| 1. |
- Al-Mashhadi, Ammar Nadhom Farman
(författare)
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High Blood Pressure in Children with Hydronephrosis
- 2018
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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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| 2. |
- Andersson, Marie, 1977, et al.
(författare)
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Normalized Urinary Flow at Puberty after Tubularized Incised Plate Urethroplasty of Hypospadias in Childhood.
- 2015
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Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 194:5, s. 1407-1413
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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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| 3. |
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| 4. |
- Arkani, Samara, et al.
(författare)
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Evaluation of the ISL1 gene in the pathogenesis of bladder exstrophy in a Swedish cohort
- 2018
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Ingår i: Human genome variation. - : Springer Nature. - 2054-345X. ; 5:1
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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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| 5. |
- Dellenmark-Blom, Michaela, 1983, et al.
(författare)
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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
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Ingår i: Quality of Life Research. - : Springer Science and Business Media LLC. - 0962-9343 .- 1573-2649. ; 28:6, s. 1389-1412
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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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| 6. |
- Fall, Magnus, 1941, et al.
(författare)
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Uro-tarmterapi : Kapitel 2
- 2019
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Ingår i: Uro-tarmterapi. Anna-Lena Hellström, Birgitta Lindehall (red.). - Lund : Studentlitteratur. - 9789144122588 ; , s. 21-43
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 7. |
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| 8. |
- Jenholt Nolbris, Margaretha, 1956, et al.
(författare)
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Development of a programme for web-based support for children – a participatory design in children and families with urinary tract disorders.
- 2016
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Ingår i: JSM Health Education and Primary Health Care. ; 1:1
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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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| 9. |
- Korberg, Izabella Baranowska, et al.
(författare)
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WNT3 involvement in human bladder exstrophy and cloaca development in zebrafish
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:18, s. 5069-5078
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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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| 10. |
- Lundin, Johanna, et al.
(författare)
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Further support linking the 22q11.2 microduplication to an increased risk of bladder exstrophy and highlighting LZTR1 as a candidate gene
- 2019
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Ingår i: Molecular Genetics and Genomic Medicine. - : Wiley. - 2324-9269. ; 7:6
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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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