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Sökning: WFRF:(Holmdahl Gundela)

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1.
  • Al-Mashhadi, Ammar Nadhom Farman (författare)
  • High Blood Pressure in Children with Hydronephrosis
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The most common cause of secondary hypertension is intrinsic renal disease, but little is known about the influence of hydronephrosis on blood pressure. In this thesis, the risk of development of hypertension in children with hydronephrosis was studied.Experimental and clinical studies were combined in order to investigate the risk of developing elevated blood pressure following conservative treatment of hydronephrosis, and to further explore underlying mechanisms. We started with a clinical study in children (study I), which in agreement with previous experimental studies, showed that blood pressure was lowered by surgical management of hydronephrosis. In parallel, an experimental study was conducted (study II) to investigate the involvement of renal sympathetic nerve activity in development of hypertension following induction of hydronephrosis caused by pelvo-ureteric junction obstruction. Renal denervation of the obstructed kidney attenuated hypertension and restored the renal excretion pattern, effects that were associated with reduced activity of both renal NADPH oxidase derived oxidative stress and components of the renin-angiotensin-aldosterone system.Based on the findings in studies I and II, we continued our studies in children with hydronephrosis, and including two control groups as comparisons with the hydronephrotic group (study III). In the same study, we further investigated potential mechanism(s) of hypertension by analyzing markers of oxidative stress and nitric oxide homeostasis in both urine and blood samples. We demonstrated increased arterial pressure and oxidative stress in children with hydronephrosis compared with healthy controls, which was restored to normal levels by surgical correction of the obstruction. Finally, in a retrospective cohort study, blood pressure of adult patients undergoing surgical management of hydronephrosis due to pelvo-ureteric junction obstruction was assessed (study IV). Similar to that demonstrated in the pediatric hydronephrotic population, blood pressure was significantly reduced by relief of the obstruction. In addition, blood pressure was increased again if the hydronephrosis recurred, and was reduced again following re-operation.It is concluded that conservative management of hydronephrosis in children is associated with a risk for development of high blood pressure, which can be reduced or even normalized by relief of the obstruction. The mechanism(s), at least in part, is coupled to increased oxidative stress.
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3.
  • Andersson, Marie, 1977, et al. (författare)
  • Normalized Urinary Flow at Puberty after Tubularized Incised Plate Urethroplasty of Hypospadias in Childhood.
  • 2015
  • Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 194:5, s. 1407-1413
  • Tidskriftsartikel (refereegranskat)abstract
    • An obstructive urinary flow pattern is frequently seen after tubularized incised plate urethroplasty for hypospadias. However, the significance of this finding has not been determined and long-term results are few. We describe postoperative long-term uroflowmetry results after puberty in males who underwent tubularized incised plate urethroplasty in childhood.
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5.
  • Andersson, Marie, 1977, et al. (författare)
  • Urological results and patient satisfaction in adolescents after surgery for proximal hypospadias in childhood
  • 2020
  • Ingår i: Journal of Pediatric Urology. - : Elsevier BV. - 1477-5131 .- 1873-4898. ; 16:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Proximal hypospadias repair is associated with a considerable complication risk. Long-term follow-up is required to present realistic expectations in pre-operative counseling. Objective: To investigate adolescents after childhood surgery for proximal hypospadias in a prospective cohort study describing the urological outcome, complication rates and patient satisfaction with penile appearance. Study design: 39 adolescents ≥14 years with penoscrotal to perineal hypospadias and primary urethroplasty (tubularized incised plate (TIP), preputial flap as Onlay or tubularized (Duckett)) from 1996 to 2005 at a single center were evaluated. The clinical assessment, at Md 16.5 years (14–25), included voiding history, genital examination including the Hypospadias Objective Scoring Evaluation (HOSE), uroflowmetry plus chart data from previous urinary flows and evaluation of patient satisfaction using the Penile Perception Score (PPS). Results: Twenty-nine patients with penoscrotal and 10 with scrotal/perineal hypospadias underwent surgery with TIP (N = 14), Onlay (N = 14) and Duckett (N = 11). Uroflows improved significantly compared with prepubertal maximal flows. Impaired flow rate (<10 mL/s) was found in 14% (5/36). Fifty-one percent (20/39) required reoperations, 29% (4/14) of TIP, 50% (7/14) of Onlay and 82% (9/11) of Duckett (p = 0.0062). Median penile length in adolescence was 8.7 cm (4.0–11.0). Forty-four percent (12/27) of patients were dissatisfied with penile length. Patients were ‘satisfied’ or ‘very satisfied’ with meatal position and shape despite HOSE for meatal position being 11% (4/38) distal, 76% (29/38) proximal glanular and 13% (5/38) coronal. TIP patients had more curvature at puberty than Duckett (p = 0.0062). Patients that had a decurvature procedure had shorter penile length (p = 0.019). Discussion: A high complication rate is previously described, predominantly within the first years. Our study shows 50% of reoperations were performed after >3 years, illustrating the need for long-term follow-up. Patient satisfaction with a deviant meatal position is rarely reported [1,2]. Our results support a conservative approach to an asymptomatic retracted meatus. Limitations of this descriptive study are the non-comparable groups and the retrospective data for correlation, impeding evaluation of prognostic outcome-factors. The shorter penile length found in patients after plication, and increased curvature after TIP, is therefore merely descriptive. However, the findings are in line with earlier publications suggesting limited use of TIP, and plication (recommending ventral lengthening instead) to avoid penile shortening and curvature in these cases [3–5]. Conclusions: The urological long-term outcome after proximal hypospadias repair is good, although late reoperations are common. In adolescence, patients were dissatisfied with the short penile length but satisfied with meatal position, indicating that in proximal hypospadias, preserving penile length and correcting curvature are prioritized over a distal meatus. [Table presented] © 2020 The Author(s)
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6.
  • Arkani, Samara, et al. (författare)
  • Evaluation of the ISL1 gene in the pathogenesis of bladder exstrophy in a Swedish cohort
  • 2018
  • Ingår i: Human genome variation. - : Springer Nature. - 2054-345X. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Bladder exstrophy is a congenital closure defect of the urinary bladder with a profound effect on morbidity. Although the malformation is usually sporadic, a genetic background is supported by an increased recurrence risk in relatives, higher concordance rates in monozygotic twins and several associated chromosomal aberrations. Recently, the ISL1 gene was presented as a candidate gene for bladder exstrophy and epispadias complex (BEEC) development in two different studies. In our study, we screened for genetic variants in the ISL1 gene in DNA from 125 Swedish patients using Sanger sequencing and array-CGH analysis. In addition, we evaluated ISL1 expression in RNA of human bladder during embryonic and fetal weeks 5–10 relative to that in lung tissue (week 9). In total, 21 single-nucleotide variants were identified, including a potentially novel missense variant, c.137C>G p.(Ala46Gly), substituting a conserved amino acid. This variant was inherited from an unaffected mother. No structural variants were identified. RNA sequencing revealed ISL1 mRNA expression during the critical time frame of human bladder development. In conclusion, we did not detect any known or likely pathogenic variants in the ISL1 gene in 125 Swedish BEEC patients, indicating that variation in the ISL1 gene is not a common genetic mechanism of BEEC development in the Swedish population.
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7.
  • Borg, Helena, et al. (författare)
  • Four-hour voiding observations detect neurogenic lower urinary tract dysfunction in neonates with anorectal malformation
  • 2021
  • Ingår i: Journal of Pediatric Urology. - : Elsevier BV. - 1477-5131. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Neurogenic lower urinary tract dysfunction (LUTD) has been reported in 20–50% of children with anorectal malformations (ARM). As neurogenic LUTD represents an inherent risk of renal deterioration and urinary tract infections, an early diagnosis is important. The gold standard for evaluating neurogenic LUTD involves invasive urodynamic testing but a useful addition should be an easy-to-perform, non-invasive method of screening. Objective: In this study, we evaluate non-invasive 4 h voiding observations as a screening method for neurogenic LUTD in ARM children. Study design: Thirty-four patients with ARM, excluding those with perineal fistulas, were evaluated using both 4 h voiding observation and urodynamic testing before and after posterior sagittal anorectoplasty (PSARP) at median ages of 0.3 and 1.1 years. In the urodynamic assessment, the gold standard for neurogenic LUTD, nine children received the diagnosis, eight innate and one post-surgery. Results: Five boys with a high urethral fistula and anomalies of the spinal cord had urodynamically diagnosed neurogenic LUTD, a dysfunction also identified in the 4 h voiding observations. The pattern was characterised both by an increase in the number of voiding and the number of interrupted voiding, urinary leakage and elevated residual urine (Figure). In three girls with a vestibular fistula and tethered cord, an urodynamic investigation identified suspected mild neurogenic LUTD. In the voiding observations, an abnormal voiding pattern was not as obvious in the girls as in the five males. One girl with cloaca showed signs of postsurgical denervation damage, which was easily identified in the 4 h voiding observations (high capacity and elevated residual urine). Discussion: In the present study, gender differences in the severity of dysfunction reflected in the free voiding pattern in infants with ARM and neurogenic LUTD is probably the result of the different underlying causes of neurogenic LUTD in boys and girls. Boys with the condition have a congenital malformation of the caudal part of the spinal cord and girls a tethering of the cord. The most obvious limitation of the study was the low number of patients. Despite this, we consider the results worth reporting, since we found that results in the free voiding observations effectively confirmed what was established in the urodynamic investigations. Conclusion: In pre-PSARP patients, 4 h voiding observations can be used to screen for severe neurogenic LUTD requiring attention and treatment. When post-surgical denervation is suspected, the voiding observation is also a good method for indicating the diagnosis.[Formula presented] © 2020 Journal of Pediatric Urology Company
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8.
  • Borg, Helena, et al. (författare)
  • Impact of spinal cord malformation on bladder function in children with anorectal malformations.
  • 2009
  • Ingår i: Journal of pediatric surgery. - : Elsevier BV. - 1531-5037 .- 0022-3468. ; 44:9, s. 1778-85
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Risk factors for the presence of neurogenic bladder dysfunction (NBD) in children born with high anorectal malformations (ARMs), were investigated, to identify the need for urodynamics in these patients. MATERIAL AND METHODS: The study included 37 patients with high ARMs (21 boys and 16 girls). Bladder function was evaluated with urodynamics both before and after anorectoplasty (posterior sagittal anorectoplasty [PSARP]). All patients were investigated with spinal radiograph. Spinal ultrasound was performed in the neonatal period, and magnetic resonance imaging was added in case of abnormal ultrasound or urodynamics and in case of cloacal malformation. RESULTS: In ARM patients with rectourethral and vestibular fistulas and cloacas, NBD was identified in 9 children (25%). The bladder dysfunction was innate in all cases except in one girl with cloaca, indicating that the risk of iatrogenic denervation seems minimal using the PSARP technique. All children with innate NBD had a spinal cord malformation either as spinal cord regression or tethering with or without a lipoma. Concerning vertebral status, almost all children with NBD had partial sacral agenesis. Abnormal perineal appearance was highly correlated to NBD in boys, especially in those with a spinal cord regression malformation. Innate NBD was not found in any child with normal spinal cord. CONCLUSION: From these results, we suggest that spinal ultrasound and perineal inspection are used as screening procedures for NBD in children with ARM. Urodynamic investigation is recommended only when spinal cord anomalies or other signs indicative of NBD are present. In case of spinal cord malformation, repeated urodynamics during follow-up is mandatory because of the risk for developing tethered cord syndrome.
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9.
  • Borg, Helena, et al. (författare)
  • Longitudinal study of bowel function in children with anorectal malformations.
  • 2013
  • Ingår i: Journal of pediatric surgery. - : Elsevier BV. - 1531-5037 .- 0022-3468. ; 48:3, s. 597-606
  • Tidskriftsartikel (refereegranskat)abstract
    • Longitudinal follow-up of changes in bowel function in children with anorectal malformations (ARMs) with or without spinal cord pathology and neurogenic bladder dysfunction (NBD) as they grow. Another purpose was to identify predictors influencing bowel functional outcome.
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10.
  • Brandström, Per, 1959, et al. (författare)
  • The Swedish Reflux Trial in Children: I. Study Design and Study Population Characteristics
  • 2010
  • Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 184:1, s. 274-279
  • Konferensbidrag (refereegranskat)abstract
    • Purpose: We compared the rates of febrile urinary tract infection, kidney damage and reflux resolution in children with vesicoureteral reflux treated in 3 ways, including antibiotic prophylaxis, endoscopic therapy and surveillance with antibiotics only for symptomatic urinary tract infection. Materials and Methods: Children 1 to younger than 2 years with grade reflux were recruited into this prospective, open, randomized, controlled, multi-center study and followed for 2 years after randomization. The main study end points were recurrent febrile urinary tract infection, renal status on dimercaptosuccinic acid scintigraphy and reflux status. Outcomes were analyzed by the intent to treat principle. Results: During a 6-year period 128 girls and 75 boys entered the study. In 96% of cases reflux was detected after urinary tract infection. The randomization procedure was successful and resulted in 3 groups matched for relevant factors. Recruitment was slower than anticipated but after patients were entered adherence to the protocol was good. Of the children 93% were followed for the intended 2 years without a treatment arm change. All except 2 patients completed 2-year followup scintigraphy. Conclusions: Recruitment was difficult but a substantial number of children were entered and randomly assigned to 3 groups with similar basic characteristics. Good adherence to the protocol made it possible to address the central study questions.
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12.
  • Dellenmark-Blom, Michaela, 1983, et al. (författare)
  • Health-related quality of life among children, adolescents, and adults with bladder exstrophy–epispadias complex: a systematic review of the literature and recommendations for future research
  • 2019
  • Ingår i: Quality of Life Research. - : Springer Science and Business Media LLC. - 0962-9343 .- 1573-2649. ; 28:6, s. 1389-1412
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Bladder exstrophy–epispadias complex (BEEC) is a rare spectrum of genitourinary malformations. Children risk long-term urinary and genital dysfunctions. To achieve a comprehensive understanding, this study aimed to review the literature on generic and disease-specific health-related quality of life (HRQOL) in BEEC patients, and methodologies used. Methods: A literature search was conducted in Pubmed/CINAHL/Embase/PsycINFO/Cochrane, from inception to May 2018. A meta-analysis of HRQOL in BEEC patients compared to healthy references was performed. Results: Twenty-one articles (published 1994–2018), describing HRQOL of children and adolescents (n = 5) and adults only (n = 5), or integrated age populations (n = 11), were identified (median sample size 24, loss to follow-up 43%, response rate 84%). Overall HRQOL was reduced in BEEC patients compared to healthy references in 4/4 studies. Impaired physical or general health in BEEC patients has been described in 9 articles, diminished mental health in 11, restricted social health in 10, and sexual health/functioning or body perception impairments in 13 articles. Urinary incontinence was the most common factor related to worse HRQOL (12 studies). In six studies, HRQOL was better than healthy norms. In eligible studies (n = 5), the pooled estimate of the effect of BEEC indicated worse HRQOL for children and adults (0 > effect sizes < 0.5). Thirty-six HRQOL assessments were used, none developed and validated for BEEC. Conclusions: HRQOL in BEEC patients may be negatively impacted, particularly considering mental and social HRQOL. Sexual health/functioning or body perception impairments may be present in adolescents and adults. However, HRQOL is heterogeneously assessed and subsequent findings are differently reported. Additional research is warranted and can be improved. © 2019, Springer Nature Switzerland AG.
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13.
  • Draaken, Markus, et al. (författare)
  • Classic Bladder Exstrophy: Frequent 22q11.21 Duplications and Definition of a 414 kb Phenocritical Region
  • 2014
  • Ingår i: Birth Defects Research. Part A: Clinical and Molecular Teratology. - : Wiley. - 1542-0760 .- 1542-0752. ; 100:6, s. 512-517
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Classic bladder exstrophy (CBE) is the most common form of the bladder exstrophy and epispadias complex. Previously, we and others have identified four patients with a duplication of 22q11.21 among a total of 96 unrelated CBE patients. Methods: Here, we investigated whether this chromosomal aberration was commonly associated with CBE/bladder exstrophy and epispadias complex in an extended case-control sample. Multiplex ligation-dependent probe amplification and microarray-based analysis were used to identify 22q11.21 duplications in 244 unrelated bladder exstrophy and epispadias complex patients (including 217 CBE patients) and 665 healthy controls. Results: New duplications of variable size were identified in four CBE patients and one control. Pooling of our previous and present data (eight duplications in 313 CBE patients) yielded a combined odds ratio of 31.86 (95% confidence interval, 4.24-1407.97). Array-based sequence capture and high-throughput targeted re-sequencing established that all breakpoints resided within the low-copy repeats 22A to 22D. Comparison of the eight duplications revealed a 414 kb phenocritical region harboring 12 validated RefSeq genes. Characterization of these 12 candidate genes through whole-mount in situ hybridization of mouse embryos at embryonic day 9.5 suggested that CRKL, THAP7, and LZTR1 are CBE candidate genes. Conclusion: Our data suggest that duplication of 22q11.21 increases CBE risk and implicate a phenocritical region in disease formation. (C) 2014 Wiley Periodicals, Inc.
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15.
  • Duong, Thi Hoa, et al. (författare)
  • Micturition pattern in young boys with posterior urethral valves—A pilot study in small boys who are potty-trained from infancy
  • 2013
  • Ingår i: Open Journal of Pediatrics. - : Scientific Research Publishing, Inc.. - 2160-8741 .- 2160-8776. ; 03, s. 358-363
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: To investigate if potty training from infancy can affect bladder dysfunction in boys with posterior urethral valves (PUV). Subjects and Meth- ods: The voiding pattern and emptying ability were followed using the 4-hour voiding observation method in 17 Vietnamese boys with PUV aged 3 months to 4 years who had been potty-trained from infancy. This group was compared with a group of healthy Viet- namese boys. Results: In the boys with PUV, the bladder volume increased according to age, and in- terrupted voiding was rare. However, when compar- ing boys with PUV with healthy boys, a significant difference was noted with more frequent voidings and lower voided volumes in the age group 0 - 1 year (P < 0.001). Despite the minimum amount of residual urine, average 8 ml or less in the boys with PUV, the age groups 1 - 2 and 2 - 4 years had significantly higher residual volumes compared with those of the healthy boys (P < 0.001). Conclusion: The findings from the 4-hour voiding observation showed few signs of dysfunctional bladder in the Vietnamese boys with PUV, including residual urine, even if there were signs of dysfunction compared with the healthy Viet- namese boys. Potty training from infancy could favor early bladder rehabilitation in boys with PUV.
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16.
  • Duong, Thi Hoa, et al. (författare)
  • Urinary bladder control during the first 3years of life in healthy children in Vietnam - A comparison study with Swedish children.
  • 2013
  • Ingår i: Journal of Pediatric Urology. - : Elsevier BV. - 1477-5131 .- 1873-4898. ; 9:6, s. 700-706
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To study outcomes of early potty training in a population of healthy children with a tradition of early potty training and to compare these findings with a group of children to whom potty training was applied later. SUBJECTS AND METHODS: Mothers and their 47 healthy children in Vietnam participated in this longitudinal study. The voiding pattern and emptying ability were followed by the 4-hvoiding observation method from 3 months to 3 years of age. A comparison is made with a group of 57 Swedish children investigated in a similar manner. RESULTS: In the group of Vietnamese children, 89% were on daily potty training at the age of 6 months. At the age of 24 months, potty training was complete for 98%. In the Swedish group, just a few (5%) had started daily potty training by the age of 24 months (p<0.001). The Vietnamese group had fewer voidings and lower voided volumes than the Swedish group. In the Vietnamese children, bladder emptying could be regarded as having been completed, with no residual urine at 9 months, compared with the Swedish group, which first showed complete emptying at the age of 36 months. CONCLUSION: Potty training performed daily affects the emptying ability positively. In the Vietnamese group, no residual urine was found at the age of 9 months. These results differ significantly from those of the group of Swedish children.
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17.
  • Falhammar, H, et al. (författare)
  • Fractures and Bone Mineral Density in Adult Women with 21-Hydroxylase Deficiency.
  • 2007
  • Ingår i: J Endocrinol Metab. - : The Endocrine Society. - 0021-972X .- 1945-7197.
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Patients with classic congenital adrenal hyperplasia (CAH) receive lifelong, often supraphysiological, glucocorticoid therapy. Pharmacologic doses of glucocorticoids are an established risk factor for osteoporosis. Objectives: To evaluate bone mineral density (BMD), fracture prevalence and markers of bone metabolism in adult females with CAH. Design: This was a cross-sectional observational study. Setting: Tertiary care referral centers. Participants: We studied 61 women, aged 18-63 years, with genetically verified CAH due to 21-hydroxylase deficiency. They were patients with salt-wasting (n = 27), simple virilising (n = 28) and non-classic 21-hydroxylase deficiency (n = 6). Sixty-one age-matched women were controls. Main outcome measures: History of fractures was recorded. Total body, lumbar spine and femoral neck BMD were measured by dual-energy X-ray absorptiometry. The WHO criteria for osteopenia and osteoporosis were used. Serum marker of bone resorption, beta-C telopeptide (CTX) was studied. Results: The mean glucocorticoid dose in hydrocortisone equivalents was 16.9 +/- 0.9 mg/m(2). Patients had lower BMD than controls at all measured sites (P < 0.001). In patients < 30 years old 48% were osteopenic vs 12% in controls (P < 0.009). In patients >/= 30 years old 73% were osteopenic or osteoporotic vs 21% in controls (P < 0.001). BMD was similar in the two classic forms and had no obvious relationship to genotypes. CTX was decreased in older patients. More fractures were reported in patients than controls (P < 0.001). The number of vertebrae and wrist fractures almost reached significance (P = 0.058). Conclusion: Women with CAH have low BMD and increased fracture risk. BMD should be monitored, adequate prophylaxis and treatment instituted, and glucocorticoid doses optimized from puberty.
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18.
  • Falhammar, Henrik, et al. (författare)
  • Increased liver enzymes in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
  • 2009
  • Ingår i: Endocrine journal. - 1348-4540. ; 56:4, s. 601-8
  • Tidskriftsartikel (refereegranskat)abstract
    • The aims were assessing liver function tests (LFT) in women with congenital adrenal hyperplasia (CAH) on glucocorticoids. Sixty-one women with genetically verified CAH due to 21-hydroxylase deficiency, aged 18-63 years were compared to 61 controls. Serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT), anthropometry and fat mass (dual energy X-ray absorptiometry) were measured. ALT and GGT were higher in the entire patient group (p=0.01 and 0.002); AST, GGT and ALP in patients > or =30 years (p=0.007-0.045); all LFT in salt-wasting (p<0.001-0.042); GGT in simple virilizing (p=0.008); ALT, GGT and ALP in Null/Null genotype (p=0.018-0.040); ALT and GGT in I2splice genotype (p<0.001 and 0.011). Using a recently proposed cut-off level for ALT (>0.317 microkat/L), 54% of patients vs 23% of controls had elevated levels (p=0.028). In patients, GGT and ALP correlated with waist circumference and with total body and trunk fat (r=0.274-0.406, p=0.001-0.043). However, ALT, GGT and ALP were increased even in non-obese patients (waist circumference < or =88 cm and body mass index <30 kg/m(2)) (p=0.012-0.045) mainly attributed to the patients > or =30 years who also demonstrated elevated insulin levels and HOMA-indices. In conclusion, compared with controls, women with CAH have higher LFT, in particular patients > or =30 years and those with severe forms, probably reflecting a higher lifetime glucocorticoid exposure. LFT were positively correlated to measurements of body fat. These women might have increased frequency of NAFLD. The finding of higher LFT also in non-obese patients suggests that not only central obesity but also glucocorticoids per se may influence.
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19.
  • Falhammar, Henrik, et al. (författare)
  • Metabolic profile and body composition in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
  • 2007
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:1, s. 110-6
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: The chronic, often supraphysiological glucocorticoid doses used in congenital adrenal hyperplasia (CAH) might increase morbidity in cardiovascular disease and diabetes. OBJECTIVE: Our aim was to assess risk factors for cardiovascular disease and diabetes in CAH women. SUBJECTS, METHODS, AND DESIGN: We compared 61 women, 18-63 yr, with CAH due to 21-hydroxylase deficiency with 61 age- and sex- matched controls. Twenty-seven were younger than 30 yr, and 34 were 30 yr or older. Anthropometry, fat and lean mass measured by dual-energy x-ray absorptiometry, serum lipids, insulin, and adrenocortical steroids were studied. MAIN OUTCOME MEASURE: Body composition and cardiovascular risk factors were the main outcome measures. RESULTS: Younger patients and controls had similar waist to hip ratio, lean and fat mass, and insulin. Older patients had higher waist to hip ratio, lean mass, and insulin than controls. Fat mass was similar to controls but higher than in younger patients. Lipid profiles were slightly more favorable in older patients than controls. Gestational diabetes was more common in patients (21% of pregnancies vs. 0, P < 0.026). Few older patients had hypertension, cardiovascular disease, or diabetes. Despite moderate glucocorticoid doses, most patients had suppressed androgens. CONCLUSIONS: No clear evidence of unfavorable cardiovascular risk factors were found. Increased fat mass and higher insulin levels were, however, found in patients older than 30 yr. High frequency of gestational diabetes is a risk marker for future diabetes. Lifelong follow-up, lifestyle modifications, and attempts to adjust and reduce the glucocorticoid doses seem important.
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20.
  • Fall, Magnus, 1941, et al. (författare)
  • Uro-tarmterapi : Kapitel 2
  • 2019
  • Ingår i: Uro-tarmterapi. Anna-Lena Hellström, Birgitta Lindehall (red.). - Lund : Studentlitteratur. - 9789144122588 ; , s. 21-43
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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21.
  • Frisén, Lars, et al. (författare)
  • Gender role behavior, sexuality, and psychosocial adaptation in women with congenital adrenal hyperplasia due to CYP21A2 deficiency
  • 2009
  • Ingår i: J Clin Endocrinol Metab. - : The Endocrine Society. ; 94:9, s. 3432-9
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Gender-atypical behavior has been described in young girls as well as in women with congenital adrenal hyperplasia (CAH) due to a CYP21A2 deficiency. OBJECTIVE: The aim of the study was to assess health-related, psychosexual, and psychosocial parameters and correlate the results to CYP21A2 genotype. DESIGN AND PARTICIPANTS: Sixty-two Swedish women with CAH and age-matched controls completed a 120-item questionnaire and a validated quality of life instrument [psychological general well-being (PGWB) formula] to identify psychosexual and psychosocial parameters. The patients were divided into four CYP21A2 genotype groups. RESULTS: The women with CAH held more male-dominant occupations (30%) compared to controls (13%) (P = 0.04), especially those in the null genotype group (55%) (P = 0.006). They also reported a greater interest in rough sports (74%) compared to controls (50%) (P = 0.007). Eight women with CAH (14%) reported a prime interest in motor vehicles, compared to none of the controls (P = 0.002). Non-heterosexual orientation was reported by 19% of women with CAH (P = 0.005), 50% in the null genotype group (P = 0.0001), 30% in I2 splice (NS), and 5% in I172N (NS). PGWB total score did not differ between patients and controls. CONCLUSION: We identified increased gender-atypical behavior in women with CAH that could be correlated to the CYP21A2 genotype. This speaks in favor of dose-dependent effects of prenatal androgens on the development of higher brain functions. The impact of the disease on upbringing and interpersonal relationships did not correlate with disease severity, indicating that other factors, such as coping strategies, are important for psychosocial adaptation. This illustrates the need for psychological support to parents and patients.
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23.
  • Hellström, Anna-Lena, 1946, et al. (författare)
  • Feeling good in daily life: from the point of view of boys with posterior urethral valves
  • 2006
  • Ingår i: J Urol. - 0022-5347. ; 176:4 Pt 2, s. 1742-6
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: We determined what is important to feel good in daily life when living with a long-term illness that requires daily treatment routines. MATERIALS AND METHODS: Seven boys between 6 and 16 years old who were born with posterior urethral valves narrated their experiences with daily life. They were on clean intermittent catheterization, had impaired renal function and 2 had undergone transplantation. RESULTS: Being involved in decisions about themselves was important, as was having their own doctor and nurse. Friends were important. Clean intermittent catheterization was something that worried them in relation to friends and made them feel uncertain about how they would react to it. The boys accepted the catheterization procedure as something that had to be done but they needed strategies to be able to comply. A single event, such as no available toilet, was enough to interrupt treatment. CONCLUSIONS: In these boys prescribed treatment was a surprisingly small part of their lives. The clean intermittent catheterization routine was sometimes experienced as an obstacle in company with friends. The new challenge might be to achieve compliance with the treatment routine in daily life in a long-term perspective.
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24.
  • Hjälmås, Kelm, 1933, et al. (författare)
  • Pediatrisk urologi
  • 2005
  • Ingår i: Urologi. - : Studentlitteratur. - 9144028741
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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25.
  • Holmdahl, Gundela, 1956, et al. (författare)
  • Boys with posterior urethral valves: outcome concerning renal function, bladder function and paternity at ages 31 to 44 years
  • 2005
  • Ingår i: J Urol. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347. ; 174:3
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: The short-term prognosis for boys with posterior urethral valves (PUV) has improved in recent decades, but the long-term prognosis in terms of renal and bladder function and fertility is still a matter of great concern. This study is a followup of boys with PUV and dilated upper urinary tract treated in 1956 to 1970 at the Children's Hospital in Goteborg, Sweden. MATERIALS AND METHODS: The records of 54 boys treated for PUV were reviewed. Of 27 boys with PUV and upper urinary tract dilation, 5 boys (18%) died at an early age and 3 boys were lost to followup during adolescence, leaving 19 to be included in the followup. They all answered a questionnaire about renal and bladder function and paternity. RESULTS: Of the 19 men 32% were uremic, 21% had moderate renal failure and 47% had not been checked since adolescence. There were signs of bladder dysfunction in 40% and all these subjects had bladder symptoms suggesting detrusor weakness as the cause. All the men were continent. The ability to father children was dependent on whether or not the man was uremic. CONCLUSIONS: This long-term followup study emphasizes the importance of checking renal and bladder function throughout life in men born with PUV. Increasing attention to bladder dysfunction and its early treatment could probably improve the long-term prognosis.
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26.
  • Holmdahl, Gundela, 1956, et al. (författare)
  • Does treatment with clean intermittent catheterization in boys with posterior urethral valves affect bladder and renal function?
  • 2003
  • Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 170:4 Pt 2
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: In boys with resected posterior urethral valves (PUV) deterioration of renal function is seen during childhood and adolescence, which may partly be caused by bladder dysfunction. We present data on renal and bladder function initially and at followup of boys with PUV in whom the bladder dysfunction has been treated since infancy. MATERIALS AND METHODS: The study included 35 boys with PUV. Bladder regimen, including early toilet training from the age of 1.5 years and detrusor relaxant drugs for the treatment of incontinence from ages 4 to 6 years, was introduced to all patients. A total of 19 boys were started on clean intermittent catheterization (CIC) at a median age of 8 months due to pronounced bladder dysfunction with poor emptying, unsafe pressure levels, high grade reflux and renal impairment. RESULTS: No serious complications of CIC have been seen during followup. Of the 19 boys 2 stopped performing CIC due to noncompliance of the parents at 1 and 3 years, respectively. Initial renal function, measured as median glomerular filtration rate (GFR) in percent of expected for age, was 60% in the CIC group and 90% in the nonCIC group. At followup at a median age of 8 years the CIC group (n = 14, 3 transplanted boys excluded) had an increase in median differential GFR (difference between followup and initial GFR) of 7% (p <0.01), which was similar increase to that of the nonCIC group. In the 2 boys who stopped performing CIC renal function deteriorated with a median differential GFR of -24%. In the CIC group detrusor instability decreased. Poor compliance was seen in 6 of the 19 boys initially and only one remained poorly compliant. In 1 of the boys who stopped performing catheterization a low compliant bladder developed. In all of the other cases bladder capacity increased more than expected for age. CONCLUSIONS: The results suggest that treatment of bladder dysfunction in boys with PUV can counteract the deterioration in renal function seen during childhood but the number of patients in our study is limited.
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27.
  • Holmdahl, Gundela, 1956, et al. (författare)
  • Four-hour voiding observation in healthy infants.
  • 1996
  • Ingår i: The Journal of urology. - 0022-5347. ; 156:5, s. 1809-12
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: We present the 4-hour voiding observation as a method for basic assessment of bladder function in infants and nontoilet trained children. MATERIALS AND METHODS: Voiding pattern, including number of voidings, voided volume, bladder capacity and residual urine for 4 hours, was determined noninvasively in 43 healthy infants. RESULTS: The infants voided an average of 1 time per hour but with great variability. Bladder capacity increased with age according to the formula, 38 + 2.5 x age (months). Mean residual urine plus or minus standard deviation was 4.6 +/- 3.0 ml. In all infants residual volume was less than 5 ml. at least once during observation. CONCLUSIONS: The 4-hour voiding observation is an easy noninvasive method of characterizing the voiding pattern, focusing especially on emptying difficulties, in infants and nontoilet trained children.
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28.
  • Holmdahl, Gundela, 1956, et al. (författare)
  • Four-hour voiding observation in young boys with posterior urethral valves.
  • 1998
  • Ingår i: The Journal of urology. - 0022-5347. ; 160:4, s. 1477-81
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: We evaluated 4-hour voiding observation as a method of basic assessment of bladder dysfunction in young boys with posterior urethral valves. MATERIALS AND METHODS: Voiding pattern, including number of voids, voided and residual urine volume, and bladder capacity, was determined noninvasively in 24 boys younger than 4 years with posterior urethral valves and compared to that of healthy age matched controls. Results were then compared to those of standard cystometry. RESULTS: The number of voids was higher, voided volume was smaller and residual urine volume was higher in the posterior urethral valve group. There was no difference in voiding pattern before and after removal of the anatomical obstruction. Voided and residual urine volume, and bladder capacity were higher on standard cystometry than on voiding observation. CONCLUSIONS: Four-hour voiding observation is an easy noninvasive method that focuses on emptying difficulties and clearly detects differences in voiding patterns between boys with posterior urethral valves and healthy, nontoilet trained children. We recommend the method as a complement to standard cystometry for the diagnosis and followup of bladder dysfunction in young boys with posterior urethral valves to identify the need for treatment.
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29.
  • Holmdahl, Gundela, 1956, et al. (författare)
  • Health-Related Quality of Life in Patients with the Bladder Exstrophy-Epispadias Complex and Relationship to Incontinence and Sexual Factors: A Review of the Recent Literature.
  • 2020
  • Ingår i: European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie. - : Georg Thieme Verlag KG. - 1439-359X. ; 30:3, s. 251-260
  • Forskningsöversikt (refereegranskat)abstract
    • The bladder exstrophy-epispadia complex (BEEC) includes malformations with midline closing defects of the lower abdomen and external genitalia. Long-term consequences with urinary incontinence and sexual dysfunction, in spite of multiple surgical interventions, are common and expected to affect the patient's health-related quality of life (HRQOL). The extent and the predictive factors are, however, not known. New patient-reported outcome research is emerging, but valid and reliable condition-specific HRQOL are still missing. The aim of this review is to summarize and discuss the latest published reports (2015-2019) on HRQOL in patients with the BEEC and its relationship to incontinence and sexual factors.
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30.
  • Holmdahl, Gundela, 1956, et al. (författare)
  • Hypospadias repair with tubularized incised plate. Is uroflowmetry necessary postoperatively?
  • 2006
  • Ingår i: Journal of pediatric urology. - : Elsevier BV. - 1873-4898 .- 1477-5131. ; 2:4, s. 304-7
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Hypospadias repair with tubularized incised plate urethroplasty (TIP) produces good cosmesis, but is reported to result in a change in urinary stream postoperatively, with an obstructive pattern. The aim of this retrospective study was to determine whether early uroflowmetry is a good method for diagnosing neourethral stricture. PATIENTS AND METHOD: In 126 boys, primary TIP repair was performed between 1999 and 2003. Uroflowmetry was performed in potty-trained boys 2 months' postoperatively (68 boys) and both 2 and 12 months (38 boys) after TIP. Boys with obstructed flow and/or clinical symptoms were calibrated in their neourethra. RESULTS: Forty-nine percent of the boys with distal hypospadias and 87% of the proximal cases had a flow rate of less than 10 ml/s at uroflowmetry 2 months after TIP, but only 12/126 boys (10%) were considered to have a neourethral stricture. There was a spontaneous increase in maximum flow rate between 2 and 12 months after TIP repair both in patients who had been calibrated and in boys in whom no intervention had been performed. CONCLUSION: Early uroflowmetry appears to be unnecessary, as the voiding history appears to be just as good at alerting a suspicion of urethral stricture after TIP repair. There is a spontaneous normalization of the urinary flow in boys after TIP repair, but the need for long-term follow up beyond puberty is great, especially in cases of proximal hypospadias.
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31.
  •  
32.
  • Holmdahl, Gundela, 1956, et al. (författare)
  • Self-catheterization during adolescence.
  • 2007
  • Ingår i: Scandinavian journal of urology and nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 41:3, s. 214-7
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: It has been suggested that clean intermittent catheterization (CIC) during the teenage years is associated with poor motivation to comply with the treatment, recurrent urinary tract infections and epididymitis. The aim of this study was to identify the main problems and complications associated with self-CIC in a group of adolescents with no overt neurological problems. MATERIAL AND METHODS: The medical records of 24 boys and girls aged >/=12 years on self-CIC with severe bladder dysfunction and intact perineal sensibility and motor function in the lower limbs were reviewed. The median age of the patients was 16.5 years (range 12-24 years) and they had been on CIC for a median of 11 years (range 2-16 years). RESULTS: No urethral damage was reported. Of the 11 patients (46%) who had good CIC routines, two had cystitis and none had epididymitis. Thirteen patients (54%) reported a poor CIC regimen at a median age of 11.5 years (range 9-16 years). In this group, 10 had recurrent cystitis, five had pyelonephritis, four had increasing creatinine levels and three of nine boys had epididymitis. CONCLUSIONS: One of the main problems associated with CIC during adolescence is poor compliance with the treatment. Epididymitis and recurrent urinary tract infections were seen more frequently in connection with poor CIC routines.
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33.
  • Holmdahl, Gundela, 1956, et al. (författare)
  • The Swedish Reflux Trial in Children: II. Vesicoureteral Reflux Outcome.
  • 2010
  • Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 184:1, s. 280-285
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: We compared reflux status in children with dilating vesicoureteral reflux treated in 3 groups, including low dose antibiotic prophylaxis, endoscopic therapy and a surveillance group on antibiotic treatment only for febrile urinary tract infection. MATERIALS AND METHODS: A total of 203 children 1 to younger than 2 years with grade III-IV reflux were recruited into this open, randomized, controlled trial. Endoscopic treatment was done with dextranomer/hyaluronic acid copolymer. The main end point was reflux status after 2 years. Data were analyzed by the intent to treat principle. RESULTS: Reflux status improved in all 3 treatment arms. Of patients in the prophylaxis, endoscopic and surveillance groups 39%, 71% and 47%, respectively, had reflux resolution or downgrading to grade I-II after 2 years. This was significantly more common in the endoscopic than in the prophylaxis and surveillance groups (p = 0.0002 and 0.0030, respectively). After 1 or 2 injections 86% of patients in the endoscopic group had no or grade I-II reflux but recurrent dilating reflux was seen in 20% after 2 years. CONCLUSIONS: Endoscopic treatment resulted in dilating reflux resolution or downgrading in most treated children. After 2 years endoscopic treatment results were significantly better than the spontaneous resolution rate or downgrading in the prophylaxis and surveillance groups. However, of concern is the common reappearance of dilating reflux after 2 years.
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34.
  •  
35.
  • Jenholt Nolbris, Margaretha, 1956, et al. (författare)
  • Development of a programme for web-based support for children – a participatory design in children and families with urinary tract disorders.
  • 2016
  • Ingår i: JSM Health Education and Primary Health Care. ; 1:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Children with urinary tract and bowel malformation often realize that they do not have the same body and genital appearance as their schoolmates. This sensitive matter affects their integrity, a private problem that not is discussed in public. It is a lack of prevention program, particularly developed in cooperation with the children. The goal with the present project was to get tools for support in daily live. The aim of the study was together with the children, family, hospital staff and researcher; develop a web-based support program to be used in home setting. The study was conducted between 2011and2015. A participatory design was employed following the approach in person centred care with a partnership between 22 children 3-7 years old, their families and the research group of 8 persons. The program was built on stories about two children, their actions in different situations and with images to support the stories. Open conversations were used for the data collection and data were analysed using qualitative content analysis. Steps of 8 themes were formed from the developing of the web-based program, which offered a user-friendly support in daily life for the children with long-term illnesses and family.
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36.
  • Korberg, Izabella Baranowska, et al. (författare)
  • WNT3 involvement in human bladder exstrophy and cloaca development in zebrafish
  • 2015
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:18, s. 5069-5078
  • Tidskriftsartikel (refereegranskat)abstract
    • Bladder exstrophy, a severe congenital urological malformation when a child is born with an open urinary bladder, is the most common form of bladder exstrophy-epispadias complex (BEEC) with an incidence of 1: 30,000 children of Caucasian descent. Recent studies suggest that WNT genes may contribute to the etiology of bladder exstrophy. Here, we evaluated WNT-pathway genes in 20 bladder exstrophy patients using massively parallel sequencing. In total 13 variants were identified in WNT3, WNT6, WNT7A, WNT8B, WNT10A, WNT11, WNT16, FZD5, LRP1 and LRP10 genes and predicted as potentially disease causing, of which seven variants were novel. One variant, identified in a patient with a de novo nonsynonymous substitution in WNT3 (p.Cys91Arg), was further evaluated in zebrafish. Knock down of wnt3 in zebrafish showed cloaca malformations, including disorganization of the cloaca epithelium and expansion of the cloaca lumen. Our study suggests that the function of the WNT3 p.Cys91Arg variant was altered, since RNA overexpression of mutant Wnt3 RNA does not result in embryonic lethality as seen with wild-type WNT3 mRNA. Finally, we also mutation screened the WNT3 gene further in 410 DNA samples from BEEC cases and identified one additional mutation c.638G> A (p.Gly213Asp), which was paternally inherited. In aggregate our data support the involvement of WNT-pathway genes in BEEC and suggest that WNT3 in itself is a rare cause of BEEC.
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37.
  • Lundin, Johanna, et al. (författare)
  • Further support linking the 22q11.2 microduplication to an increased risk of bladder exstrophy and highlighting LZTR1 as a candidate gene
  • 2019
  • Ingår i: Molecular Genetics and Genomic Medicine. - : Wiley. - 2324-9269. ; 7:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The bladder exstrophy-epispadias complex (BEEC) is a congenital malformation of the bladder and urethra. The underlying causes of this malformation are still largely unknown; however, aside from environment, genetics is thought to play an essential role. The recurrent 22q11.2 microduplication is the most persistently detected genetic aberration found in BEEC cases. Methods: We performed array comparative genomic hybridization (array-CGH) analysis of 76 Swedish BEEC patients. Statistical analysis was performed on current dataset pooled with previously published data on the 22q11.2 microduplication in BEEC patients. We performed massive parallel sequencing (MPS) of the 22q11.2 region in 20 BEEC patients without the 22q11.2 microduplication followed by functional studies. Results: We identified three additional cases with the 22q11.2 microduplication. Pooling data from this study with previously published reports showed a statistically significant enrichment of the 22q11.2 microduplication in BEEC patients (2.61% in cases vs. 0.08% in controls; OR = 32.6; p = 8.7 × 10−4). MPS of the 22q11.2 region in 20 BEEC patients without the 22q11.2 microduplication identified a novel variant in LZTR1 (p.Ser698Phe) in one patient. Functional evaluation of the LZTR1 p.Ser698Phe variant in live NIH 3T3 cells showed that the concentration and cytoplasmic mobility differ between the Lztr1wt and Lztr1mut, indicating a potential functional effect of the LZTR1mut. Conclusion: Our study further emphasizes the involvement of the 22q11.2 region in BEEC development and highlights LZTR1 as a candidate gene underlying the urogenital malformation.
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38.
  • Nordenskjöld, A., et al. (författare)
  • Copy number variants suggest different molecular pathways for the pathogenesis of bladder exstrophy
  • 2023
  • Ingår i: American Journal of Medical Genetics, Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 191:2, s. 378-390
  • Tidskriftsartikel (refereegranskat)abstract
    • Bladder exstrophy is a rare congenital malformation leaving the urinary bladder open in the midline of the abdomen at birth. There is a clear genetic background with chromosome aberrations, but so far, no consistent findings apart from 22q11-duplications detected in about 2%–3% of all patients. Some genes are implicated like the LZTR1, ISL1, CELSR3, and the WNT3 genes, but most are not explained molecularly. We have performed chromosomal microarray analysis on a cohort of 140 persons born with bladder exstrophy to look for submicroscopic chromosomal deletions and duplications. Pathogenic or possibly pathogenic microdeletions or duplications were found in 16 patients (11.4%) and further 9 with unknown significance. Two findings were in regions linked to known syndromes, two findings involved the same gene (MCC), and all other findings were unique. A closer analysis suggests a few gene networks that are involved in the pathogenesis of bladder exstrophy; the WNT-signaling pathway, the chromosome 22q11 region, the RIT2 and POU families, and involvement of the Golgi apparatus. Bladder exstrophy is a rare malformation and is reported to be associated with several chromosome aberrations. Our data suggest involvement of some specific molecular pathways.
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39.
  • Nordenskjöld, Agneta, et al. (författare)
  • Type of mutation and surgical procedure affect long-term quality of life for women with congenital adrenal hyperplasia.
  • 2008
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:2, s. 380-6
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: In congenital adrenal hyperplasia (CAH) caused by different mutations, feminizing surgery is mostly performed in childhood, and many patients are lost to follow-up. OBJECTIVE/PATIENTS: A follow-up study on 62 CAH women aged 18-63 yr and 62 age-matched controls to correlate findings of both operative method and mutation was performed. DESIGN: Semistructured interviews were performed in cases and controls, as well as a gynecological examination in the cases. The results were correlated with disease-causing mutations and earlier surgical procedures if performed. SETTING: The study was conducted at university hospital referral clinics. MAIN OUTCOME MEASURES: Gynecological examination in all cases correlated to previous surgery (n = 49), type of mutation, and questionnaire responses. RESULTS: Half of the CAH women claimed that the disease affected their sex life. The women were less satisfied with their genitals, whether operated or not. Clitoris size and functions were affected by the surgical method. Five women had a clinically evident vaginal stenosis on examination. However, almost half of patients experienced a narrow vagina. The overall psychosexual aspects of life were affected in these patients with later sexual debut, fewer pregnancies and children, and an increased incidence of homosexuality. These quality of life factors were correlated to the severity of the mutations. CONCLUSIONS: The overall quality of life in adult women with CAH is affected both by the type of mutation and operative procedure. Indications for clitoroplasty should be restrictive. Medical, surgical, and psychological treatment should be centralized.
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40.
  • Nordenström, Anna, et al. (författare)
  • Sexual function and surgical outcome in women with congenital adrenal hyperplasia due to CYP21A2 deficiency: clinical perspective and the patients' perception.
  • 2010
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95:8, s. 3633-40
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Females with congenital adrenal hyperplasia (CAH) due to a CYP21A2 deficiency are exposed to androgens during fetal development, resulting in virilization of the external genitalia. Little is known about how these women feel that the disease has affected their lives regarding surgery and psychosexual adaptation. OBJECTIVE: Our objective was to investigate the correlation between the surgical results, the self-perceived severity of the disease, and satisfaction with sexual life and relate the results to the CYP21A2 genotype. DESIGN AND PARTICIPANTS: Sixty-two Swedish women with CAH and age-matched controls completed a 120-item questionnaire, and a composite score for sexual function was constructed. The surgical outcome, including genital appearance and clitoral sensitivity, was evaluated by clinical examination. The patients were divided into four CYP21A2 genotype groups. RESULTS: The sexual function score, but not for genital appearance, was higher in the patients satisfied with their sexual life. This was also true of the patients who were satisfied with the surgical result. There were discrepancies between the patients' perception of the impact of the condition on their sexual life and what health professionals would assume from clinical examination. The patients in the null genotype group scored lower on sexual function and satisfaction with their sexual life and had more surgical complications, also compared with the slightly less severe I2-splice genotype group. CONCLUSION: Our data show that the null genotype group was considerably more affected by the condition than the other groups and should be regarded as a subgroup, both psychologically and from a surgical perspective. Genotyping adds clinically valuable information.
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41.
  • Nordenström, Josefin, et al. (författare)
  • Changes in differential renal function after pyeloplasty in infants and children.
  • 2020
  • Ingår i: Journal of pediatric urology. - : Elsevier BV. - 1873-4898 .- 1477-5131. ; 16:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Ureteropelvic junction obstruction (UPJO) is one of the most common causes of hydronephrosis in pediatric populations. Many need surgical intervention. The aim of surgery is preserving renal function and reducing symptoms such as urinary tract infections and pain.The objectives were to evaluate differential renal function (DRF) in infants and children after surgery for UPJO and to identify factors predicting postoperative improvement. The difference in outcomes between patients with antenatal hydronephrosis and those diagnosed later was evaluated.A total of 85 children (63 boys and 22 girls) aged 0-16 years, treated for UPJO with dismembered pyeloplasty, were followed up as per a structured protocol including ultrasounds and renal scans (MAG-3) pre-operatively and three and 18 months postoperatively. Five children with bilateral or single kidney UPJO were excluded. Patient records were retrospectively reviewed, and the patients were grouped as per prenatal (group 1, n=23) or postnatal (group 2, n=57) diagnosis. Univariable and multivariable logistic regression analyses searching for factors predicting >5% postoperative improvement in DRF on the obstructed side were performed. Factors included in analyses were age at diagnosis and surgery, sex, type of presentation, cause of obstruction, estimated glomerular filtration rate, pre-operative DRF, anteroposterior diameter (APD), APD/renal parenchymal thickness, and grade of hydronephrosis as per the Onen alternative grading system (grade 1-4).Pre-operative DRF on the obstructed side was a mean of 42% (standard deviation, 12), with no difference between the groups. The median age at surgery was 0.9 (0.2-10) and 8.1 (0.6-16) years in groups 1 and 2, respectively (P<0.001). The majority had unchanged DRF 18 months postoperatively, 19 (27%) patients improved by >5%, and one deteriorated. The proportion of patients with improved DRF was higher in group 1 (n=10; 45%, P=0.026). Anteroposterior diameter, APD/parenchymal thickness, pre-operative DRF, and antenatal diagnosis were predictors in the univariable analyses, and high APD (odds ratio [OR] = 1.1, P=0.0023), antenatal diagnosis (OR = 0.23, P=0.048), and low pre-operative DRF (OR = 0.90, P=0.0045) built the best model of independent factors predicting improvement in DRF in multivariable analyses (Summary Figure).The limitation of the study is that it is retrospective, but it has the advantage of auniform follow-up protocol, including patients from a five-year period, with few lost to follow-up. The results can be of interest in evaluating factors of importance for predicting recovery of function in obstructive uropathies in children.The majority of children had preserved or improved function after surgery for UPJO. Those with an antenatal diagnosis displayed a greater ability to catch up in DRF, and high APD, antenatal diagnosis, and low pre-operative DRF were independent predictive factors of an improvement in renal function after pyeloplasty.
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42.
  •  
43.
  • Nordenström, Josefin, et al. (författare)
  • The Swedish Infant High-grade Reflux Trial - Bladder function.
  • 2017
  • Ingår i: Journal of pediatric urology. - : Elsevier BV. - 1873-4898 .- 1477-5131. ; 13:2, s. 139-145
  • Tidskriftsartikel (refereegranskat)abstract
    • It has been suggested that infants with high-grade vesicoureteral reflux (VUR) have lower urinary tract dysfunction (LUTD) that is characterised by large bladder capacity (BC) and increased post-void residual (PVR). However, most of these infants have normal or small BC in early infancy and develop large capacity during the first year of life.This study aimed to see whether LUTD development during the infant years in children with high-grade VUR could be prevented by early reflux resolution.For early VUR intervention, endoscopic treatment (ET) was used in a randomised trial comprising 77 infants (55 boys) aged <8 months with VUR grade 4-5 (n=30/n=47); 39 were randomised to antibiotic prophylaxis and 38 to ET. Voiding cystourethrogram, free voiding observation (FVO) and renal scintigraphy were performed at baseline and after 1 year. Bladder capacity and PVR were obtained from FVO. LUTD was defined as a BC of ≥150% of expected and a PVR of ≥20ml.There were no differences in bladder function variables seen between the treatment groups, despite significant differences in VUR resolution. Analysing bladder function related to VUR outcome (VUR grade ≤2 vs grade >2), independent of treatment, showed that VUR grade ≤2 was associated with a smaller BC at 1 year (P=0.050) (a tendency already seen at baseline) and a lower PVR at baseline (P=0.010). PVR increased from baseline to 1 year (P=0.037) in children with grade ≤2 VUR (Summary Table). The group with persistent bilateral grade 5 VUR at 1 year had more abnormal bladder variables compared with other study subjects, with a tendency of larger BC (P=0.057), higher PVR (P=0.0073) and more LUTD (P=0.029) at baseline and a larger BC at 1 year (P=0.016). In explanatory analyses, using logistic regression, a high PVR at baseline was identified as a predictor of VUR grade >2 (P=0.046), persistent bilateral grade 5 VUR (P=0.022), recurrent urinary tract infection (P=0.034), and only a tendency was seen regarding new renal damage (P=0.053).There was no between-group difference seen in bladder function. In children with VUR resolution at follow-up, independent of treatment, BC decreased, whereas PVR increased. High PVR at baseline was a predictive factor for both non-resolution of high-grade VUR and recurrent urinary tract infection. The results suggest that LUTD cannot be prevented by early VUR resolution, but rather is an important prognostic factor for VUR outcome in both endoscopic and prophylactic treatment.
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44.
  • Nordenström, Josefin, et al. (författare)
  • The Swedish infant high-grade reflux trial: Study presentation and vesicoureteral reflux outcome.
  • 2017
  • Ingår i: Journal of pediatric urology. - : Elsevier BV. - 1873-4898 .- 1477-5131. ; 13:2, s. 130-138
  • Tidskriftsartikel (refereegranskat)abstract
    • High-grade vesicoureteral reflux (VUR) in infants is associated with congenital renal abnormalities, recurrent UTI, and bladder dysfunction. Endoscopic treatment (ET) is a well-established method in children with low to moderate reflux grades, but there is a lack of randomised controlled trials regarding the use of ET versus continuous antibiotic prophylaxis in infants with high-grade VUR.This study aimed to determine whether high-grade VUR in infants can be treated with endoscopic injection and whether ET is superior to antibiotic prophylaxis in the treatment of VUR.This prospective, randomised, controlled, multicentre, 1-year follow-up trial comprised 77 infants (55 boys, 22 girls) <8 months of age with VUR grade 4-5 (n=30/n=47). Of the infants, 52 (68%) had bilateral VUR. Thirty-nine were randomised to antibiotic prophylaxis and 38 to ET (with prophylaxis until resolution). Voiding cystourethrogram, ultrasound, renal scintigraphy, and free voiding observation were performed at study entry and after 1 year to evaluate VUR grade, and renal and bladder function.VUR grade ≤2 was seen in 22 (59%) infants in the endoscopy group and eight (21%) in the prophylaxis group at follow-up (p=0.0014). The success rate in the endoscopy group was 100% in unilateral grade 4, falling to 31% in bilateral grade 5 (p=0.0094). Correspondingly, the results in the prophylaxis group were 40% in grade 4 down to 0% in bilateral grade 5 (p=0.037) (Table). Logistic regression analyses identified ET, VUR grade 4, unilaterality, and low residual urine at baseline as positive predictors of VUR down-grading to ≤2 (area under ROC curve 0.88). In four patients with reflux resolution after one injection, dilating reflux recurred at the 1-year follow-up. One patient had a UTI possibly related to ET. In our material four patients required re-implantation, of whom one was obstructive after injection.The opportunity to offer even small infants with high-grade VUR an alternative, minimally invasive treatment option is a great advance in paediatric urology. In this high-risk group, bilateral VUR grade 5 stands out with its poor bladder function and low chance of resolution. The recurrence rate of dilating VUR aftersuccessful ET is consistent with previous studies. The limitations are the relatively small number of patients and the short follow-up.High-grade VUR in infants can be treated with injection therapy and the resolution rate is higher than that of prophylaxis treatment. The complication rate is low and VUR grade 4, unilaterality, and low residual urine are favourable for the resolution and down-grading of VUR.
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45.
  • Ortqvist, Lisa, et al. (författare)
  • Longterm followup of adult men born with hypospadias: Urological and cosmetic results. : Long-Term Followup of Men Born with Hypospadias: Urological and Cosmetic Results
  • 2015
  • Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 193:3, s. 975-982
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: We present data on long-term functional and cosmetic results after hypospadias surgery. MATERIALS AND METHODS: Males older than 18 years with hypospadias treated in Sweden were asked to participate in the study, as well as age matched controls and circumcised men. All participants answered questionnaires, and a subgroup was examined during an outpatient visit. Relationships with outcome were analyzed using analysis of variance and regression analysis. RESULTS: A total of 167 patients with a mean age of 34 years and 169 controls with a mean age of 33 years answered the questionnaire. Of the patients 63% had distal, 24% mid and 13% proximal hypospadias. A total of 46 patients and 49 controls presented for physical examination. Patients were significantly less satisfied with the penile cosmetic outcome regarding all parameters of the Penile Perception Score. There was a difference in penile length between patients and controls (mean 9.7 vs 11.6 cm, p <0.001). More patients than controls reported voiding dysfunction symptoms (p = 0.003). Patients had a lower maximum urinary flow rate than controls (p = 0.001). These differences were most prominent between patients with proximal hypospadias and controls. CONCLUSIONS: Men operated on for hypospadias were less satisfied with the cosmetic result than controls, and had a shorter penile length. Patients presented with more symptoms of voiding dysfunction and displayed a lower maximum urinary flow rate. Patients with proximal hypospadias were more affected than those with milder hypospadias. Our results indicate that patients with hypospadias can be subgrouped and that those with severe phenotypes should be followed more closely during childhood as well as later in adulthood.
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46.
  • Rieke, Johanna Magdalena, et al. (författare)
  • SLC20A1Is Involved in Urinary Tract and Urorectal Development
  • 2020
  • Ingår i: Frontiers in Cell and Developmental Biology. - : FRONTIERS MEDIA SA. - 2296-634X. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies in developingXenopusand zebrafish reported that the phosphate transporterslc20a1ais expressed in pronephric kidneys. The recent identification ofSLC20A1as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role ofSLC20A1in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish orthologslc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detectedSLC20A1in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequencedSLC20A1in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelicde novovariants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novelde novovariant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact ofSLC20A1variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggestSLC20A1is involved in urinary tract and urorectal development and implicateSLC20A1as a disease-gene for BEEC.
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47.
  • Sillén, Ulla, 1946, et al. (författare)
  • The Swedish Reflux Trial in Children: V. Bladder Dysfunction.
  • 2010
  • Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 184:1, s. 298-304
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: We investigated the prevalence and types of lower urinary tract dysfunction in children with vesicoureteral reflux grades III and IV, and related improved dilating reflux, renal damage and recurrent urinary tract infection to dysfunction. MATERIALS AND METHODS: A total of 203 children between ages 1 to less than 2 years with reflux grades III and IV were recruited into this open, randomized, controlled, multicenter study. Voiding cystourethrography and dimercapto-succinic acid scintigraphy were done at study entry and 2-year followup. Lower urinary tract function was investigated by noninvasive methods, at study entry with 4-hour voiding observation in 148 patients and at 2 years by structured questionnaire and post-void residual flow measurement in 161. RESULTS: At study entry 20% of patients had lower urinary tract dysfunction, characterized by high bladder capacity and increased post-void residual urine. At 2 years there was dysfunction in 34% of patients. Subdivision into groups characteristic of children after toilet training revealed that 9% had isolated overactive bladder and 24% had voiding phase dysfunction. There was a negative correlation between dysfunction at 2 years and improved dilating reflux (p = 0.002). Renal damage at study entry and followup was associated with lower urinary tract dysfunction at 2 years (p = 0.001). Recurrent urinary tract infections were seen in 33% of children with and in 20% without dysfunction (p = 0.084). CONCLUSIONS: After toilet training a third of these children with dilating reflux had lower urinary tract dysfunction, mainly voiding phase problems. Dysfunction was associated with persistent reflux and renal damage while dysfunction at study entry did not predict the 2-year outcome.
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48.
  • Sillén, Ulla, 1946, et al. (författare)
  • The voiding pattern in infants with dilating reflux.
  • 1999
  • Ingår i: BJU international. - 1464-4096. ; 83:1, s. 83-7
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To determine whether the voiding pattern in infants with dilating vesico-ureteric reflux (VUR) differs from that in healthy infants, thus supporting the existence of bladder dysfunction in infants with VUR. PATIENTS AND METHODS: Forty-one infants (33 boys and eight girls) with dilating VUR (grades 3-5) were studied using a noninvasive 4-hourly voiding record described previously in studies of the voiding pattern of healthy infants, and the results compared with those obtained from healthy infants of similar age. RESULTS: The voiding pattern in the boys with VUR was characterized by small frequent voids and interrupted voids in more patients (36%) than in healthy boys (15%). Conversely, the girls with VUR were infrequent voiders of relatively high volumes. Residual urine was significantly increased in both boys and girls, as was bladder capacity, although not significantly. CONCLUSIONS: The free voiding pattern in infants with dilating reflux differs from that seen in healthy infants of comparable age. The characteristics for boys and girls differed but was in accordance with that seen in invasive urodynamic studies, suggesting refluxing infants to have a bladder dysfunction.
  •  
49.
  • Sillén, Ulla, 1946, et al. (författare)
  • Treatment of bladder dysfunction and high grade vesicoureteral reflux does not influence the spontaneous resolution rate.
  • 2007
  • Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 177:1
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: We investigated whether the treatment of bladder dysfunction in infants with congenital high grade vesicoureteral reflux could influence the spontaneous resolution rate of the reflux and the number of recurrent urinary tract infections. MATERIALS AND METHODS: A total of 115 infants with high grade vesicoureteral reflux were included in a followup study of bladder function and reflux resolution between 1993 and 1999. The present study deals with 20 of these infants with mainly grade V reflux, most of whom had recurrent urinary tract infections in combination with high post-void residual and high bladder capacity. Treatment with clean intermittent catheterization was instituted during infancy in these 20 patients and continued until a median age of 4 years. RESULTS: Bladder capacity was high at presentation and at all followup investigations in the clean intermittent catheterization treated group. Moreover, residual urine was high at presentation and especially between ages 1 and 2 years. However, after bladder control was achieved this residual decreased and consisted mainly of reflux urine. In only 1 girl did reflux resolve spontaneously during the 4-year followup period. A total of 18 patients were treated surgically at the end of this period, and clean intermittent catheterization could be stopped a few months later in all but 2. Urinary tract infection recurrences were uncommon after the institution of treatment. CONCLUSIONS: The treatment of bladder dysfunction characterized by a high capacity bladder with poor emptying in infants with congenital high grade reflux does not influence the rate of spontaneous resolution. On the other hand, the tendency toward recurrent urinary tract infections appears to decrease with treatment.
  •  
50.
  • Simeonsdotter Svensson, Agneta, 1950, et al. (författare)
  • Health, Wellbeing and Self-Esteem: Web-Based Support in Children with Urogenital or Bowel Malformation
  • 2016
  • Ingår i: Open Journal of Pediatrics. - : Scientific Research Publishing, Inc.. - 2160-8741 .- 2160-8776. ; 6:1, s. 82-90
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. Introduction Long-term illness is usually a challenge for both children and their families [1]. Children with urogenital malformation or bowel disturbances are a vulnerable group who are at greater risk of experiencing ill health. They are often supported in situations related to their malformation by parents and others. When at school, the child suddenly has to face and cope with situations they are not used to; they often feel excluded, afraid of relationships with the opposite sex and subjected to bullying [2]-[4]. They express a great need for support in daily life [5]-[8]. The social and emotional consequences of long-term illness need to be addressed [9]. However, there is lack of studies investigating prevention of ill health in this group of children. Health promotion is the process of enabling people to increase their control over, and to improve their health. To reach a state of complete physical, mental and social wellbeing, the child must be able to identify and to realize aspirations, to satisfy needs, and to change or cope with the environment. Health is, therefore, seen as a resource, not the objective, in everyday life. Health is a positive concept that emphasizes social and personal resources, as well as physical capacities. Health promotion is not just the responsibility of the health sector; it goes beyond healthy lifestyles to wellbeing [10]. However, the needs of children with the same disease are not necessarily the same. Person-centred care (PCC) is explained as focusing on the person and not on the illness. The purpose is to make care and treatment more personal and to understand behaviour and symptoms from the perspective of the individual patient. To do this, it is important to proceed from knowledge of the sick person’s living patterns and priorities [11]. Studies have been conducted with positive outcomes, mainly for adults with long-term illness but also for young people [12]-[15]. The present study is part of a larger project studying health and wellbeing using person-centred, web-based learning in children with severe urogenital, urological and bowel malformations [16] [17]. Findings from the studies in this project are qualitative in design and show the development of the intervention. The use of SKYPE for interviewing children was also evaluated. This method can be used in the child’s home and is convenient for both the child and the family. The ability to use the body language also facilitated the understanding of the conversation, particularly in the youngest children. The intervention could identify wellbeing, resources, needs, and wishes. The children were interested and able to discuss relations, emotions and their own body. That learning had taken place was shown by realizing something new, reflecting on it, and then using the knowledge in a new context in their daily lives. The aim of the study was to investigate the effect on health/wellbeing and self-esteem, before and after oneyear intervention in children aged 3 - 7 years born with malformations in the urethra, bladder, genitals and/or bowel. The results of the intervention, person-centred, web-based learning support, are compared with the findings in a control group of healthy children.
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