter dysfunction and minimal meatal deformities in girls. PATIENTS AND METHODS: From January 1995 to June 1996 all girls referred for urodynamics to investigate non-neuropathic bladder sphincter dysfunction were examined for meatal anomalies. Two types of meatal anomalies were recognized, i.e. hypospadias, in which the urethral meatus is displaced dorsally and meatal web or covered hypospadias, in which there is a mucosal web on the dorsal side of the urethral meatus that deflects the urinary stream anteriorly. The girls presenting with minimal meatal deformities were compared with those presenting a normal meatal configuration for their history and video-urodynamic features. RESULTS: During the study, 288 girls were referred for video-urodynamics; 88 presented with meatal anomalies (24 hypospadias and 64 covered hypospadias) and comprised the study group; all other girls were considered as the control group. Incontinence during the day was more frequent in the study group (56%) than in the control group (34%) (P=0.003). Nocturnal enuresis was more frequent in the control group (87%) than in the study group (68%, P=0.006). Urge was more frequent in the study group (80%) than in the control group (65%, P=0.02), as was anterior deflection of the urinary stream (voiding over the toilet rim), in 48% and 4.5%, respectively (P<0.001). On video-urodynamics, dysfunctional voiding (detrusor sphincter dyscoordination during voiding) was more frequent in the study group (59%) than in the control group (38%, P=0.009), and vaginal voiding was more frequent in the study group (40%) than in the control group (11.5%, P<0.001). CONCLUSION: Girls presenting with meatal anomalies have more severe dysfunction, as estimated by urodynamics. Although the natural history of these anomalies and the incidence in the normal population is not known, it is thought that there is an aetiological correlation between the functional voiding disorders and the meatal anomaly. Surgical treatment to correct the anomalies is proposed.