| 1. |
- Meisgen, Sabrina, et al.
(författare)
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The HLA locus contains novel foetal susceptibility alleles for congenital heart block with significant paternal influence
- 2014
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 275:6, s. 640-651
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The main aim of this study was to identify foetal susceptibility genes on chromosome six for Ro/SSA autoantibody-mediated congenital heart block.SUBJECTS AND DESIGN: Single nucleotide polymorphism (SNP) genotyping of individuals in the Swedish Congenital Heart Block (CHB) study population was performed. Low-resolution HLA-A, -Cw and -DRB1 allele typing was carried out in 86 families comprising 339 individuals (86 Ro/SSA autoantibody-positive mothers, 71 fathers, 87 CHB index cases, and 95 unaffected siblings).RESULTS: A case-control comparison between index cases and population-based out-of-study controls (n=1710) revealed association of CHB with 15 SNPs in the 6p21.3 MHC locus at a chromosome-wide significance of p<2.59×10(-6) (OR 2.21-3.12). In a family-based analysis of association of SNP markers as well as distinct MHC class I and II alleles with CHB, HLA-DRB1*04 and HLA-Cw*05 variants were significantly more frequently transmitted to affected individuals (p<0.03 and p<0.05, respectively), while HLA-DRB1*13 and HLA-Cw*06 variants were significantly less often transmitted to affected children (p<0.04 and p<0.03). We further observed marked association of increased paternal (but not maternal) HLA-DRB1*04 transmission to affected offspring (p<0.02).CONCLUSIONS: HLA-DRB1*04 and HLA-Cw*05 were identified as novel foetal HLA allele variants that confer susceptibility to CHB in response to Ro/SSA autoantibody exposure, while DRB1*13 and Cw*06 emerged as protective alleles. Additionally, we demonstrated a paternal contribution to foetal susceptibility to CHB for the first time.
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| 2. |
- Ambrosi, Aurelie, et al.
(författare)
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Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern
- 2012
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Ingår i: Annals of the Rheumatic Diseases. - London : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 71:3, s. 334-340
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Tidskriftsartikel (refereegranskat)abstract
- Objective Congenital heart block may develop in the fetuses of Ro/SSA-positive and La/SSB-positive mothers. Recurrence rates of only 10-20% despite persisting maternal antibodies indicate that additional factors are critical for the establishment of heart block. The authors investigated the influence of other maternal and fetal factors on heart block development in a Swedish population-based cohort. less thanbrgreater than less thanbrgreater thanMethods The influence of fetal gender, maternal age, parity and time of birth on heart block development was analysed in 145 families, including Ro/La-positive (n=190) and Ro/La-negative (n=165) pregnancies. less thanbrgreater than less thanbrgreater thanResults There was a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was, however, significantly higher than in pregnancies resulting in babies without heart block (pandlt;0.05). Seasonal timing of pregnancy influenced the outcome. Gestational susceptibility weeks 18-24 occurring during January-March correlated with a higher proportion of children with heart block and lower vitamin D levels during the same period in a representative sample of Swedish women and a corresponding higher proportion of children with heart block born in the summer (pandlt;0.02). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies. less thanbrgreater than less thanbrgreater thanConclusion This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for heart block development in children of Ro/La-positive women. These observations may be useful for counselling when pregnancy is considered.
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| 3. |
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Nygren, Anders, et al.
(författare)
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Rapid Cardiovascular Effects of Growth Hormone treatment in short prepubertal children. Impact of treatment duration.
- 2012
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 77:6, s. 877-884
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Previous studies show that growth hormone (GH) treatment increases cardiac dimensions in short children with GH deficiency (GHD) and has diverse cardiac effects in children with idiopathic short stature (ISS). This study was performed to assess the effect of GH on the cardiovascular system in short children with a broad range of GH secretion and GH sensitivity/responsiveness. DESIGN AND PATIENTS: In this prospective, multicentre study, short prepubertal children diagnosed with isolated GHD (89) or ISS (38) were followed during two years of GH treatment. They were randomized to receive either a standard (43 μg/kg/d) or individualized GH dose (range 17-100 μg/kg/d) based on GH responsiveness estimated by a prediction model and distance to target height. Echocardiography, blood pressure and electrocardiography were performed at baseline, 3, 12 and 24 months. RESULTS: Left ventricular mass (LVM) indexed to body surface area increased significantly during two years of GH treatment in both GHD and ISS irrespective of randomized dose. This change was already apparent at three months, when standard deviation scores (SDS) of wall thickness and diameter were increased. At 24 months, left ventricular diameter SDS remained increased whereas myocardial thickness SDS returned to baseline values. There was no impairment of systolic or diastolic function. There was no correlation with treatment dose and LVM SDS at 24 months. CONCLUSIONS: Irrespective of GH status, there was a rapid increase in LVM during GH treatment in short children. At 3 months, wall thickness and diameter were increased whereas only diameter remained increased at 24 months. © 2012 Blackwell Publishing Ltd.
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| 8. |
- Olsson, Karl Wilhelm, 1985-, et al.
(författare)
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Exploration of potential biochemical markers for persistence of patent ductus arteriosus in preterm infants at 22–27 weeks’ gestation
- 2019
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 86, s. 333-338
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundEarly identification of infants at risk for complications from patent ductus arteriosus (PDA) may improve treatment outcomes. The aim of this study was to identify biochemical markers associated with persistence of PDA, and with failure of pharmacological treatment for PDA, in extremely preterm infants.MethodsInfants born at 22–27 weeks’ gestation were included in this prospective study. Blood samples were collected on the second day of life. Fourteen biochemical markers associated with factors that may affect PDA closure were analyzed and related to persistent PDA and to the response of pharmacological treatment with ibuprofen.ResultsHigh levels of B-type natriuretic peptide, interleukin-6, -8, -10, and -12, growth differentiation factor 15 and monocyte chemotactic protein 1 were associated with persistent PDA, as were low levels of platelet-derived growth factor. High levels of erythropoietin were associated with both persistent PDA and failure to close PDA within 24 h of the last dose of ibuprofen.ConclusionsHigh levels of inflammatory markers were associated with the persistence of PDA. High levels of erythropoietin were associated with both the persistence of PDA and failure to respond to pharmacological treatment.
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| 9. |
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| 10. |
- Olsson, Karl Wilhelm, 1985-
(författare)
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Persistent ductus arteriosus in extremely preterm infants
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patent ductus arteriosus (PDA) is common in infants born <28 weeks gestational age (GA) and associated with significant morbidity. Despite extensive research efforts, the indications for PDA treatment remain controversial. The aims of these studies were to gain knowledge of factors affecting ductal closure during the early postnatal period and provide better means for identification of preterm infants that may benefit from PDA treatment.In Paper I, infants born <28 weeks GA and pharmacologically treated for PDA were retrospectively identified and their echocardiographic examinations were reviewed. Twenty-nine (52%) infants successfully closed and 27 (48%) infants failed to close PDA during treatment. High maximal ductal flow velocity (Vmax) was independently associated with closure (OR 3.04, p=0.049).Paper II prospectively included infants born <28 weeks GA and assessed early respiratory, circulatory and echocardiographic parameters. PDA was persistent in 18 (30%) and ultimately closed or insignificant in 42 (70%) infants. Echocardiographic criteria for hemodynamically significant PDA on days 2-7 did not predict persistent PDA (p=1.000). Mechanical ventilation (p=0.025), high mean airway pressure (p=0.020) and low Vmax (p=0.024) during day two were associated with future persistent PDA.Blood samples were obtained during the second day of life from 47 of the infants in Paper II and serum markers previously associated with PDA or factors affecting PDA were analyzed for Paper III. Inflammatory markers and erythropoietin (EPO) were elevated in infants with future persistent PDA. EPO levels were also higher in infants that did not close PDA during pharmacological treatment.In Paper IV, 44 infants born <28 weeks GA with surgically ligated PDA were retrospectively compared to non-surgically treated controls. Ligated infants had larger ductal diameter prior to, and lack of diameter decrease after pharmacological treatment for PDA (p=0.048 and p=0.022 respectively), and higher incidence of severe bronchopulmonary dysplasia (p=0.025). Longer periods with invasive ventilation was independently associated with ligation (OR 1.04, p=0.018).In conclusion, early hsPDA do not predict persistence of ductus arteriosus in extremely preterm infants, but Vmax and EPO are promising early markers for prediction of persistence and should be subjects of future studies.
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| 11. |
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| 12. |
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| 13. |
- Bland, Richard D., et al.
(författare)
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Gunnar Sedin
- 2014
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Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 103:8, s. 893-893
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 14. |
- Charisopoulou, Dafni, 1972-
(författare)
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Myocardial electromechanical function in long QT syndrome
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- AIM: The aim of this thesis is to assess, in LQTS and according to genotype, the myocardial electromechanical (EM) function response to exercise, its relation to symptoms and its response to b-blocker therapy. To achieve this aim, we conducted 4 studies with the following specific objectives: i. To study the ventricular repolarization (QTc interval) behaviour during stress and its potential haemodynamic effects, as reflected in left ventricular filling and stroke volume response to exercise.ii. To access the exercise response of electromechanical coupling, expressed by the electromechnical window (EMW), and its relation to symptoms.iii. To access for potential mechanical disturbances during stress by studying the myocardial contraction response to exercise, its effects on myocardial diastolic function and their relation to co-existent ventricular repolarization disturbances.iv. To investigate the myocardial behaviour during early relaxation an most particularly the longitudinal apico-basal relaxation sequence, its synamic response to exercise and any potentia contribution to the development of symptoms.v. To investigate the effect of b-blocker therapy on the above electromechanical parameters at rest and during exercise. METHODS: Forty seven (age 45±15yrs, 25 female, 20 symptomatic) LQTS mutation carriers and 35 healthy individuals (matched for age and sex) underwent an exercise test (Bruce protocol). ECG and doppler and speckle-tracking echo parameters were recorded at rest, peak exercise and recovery. RESULTS: We found that abnormal ventricular repolarization in LQTS carriers was related to marked LV mechanical dispersion and to abnormally reversed LV end-systolic electromechanical relationship and longitudinal early relaxation sequence. These phenomena worsened at peak exercise, especially in LQT1 carriers, and were related to impaired LV daistolic function and attenuated stroke volume response to exercise. Such abnormal electromechanical responses to exercise were more pronounces in LQTS subjects with previous adverse cardiac events and could better identigy these subjects than QTc interval alone. These disturbances were also less pronounced in LQTS carriers treated with b-blockers. CONCLUSION: Incorporating stress-echocardiograhic evaluation of electromechanical parameters in the routine assessment of LQTS individuals may help better stratification, symptom interpretation and management.
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| 15. |
- Chetaille, Philippe, et al.
(författare)
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Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:11, s. 1245-1249
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Tidskriftsartikel (refereegranskat)abstract
- The pacemaking activity of specialized tissues in the heart and gut results in lifelong rhythmic contractions. Here we describe a new syndrome characterized by Chronic Atrial and Intestinal Dysrhythmia, termed CAID syndrome, in 16 French Canadians and 1 Swede. We show that a single shared homozygous founder mutation in SGOL1, a component of the cohesin complex, causes CAID syndrome. Cultured dermal fibroblasts from affected individuals showed accelerated cell cycle progression, a higher rate of senescence and enhanced activation of TGF-beta signaling. Karyotypes showed the typical railroad appearance of a centromeric cohesion defect. Tissues derived from affected individuals displayed pathological changes in both the enteric nervous system and smooth muscle. Morpholino-induced knockdown of sgol1 in zebrafish recapitulated the abnormalities seen in humans with CAID syndrome. Our findings identify CAID syndrome as a novel generalized dysrhythmia, suggesting a new role for SGOL1 and the cohesin complex in mediating the integrity of human cardiac and gut rhythm.
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| 16. |
- Ekman Joelsson, B M, et al.
(författare)
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The outcome of children born with pulmonary atresia and intact ventricular septum in Sweden from 1980 to 1999.
- 2001
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Ingår i: Scandinavian cardiovascular journal : SCJ. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 35, s. 192-
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the outcome of all children born with pulmonary atresia and intact ventricular septum in Sweden between 1980 and 1999. DESIGN: Retrospective study of medical records with review of the initial, preoperative angiocardiographic and echocardiographic examinations. RESULTS: A total of 84 children were born with pulmonary atresia and intact ventricular septum, giving an incidence of 4.2 per 100,000 live births. In all, 77 were operated on with a 1-year survival rate of 75%. Thirty-six children had ventriculocoronary communications, with a 1-year survival rate of 50%. At the end of the study period, 52 children were alive, 32 with biventricular repair, and 19 with univentricular repair. Follow-up time was 14 days-20 years (median, 6 years). Statistical analysis of incremental risk factors for death showed statistical significance for low birth weight, male sex, muscular pulmonary atresia, and having a systemic-to-pulmonary shunt as the sole initial intervention. CONCLUSION: Complete national data of all patients born with pulmonary atresia and intact ventricular septum during 1980-1999 in Sweden revealed a total mortality in accordance with previous reports for results for surgery. Further improvements demand a thorough preoperative investigation of the cardiac anatomy, particularly of the ventriculocoronary communications, to enable right ventricular decompression whenever possible.
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| 17. |
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| 18. |
- Ekvall, Sara, 1982-, et al.
(författare)
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Novel association of neurofibromatosis type 1-causing mutations in families with neurofibromatosis-Noonan syndrome
- 2014
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Ingår i: American Journal of Medical Genetics. Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 164:3, s. 579-587
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Tidskriftsartikel (refereegranskat)abstract
- Neurofibromatosis-Noonan syndrome (NFNS) is a rare condition with clinical features of both neurofibromatosis type 1 (NF1) and Noonan syndrome (NS). All three syndromes belong to the RASopathies, which are caused by dysregulation of the RAS-MAPK pathway. The major gene involved in NFNS is NF1, but co-occurring NF1 and PTPN11 mutations in NFNS have been reported. Knowledge about possible involvement of additional RASopathy-associated genes in NFNS is, however, very limited. We present a comprehensive clinical and molecular analysis of eight affected individuals from three unrelated families displaying features of NF1 and NFNS. The genetic etiology of the clinical phenotypes was investigated by mutation analysis, including NF1, PTPN11, SOS1, KRAS, NRAS, BRAF, RAF1, SHOC2, SPRED1, MAP2K1, MAP2K2, and CBL. All three families harbored a heterozygous NF1 variant, where the first family had a missense variant, c.5425C>T;p.R1809C, the second family a recurrent 4bp-deletion, c.6789_6792delTTAC;p.Y2264Tfs*6, and the third family a splice-site variant, c.2991-1G>A, resulting in skipping of exon 18 and an in-frame deletion of 41 amino acids. These NF1 variants have all previously been reported in NF1 patients. Surprisingly, both c.6789_6792delTTAC and c.2991-1G>A are frequently associated with NF1, but association to NFNS has, to our knowledge, not previously been reported. Our results support the notion that NFNS represents a variant of NF1, genetically distinct from NS, and is caused by mutations in NF1, some of which also cause classical NF1. Due to phenotypic overlap between NFNS and NS, we propose screening for NF1 mutations in NS patients, preferentially when café-au-lait spots are present.
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| 19. |
- Frid, Christina, et al.
(författare)
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Long-term survival in children with atrioventricular septal defect and common atrioventricular valvar orifice in Sweden.
- 2004
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Ingår i: Cardiology in the young. - : Cambridge University Press (CUP). - 1047-9511 .- 1467-1107. ; 14:1, s. 24-31
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The survival for patients with atrioventricular septal defect has improved markedly over the last decades and, during the same period, the survival of children with Down's syndrome has also increased. The aim of our study was to investigate long-term survival in patients having atrioventricular septal defect with common valvar orifice, but without associated significant congenital heart defects, in the setting of Down's syndrome, comparing the findings to those in chromosomally normal children with the same malformation. METHODS AND RESULTS: In a population-based retrospective study, we scrutinised the medical records from 801 liveborn children with atrioventricular septal defect born in Sweden during the period 1973 through 1997. Data on gender, presence or absence of Down's syndrome, associated congenital heart defects, date of birth, operation and death were recorded and followed up until 2001. An isolated atrioventricular septal defect with common atrioventricular valvar orifice was present in 502 children, of whom 86% had Down's syndrome. We found a significant reduc tion over time in age at operation, and in postoperative mortality at 30 days, from 28 to 1%. Using a multiple logistic regression model, we found no significant differences in mortality between genders, nor between those with or without Down's syndrome. Early corrective surgery could not be identified as a significant independent factor for survival. The 5-year postoperative survival in patients with Down's syndrome increased from 65% over the period from 1973 through 1977, to about 90% in the period 1993 through 1997, and the same trend was observed in chromosomally normal patients. CONCLUSIONS: Survival in uncomplicated atrioventricular septal defect with common atrioventricular valvar orifice has greatly increased, and surgical correction is now equally successful in patients with Down's syndrome and chromosomally normal patients, and for both genders. Death in connection with surgery is no longer the major threat, and focus must now be on long-term follow-up.
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| 20. |
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| 21. |
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| 22. |
- Hamberg, Anna-Karin, 1964-, et al.
(författare)
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Warfarin dose prediction in children using pharmacometric bridging : comparison with published pharmacogenetic dosing algorithms
- 2013
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 69:6, s. 1275-1283
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Tidskriftsartikel (refereegranskat)abstract
- PurposeNumerous studies have investigated causes of warfarin dose variability in adults whereas studies in children are limited both in numbers and size. Mechanism-based population modelling provides an opportunity to condense and propagate prior knowledge from one population to another. The main objectives with this study were to evaluate the predictive performance of a theoretically bridged adult warfarin model in children, and to compare accuracy in dose prediction relative to published warfarin algorithms for children.MethodAn adult population PK/PD-model for warfarin, with CYP2C9 and VKORC1 genotype, age and target INR as dose predictors, was bridged to children using allometric scaling methods. Its predictive properties were evaluated in an external dataset of children 0-18 years old, including comparison of dose prediction accuracy with three pharmacogenetics-based algorithms for children.ResultsOverall, the bridged model predicted INR response well in 64 warfarin treated Swedish children (median age 4.3 years), but with a tendency to over predict INR in children ≤ 2 years old. The bridged model predicted 20 of 49 children (41%) within ± 20% of actual maintenance dose (median age 7.2 years). In comparison the published dosing algorithms predicted 33-41% of the children within ± 20% of actual dose. Dose optimization with the bridged model based on up to three individual INR observations increased the proportion within ± 20% of actual dose to 70%.ConclusionA mechanism-based population model developed on adult data provides a promising first step towards more individualized warfarin therapy in children.
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| 23. |
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| 24. |
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| 25. |
- Jonzon, Anders
(författare)
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Arytmier hos barn
- 2006
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Ingår i: Barnbladet. ; :3, s. 12-14
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 26. |
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| 27. |
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| 28. |
- Lutzen, Therese, et al.
(författare)
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Syndrom och hjärtfel
- 2006
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Ingår i: Pediatrisk Endokrinologi. ; 20, s. 52-59
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Tidskriftsartikel (refereegranskat)
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| 29. |
- Markasz, Laszlo, et al.
(författare)
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CD44 and RHAMM expression patterns in the human developing lung
- 2021
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Ingår i: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 89, s. 134-142
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Tidskriftsartikel (refereegranskat)abstract
- Background: The hyaluronan (HA) receptors CD44 and RHAMM (CD168) are involved in cellular proliferation, differentiation, and motility. As previously investigated, HA and RHAMM expression in human neonatal lungs correlates to gestational age (GA) and air content.Methods: CD44 immunofluorescence was analyzed in postmortem lung samples from infants (n=93;22-41GA) by digital image analysis together with clinical data, including RHAMM expression, lung air and HA content by hierarchical clustering.Results: Five groups were defined according to RHAMM/CD44 expression, GA, and postnatal age (PNA): extremely-to-very preterm (EVP;22-31GA; Groups 1-2), moderately preterm-to-term (MPT;31-41GA; Groups 3-4) and mixed preterm-to-term (27-40GA; Group 5). CD44 correlated linearly with RHAMM in MPT (r=0.600;p<0.004). In EVP, high CD44 and low RHAMM corresponded with high PNA and lung air content independently of HA and GA (Group 1 vs 2;p<0.05 respectively). In MPT, high and low CD44 corresponded with low and high RHAMM independently of GA, HA and lung air content (Group 3 vs 4;p<0.001). No correlation between CD44 and GA/PNA at death was observed. Conclusions: A linear correlation between CD44 and RHAMM expression occurs during the late saccular phase of lung development at birth, whereas postnatal influences on CD44 and RHAMM expression in extremely-to-very preterm infants cannot be excluded.
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| 30. |
- Matsson, Hans, et al.
(författare)
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Alpha-cardiac actin mutations produce atrial septal defects.
- 2008
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 17:2, s. 256-65
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Tidskriftsartikel (refereegranskat)abstract
- Atrial septal defect (ASD) is one of the most frequent congenital heart defects (CHDs) with a variable phenotypic effect depending on the size of the septal shunt. We identified two pedigrees comprising 20 members segregating isolated autosomal dominant secundum ASD. By genetic mapping, we identified the gene-encoding alpha-cardiac actin (ACTC1), which is essential for cardiac contraction, as the likely candidate. A mutation screen of the coding regions of ACTC1 revealed a founder mutation predicting an M123V substitution in affected individuals of both pedigrees. Functional analysis of ACTC1 with an M123V substitution shows a reduced affinity for myosin, but with retained actomyosin motor properties. We also screened 408 sporadic patients with CHDs and identified a case with ASD and a 17-bp deletion in ACTC1 predicting a non-functional protein. Morpholino (MO) knockdown of ACTC1 in chick embryos produces delayed looping and reduced atrial septa, supporting a developmental role for this protein. The combined results indicate, for the first time, that ACTC1 mutations or reduced ACTC1 levels may lead to ASD without signs of cardiomyopathy.
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| 31. |
- Michaëlsson, Magnus, et al.
(författare)
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Isolated congenital complete atrioventricular heart block in adult life : A prospective study
- 1995
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 92:3, s. 442-449
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The prognosis of congenital complete atrioventricular block (CCHB) is usually considered favorable in adults. This belief is based on studies comprising a limited number of patients and with rather short observation times. In the present study, the natural history of the disease was investigated by a prospective follow-up through decades of adult life of patients with a large group having well-defined CCHB without structural heart disease. METHODS AND RESULTS: The diagnostic criteria of CCHB proposed by Yater were applied. Patients registered as having CCHB in 1964, supplemented by younger patients all without symptoms during their first 15 years of life, were selected. The study was limited to patients with isolated, complete, permanent block. An interview was conducted with all patients and clinical follow-up data obtained. There were finally 102 patients, 61 women and 41 men. In November 1994, the time of observation, after the age of 15 years in survivors, was between 7 and 30 years. The mean age at follow-up or at death was 38 years, median age 37 years, and range 16 to 66 years. Stokes-Adams (SA) attacks occurred in 27 patients, in 8 with a fatal outcome. The first attack was fatal in 6 of these 8 patients. Nineteen survived and a pacemaker (PM) was implanted thereafter. Another 8 patients received a PM because of repeated fainting spells, and 27 others have had a PM implanted for other reasons such as fatigue, effort dyspnea, dizziness, ectopies during exercise tests, mitral regurgitation, and a low ventricular rate (VR). VR decreased with age, with a mean rate at 15 years of 46 beats per minute (bpm), at 16 to 20 years of 43 bpm, at 21 to 30 years of 41 bpm, at 31 to 40 years of 40 bpm, and after 40 years of age of 39 bpm. SA attacks occurred in all 7 patients with prolonged QTc time. Low VR at rest or at work, presence of bundle-branch block pattern, low working capacity, and ectopies at rest and/or during effort were not statistically significant risk factors. SA attacks occurred in 6 patients without any of these signs. Mitral regurgitation developed in 16 patients and 4 died. A PM reduced the risk of death. A change to a lower degree of block occurred in 6 patients. CONCLUSIONS: Prophylactic PM treatment is recommended even for symptom-free adults with CCHB because of the high incidence of unpredictable SA attacks with considerable mortality from first attacks, a gradually decreasing VR, significant morbidity, and a high incidence of "acquired" mitral insufficiency.
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| 32. |
- Michaëlsson, Magnus, et al.
(författare)
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Natural history of congenital complete atrioventricular block
- 1997
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Ingår i: Pacing and Clinical Electrophysiology. - : Wiley. - 0147-8389 .- 1540-8159. ; 20:8 Pt 2, s. 2098-2101
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Tidskriftsartikel (refereegranskat)abstract
- An update of studies on the natural history of congenital complete AV block is presented. A risk for heart failure, syncope, and sudden death is present at any age including fetal life. Unfavorable prognostic signs in utero are low and decreasing ventricular rate (VR), hydrops, AV valve regurgitation, and low aortic flow velocity. Indications for pacing in infancy are congestive heart failure, ventricular rate < 55 beats/min in isolated block and < 65 beats/min with associated disease, prolonged OTc, syncope attacks, frequent ventricular ectopic beats, and alternating ventricular pacemakers. Indications for immediate pacing in childhood and adult life are syncope, presyncope, VR rates lower than median for age, periods of junctional exit block, prolongation of QTc and mitral regurgitation, and change of ventricular pacemaker. Pacing is recommended to all patients older than 15 years.
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| 33. |
- Naumburg, Estelle, et al.
(författare)
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Perinatal exposure to infection and risk of childhood leukemia
- 2002
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Ingår i: Medical and Pediatric Oncology. - : Wiley. - 0098-1532 .- 1096-911X. ; 38, s. 391-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A population-based case-control study was conducted to investigate the association between childhood leukemia and infectious exposures during pregnancy and early neonatal period.PROCEDURE: Children born and diagnosed with leukemia between 1973 and 1989 in Sweden (578 lymphatic, 74 myeloid) were selected as cases. One control was randomly selected for each case and individually matched by sex, month, and year of birth. Children with Down's syndrome were excluded. Exposure data were blindly abstracted from antenatal, obstetric, and other standardized medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by conditional logistic regression.RESULTS: A history of maternal infection was not significantly associated with childhood leukemia, OR = 1.25 (95% CI 0.95-1.65). Maternal lower genital tract infection significantly increased the risk of childhood leukemia, OR = 1.78 (95% CI 1.17-2.72), and especially for children over 4 years of age at diagnosis, OR = 2.01 (95% CI 1.12-3.80). Neonatal infection was not associated with the risk of leukemia. The results remained unaltered after adjustment for potential confounders, and separate analyses for myeloid and lymphoid leukemia.CONCLUSIONS: We could document an association between exposure to maternal lower genital tract infection in utero, and a subsequent risk for childhood leukemia, which indicate the importance of an early exposure.
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| 34. |
- Naumburg, Estelle, et al.
(författare)
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Supplementary oxygen and risk of childhood lymphatic leukaemia
- 2002
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Ingår i: Acta Paediatrica. - 0803-5253 .- 1651-2227. ; 91, s. 1328-
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Childhood leukaemia has been linked to several factors, such as asphyxia and birthweight, which in turn are related to newborn resuscitation. Based on the findings from a previous study a population-based case-control study was performed to investigate the association between childhood leukaemia and exposure to supplementary oxygen and other birth-related factors.METHODS: Children born in Sweden and diagnosed with lymphatic leukaemia between 1973 and 1989 (578 cases) were individually matched by gender and date of birth to a randomly selected control. Children with Down's syndrome were excluded. Exposure data were blindly gathered from antenatal, obstetric and other standardized medical records. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated by conditional logistic regression.RESULTS: Resuscitation with 100% oxygen with a facemask and bag immediately postpartum was significantly associated with an increased risk of childhood lymphatic leukaemia (OR = 2.57, 95% Cl 1.21-6.82). The oxygen-related risk further increased if the manual ventilation lasted for 3 min or more (OR = 3.54, 95% CI 1.16-10.80). Low Apgar scores at 1 and 5 min were associated with a non-significantly increased risk of lymphatic leukaemia. There were no associations between lymphatic leukaemia and supplementary oxygen later in the neonatal period or other birth-related factors.CONCLUSION: Resuscitation with 100% oxygen immediately postpartum is associated with childhood lymphatic leukaemia, but further studies are warranted to confirm the findings.
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| 35. |
- Nilsson, Manja C. A., 1966-, et al.
(författare)
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Hypercapnic acidosis transiently weakens hypoxic pulmonary vasoconstriction in anesthetized pigs, without affecting the endogenous pulmonary nitric oxide production.
- 2012
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 38:3, s. 509-517
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Hypercapnic acidosis often occurs in critically ill patients and during protective mechanical ventilation; however, the effect of hypercapnic acidosis on endogenous nitric oxide (NO) production and hypoxic pulmonary vasoconstriction (HPV) presents conflicting results. The aim of this study is to test the hypothesis that hypercapnic acidosis augments HPV without changing endogenous NO production in both hyperoxic and hypoxic lung regions in pigs. Methods Sixteen healthy anesthetized pigs were separately ventilated with hypoxic gas to the left lower lobe (LLL) and hyperoxic gas to the rest of the lung. Eight pigs received 10% carbon dioxide (CO2) inhalation to both lung regions (hypercapnia group), and eight pigs formed the control group. NO concentration in exhaled air (ENO), nitric oxide synthase (NOS) activity, cyclic guanosine monophosphate (cGMP) in lung tissue, and regional pulmonary blood flow were measured. Results There were no differences between the groups for ENO, Ca2+-independent or Ca2+-dependent NOS activity, or cGMP in hypoxic or hyperoxic lung regions. Relative perfusion to LLL (Q LLL/Q T) was reduced similarly in both groups when LLL hypoxia was induced. During the first 90 min of hypercapnia, Q LLL/Q T increased from 6% (1%) [mean (standard deviation, SD)] to 9% (2%) (p < 0.01), and then decreased to the same level as the control group, where Q LLL/Q T remained unchanged. Cardiac output increased during hypercapnia (p < 0.01), resulting in increased oxygen delivery (p < 0.01), despite decreased PaO2 (p < 0.01). Conclusions Hypercapnic acidosis does not potentiate HPV, but rather transiently weakens HPV, and does not affect endogenous NO production in either hypoxic or hyperoxic lung regions.
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| 36. |
- Olsson, Karl Wilhelm, 1985-, et al.
(författare)
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A High Ductal Flow Velocity is Associated with Successful Pharmacological Closure of Patent Ductus Arteriosus in Infants 22-27 Weeks Gestational Age
- 2012
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Ingår i: Critical Care Research and Practice. - : Hindawi Limited. - 2090-1305 .- 2090-1313. ; , s. 715265-
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To identify factors affecting closure of patent ductus arteriosus (PDA) in newborn infants born at 22-27 weeks gestational age (GA) during pharmacological treatment with cyclooxygenase inhibitors.Method:Infants born at 22-27 weeks of GA between January 2006 and December 2009 who had been treated pharmacologically for PDA were identified retrospectively. Medical records were assessed for clinical, ventilatory and outcome parameters. Echocardiographic examinations during treatment were reviewed.Results:Fifty-six infants were included in the study. Overall success rate of ductal closure with pharmacological treatment was 52%. Infants whose PDA was successfully closed had a higher GA (25+4 weeks vs. 24+3 weeks; P=0.047), and a higher pre-treatment left to right maximal ductal flow velocity (1.6 m/s vs. 1.1 m/s; P=0.023). Correcting for GA, preeclampsia, antenatal steroids, and age at treatment start, a higher maximal ductal flow velocity was still associated with successful ductal closure (OR 3.04, p=0.049).Conclusion:Maximal ductal flow velocity was independently associated with success of PDA treatment.
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| 37. |
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| 38. |
- Olsson, Karl Wilhelm, 1985-, et al.
(författare)
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Early haemodynamically significant patent ductus arteriosus does not predict future persistence in extremely preterm infants
- 2019
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Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 108:9, s. 1590-1956
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Tidskriftsartikel (refereegranskat)abstract
- AimWe assessed whether early haemodynamically significant patent ductus arteriosus (hsPDA) predicted persistent patent ductus arteriosus (PDA) in extremely preterm infants.MethodsThis prospective observational study of 60 infants born at 22–27 weeks of gestational age (GA) without any major congenital anomalies or heart defects was conducted at Uppsala University Children's Hospital from November 2012 to May 2015. Respiratory and systemic circulatory parameters were continuously recorded, and echocardiographic examinations performed daily during the first three days of life. Pharmacological treatment was initiated if hsPDA was found on days two to seven. Persistent PDA was diagnosed if hsPDA remained after pharmacological treatment or pharmacological treatment was contraindicated.ResultsThe infants (56% male) had a median GA of 25 + 2 weeks and 50% received pharmacological treatment. PDA was persistent in 30% and ultimately closed or insignificant in 70%. hsPDA on days two to seven was not associated with future persistent PDA (p = 1.000). Mechanical ventilation (p = 0.025), high mean airway pressure (p = 0.020) and low ductal maximal flow velocity (Vmax) (p = 0.024) on day two were associated with future persistent PDA.ConclusionEarly hsPDA did not predict persistent PDA, but the early need for assisted ventilation and low ductal Vmax were associated with future persistent PDA in these extremely preterm infants.
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| 39. |
- Olsson, Karl Wilhelm, 1985-, et al.
(författare)
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Low Ductal Peak Flow Velocity Prior to Pharmacological Patent Ductus Arteriosus Treatment Predicts Treatment Failure in Extremely Preterm Infants
- 2010
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Konferensbidrag (refereegranskat)abstract
- BACKGROUNDPatent ductus arteriosus (PDA) is frequent in preterm infants and associated with increased mortality and morbidity. Low gestational ages (GA), sepsis and lack of prenatal steroid exposure are previously identified predictors of pharmacological PDA treatment failure.OBJECTIVETo identify early factors affecting ductal closure during pharmacological treatment in extremely preterm infants, with special focus on pulmonary circulation.DESIGN/METHODSNewborn infants, born at 22-27 gestational weeks between January 2006 and December 2008 at Uppsala University Children's Hospital and pharmacologically treated for PDA, were retrospectively identified (Figure 1). Medical charts were assessed for the first day of life, for the days of echocardiographic examination and for the days of treatment. Perinatal factors, vital parameters, ventilatory settings, treatments, fluid intake, complications and outcomes were registered and pre-treatment echocardiography was reviewed. Follow-up echocardiography defined successful or failed ductal closure. RESULTSThirty-two infants were identified (Figure 1). Prophylactic treatment was initiated 3 days after birth (range 1-8) in both groups (P=0.952) with one single course of 3-5 doses indomethacin (n=28) or ibuprofen (n=3).Infants who failed closure had lower GA (23+6 weeks vs. 25+6 weeks, P=0.048), higher median heart rate during first day of life (155 bpm vs. 145 bpm, P=0.027), were on ventilator 20%, P=0.004), and required longer total time of ventilatory support during hospital stay (28 days vs. 4 days, P=0.013). Other perinatal factors, vital parameters, treatments and fluid intake and incidences of BPD, IVH, NEC and ROP were similar between groups.Pre-treatment echocardiography revealed lower left to right ductal peak flow velocity in infants that failed closure (P=0.009, Figure 2). When adjusted for ductal diameter, low peak flow velocity was still associated with pharmacological treatment failure (P=0.017), indicating that higher pulmonary arterial pressure might oppose ductal constriction after birth (Figure 3). CONCLUSIONSLow ductal peak flow velocity is an early predictor of pharmacological PDA treatment failure in extremely preterm infants, possibly reflecting the influence of pulmonary arterial pressure on ductus constriction.
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| 40. |
- Rieger-Fackeldey, Esther, et al.
(författare)
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Bronchopulmonary C-fibers modulate the breathing pattern in surfactant-depleted juvenile cats
- 2008
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Ingår i: Respiratory Physiology & Neurobiology. - : Elsevier BV. - 1569-9048 .- 1878-1519. ; 160:3, s. 341-349
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the influence of nonmyelinated C-fibers on the breathing pattern by cooling the vagal nerves to temperatures at which myelinated nerve transmission from pulmonary stretch receptors is blocked (+7 degrees C) and further at which nonmyelinated fiber input is blocked (0 degrees C), in anaesthetized spontaneously breathing juvenile cats with normal (L(N)), surfactant-depleted (L(D)) and surfactant-treated (L(T)) lungs. In L(N), vagal cooling from +7 to 0 degrees C decreased respiratory frequency (f(R); -8%; p < 0.01), and increased tidal volume (V(T); +40%; p < 0.01). In the presence of shallow fast breathing in L(D), f(R) decreased (+38 to +7 degrees C: -26%; p < 0.015 and +7 to 0 degrees C: -24%; p < 0.001) and V(T) increased (+37%; p < 0.049 and +88%; p < 0.016). In L(T), f(R) decreased (+7 to 0 degrees C: -21%; p < 0.001), whereas V(T) remained the same at 0 degrees C (+12%; NS). These findings show for the first time that the activity of bronchopulmonary C-fibers have a prominent role in modulating the breathing pattern in juvenile cats with surfactant-depleted lungs.
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| 41. |
- Rieger-Fackeldey, Esther, et al.
(författare)
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Inhibition of breathing after Surfactant Depletion is Achieved at a Higher Arterial PCO2 during Ventilation with Liquid than with Gas
- 2005
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 6, s. 24-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundInhibition of phrenic nerve activity (PNA) can be achieved when alveolar ventilation is adequate and when stretching of lung tissue stimulates mechanoreceptors to inhibit inspiratory activity. During mechanical ventilation under different lung conditions, inhibition of PNA can provide a physiological setting at which ventilatory parameters can be compared and related to arterial blood gases and pH.ObjectiveTo study lung mechanics and gas exchange at inhibition of PNA during controlled gas ventilation (GV) and during partial liquid ventilation (PLV) before and after lung lavage.MethodsNine anaesthetised, mechanically ventilated young cats (age 3.8 ± 0.5 months, weight 2.3 ± 0.1 kg) (mean ± SD) were studied with stepwise increases in peak inspiratory pressure (PIP) until total inhibition of PNA was attained before lavage (with GV) and after lavage (GV and PLV). Tidal volume (Vt), PIP, oesophageal pressure and arterial blood gases were measured at inhibition of PNA. One way repeated measures analysis of variance and Student Newman Keuls-tests were used for statistical analysis.ResultsDuring GV, inhibition of PNA occurred at lower PIP, transpulmonary pressure (Ptp) and Vt before than after lung lavage. After lavage, inhibition of inspiratory activity was achieved at the same PIP, Ptp and Vt during GV and PLV, but occurred at a higher PaCO2 during PLV. After lavage compliance at inhibition was almost the same during GV and PLV and resistance was lower during GV than during PLV.ConclusionInhibition of inspiratory activity occurs at a higher PaCO2 during PLV than during GV in cats with surfactant-depleted lungs. This could indicate that PLV induces better recruitment of mechanoreceptors than GV.
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| 42. |
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| 43. |
- Rieger-Fackeldey, Esther, et al.
(författare)
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Pulmonary stretch receptor activity during partial liquid ventilation with different pressure waveforms
- 2020
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Ingår i: Respiratory Physiology & Neurobiology. - : Elsevier BV. - 1569-9048 .- 1878-1519. ; 276
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of the present study was to investigate pulmonary stretch receptor activity (PSR) under different peak inspiratory pressures (PIPs) and inspiratory pressure waveforms during partial liquid (PLV) and gas ventilation (GV).METHODS: PSR instantaneous impulse frequency (PSRfimp) was recorded from single fibers in the vagal nerve during PLV and GV in young cats. PIPs were set at 1.2/1.8/2.2/2.7 kPa, and square and sinusoidal pressure waveforms were applied.RESULTS: PSRfimp at the start of inspiration increased with increasing PIPs, and was steeper and higher with square than with sinusoidal waveforms (p < 0.05). Total number of impulses, peak and mean PSRfimp were lower during PLV than GV at the lowest and highest PIPs (p < 0.025). Time to peak PSRfimp was shorter with square than with sinusoidal waveforms at all pressures and ventilations (p < 0.005). Irrespective of waveform, lower PIPs yielded lower ventilation during PLV.CONCLUSION: As assessed by PSRfimp, increased PIPs do not expose the lungs to more stretching during PLV than during GV, with only minor differences between square and sinusoidal waveforms.
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| 44. |
- Rieger-Fackeldey, Esther, 1960-
(författare)
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Regulation of Breathing under Different Pulmonary Conditions
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The breathing pattern of preterm infants is immature and is associated with a variety of reflexes. In a patient on the ventilator these reflexes interfere with spontaneous breathing. A better understanding of the immature control of breathing could lead to further improvements in ventilatory techniques. This thesis concerns studies of pulmonary stretch receptor (PSR) and phrenic nerve activity as part of the regulation of breathing in an animal model.During assist/control ventilation with three different inspiratory pressure waveforms in animals with healthy lungs, squarewave pressure waveform strongly inhibits spontaneous inspiratory activity.During partial liquid ventilation (PLV) in animals with healthy lungs, all PSRs studied maintained their phasic character, with increased impulse frequency during inspiration. PSR activity was not higher during PLV than during gas ventilation (GV), indicating that there was no extensive stretching of the lung during PLV.During proportional assist ventilation (PAV) the applied airway pressure is servo-controlled proportionally to the ongoing breathing effort, thereby interacting with the activity of PSRs. Peak PSR activity was higher and occurred earlier during PAV than during CPAP. The regulation of breathing is maintained during PAV in surfactant-depleted animals before and early after surfactant instillation, with a higher ventilatory response and a lower breathing effort than during CPAP in both conditions.Both lung mechanics and gas exchange influence the regulation of breathing. Inhibition of inspiratory activity occurred at a lower arterial pH and a higher PaCO2 during PLV than during GV in animals with surfactant-depleted lungs, which might be related to recruitment of a larger number of pulmonary stretch receptors during PLV.In summary, selected aspects of the regulation of breathing were studied in an animal model with different ventilatory techniques under different lung conditions similar to those that can occur in infants.
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| 45. |
- Salomonsson, S., et al.
(författare)
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A Population-based Investigation of the Autoantibody Profile in Mothers of Children with Atrioventricular Block
- 2011
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Ingår i: Scandinavian Journal of Immunology. - Oxford : Blackwell Publishing. - 0300-9475 .- 1365-3083. ; 74:5, s. 511-517
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Tidskriftsartikel (refereegranskat)abstract
- The objective of the study was to investigate the antigen specificity and occurrence of individual autoantibodies in mothers of children diagnosed with atrioventricular (AV) block in a nation-wide setting. Patients with AV block detected before 15 years of age were identified using national quality registries as well as a network of pediatric and adult cardiologists and rheumatologists at the six university hospitals in Sweden. Patients with gross heart malformations, surgically or infectiously induced blocks were excluded. Blood samples were obtained from the mothers and maternal autoantibody profile, including the occurrence of antibodies against Ro52, Ro60, La, SmB, SmD, RNP-70k, RNP-A, RNP-C, CENP-C, Scl-70, Jo-1, ribosomal RNP and histones was investigated in 193 mothers of children with AV block by immunoblotting and ELISA. Autoantibody reactivity was detected in 48% (93/193) of the mothers of children with AV block. In autoantibody-positive mothers, the vast majority, 95% (88/93), had antibodies against Ro52, while 63% (59/93) had autoantibodies to Ro60 and 58% (54/93) had autoantibodies to La. In addition, 13% (12/93) of the autoantibody-positive mothers had antibodies to other investigated antigens besides Ro52, Ro60 and La, and of these anti-histone antibodies were most commonly represented, detected in 8% (7/93) of the mothers. In conclusion, this Swedish population-based study confirms that maternal autoantibodies may associate with heart block in the child. Further, our data demonstrate a dominant role of Ro52 antibodies in association with AV block.
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| 46. |
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| 47. |
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| 48. |
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| 49. |
- Sindelar, Richard, et al.
(författare)
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Effects of the inspiratory pressure waveform during patient-triggered ventilation on pulmonary stretch receptor and phrenic nerve activity in cats
- 2001
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 29:6, s. 1207-1214
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To examine the effects of square wave, sinusoidal, and linear inspiratory pressure waveforms during pressure-controlled assist/control ventilation on the firing pattern of pulmonary stretch receptors and phrenic nerve activity.Design:Experimental, comparative study.Setting:Research laboratory at a university biomedical center.Subjects:Nine anesthetized, endotracheally intubated young cats (2.5–3.4 kg).Intervention:With interposed periods of continuous positive airway pressure (0.2 kPa), each cat was exposed to periods of assist/control ventilation with three different pressure waveforms, where the peak inspiratory pressure (0.74 ± 0.13 kPa), end-expiratory pressure (0.2 ± 0.02 kPa), and tidal volume (14.9 ± 5.22 mL/kg) were kept constant. Preset controlled ventilator rate was set below the rate of spontaneous breathing, and the mechanical inflation time equaled the inspiratory time during spontaneous breathing on continuous positive airway pressure.Measurements and Main Results:Respiratory rate and arterial blood gases did not change between the three pressure waveforms during assist/control ventilation. Peak pulmonary stretch receptor activity was lower and mean phrenic nerve activity higher during continuous positive airway pressure than during assist/control ventilation (p < .05). Peak inspiratory pulmonary stretch receptor activity was the same with all three pressure waveforms (82 ± 17 impulses·sec-1) but occurred earlier with square wave than with sinusoidal or linear pressure waveforms (p < .05). The total number of impulses in the phrenic nerve activity burst was smaller with square wave than with the other two pressure waveforms (0.21 ± 0.17 vs. 0.33 ± 0.27 and 0.42 ± 0.30 arbitrary units;p < .05), and the phrenic nerve activity burst duration was shorter with square wave (1.10 ± 0.45 vs. 1.54 ± 0.36 and 1.64 ± 0.25 secs;p < .05).Conclusion:Square wave pressure waveform during pressure-controlled assist/control ventilation strongly inhibits spontaneous inspiratory activity in cats. One mechanism for this inhibition is earlier and sustained peak pulmonary stretch receptor activity during inspiration. These findings show that differences in inspiratory pressure waveforms influence the spontaneous breathing effort during assist/control ventilation in cats.
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| 50. |
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