| 1. |
- Granstrom, Anna Lof, et al.
(författare)
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Adult outcomes after surgery for Hirschsprung's disease : Evaluation of bowel function and quality of life
- 2015
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Ingår i: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 50:11, s. 1865-1869
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Hirschsprung's disease (HSCR) is treated surgically. There is a risk for faecal incontinence and constipation postoperatively. The long-term bowel functional outcome in adults and quality of life are sparsely studied. The aim of this study was to assess bowel function and quality of life in patients who had undergone surgery for HSCR during childhood. Methods: All patients treated between 1969 and 1994 at St. Goran's Children's Hospital in Stockholm were invited to participate in the study. After consent, the patients received questionnaires containing general questions, validated questions on bowel function, questions about urinary function, SF-36 health survey (SF-36) and the Gastrointestinal Quality of Life Index (GIQLI). Clinical data were extracted from the case records. Controls matched for sex and age were randomly selected from the National Swedish Population Register. Results: 48 of 60 (80%) invited patients responded to the questionnaires. Nine patients were excluded since the HSCR diagnosis could not be confirmed. The median age of the included patients was 28 (20-43) years. Most patients had undergone Soave's operation (73.4%) and two patients had a stoma at the time of follow-up. The bowel function was impaired in the HSCR group compared to controls, especially problems with flatulence, need to strain at defecation and several defecations for emptying. Patients in the HSCR group also had significantly more problems with faecal incontinence than controls. Quality of life according to SF-36 did not differ significantly between patients and controls, but the GIQLI score showed a significantly worse outcome in the HSCR group compared to the controls. Conclusion: General quality of life in adults treated for HSCR during childhood is comparable to controls. However, they have impaired bowel function and gastrointestinal quality of life.
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| 2. |
- Humes, David J., et al.
(författare)
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Risk of venous thromboembolism in children after general surgery
- 2015
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Ingår i: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 50:11, s. 1870-1873
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Tidskriftsartikel (refereegranskat)abstract
- Background/purpose: The purpose of the study was to determine absolute and relative rates of venous thromboembolism (VTE) following general surgical procedures in children compared to the general population. Methods: We analyzed data from all patients under the age of 18 years in the Clinical Practice Research Datalink, linked to Hospital Episode Statistics from England (2001-2011) undergoing a general surgical procedure and population controls. Crude rates of VTE and adjusted hazard ratios were calculated using Cox regression. Results: We identified 15,637 children who had a surgical procedure with 161,594 controls. Six children undergoing surgery had a VTE diagnosed in the year after compared to five children in the population cohort. The overall rate of VTE following surgery was 0.4 per 1000 person years (pyrs) (95% confidence interval [CI] 0.15-0.88) compared to 0.04 per 1000 pyrs (95% CI 0.02-0.09) in the population cohort. This represented a 9 fold increase in risk compared to the population cohort (adjusted hazard ratio [HR] 8.80; 95% CI 2.59-29.94). Conclusions: Children are at increased risk for VTE following general surgical procedures compared to the general population however the absolute risk is small and given this the benefits of thromboprophylaxis need to be balanced against the risk of complications following its use.
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| 3. |
- 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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| 4. |
- Ludvigsson, Jonas F., 1969-, et al.
(författare)
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A large nationwide population-based case-control study of the association between intussusception and later celiac disease
- 2013
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Ingår i: BMC Gastroenterology. - : BioMed Central. - 1471-230X .- 1471-230X. ; 13, s. 89-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Case reports and case series studies suggest a positive association between intussusception and celiac disease (CD). Methods: We contacted Sweden's 28 pathology departments and obtained data on 29,096 patients with biopsy-verified CD (equal to Marsh stage 3) through biopsy reports. Patients with CD were matched for age, sex, calendar period and county of residence with up to five reference individuals from the general population (n = 144,522). Cases of intussusception were identified from nationwide inpatient, hospital-based outpatient and day-surgery data from the Swedish Patient Register. Odds ratios (ORs) for future CD in patients with intussusception were estimated using conditional logistic regression. Results: 34 (0.12%) individuals with CD had a diagnosis of intussusception vs. 143 (0.10%) reference individuals, suggesting that intussusception was not a risk factor for later CD (OR = 1.17; 95% confidence interval (CI) = 0.82-1.67). The OR for CD in patients with at least two records of intussusception was 0.40 (95% CI = 0.06-2.99). In contrast, a post-hoc analysis showed that CD was associated with a statistically significantly increased risk of intussusception after CD diagnosis (hazard ratio = 1.95; 95% CI = 1.01-3.77); however, this analysis was based on only 12 cases with both CD and intussusception. Conclusion: We found no association between intussusception and future CD; and a mostly modest increased risk of intussusception after a diagnosis of CD.
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| 5. |
- Lundin, Kristina, et al.
(författare)
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Frequent finding of the androgen receptor A645D variant in normal population.
- 2006
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 91:2006 May 16, s. 3228-3231
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Tidskriftsartikel (refereegranskat)abstract
- Background: The androgen receptor A645D mutation has been described in one patient with ambiguous genitalia and one boy with normal phenotype. Objective: Because of this phenotypic variation, we screened a cohort of men from the general population (n = 293) as well as men with the following disorders of the genital tract for the mutation: men with prostate cancer (n = 89), testicular cancer (n = 87), and infertility (n = 103). We also investigated the influence of the polymorphic CAG and GGN repeats on the phenotypic outcome. Results: The A645D variant was found in three men from the general population (1.0%). These men did not differ regarding testosterone or LH concentrations, compared with the rest of this population. In addition, two men with prostate cancer (2.3%) and one infertile man (1.0%) presented with the mutation. No statistical differences in frequency were noted between the study groups, and none of these individuals had any genital malformations. All men who presented with the mutation carried an extraordinarily short GGN repeat of 10 base triplets in combination with long CAG repeats of 26-28 (average 27.3). In contrast, men with GGN = 10, but CAG less than 26 did not have the A645D mutation. A single-nucleotide polymorphism analysis revealed that the A645D variant has emerged from the most common haplogroup in our population. Conclusions: We conclude that the A645D mutation, which is present in 1% of the general Swedish population, is linked to GGN10 and long CAG repeats. Its effect on androgen receptor function is currently unknown.
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| 6. |
- Soderhall, Cilla, et al.
(författare)
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A Case with Bladder Exstrophy and Unbalanced X Chromosome Rearrangement
- 2014
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Ingår i: European Journal of Pediatric Surgery. - : Georg Thieme Verlag KG. - 1439-359X .- 0939-7248. ; 24:4, s. 353-359
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Bladder exstrophy is a rare congenital malformation of the bladder and is believed to be a complex disorder with genetic and environmental background. We describe a young adult female with an isolated bladder exstrophy and with an X chromosome aberration. Patients and Methods Karyotyping identified an X chromosome rearrangement that was further characterized with array comparative genomic hybridization (CGH) and confirmed by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization (FISH) analysis. Results The identified X chromosome rearrangement in our index patient consists of a gain of chromosomal material in region Xq26.3-> qter and loss in region Xp22.12->pter. This aberration was also carried by her mother and sister, none with bladder exstrophy. All three have a disproportionate short stature, as expected due to the deletion of one of the copies of the SHOX gene on Xp22.3. X-inactivation studies revealed a complete skewed inactivation pattern in carriers. Crossover events in the maternal germline furthermore resulted in different genetic material on the rearranged X chromosome between the index patient and her sister. Conclusion Our findings suggest an X-linked genetic risk factor for bladder exstrophy.
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| 7. |
- Svenningsson, Anna, et al.
(författare)
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Genome-wide linkage analysis in families with infantile hypertrophic pyloric stenosis indicates novel susceptibility loci
- 2012
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Ingår i: Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1434-5161 .- 1435-232X. ; 57:2, s. 115-121
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Tidskriftsartikel (refereegranskat)abstract
- Infantile hypertrophic pyloric stenosis (IHPS) is a common cause of upper gastrointestinal obstruction during infancy. A multifactorial background of the disease is well established. Multiple susceptibility loci including the neuronal nitric oxide synthase (NOS1) gene have previously been linked to IHPS, but contradictory results of linkage studies in different materials indicate genetic heterogeneity. To identify IHPS susceptibility loci, we conducted a genome-wide linkage analysis in 37 Swedish families. In regions where the Swedish material showed most evidence in favor of linkage, 31 additional British IHPS families were analyzed. Evidence in favor of significant linkage was observed in the Swedish material to two loci on chromosome 2q24 (non-parametric linkage (NPL)=3.77) and 7p21 (NPL=4.55). In addition, evidence of suggestive linkage was found to two loci on chromosome 6p21 (NPL=2.97) and 12q24 (NPL=2.63). Extending the material with British samples did not enhance the level of significance. Regions with linkage harbor interesting candidate genes, such as glucagon-like peptide-2 (GLP-2 encoded by the glucagon gene GCG), NOS1, motilin (MLN) and neuropeptide Y (NPY). The coding exons for GLP-2, and NPY were screened for mutations with negative results. In conclusion, we could confirm suggestive linkage to the region harboring the NOS1 gene and detected additional novel susceptibility loci for IHPS. Journal of Human Genetics (2012) 57, 115-121; doi:10.1038/jhg.2011.137; published online 8 December 2011
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| 8. |
- Zhang, Rong, et al.
(författare)
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ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Previously genome-wide association methods in patients with classic bladder exstrophy (CBE) found association with ISL1, a master control gene expressed in pericloacal mesenchyme. This study sought to further explore the genetics in a larger set of patients following-up on the most promising genomic regions previously reported. Genotypes of 12 markers obtained from 268 CBE patients of Australian, British, German Italian, Spanish and Swedish origin and 1,354 ethnically matched controls and from 92 CBE case-parent trios from North America were analysed. Only marker rs6874700 at the ISL1 locus showed association (p = 2.22 x 10(-08)). A meta-analysis of rs6874700 of our previous and present study showed a p value of 9.2 x 10(-19). Developmental biology models were used to clarify the location of ISL1 activity in the forming urinary tract. Genetic lineage analysis of Isl1-expressing cells by the lineage tracer mouse model showed Isl1-expressing cells in the urinary tract of mouse embryos at E10.5 and distributed in the bladder at E15.5. Expression of isl1 in zebrafish larvae staged 48 hpf was detected in a small region of the developing pronephros. Our study supports ISL1 as a major susceptibility gene for CBE and as a regulator of urinary tract development.
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