| 1. |
- Borg, Helena, et al.
(författare)
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Impact of spinal cord malformation on bladder function in children with anorectal malformations.
- 2009
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Ingår i: Journal of pediatric surgery. - : Elsevier BV. - 1531-5037 .- 0022-3468. ; 44:9, s. 1778-85
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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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| 2. |
- Elofsson, Helena, 1976-
(författare)
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Sperm motility in Gasterosteiform fishes : The role of salinity and ovarian fluid
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In externally fertilising fishes, various factors in the surrounding environment may influence the viability of the sperm and eggs, thus determining the success of reproduction. In this thesis, the influence of salinity and ovarian fluid on sperm motility has been investigated in three Gasterosteiform fishes.The three-spined stickleback, Gasterosteus aculeatus, has successfully invaded fresh water and differs from most other fishes in its ability to spawn in waters of all salinities. Our results show that sperm of the three-spined is strongly stimulated by the ovarian fluid surrounding the eggs. In fresh water, where the period of motility is only about a minute, ovarian fluid prolongs motility to last several hours. We show that this effect is due to fluid’s ionic content and that the fluid remains in the nest, surrounding the eggs, for a prolonged time due to the proteins and/or other macromolecules in the fluid. Our results explain how successful spawning can occur in fresh water despite that it takes several minutes for all three-spined stickleback eggs to be fertilised. The stimulating effect of ovarian fluid may be one of the factors that have enabled the originally marine three-spined stickleback to colonise fresh water.The fifteen-spined stickleback, Spinachia spinachia, is exclusively marine. We found their sperm motility to be good in seawater, reduced in brackish water, and non-existent in freshwater. The presence of ovarian fluid made no difference in any salinity, a factor that might have contributed to their inability to colonise fresh water. Being regarded as a primitive member of the stickleback family, the lack of response to ovarian fluid suggests that this is not a primitive trait among the sticklebacks.The male straight-nose pipefish, Nerophis ophidion carries the eggs attached to its ventral surface. Fertilisation has previously been suggested to be external, but our results show that their sperm are not motile in seawater alone, but in a mixture of seawater and ovarian fluid. This result, together with the finding of some sperm in the female genital area, and that the sperm head is elongated, suggests that the fertilisation in the straight-nose pipefish occurs in close proximity with the eggs and ovarian fluid. This could then explain why the straight-nose pipefish has minute testes and complete confidence of paternity.
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| 3. |
- Gonzalez, Henrik, et al.
(författare)
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Identification of novel candidate protein biomarkers for the post-polio syndrome — Implications for diagnosis, neurodegeneration and neuroinflammation
- 2009
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 71:6, s. 670-681
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Tidskriftsartikel (refereegranskat)abstract
- Survivors of poliomyelitis often develop increased or new symptoms decades after the acute infection, a condition known as post-polio syndrome (PPS). The condition affects 20-60% of previous polio patients, making it one of the most common causes of neurological deficits worldwide. The underlying pathogenesis is not fully understood and accurate diagnosis is not feasible. Herein we investigated whether it was possible to identify proteomic profile aberrations in the cerebrospinal fluid (CSF) of PPS patients. CSF from 15 patients with well-defined PPS were analyzed for protein expression profiles. The results were compared to data obtained from nine healthy controls and 34 patients with other non-inflammatory diseases which served as negative controls. In addition, 17 samples from persons with secondary progressive multiple sclerosis (SPMS) were added as relevant age-matched references for the PPS samples. The CSF of persons with PPS displayed a disease-specific and highly predictive (p=0.0017) differential expression of five distinct proteins: gelsolin, hemopexin, peptidylglycine alpha-amidating monooxygenase, glutathione synthetase and kallikrein 6, respectively, in comparison with the control groups. An independent ELISA confirmed the increase of kallikrein 6. We suggest that these five proteins should be further evaluated as candidate biomarkers for the diagnosis and development of new therapies for PPS patients.
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| 4. |
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| 5. |
- Henningson, Maria, et al.
(författare)
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Absence of the common IGF1 19 CA-repeat allele is more common among BRCA1 mutation carriers than among non-carriers from BRCA1 families.
- 2007
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Ingår i: Familial Cancer. - : Springer Science and Business Media LLC. - 1389-9600 .- 1573-7292. ; 6:4, s. 445-452
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Tidskriftsartikel (refereegranskat)abstract
- BRCA1 mutations predispose to early-onset breast cancer. We previously reported an association between absence of the common IGF1 19 CA-repeat allele (IGF1-19/-19) and being a BRCA1 mutation carrier in young women from breast cancer high-risk families. Others have reported a four-fold risk of premenopausal breast cancer in women with a family history and the IGF1-19/-19 genotype. The aim of this study was to investigate whether the IGF1-19/-19 genotype was associated with being a BRCA1 mutation carrier among women from BRCA1 families. DNA was available from 268 women with known BRCA1 status from the South Swedish Health Care Region. IGF1 genotyping was successfully performed with fragment analysis in 211 women from 96 families. The IGF1-19/-19 genotype was significantly more common among BRCA1 mutation carriers (14.2%) than among non-carriers (4.8%), OR 3.3 (95%CI 1.11-9.78, P = 0.03) adjusted for family clustering. We confirmed our previous finding of an association between the IGF1-19/-19 genotype and BRCA1 mutation status. Since the IGF1-19/-19 genotype in combination with OC use or multiparity confers an increased risk for early onset breast cancer in high-risk women and in women from the general population, future studies are needed to elucidate the importance of the IGF1-19/-19 genotype concerning the variability in breast cancer risk among BRCA1 mutation carriers.
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| 6. |
- Henningson, Maria, et al.
(författare)
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CYP17 genotype is associated with short menstrual cycles, early oral contraceptive use and BRCA mutation status in young healthy women
- 2007
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Ingår i: Molecular Human Reproduction. - : Oxford University Press (OUP). - 1460-2407. ; 13:4, s. 231-236
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Tidskriftsartikel (refereegranskat)abstract
- The CYP17 gene is involved in steroid hormone metabolism and has been proposed as a low penetrance gene for breast cancer. We aimed to investigate the associations between the CYP17 genotype and breast cancer risk factors, such as age at menarche, menstrual cycle length, oral contraceptive (OC) use, and BRCA mutation status among 258 healthy young women, aged <= 40, from 158 breast cancer high-risk families. Questionnaires including questions on reproductive factors and OC use were completed and blood samples were obtained from all women. CYP17 (rs743572) was genotyped with sequencing in 254 women. The main findings were that short menstrual cycles (< 27 days) were significantly more common with increasing number of variant A2 alleles (8%, 17% and 32%; P-trend = 0.002, adjusted for family clustering). Each A2 allele was associated with a 7 months earlier OC start (17.8, 17.0, and 16.6 years; P-trend = 0.014, adjusted for age at menarche, ever-smoking and family clustering). Homozygosity for the A2 allele was more common among known non-carriers from BRCA1/2 families compared with other high-risk women OR 2.92 (95% CI 1.49-5.73; P = 0.002, adjusted for family clustering). We found no association between CYP17 genotype and age at menarche. In conclusion, this study suggests that short menstrual cycles, age at first OC use and BRCA mutation status may need to be considered in studies exploring the relationships between CYP17 and risk factors for early onset breast cancer.
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| 7. |
- Hietala, M, et al.
(författare)
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Testosterone levels in relation to oral contraceptive use and the androgen receptor CAG and GGC length polymorphisms in healthy young women
- 2007
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 22:1, s. 83-91
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The combined effect from the androgen receptor (AR) CAG and GGC length polymorphisms on testosterone levels has not been studied in young women. METHODS: Testosterone levels were measured in blood drawn on both menstrual cycle days 5-10 and 18-23 in 258 healthy women, aged <= 40 years, from high-risk breast cancer families. CAG and GGC length polymorphisms were analysed by PCR and fragment analyses. All women completed a questionnaire including information on oral contraceptive (OC) use and reproductive factors. RESULTS: OC users had lower median testosterone levels than non-users during cycle days 5-10 and 18-23 (P <= 0.005 for both). The BRCA mutation status was associated neither with testosterone levels nor with CAG or GGC length polymorphism. The CAG length polymorphism was not associated with testosterone levels. The cumulative number of long GGC alleles (>= 17 repeats) was significantly associated with lower testosterone levels in OC users during cycle days 5-10 (P-trend =0.014), but not during cycle days 18-23 or in non-users. The interaction between the GGC length polymorphism and OC status was highly significant during cycle days 5-10 (P = 0.002) and near-significant during days 18-23 (P = 0.07). Incident breast cancer was more common in women with two short GGC alleles (log-rank P = 0.003). CONCLUSION: The GGC repeat length was the only significant genetic factor modifying the testosterone levels in current OC users from high-risk families. Homozygosity for the short GGC allele may be linked to the increased risk of early-onset breast cancer after OC exposure in high-risk women.
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| 8. |
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| 9. |
- Jernström, Helena, et al.
(författare)
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High follicular phase luteinizing hormone levels in young healthy BRCA1 mutation carriers: Implications for breast and ovarian cancer risk.
- 2005
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Ingår i: Molecular Genetics and Metabolism. - : Elsevier BV. - 1096-7192. ; 86:1-2, s. 320-327
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Tidskriftsartikel (refereegranskat)abstract
- BRCA1 mutation carriers have up to 80% life-time risk of developing breast cancer and 20-40% risk of developing ovarian cancer. High LH levels have been linked to increased risks of both breast and ovarian cancers in some studies and it is unknown whether gonadotropin levels are associated with BRCA1 mutation status. The aim of the study was to explore whether gonadotropin levels were associated with BRCA1 mutation status among healthy <= 40-year-old-women from hereditary breast cancer families. All women completed a questionnaire including information on reproductive factors and OC use. We measured height, weight, breast volumes, and plasma levels of LH, FSH, and estradiol (E2) once during menstrual cycle days 5-10 and once again during cycle days 18-23 in 43 non-carriers from BRCA1 families, 20 BRCA1 mutation carriers, and 101 women from non-BRCA1/2 families. The strongest predictors of high LH levels among BRCA1 mutation carriers and non-carriers during cycle days 5-10 were being a BRCA1 mutation carrier (p = 0.002), lack of current OC use (p = 0.003), and being nulliparous (p = 0.01), adjusted for age and menstrual cycle day when the samples were obtained. This association was seen both in non-OC users and current OC users but was only significant in the former group (p = 0.005). Because of multiple analyses it is possible that our finding is a result of a Type 1 statistical error. After a permutation test the new adjusted p value in non-OC users was 0.05. FSH and E2 were similar in non-carriers, BRCA1 mutation carriers and women from non-BRCA1/2 families. We found significantly elevated LH levels in the follicular phase among young healthy BRCA1 mutation carriers compared with non-carriers from BRCA1 families. This is a small study and confirmatory studies are warranted to establish whether elevated LH levels are part of the BRCA1 phenotype and may be manipulated in order to reduce cancer risks in BRCA1 mutation carriers.
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| 10. |
- Jernström, Helena, et al.
(författare)
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Impact of teenage oral contraceptive use in a population-based series of early-onset breast cancer cases who have undergone BRCA mutation testing
- 2005
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 41:15, s. 2312-2320
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Tidskriftsartikel (refereegranskat)abstract
- Oral contraceptive (OC) use in young women has been associated with an increased risk of breast cancer. This matched case-control study aims to elucidate the combined effects of OC use and genetic factors in a population-based series of BRCA1/2 mutation-tested early-onset breast cancers. A first invasive breast cancer was diagnosed in 259 women aged <= 40 years between 1990 and 1995 in the South Swedish Health Care Region. A total of 245 women were included in this study. Information on family history of cancer, reproductive factors, smoking and OC use was obtained from questionnaires or patient charts. Three age-matched controls per case were chosen from a prospective South Swedish cohort. Ever OC use and current OC use were not associated with breast cancer. Cases were more likely to have used OCs before age 20 years (adjusted odds ratio (OR) 2.10 (95% CI 1.32-3.33)) and before their first child (adjusted OR 1.63 (95% CI 1.02-2.62)). When stratified by age, the effect of early OC use was limited to women diagnosed prior to age 36 years (OR 1.53 (1.17-1.99) per year of OC use prior to age 20 years). The risks were similar for low-dose and high-dose OCs. The probability of being a BRCA1/2 mutation carrier was three times higher among cases who started OC use prior to age 20 years compared with cases who started at age 20 years or older or who had never used OCs. However, the duration of OC use was similar among cases with and without BRCA1/2 mutations. No association was seen with a first-degree family history of breast cancer. Each year of OC use prior to age 20 years conferred a significantly increased risk for early-onset breast cancer, while there was no risk associated with use after age 20 years.
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