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Sökning: WFRF:(Nilsson Staffan 1956)

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1.
  • Bergström, Petra, et al. (författare)
  • Association of NFE2L2 and KEAP1 haplotypes with amyotrophic lateral sclerosis.
  • 2014
  • Ingår i: Amyotrophic lateral sclerosis & frontotemporal degeneration. - : Informa UK Limited. - 2167-9223 .- 2167-8421. ; 15:1-2, s. 130-137
  • Tidskriftsartikel (refereegranskat)abstract
    • Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron syndrome influenced by oxidative stress. The transcription factor Nrf2 and its repressor Keap1 constitute an important defence system in cellular protection against oxidative stress. Here we hypothesize that common genetic variations in the genes NFE2L2 and KEAP1, encoding Nrf2 and Keap1, may influence the risk and phenotype of ALS. Five hundred and twenty-two Swedish patients with sporadic ALS (SALS) and 564 Swedish control subjects were studied. Eight tag SNPs in NFE2L2 and three tag SNPs in KEAP1 were genotyped by allelic discrimination and three functional NFE2L2 promoter SNPs were genotyped by sequencing. One NFE2L2 haplotype (GGGAC) was associated with decreased risk of SALS (OR = 0.62 per allele, p = 0.003) and one haplotype in KEAP1 (CGG) was associated with later SALS onset (+3.4 years per allele, p = 0.015). When stratified by subgroup, one haplotype in NFE2L2, GAGCAGA including three functional promoter SNPs associated with high Nrf2 protein expression, was associated with 4.0 years later disease onset per allele in subgroup ALS (p = 0.008). In conclusion, these results suggest that variations in NFE2L2 and KEAP1, encoding two central proteins in cellular oxidative stress defence, may influence SALS pathogenesis.
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2.
  • Einarsdottir, Sigrun, et al. (författare)
  • Deficiency of SARS-CoV-2 T-cell responses after vaccination in long-term allo-HSCT survivors translates into abated humoral immunity.
  • 2022
  • Ingår i: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 6:9, s. 2723-2730
  • Tidskriftsartikel (refereegranskat)abstract
    • Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological diseases are at risk of severe disease and death from COVID-19. To determine the safety and immunogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines, samples from 50 infection-naive allo-HSCT recipients (median, 92 months from transplantation, range, 7-340 months) and 39 healthy controls were analyzed for serum immunoglobulin G (IgG) against the receptor binding domain (RBD) within spike 1 (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; anti-RBD-S1 IgG) and for SARS-CoV-2-specific T-cell immunity, reflected by induction of T-cell-derived interferon-γ in whole blood stimulated ex vivo with 15-mer SI-spanning peptides with 11 amino acid overlapS1-spanning peptides. The rate of seroconversion was not significantly lower in allo-transplanted patients than in controls with 24% (12/50) and 6% (3/50) of patients remaining seronegative after the first and second vaccination, respectively. However, 58% of transplanted patients lacked T-cell responses against S1 peptides after 1 vaccination compared with 19% of controls (odds ratio [OR] 0.17; P = .009, Fisher's exact test) with a similar trend after the second vaccination where 28% of patients were devoid of detectable specific T-cell immunity, compared with 6% of controls (OR 0.18; P = .02, Fisher's exact test). Importantly, lack of T-cell reactivity to S1 peptides after vaccination heralded substandard levels (<100 BAU/mL) of anti-RBD-S1 IgG 5 to 6 months after the second vaccine dose (OR 8.2; P = .007, Fisher's exact test). We conclude that although allo-HSCT recipients achieve serum anti-RBD-S1 IgG against SARS-CoV-2 after 2 vaccinations, a deficiency of SARS-CoV-2-specific T-cell immunity may subsequently translate into insufficient humoral responses.
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3.
  • Melke, Jonas, 1971, et al. (författare)
  • A polymorphism in the serotonin receptor 3A (HTR3A) gene and its association with harm avoidance in women.
  • 2003
  • Ingår i: Archives of general psychiatry. - : American Medical Association (AMA). - 0003-990X. ; 60:10, s. 1017-23
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The brain neurotransmitter serotonin is known to affect various aspects of human behavior, including personality traits. Serotonin receptor type 3 is a ligand-gated channel encoded by 2 different subunit genes, HTR3A and HTR3B. A polymorphism (C178T) in the 5' region of the HTR3A gene has recently been identified and suggested to be of functional importance. OBJECTIVE: To elucidate the possible association between the C178T polymorphism in the HTR3A gene and personality traits in women. DESIGN: Two independent samples of 35- to 45-year-old Swedish women were recruited using the population register. Sample 1 (n = 195) was assessed via the Karolinska Scales of Personality and the Temperament and Character Inventory; sample 2 (n = 175) was assessed using the latter only. Both samples were genotyped with respect to the C178T polymorphism in the HTR3A gene. The A1596G polymorphism in the same gene was also investigated. RESULTS: A significant association between C178T genotype and the Temperament and Character Inventory factor harm avoidance was observed in sample 1 (corrected for multiple comparisons P =.04); this finding was subsequently replicated in sample 2 (P =.004) (pooled populations: P<.001). In the pooled sample, all harm avoidance subscales were found to be significantly associated with the C178T polymorphism: anticipatory worry (P =.001), fear of uncertainty (P<.001), shyness (P<.001), and fatigability and asthenia (P =.008). In addition, a significant association was found in sample 1 between the C178T polymorphism and the Karolinska Scales of Personality nonconformity factor (corrected P =.002), including the subscales of social desirability (P<.001), indirect aggression (P =.002), verbal aggression (P =.05), and irritability (P<.001). Participants homozygous for the less common T allele (<4%) differed from the remaining women by displaying lower ratings on harm avoidance and nonconformity. CONCLUSION: The C178T polymorphism in the HTR3A gene may affect the personality trait of harm avoidance in women.
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4.
  • Tomic, Tajana Tesan, et al. (författare)
  • MYO5B mutations in pheochromocytoma/paraganglioma promote cancer progression
  • 2020
  • Ingår i: PLOS Genetics. - : Public Library of Science. - 1553-7390 .- 1553-7404. ; 16:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Identification of additional cancer-associated genes and secondary mutations driving the metastatic progression in pheochromocytoma and paraganglioma (PPGL) is important for subtyping, and may provide optimization of therapeutic regimens. We recently reported novel recurrent nonsynonymous mutations in the MYO5B gene in metastatic PPGL. Here, we explored the functional impact of these MYO5B mutations, and analyzed MYO5B expression in primary PPGL tumor cases in relation to mutation status. Immunohistochemistry and mRNA expression analysis in 30 PPGL tumors revealed an increased MYO5B expression in metastatic compared to non-metastatic cases. In addition, subcellular localization of MYO5B protein was altered from cytoplasmic to membranous in some metastatic tumors, and the strongest and most abnormal expression pattern was observed in a paraganglioma harboring a somatic MYO5B:p.G1611S mutation. In addition to five previously discovered MYO5B mutations, the present study of 30 PPGL (8 previous and 22 new samples) also revealed two, and hence recurrent, mutations in the gene paralog MYO5A. The three MYO5B missense mutations with the highest prediction scores (p.L587P, p.G1611S and p.R1641C) were selected and functionally validated using site directed mutagenesis and stable transfection into human neuroblastoma cells (SK-N-AS) and embryonic kidney cells (HEK293). In vitro analysis showed a significant increased proliferation rate in all three MYO5B mutated clones. The two somatically derived mutations, p.L587P and p.G1611S, were also found to increase the migration rate. Expression analysis of MYO5B mutants compared to wild type clones, demonstrated a significant enrichment of genes involved in migration, proliferation, cell adhesion, glucose metabolism, and cellular homeostasis. Our study validates the functional role of novel MYO5B mutations in proliferation and migration, and suggest the MYO5-pathway to be involved in the malignant progression in some PPGL tumors. © 2020 Tomic et al.
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5.
  • Törnell, Andreas, 1994, et al. (författare)
  • Rapid cytokine release assays for analysis of SARS-CoV-2-specific T cells in whole blood.
  • 2022
  • Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 226:2, s. 208-216
  • Tidskriftsartikel (refereegranskat)abstract
    • Waning of IgG antibodies against SARS-CoV-2 complicates diagnosis of past infection. Durability of T cell memory against SARS-CoV-2 remains unclear, and most current T cell protocols are unsuited for large-scale automation.Whole blood samples from 31 patients with verified past COVID-19 and 46 controls, out of which 40 received SARS-CoV-2 vaccine were stimulated with peptides spanning the nucleocapsid (NC) or spike 1 (S1) regions of SARS-CoV-2 and analyzed for interferon-γ (IFN-γ) in supernatant plasma. Diagnostic accuracy of these assays was evaluated against serum anti-NC and anti-receptor-binding domain S1 IgG.Induction of IFN-γ in whole blood by NC or S1 peptides diagnosed past COVID-19 with high accuracy (AUC=0.93, AUC=0.95, respectively). In accordance with previous studies, NC-IgG levels rapidly waned with only 5/17 patients (29%) remaining seropositive >180 days after infection. By contrast, NC-peptide-induced T cell memory responses remained in 13/17 (76%) subjects >180 days after infection (P=0.012 vs. NC-IgG, McNemar test). After two vaccine doses, 18/18 donors exhibited S1-specific T cell memory.Cytokine release assays for the monitoring of T cell memory in whole blood may be useful for evaluation of complications following unverified past COVID-19 and for long-term assessment of vaccine-induced T cell immunity.
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6.
  • Abel, Frida, 1974, et al. (författare)
  • Imbalance of the mitochondrial pro- and anti-apoptotic mediators in neuroblastoma tumours with unfavourable biology.
  • 2005
  • Ingår i: European journal of cancer (Oxford, England : 1990). - : Elsevier BV. - 0959-8049. ; 41:4, s. 635-46
  • Tidskriftsartikel (refereegranskat)abstract
    • It has been proposed that a lack of apoptosis plays an important role in neuroblastoma (NB) progression. We therefore screened cDNA array filters, including 198 apoptotic genes, in order to identify mRNA transcripts that are differentially expressed in tumours with unfavourable versus favourable biology. Twenty-one genes were analysed further using real-time reverse-transcriptase-polymerase chain reaction (RT-PCR). Significantly lower levels of DNCL1 (PIN; P(c)(corrected) = 0.0054) and NTRK1 (TrkA; P(c) = 0.039) were found in NB tumours with unfavourable biology. In addition, BID, BCL2, APAF1, CASP2, CASP3 and CASP9 were found to be preferentially expressed in tumours with favourable biology, whereas CDKN1A (p21), IL2RA, and MCL1, were found to be preferentially expressed in NB tumours with unfavourable biology. In conclusion, mRNA levels of transcripts encoding pro-apoptotic mediators of the mitochondrial apoptotic pathway were found to be expressed to a lower extent in tumours with unfavourable biology. Our data also suggest that the mitochondrial pathway is suppressed in advanced stages of NB tumours, due to an imbalance between anti-apoptotic and pro-apoptotic mediators which is a finding that may have therapeutic significance.
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7.
  • Abel, Frida, 1974, et al. (författare)
  • Mutations in the N-terminal domain of DFF45 in a primary germ cell tumor and in neuroblastoma tumors.
  • 2004
  • Ingår i: International journal of oncology. - 1019-6439 .- 1791-2423. ; 25:5, s. 1297-302
  • Tidskriftsartikel (refereegranskat)abstract
    • DFF45 has essential functions in the final stage of apoptosis by acting both as a folding chaperone and a DNase inhibitor of DFF40. The gene encoding DFF45 (DFFA) maps to the consensus deleted region in primary neuroblastoma (NB; 1p36.2-3) and within the homozygously deleted region in an NB cell line (1p36.2). DFF45 is therefore an attractive candidate NB tumor suppressor. In a previous study we found a rare allele variant, causing a non-polar to a polar amino acid exchange (Ile69Thr) in a preserved hydrophobic patch of DFF45, and we also found DFFA to be preferentially expressed in favorable NB tumors. We have extended the previous study and performed mutation analyses in another 56 NB tumors (100 in total) as well as a set of other tumors for coding mutations in DFFA. We have also performed studies of the DFFA expression in tumors using real-time PCR. We found a missense mutation (Ile15Met) in the remaining allele of a teratoma with heterozygous deletion of 1p, and a three base-pair deletion in an NB of unknown stage causing a deletion of amino acid 37 in DFF45. The one-base substitution detected in the teratoma was not present in the patients constitutional DNA, i.e. it is a true mutation present in the tumor DNA only. In conclusion, three different coding alterations have been found in the region encoding the N-terminal regulatory domain of DFF45, responsible for binding and achieving its chaperone and inhibitor functions on other proteins. Moreover, by real-time RT-PCR expression study, we found the mRNA level of DFFA to be significantly (p=0.038) reduced by a factor of 1.7 times in NB tumors of unfavorable outcome.
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8.
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9.
  • Abrahamsson, Hasse, 1943, et al. (författare)
  • Familial intestinal degenerative neuropathy with chronic intestinal pseudo-obstruction linked to a gene locus with duplication in chromosome 9
  • 2019
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 54:12, s. 1441-1447
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Intestinal degenerative neuropathy without extra-intestinal involvement occurs as familial forms (FIDN) but the genetics behind is unknown. We studied a Swedish family with autosomal dominant disease and several cases of chronic intestinal pseudo-obstruction (CIP). Methods: We included 33 members of a family sharing a male ancestor. Chronic intestinal symptoms including diarrhoea occurred in 11, four had severe CIP. DNA was analysed with SNP-microarray (Affymetrix), linkage (Allegro Software) and gene dosage (CNAG 3.0). Results: Genetic linkage was found to the short arm of Ch9 to a 9.7 Mb region with 45 protein-coding genes, 22 of which were duplicated (1.2 Mb duplication) (dup(9)(p21.3) with breaking point in the FOCAD-gene. Lod score for the region was 3.4. Fourteen subjects were duplication carriers including all 11 subjects having severe chronic symptoms/CIP. Nineteen subjects had no duplication. The occurrence of gastrointestinal symptoms in the family was strongly linked to duplication carrier-ship (p = .0005). The two branches of the family had separate maternal ancestors (A and B). Including the previous generation, severe disease (overt CIP and/or death from intestinal failure) was assessed to occur in 100% (5/5) of duplication carriers in branch A and in 21% (3/14) in branch B (p = .005). In branch B the onset of symptoms was later (median 38 vs. 24 yrs) and three duplication carriers were symptom-free. Conclusions: In this family with autosomal dominant hereditary intestinal neuropathy, the disorder is linked to a 9.7 Mb region in Ch9 including a 1.2 Mb duplication. There is a significant difference in disease expressivity between family branches, seemingly related to separate maternal ancestors.
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10.
  • Alexanderson, Camilla, 1978, et al. (författare)
  • A single early postnatal estradiol injection affects morphology and gene expression of the ovary and parametrial adipose tissue in adult female rats.
  • 2010
  • Ingår i: The Journal of steroid biochemistry and molecular biology. - : Elsevier BV. - 1879-1220 .- 0960-0760. ; 122:1-3, s. 82-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Events during early life can affect reproductive and metabolic functions in adulthood. We evaluated the programming effects of a single early postnatal estradiol injection (within 3h after birth) in female rats. We assessed ovarian and parametrial adipose tissue morphology, evaluated gene expression related to follicular development and adipose tissue metabolism, and developed a non-invasive volumetric estimation of parametrial adipose tissue by magnetic resonance imaging. Estradiol reduced ovarian weight, increased antral follicle size and number of atretic antral follicles, and decreased theca interna thickness in atretic antral follicles. Adult estradiol-injected rats also had malformed vaginal openings and lacked corpora lutea, confirming anovulation. Estradiol markedly reduced parametrial adipose tissue mass. Adipocyte size was unchanged, suggesting reduced adipocyte number. Parametrial adipose tissue lipoprotein lipase activity was increased. In ovaries, estradiol increased mRNA expression of adiponectin, complement component 3, estrogen receptor alpha, and glucose transporter 3 and 4; in parametrial adipose tissue, expression of complement component 3 was increased, expression of estrogen receptor alpha was decreased, and expression of leptin, lipoprotein lipase, and hormone-sensitive lipase was unaffected. These findings suggest that early postnatal estradiol exposure of female rats result in long-lasting effects on the ovary and parametrial adipose tissue at adult age.
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11.
  • Annerbrink, Kristina, 1974, et al. (författare)
  • Associations between the angiotensin-converting enzyme insertion/deletion polymorphism and monoamine metabolite concentrations in cerebrospinal fluid
  • 2010
  • Ingår i: Psychiatry Research. - : Elsevier BV. - 1872-7123 .- 0165-1781. ; 179:2, s. 231-234
  • Tidskriftsartikel (refereegranskat)abstract
    • Angiotensin II has been suggested to influence central dopamine and serotonin turnover. Since the angiotensin-converting enzyme (ACE) plays a key role in angiotensin regulation by converting inactive angiotensin 1 to active angiotensin II, we hypothesised that the functional insertion/deletion (I/D) polymorphism in the ACE gene, which has previously been suggested to be associated with, depression and panic disorder, may influence monoamine activity. A well-established technique for assessing brain monoamine turnover in humans is to measure concentrations of monoamine metabolites in the cerebrospinal fluid (CSF). We thus investigated possible associations between the ACE I/D polymorphism and CSF monoamine metabolite concentrations in a population of healthy male subjects. After having found such an association between the ACE I/D polymorphism and CSF levels of the dopamine metabolite homovanillic acid and the serotonin metabolite 5-hydroxyindoleacetic acid in this sample, I carriers displaying lower levels, we tried to replicate this observation in a population of violent male offenders from which also both CSF and DNA were available. Also in this sample, the same associations were found. Our results suggest that the ACE I/D polymorphism may play a role in the modulation of serotonergic and dopaminergic turnover in men. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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12.
  • Annerbrink, Kristina, 1974, et al. (författare)
  • Catechol O-methyltransferase val158-met polymorphism is associated with abdominal obesity and blood pressure in men.
  • 2008
  • Ingår i: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 57:5, s. 708-711
  • Tidskriftsartikel (refereegranskat)abstract
    • Catechol O-methyltransferase (COMT) degrades catecholamines and estrogens, both of which are of known importance for cardiovascular risk factors such as obesity and hypertension. The gene coding for COMT contains a val158-met polymorphism that exerts a considerable influence on enzymatic activity. We hypothesized that this polymorphism might influence risk factors for cardiovascular disease. Deoxyribonucleic acid samples and data regarding blood pressure and anthropometry were collected from 240 Swedish men, all 51 years old. Subjects homozygous for the low-activity allele (met) displayed higher blood pressure, heart rate, waist-to-hip ratio, and abdominal sagittal diameter as compared with heterozygous subjects, who in turn displayed higher blood pressure, heart rate, waist-to-hip ratio, and abdominal sagittal diameter than subjects homozygous for the high-activity allele (val). All measured variables were significantly correlated; however, the associations between COMT val158-met and cardiovascular variables, and the association between COMT val158-met and anthropometry, respectively, were partly independent of each other, as revealed by multiple linear regression.
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13.
  • Aurelius, Johan, 1980, et al. (författare)
  • Anthracycline-based consolidation may determine outcome of post-consolidation immunotherapy in AML
  • 2019
  • Ingår i: Leukemia & Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 60:11, s. 2771-2778
  • Tidskriftsartikel (refereegranskat)abstract
    • Consolidation chemotherapy in acute myeloid leukemia (AML) aims at eradicating residual leukemic cells and mostly comprises high-dose cytarabine with or without the addition of anthracyclines, including daunorubicin. Immunogenic cell death (ICD) may contribute to the efficacy of anthracyclines in solid cancer, but the impact of ICD in AML is only partly explored. We assessed aspects of ICD, as reflected by calreticulin expression, in primary human AML blasts and observed induction of surface calreticulin upon exposure to daunorubicin but not to cytarabine. We next assessed immune phenotypes in AML patients in complete remission (CR), following consolidation chemotherapy with or without anthracyclines. These patients subsequently received immunotherapy with histamine dihydrochloride (HDC) and IL-2. Patients who had received anthracyclines for consolidation showed enhanced frequencies of CD8(+) T-EM cells in blood along with improved survival. We propose that the choice of consolidation therapy prior to AML immunotherapy may determine clinical outcome.
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14.
  • Axelsson, M, et al. (författare)
  • Glial fibrillary acidic protein: a potential biomarker for progression in multiple sclerosis.
  • 2011
  • Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 1432-1459 .- 0340-5354. ; 258:5, s. 882-8
  • Tidskriftsartikel (refereegranskat)abstract
    • The major intermediate cytoskeletal protein of astrocytes, glial fibrillary acidic protein (GFAP), and that of axons, neurofilament light protein (NFL), may both be released into the cerebrospinal fluid (CSF) during pathological processes in the central nervous system (CNS). We investigated GFAP and NFL levels in CSF as possible biomarkers for progression in multiple sclerosis (MS). Patients with relapsing-remitting MS (RRMS, n = 15) or secondary progressive MS (SPMS, n = 10) and healthy control subjects (n = 28) were examined twice with an interval of 8-10 years apart. Neurological deficits were scored with the Expanded Disability Status Scale (EDSS). GFAP and NFL levels were determined in CSF by enzyme-linked immunosorbent assay (ELISA). GFAP levels and NFL levels correlated with age (r and r (s) = 0.50, p = 0.006). Adjusting for age, MS patients had increased GFAP levels compared with controls (p = 0.03) and GFAP levels correlated with neurological disability (EDSS, r = 0.51, p < 0.05) and disease progression [Multiple Sclerosis Severity Score (MSSS), r = 0.47, p < 0.05]. The mean annual increase of GFAP was 6.5 ng/L for controls, 8.1 ng/L for RRMS patients, and 18.9 ng/L for SPMS patients. GFAP level at the first examination had predictive value for neurological disability 8-10 years later (EDSS, r = 0.45, p < 0.05) but not for EDSS increase between the examinations. NFL levels were not significantly increased in MS patients compared with controls and had no relationship to disability or progression and no prognostic value for disability development. GFAP, a marker for astrogliosis, is a potential biomarker for MS progression and may have a role in clinical trials for assessing the impact of therapies on MS progression.
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15.
  • Barbosa, Edna J L, 1961, et al. (författare)
  • Extracellular water and blood pressure in adults with growth hormone (GH) deficiency: a genotype-phenotype association study.
  • 2014
  • Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Growth hormone deficiency (GHD) in adults is associated with decreased extracellular water volume (ECW). In response to GH replacement therapy (GHRT), ECW increases and blood pressure (BP) reduces or remains unchanged. Our primary aim was to study the association between polymorphisms in genes related to renal tubular function with ECW and BP before and 1 year after GHRT. The ECW measures using bioimpedance analysis (BIA) and bioimpedance spectroscopy (BIS) were validated against a reference method, the sodium bromide dilution method (Br(-)).
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16.
  • Barbosa, Edna J L, 1961, et al. (författare)
  • Genotypes associated with lipid metabolism contribute to differences in serum lipid profile of GH-deficient adults before and after GH replacement therapy.
  • 2012
  • Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 167:3, s. 353-62
  • Tidskriftsartikel (refereegranskat)abstract
    • bjective: GH deficiency (GHD) in adults is associated with an altered serum lipid profile that responds to GH replacement therapy (GHRT). This study evaluated the influence of polymorphisms in genes related to lipid metabolism on serum lipid profile before and after 1 year of GHRT in adults. Design and methods: In 318 GHD patients, total cholesterol (TC) serum concentrations, LDL-C, HDL-C, and triglycerides (TG) were assessed. Using a candidate gene approach, 20 single nucleotide polymorphisms (SNPs) were genotyped. GH dose was individually titrated to obtain normal serum IGF1 concentrations. Results: At baseline, the minor alleles of cholesteryl ester transfer protein (CETP) gene SNPs rs708272 and rs1800775 were associated with higher serum TC and apolipoprotein E (APOE) gene SNP rs7412 with lower TC concentrations; CETP SNPs rs708272, rs1800775, and rs3764261 and apolipoprotein B (APOB) gene SNP rs693 with higher serum HDL-C; APOE SNP rs7412, peroxisome proliferator-activated receptor gamma (PPARG) gene SNP rs10865710 with lower LDL-C, and CETP SNP rs1800775 with higher LDL-C; and APOE/C1/C4/C2 cluster SNP rs35136575 with lower serum TG. After treatment, APOB SNP rs676210 GG genotype was associated with larger reductions in TC and LDL-C and PPARG SNP rs10865710 CC genotype with greater TC reduction. All associations remained significant when adjusted for age, sex, and BMI. Conclusions: In GHD adults, multiple SNPs in genes related to lipid metabolism contributed to individual differences in baseline serum lipid profile. The GH treatment response in TC and LDL-C was influenced by polymorphisms in the APOB and PPARG genes.
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17.
  • Bergman, Annika, et al. (författare)
  • Genome-wide linkage scan for breast cancer susceptibility loci in Swedish hereditary non-BRCA1/2 families : Suggestive linkage to 10q23.32-q25.3
  • 2007
  • Ingår i: Genes, Chromosomes and Cancer. - : John Wiley & Sons. - 1045-2257 .- 1098-2264. ; 46:3, s. 302-309
  • Tidskriftsartikel (refereegranskat)abstract
    • The two breast cancer genes BRCA1 and BRCA2 were identified more than 10 years ago and, depending on population, mutations in these genes are responsible for a varying percentage of familial breast cancer. In more than half the families, the increased risk of breast cancer cannot be explained by mutations in these genes, and the goal of this study was to locate novel susceptibility genes. One of the main difficulties in identifying the cause of hereditary non-BRCA1/BRCA2 breast cancer is genetic heterogeneity, possibly due to multiple, incompletely penetrant susceptibility genes, along with ethnic and geographic differences. In this study, one large family and 13 small to medium-sized families with multiple cases of breast cancer were analyzed by genome-wide linkage analysis. The genome scan was performed by genotype analysis of 10,000 SNP markers on microarrays. The strongest evidence of linkage (HLOD 2.34) was obtained on chromosome region 10q23.32-q25.3. A further two regions were identified, with LOD scores above 2.10 on 12q14-q21 and 19p13.3-q12. In a subset of families of western Swedish origin, two regions generated LOD scores exceeding 1.8: 10q23.32-q25.3 and 19q13.12-q13.32. The large family in the study exceeded LOD 1.5 in three regions: 10q23.32-q25.3, 19q13.12-q13.32, and 17p13. Our results indicate that one or more of the suggested regions may harbor genes that are involved in the development of breast cancer. 
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18.
  • Bjursell, Cecilia, 1971, et al. (författare)
  • PMM2 mutation spectrum, including 10 novel mutations, in a large CDG type 1A family material with a focus on Scandinavian families.
  • 2000
  • Ingår i: Human mutation. - 1098-1004 .- 1059-7794. ; 16:5, s. 395-400
  • Tidskriftsartikel (refereegranskat)abstract
    • Carbohydrate-deficient glycoprotein syndrome type IA (CDG IA) is an autosomal recessive disease characterized clinically by severe involvement of the central and peripheral nervous system, and biochemically by complex defects in carbohydrate residues in a number of serum glycoproteins. CDG IA is caused by mutations in the PMM2 gene located in chromosome region 16p13. In this study, 61 CDG type IA patients (122 chromosomes) were screened for mutations in the PMM2 gene using a combination of SSCP and sequence analysis. More than 95% of the mutations could be detected. All of them were missense mutations. Mutations 422G>A and 357C>A were strikingly more common in the material and comprised 58% of mutations detected. Of the 20 mutations found, 10 were not reported previously. Seven mutations, e.g. 26G>A (five alleles) and 548T>C (seven alleles), were found only in Scandinavian families. The most common genotype was 357C>A/422G>A (36%). Three patients were homozygous, 357C>A/357C>A (two cases), and 548T>C/548T>C (one case). No patients homozygous for the most common mutation 422G>A were detected. The different mutations were clustered e.g., in that most were located in exon 5 (five) and exon 8 (six), while no mutation was detected in exon 2. When the frequencies of each mutation were included, exon 5 comprised 61% (65 chromosomes) of the mutations; in Scandinavian patients the frequency of these mutations was 72%. Thus, analysis of exon five in these patients enables both reliable and time-saving first screening in prenatal diagnostic cases. This could be followed by a second step of additional strategies for the detection of other mutations.
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19.
  • Carén, Helena, 1979, et al. (författare)
  • High-risk neuroblastoma tumors with 11q-deletion display a poor prognostic, chromosome instability phenotype with later onset.
  • 2010
  • Ingår i: PNAS. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 107:9, s. 4323-4328
  • Tidskriftsartikel (refereegranskat)abstract
    • Analysis of chromosomal aberrations is used to determine the prognosis of neuroblastomas (NBs) and to aid treatment decisions. MYCN amplification (MNA) alone is an incomplete poor prognostic factor, and chromosome 11q status has recently been included in risk classification. We analyzed 165 NB tumors using high-density SNP microarrays and specifically compared the high-risk groups defined by MNA (n = 37) and 11q-deletion (n = 21). Median patient age at diagnosis was 21 months for MNA tumors and 42 months for 11q-deletion tumors, and median survival time after diagnosis was 16 months for MNA and 40 months for 11q deletion. Overall survival (at 8 years) was approximately 35% in both groups. MNA and 11q deletion were almost mutually exclusive; only one case harbored both aberrations. The numbers of segmental aberrations differed significantly; the MNA group had a median of four aberrations, whereas the 11q-deletion group had 12. The high frequency of chromosomal breaks in the 11q-deletion group is suggestive of a chromosomal instability phenotype gene located in 11q; one such gene, H2AFX, is located in 11q23.3 (within the 11q-deletion region). Furthermore, in the groups with segmental aberrations without MNA or 11q deletion, the tumors with 17q gain have worse prognosis than those with segmental aberrations without 17q gain, which have a favorable outcome. This study has implications for therapy in different risk groups and stresses that genome-wide microarray analyses should be included in clinical management to fully evaluate risk, aid diagnosis, and guide treatment.
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20.
  • Carén, Helena, 1979, et al. (författare)
  • Identification of epigenetically regulated genes that predict patient outcome in neuroblastoma
  • 2011
  • Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 11, s. 66-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Epigenetic mechanisms such as DNA methylation and histone modifications are important regulators of gene expression and are frequently involved in silencing tumor suppressor genes. Methods: In order to identify genes that are epigenetically regulated in neuroblastoma tumors, we treated four neuroblastoma cell lines with the demethylating agent 5-Aza-2'-deoxycytidine (5-Aza-dC) either separately or in conjunction with the histone deacetylase inhibitor trichostatin A (TSA). Expression was analyzed using whole-genome expression arrays to identify genes activated by the treatment. These data were then combined with data from genome-wide DNA methylation arrays to identify candidate genes silenced in neuroblastoma due to DNA methylation. Results: We present eight genes (KRT19, PRKCDBP, SCNN1A, POU2F2, TGFBI, COL1A2, DHRS3 and DUSP23) that are methylated in neuroblastoma, most of them not previously reported as such, some of which also distinguish between biological subsets of neuroblastoma tumors. Differential methylation was observed for the genes SCNN1A (p < 0.001), PRKCDBP (p < 0.001) and KRT19 (p < 0.01). Among these, the mRNA expression of KRT19 and PRKCDBP was significantly lower in patients that have died from the disease compared with patients with no evidence of disease (fold change -8.3, p = 0.01 for KRT19 and fold change -2.4, p = 0.04 for PRKCDBP). Conclusions: In our study, a low methylation frequency of SCNN1A, PRKCDBP and KRT19 is significantly associated with favorable outcome in neuroblastoma. It is likely that analysis of specific DNA methylation will be one of several methods in future patient therapy stratification protocols for treatment of childhood neuroblastomas.
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21.
  • Enerbäck, Charlotta, 1965, et al. (författare)
  • Stronger association with HLA-Cw6 than with corneodesmosin (S-gene) polymorphisms in Swedish psoriasis patients.
  • 2000
  • Ingår i: Archives of dermatological research. - : Springer Science and Business Media LLC. - 0340-3696 .- 1432-069X. ; 292:11, s. 525-30
  • Tidskriftsartikel (refereegranskat)abstract
    • Psoriasis vulgaris is strongly associated with certain human leukocyte antigens, especially in early onset. The purpose of this study was to study the HLA-Cw6 allele and its contribution to disease susceptibility in a set of 104 families with at least two affected siblings. A sequencing method was utilized to examine the two exons that build up the antigen binding site of the C locus receptor. DNA from patients homozygous for Cw6 based on haplotype information were sequenced. The results confirmed the identity of the Cw6 allele in affected individuals with the consensus sequence for Cw*0602. We screened the set of families for psoriasis patients homozygous for Cw6 and found 11 individuals with a mean age at onset of 16.1 years. The corresponding figure for the Cw6 heterozygotes was 18.45 years and for the Cw6-negatives 22.36 years. This is indicative of a gene dose effect. We performed a transmission disequilibrium test (TDT) on the Cw6 allele per se, used as a biallelic marker. The analysis resulted in a P-value of 5.3 x 10(-17) (t167/nt45). This greatly exceeds our previous results of a TDT in the region, including microsatellite markers and single nucleotide polymorphisms (SNPs) in the coding part of the S gene (corneodesmosin), which is a suggested candidate gene in the region. The maximum nonparametric linkage (NPL) value was also reached using HLA-C as a marker. We conclude that Cw6 is the allele which shows the highest degree of association with psoriasis in our set of families and we propose that it directly influences the age at onset of the disease rather than increasing the genetic load in accordance with a polygenic theory.
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22.
  • Glad, Camilla A M, 1981, et al. (författare)
  • SNPs within the GH-signaling pathway are associated with the early IGF1 response to GH replacement therapy in GHD adults.
  • 2014
  • Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 170:1, s. 101-7
  • Tidskriftsartikel (refereegranskat)abstract
    • GH-deficient (GHD) adults have reduced serum concentrations of IGF1. GH replacement therapy increases serum IGF1 concentrations, but the interindividual variation in treatment response is large and likely influenced by genetic factors. This study was designed to test the hypothesis that single-nucleotide polymorphisms (SNPs) in genes within the GH signaling pathway influence the serum IGF1 response to GH replacement.
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23.
  • Hansson, Caroline, 1981, et al. (författare)
  • A possible association between panic disorder and a polymorphism in the preproghrelin gene
  • 2013
  • Ingår i: Psychiatry Research. - : Elsevier. - 0165-1781 .- 1872-7123. ; 206:1, s. 22-25
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the study was to investigate whether polymorphisms in the preproghrelin gene are associated with anxiety disorders, such as panic disorder, in humans. Panic disorder is a severe anxiety disorder, characterized by sudden attacks of intense fear or anxiety in combination with somatic symptoms. The preproghrelin gene codes for two gut-derived circulating peptides that have been linked to anxiety-like behaviour in rodents: ghrelin (an orexigenic, pro-obesity hormone) and obestatin. In the present study, we genotyped three missense mutations in the preproghrelin gene in 215 patients suffering from panic disorder and in 451 controls. The A allele of the rs4684677 polymorphism was significantly associated with panic disorder, while there were no significant associations with the two other polymorphisms studied. We conclude that the rs4684677 (Gln90Leu) polymorphism in the preproghrelin gene may be associated with increased risk of panic disorder. It will be important to confirm these findings in additional panic disorder patient groups.
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24.
  • Henningsson, Susanne, 1977, et al. (författare)
  • Sex steroid-related genes and male-to-female transsexualism
  • 2005
  • Ingår i: Psychoneuroendocrinology. - Oxford : Pergamon Press. - 0306-4530 .- 1873-3360. ; 59:5, s. 412-412
  • Tidskriftsartikel (refereegranskat)abstract
    • Transsexualism is characterised by Lifelong discomfort with the assigned sex and a strong identification with the opposite sex. The cause of transsexualism is unknown, but it has been suggested that an aberration in the early sexual differentiation of various brain structures may be involved. Animal experiments have revealed that the sexual differentiation of the brain is mainly due to an influence of testosterone, acting both via androgen receptors (ARs) and-after aromatase-catalyzed conversion to estradiol-via estrogen receptors (ERs). The present study examined the possible importance of three polymorphisms and their pairwise interactions for the development of male-to-female transsexualism: a CAG repeat sequence in the first exon of the AR gene, a tetra nucleotide repeat polymorphism in intron 4 of the aromatase gene, and a CA repeat polymorphism in intron 5 of the ER beta gene. Subjects were 29 Caucasian male-to-female transsexuals and 229 healthy mate controls. Transsexuals differed from controls with respect to the mean Length of the ER repeat polymorphism, but not with respect to the length of the other two studied polymorphisms. However, binary logistic regression analysis revealed significant partial effects for all three polymorphisms, as well as for the interaction between the AR and aromatase gene polymorphisms, on the risk of developing transsexualism. Given the small number of transsexuals in the study, the results should be interpreted with the utmost caution. Further study of the putative role of these and other sex steroid-related genes for the development of transsexualism may, however, be worthwhile.
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25.
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26.
  • Hieronymus, Fredrik, 1986, et al. (författare)
  • A mega-analysis of fixed-dose trials reveals dose-dependency and a rapid onset of action for the antidepressant effect of three selective serotonin reuptake inhibitors
  • 2016
  • Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 6:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The possible dose-dependency for the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs) remains controversial. We believe we have conducted the first comprehensive patient-level mega-analysis exploring this issue, one incentive being to address the possibility that inclusion of low-dose arms in previous meta-analyses may have caused an underestimation of the efficacy of these drugs. All company-sponsored, acute-phase, placebo-controlled, fixed-dose trials using the Hamilton Depression Rating Scale (HDRS) and conducted to evaluate the effect of citalopram, paroxetine or sertraline in adult major depression were included (11 trials, n = 2859 patients). The single-item depressed mood, which has proven a more sensitive measure to detect an antidepressant signal than the sum score of all HDRS items, was designated the primary effect parameter. Doses below or at the lower end of the usually recommended dose range (citalopram: 10-20 mg, paroxetine: 10 mg; sertraline: 50 mg) were superior to placebo but inferior to higher doses, hence confirming a dose-dependency to be at hand. In contrast, among doses above these, there was no indication of a dose-response relationship. The effect size (ES) after exclusion of suboptimal doses was of a more respectable magnitude (0.5) than that usually attributed to the antidepressant effect of the SSRIs. In conclusion, the observation that low doses are less effective than higher ones challenges the oft-cited view that the effect of the SSRIs is not dose-dependent and hence not caused by a specific, pharmacological antidepressant action. Moreover, we suggest that inclusion of suboptimal doses in previous meta-analyses has led to an underestimation of the efficacy of these drugs.
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27.
  • Hieronymus, Fredrik, 1986, et al. (författare)
  • Consistent superiority of selective serotonin reuptake inhibitors over placebo in reducing depressed mood in patients with major depression.
  • 2016
  • Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 21:4, s. 523-30
  • Tidskriftsartikel (refereegranskat)abstract
    • The recent questioning of the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs) is partly based on the observation that approximately half of company-sponsored trials have failed to reveal a significant difference between active drug and placebo. Most of these have applied the Hamilton depression rating scale to assess symptom severity, the sum score for its 17 items (HDRS-17-sum) serving as effect parameter. In this study, we examined whether the negative outcomes of many SSRI trials may be partly caused by the use of this frequently questioned measure of response. We undertook patient-level post-hoc analyses of 18 industry-sponsored placebo-controlled trials regarding paroxetine, citalopram, sertraline or fluoxetine, and including in total 6669 adults with major depression, the aim being to assess what the outcome would have been if the single item depressed mood (rated 0-4) had been used as a measure of efficacy. In total, 32 drug-placebo comparisons were reassessed. While 18 out of 32 comparisons (56%) failed to separate active drug from placebo at week 6 with respect to reduction in HDRS-17-sum, only 3 out of 32 comparisons (9%) were negative when depressed mood was used as an effect parameter (P<0.001). The observation that 29 out of 32 comparisons detected an antidepressant signal from the tested SSRI suggests the effect of these drugs to be more consistent across trials than previously assumed. Further, the frequent use of the HDRS-17-sum as an effect parameter may have distorted the current view on the usefulness of SSRIs and hampered the development of novel antidepressants.Molecular Psychiatry advance online publication, 28 April 2015; doi:10.1038/mp.2015.53.
  •  
28.
  • Hieronymus, Fredrik, 1986, et al. (författare)
  • Efficacy of selective serotonin reuptake inhibitors in the absence of side effects: a mega-analysis of citalopram and paroxetine in adult depression
  • 2018
  • Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 23:8, s. 1731-1736
  • Tidskriftsartikel (refereegranskat)abstract
    • It has been suggested that the superiority of antidepressants over placebo in controlled trials is merely a consequence of side effects enhancing the expectation of improvement by making the patient realize that he/she is not on placebo. We explored this hypothesis in a patient-level post hoc-analysis including all industry-sponsored, Food and Drug Administration-registered placebo-controlled trials of citalopram or paroxetine in adult major depression that used the Hamilton Depression Rating Scale (HDRS) and included a week 6 symptom assessment (n=15). The primary analyses, which compared completers on active treatment without early adverse events to completers on placebo (with or without adverse events) with respect to reduction in the HDRS depressed mood item showed larger symptom reduction in patients given active treatment, the effect sizes being 0.48 for citalopram and 0.33 for paroxetine. In actively treated subjects reporting early adverse events, who also outperformed those given placebo, the severity of the adverse events did not predict response. Several sensitivity analyses, for example, including (i) those using change of the sum of all HDRS-17 items as effect parameter, (ii) those excluding all subjects with adverse events (that is, also those on placebo) and (iii) those based on the intention-to-treat population, were all in line with the primary analyses. The finding that both paroxetine and citalopram are clearly superior to placebo also when not producing adverse events, as well as the lack of association between adverse event severity and response, argue against the theory that antidepressants outperform placebo solely or largely because of their side effects.
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29.
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30.
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31.
  • Hieronymus, Fredrik, 1986, et al. (författare)
  • Influence of baseline severity on the effects of SSRIs in depression: an item-based, patient-level post-hoc analysis
  • 2019
  • Ingår i: Lancet Psychiatry. - : Elsevier BV. - 2215-0374 .- 2215-0366. ; 6:9, s. 745-752
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Reports claiming that antidepressants are effective only in patients with severe depression have affected treatment guidelines but these reports usually use a disputed measure of improvement, a decrease in the sum-score of the 17-item Hamilton Depression Rating Scale (HDRS-17), and are based on group-level rather than patient-level data. Method In this item-based, patient-level, post-hoc analysis, we pooled data from all completed, acute-phase, placebo-controlled, industry-sponsored, H DRS-based trials of the SSRIs citalopram, paroxetine, or sertraline in adult major depression. Patient-level data were pooled and subjected to item-based post-hoc analyses to assess the effect of baseline severity of depression on the response to treatment as assessed with HDRS-17 sum score, the depressed mood item of the HDRS, a six-item HDRS subscale (HDRS-6), and the remaining 11 HDRS items not included in this subscale (non-HDRS-6). Patients were defined as having non-severe depression if they had a baseline HDRS-17 sum score of 18 points or less and as having severe depression if they had a score of 27 points or more. Findings Our study population consisted of 8262 patients from 28 placebo-controlled SSRI trials. Participants were treated with either citalopram (n=744), paroxetine (n=2981), sertraline (n=1202), fluoxetine (active-control group; n=754), or placebo (n=2581). 654 patients were defined as having non-severe depression and 1377 as having severe depression. Patients with non-severe and severe depression did not differ with respect to SSRI-induced decrease in depressed mood and other HDRS symptoms belonging to the HDRS-6 subscale. However, after exclusion of patients with rare extreme baseline values, a positive association was seen between severity and efficacy when using HDRS-17 sum score as the effect parameter. This result was largely due to a more pronounced response to treatment with respect to non-HDRS-6 items in patients with severe depression than in those with non-severe depression. This outcome could be explained by non-HDRS-6 items, more so than HDRS-6 items, being more severe and prevalent at baseline in severe than in non-severe cases; hence, less room was left for improvement in these areas in patients with non-severe depression. Interpretation The use of an outcome measure that includes symptoms that rate low at baseline in patients with non-severe depression might result in the interpretation that SSRIs are ineffective in these patients. With respect to alleviation of HDRS-6 items, SSRIs appear to be as effective in patients with non-severe depression as in those with severe depression. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
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32.
  • Hieronymus, Fredrik, 1986, et al. (författare)
  • The alleged ineffectiveness of SSRIs in depression is an artefact caused by the use of an inappropriate measure of efficacy
  • 2014
  • Ingår i: International Journal of Neuropsychopharmacology vol. 17 Supplement 1. 29th CINP World Congress of Neuropsychopharmacology, Vancouver, Canada, 22–26 June 2014. - New York : Cambridge University Press. - 1461-1457 .- 1469-5111.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Objective: Many studies have questioned if summation of the scores of the 17 disparate items constituting the Hamilton Depression Rating Scale (HDRS-17) is a reliable index of severity in depression; yet the cur- rent questioning of the ef fi cacy of antidepressant drugs is to a large extent based on the assumption that response to treatment is reliably re fl ected by this instrument. We aimed to investigate the possibility that the shortcom- ings of the HDRS may contribute to the failure of antidepressants to out- perform placebo in many trials. Methods: We analyzed thirteen industry-sponsored trials of selective serotonin reuptake inhibitors (SSRIs) comprising twenty-four drug- placebo comparisons and including patient-level data from 5381 subjects (administered paroxetine, citalopram, fl uoxetine, or placebo), the aim being to assess what the outcome would have been if the single item de- pressed mood (rated 0 – 4) had been used as measure of ef fi cacy. Results: While 12 out of 24 comparisons (50%) revealed a signi fi cant difference between active drug and placebo at week 6 with respect to re- duction in HDRS-17-sum, 23 out of 24 comparisons (96%) showed the ac- tive drug to be superior to placebo in reducing depressed mood. Correspondingly, a pooled analysis of all cases showed the effect size when assessed using the HDRS-17-sum to be 0.30, whereas it, when mea- sured using the depressed mood item alone, was 0.42. Conclusion: While not claiming that measuring one item only is the most appropriate way of recording symptom severity in depression, we do suggest that the inclusion of a number of varying symptoms in the as- sessment, some of which may be side-effects of treatment and/or are unre- lated to the disorder, reduces the sensitivity to detect a difference between active drug and placebo. This lack of sensitivity of HDRS-17 might partly explain why a high fraction of antidepressant trials fail to reveal a signi fi - cant difference between treatment groups
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33.
  • Ho, Hoi-Por, 1962, et al. (författare)
  • Association between a functional polymorphism in the progesterone receptor gene and panic disorder in women.
  • 2004
  • Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530. ; 58:2, s. 109-110
  • Tidskriftsartikel (refereegranskat)abstract
    • Although genetic factors are known to be important risk factors for panic disorder there is as yet no conclusive data regarding specific gene variants. Prompted by evidence supporting progesterone to influence the pathophysiology of panic disorder, polymorphisms in the progesterone receptor gene, a single nucleotide polymorphism (G331A) and an insertion/deletion polymorphism (PROGINS) were investigated in 72 patients with panic disorder and 452 controls. The frequency of the A-allele of the G331A polymorphism was higher in panic disorder patients than in controls (p = 0.01). When male and female patients were analyzed separately, the association was observed in female patients only (p = 0.0009), with an odds ratio of 3.5. No differences between groups were observed for the PROGINS polymorphism. In conclusion, these data suggest that the G331A polymorphism in the progesterone receptor gene may influence the risk for panic disorder in women.
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34.
  • Håkansson, Anna, 1978, et al. (författare)
  • Interaction of polymorphisms in the genes encoding interleukin-6 and estrogen receptor beta on the susceptibility to Parkinson's disease.
  • 2005
  • Ingår i: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. - : Wiley. - 1552-4841 .- 1552-485X. ; 133:1, s. 88-92
  • Tidskriftsartikel (refereegranskat)abstract
    • The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system and increased levels of IL-6 have been found in patients with Parkinson's disease (PD). It is known that estrogen inhibits the production of IL-6, via action on estrogen receptors, thereby pointing to an important influence of estrogen on IL-6. In a previous study, we reported an association between a G/A single nucleotide polymorphism (SNP) at position 1730 in the gene coding for estrogen receptor beta (ERbeta) and age of onset of PD. To investigate the influence of a G/C SNP at position 174 in the promoter of the IL-6 gene, and the possible interaction of this SNP and the ERbeta G-1730A SNP on the risk for PD, the G-174C SNP was genotyped, by pyrosequencing, in 258 patients with PD and 308 controls. A significantly elevated frequency of the GG genotype of the IL-6 SNP was found in the patient group and this was most obvious among patients with an early age of onset (
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35.
  • Håkansson, Anna, 1978, et al. (författare)
  • Investigation of genes coding for inflammatory components in Parkinson's disease.
  • 2005
  • Ingår i: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 0885-3185 .- 1531-8257. ; 20:5, s. 569-73
  • Tidskriftsartikel (refereegranskat)abstract
    • Several findings obtained recently indicate that inflammation may contribute to the pathogenesis in Parkinson's disease (PD). Genetic variants of genes coding for components involved in immune reactions in the brain might therefore influence the risk of developing PD or the age of disease onset. Five single nucleotide polymorphisms (SNPs) in the genes coding for interferon-gamma (IFN-gamma; T874A in intron 1), interferon-gamma receptor 2 (IFN-gamma R2; Gln64Arg), interleukin-10 (IL-10; G1082A in the promoter region), platelet-activating factor acetylhydrolase (PAF-AH; Val379Ala), and intercellular adhesion molecule 1 (ICAM-1; Lys469Glu) were genotyped, using pyrosequencing, in 265 patients with PD and 308 controls. None of the investigated SNPs was found to be associated with PD; however, the G1082A polymorphism in the IL-10 gene promoter was found to be related to the age of disease onset. Linear regression showed a significantly earlier onset with more A-alleles (P = 0.0095; after Bonferroni correction, P = 0.048), resulting in a 5-year delayed age of onset of the disease for individuals having two G-alleles compared with individuals having two A-alleles. The results indicate that the IL-10 G1082A SNP could possibly be related to the age of onset of PD.
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36.
  • Javanmardi, Niloufar, et al. (författare)
  • Low Frequency ALK Hotspots Mutations In Neuroblastoma Tumours Detected By Ultra-deep Sequencing: Implications For ALK Inhibitor Treatment
  • 2019
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • The ALK tyrosine kinase receptor is oncogenically activated in neuroblastoma. Whereas numerous ALK fusion genes have been reported in different malignancies, in neuroblastoma ALK is mainly activated through point mutations. Three hotspot residues (F1174, F1245, and R1275) account for 85% of mutant ALK seen in neuroblastoma. In a cohort of 105 Swedish neuroblastoma cases of all stages, these hotspot regions were re-sequenced (> 5000X). ALK mutations were detected in 16 of 105 patients (range of variant allele fraction: 2.7-60%). Mutations at the F1174 and F1245 hotspot were observed in eleven and three cases respectively. ALK mutations were also detected at the I1171 and L1240 codons in one tumor each. No mutations were detected at R1275. Sanger sequencing could confirm ALK status for all mutated samples with variant allele fraction above 15%. Four of the samples with subclonal ALK mutation fraction below this would have gone undetected relying on Sanger sequencing only. No distinct mutation spectrum in relation to neuroblastoma tumours genomic subtypes could be detected although there was a paucity of ALK mutations among 11q-deleted tumors. As ALK mutations status opens up an excellent opportunity for application of small molecule inhibitors targeting ALK, early and sensitive detection of ALK alterations is clinically important considering its potential role in tumour progression.
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37.
  • Kanberg, Nelly, et al. (författare)
  • Neurochemical signs of astrocytic and neuronal injury in acute COVID-19 normalizes during long-term follow-up.
  • 2021
  • Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 70
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurologic manifestations are well-recognized features of coronavirus disease 2019 (COVID-19). However, the longitudinal association of biomarkers reflecting CNS impact and neurological symptoms is not known. We sought to determine whether plasma biomarkers of CNS injury were associated with neurologic sequelae after COVID-19.Patients with confirmed acute COVID-19 were studied prospectively. Neurological symptoms were recorded during the acute phase of the disease and at six months follow-up, and blood samples were collected longitudinally. Healthy age-matched individuals were included as controls. We analysed plasma concentrations of neurofilament light-chain (NfL), glial fibrillary acidic protein (GFAp), and growth differentiation factor 15 (GDF-15).One hundred patients with mild (n=24), moderate (n=28), and severe (n=48) COVID-19 were followed for a median (IQR) of 225 (187-262) days. In the acute phase, patients with severe COVID-19 had higher concentrations of NfL than all other groups (all p < 0·001), and higher GFAp than controls (p < 0·001). GFAp was also significantly increased in moderate disease (p < 0·05) compared with controls. NfL (r=0·53, p < 0·001) and GFAp (r=0·39, p < 0·001) correlated with GDF-15 during the acute phase. After six months, NfL and GFAp concentrations had normalized, with no persisting group differences. Despite this, 50 patients reported persistent neurological symptoms, most commonly fatigue (n=40), "brain-fog" (n=29), and changes in cognition (n=25). We found no correlation between persistent neurological symptoms and CNS injury biomarkers in the acute phase.The normalization of CNS injury biomarkers in all individuals, regardless of previous disease severity or persisting neurological symptoms, indicates that post COVID-19 neurological sequelae are not accompanied by ongoing CNS injury.The Swedish State Support for Clinical Research, SciLifeLab Sweden, and the Knut and Alice Wallenberg Foundation have provided funding for this project.
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38.
  • Kindblom, Jenny, 1971, et al. (författare)
  • BMI Changes during Childhood and Adolescence as Predictors of Amount Adult Subcutaneous and Visceral Adipose Tissue in Men - the GOOD Study.
  • 2009
  • Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 58:4, s. 867-874
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. The amount of visceral adipose tissue is a risk factor for the metabolic syndrome. It is unclear how body mass index (BMI) changes during childhood and adolescence predict adult fat distribution. We hypothesized that there are critical periods during development for the prediction of adult subcutaneous and visceral fat mass by BMI changes during childhood and adolescence. Research Design and Methods. Detailed growth charts were retrieved for the men participating in the population-based Gothenburg Osteoporosis and Obesity Determinants (GOOD) study (n=612). Body composition was analysed using Dual X-Ray Absorptiometry and adipose tissue areas using abdominal computed tomography at 18-20 years of age. Results. The main finding in the present study was that subjects with increases in BMI Z-score of >1 SD during adolescence had, independent of prepubertal BMI, both larger subcutaneous (+138%; p<0.001) and visceral adipose tissue areas (+91%; p< 0.001) than subjects with unchanged BMI Z-score. In contrast, subjects with increases in BMI Z-score of >1 SD during late childhood had larger amount adult subcutaneous adipose tissue (+83%; p< 0.001) than subjects with unchanged BMI Z-score, but unaffected amount of visceral adipose tissue. BMI changes during adolescence predict both visceral and subcutaneous adipose tissue of the abdomen while BMI changes during late childhood predict only the subcutaneous adipose tissue. Conclusions. The amount of visceral adipose tissue in young adult men was associated with BMI changes specifically during adolescence, while the amount of subcutaneous adipose tissue was associated with BMI changes during both late childhood and adolescence.
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39.
  • Kindblom, Jenny, 1971, et al. (författare)
  • Pubertal timing is an independent predictor of central adiposity in young adult males: the Gothenburg osteoporosis and obesity determinants study
  • 2006
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 0012-1797 .- 1939-327X. ; 55:11, s. 3047-52
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of puberty and normal variations in pubertal timing for the development of obesity in men is unclear. The aim of the current study was to investigate the impact of pubertal timing and prepubertal BMI (kg/m(2)) for young adult BMI and fat mass distribution. Detailed growth charts from birth to age 18-20 years were retrieved for the men participating in the population-based Gothenburg Osteoporosis and Obesity Determinants study. Age at peak height velocity (PHV) and BMI at age 10 years were estimated for 579 subjects, and PHV was used as an assessment of pubertal timing. The fat mass characterization and distribution were analyzed using dual X-ray absorptiometry and peripheral as well as abdominal computed tomography at age 18.9 +/- 0.5 years. We demonstrate that age at PHV is an independent negative predictor of young adult BMI and whole-body fat mass. Interestingly, age at PHV is an independent negative predictor of central, but not peripheral, fat mass. In contrast, BMI at 10 years of age predicts both central and peripheral subcutaneous fat mass. In conclusion, we demonstrate that early pubertal onset specifically predicts a central fat mass distribution, while a predominantly subcutaneous obese phenotype is strongly predicted by a high prepubertal BMI.
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40.
  • Lagging, Martin, 1965, et al. (författare)
  • Reply.
  • 2014
  • Ingår i: Hepatology (Baltimore, Md.). - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 60:6, s. 2130-1
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
41.
  • Lindh, Magnus, 1960, et al. (författare)
  • Dynamic tailoring of treatment durations improves efficiency of hepatitis C treatment with pegylated interferon and ribavirin
  • 2013
  • Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 20:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The treatment durations for hepatitis C are guided by the analysis of hepatitis C virus (HCV) RNA in blood at certain time points. This multicentre, randomized open label trial evaluated the utility and performance of individualized treatment durations guided by viral decline rates in 103 patients with HCV genotype 1 infection. Pegylated interferon 2a and ribavirin were given as standard of care (SOC) for 24, 48 or 72 weeks or as dynamic treatment (DT) for 24–72 weeks. The DT duration was based on the time point when log HCV RNA would reach 0 log copies/mL, as estimated by the second-phase decline. The rate of sustained virologic response was 63% for SOC and 54% for DT, but this difference was not significant in multiple regression analysis taking predictive factors such as interleukin-28B genotypes, age and baseline viremia into account (P = 0.45). The mean required treatment time per cured patient was 51 weeks for DT as compared with 58 weeks for SOC (P = 0.22) when given per protocol (n = 95) and was significantly shorter (42 vs 51 weeks) among patients who achieved undetectable HCV RNA (P = 0.01). We conclude that DT was feasible and increased efficiency. The estimated time point for 0 log viral copies/mL is a new and quantitative response variable, which may be used as a complement to the qualitative variable rapid virologic response. The outcome parameter treatment weeks per cured patient could become a useful tool for comparing treatment efficiency also in the era of directly acting antivirals.
  •  
42.
  • Lindh, Magnus, 1960, et al. (författare)
  • Hepatitis C treatment response kinetics and impact of baseline predictors.
  • 2011
  • Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1365-2893 .- 1352-0504. ; 18:6, s. 400-407
  • Tidskriftsartikel (refereegranskat)abstract
    • Summary.  The optimal duration of treatment for hepatitis C virus (HCV) infections is highly variable but critical for achieving cure (sustained virological response, SVR). We prospectively investigated the impact of age, fibrosis, baseline viraemia and genotype on the early viral kinetics and treatment outcome. Patients treated with peginterferon alfa-2a and ribavirin in standard dosing were included: 49 with genotype 1 treated for 48 weeks and 139 with genotype 2 or 3 treated for 24 weeks. The reduced SVR rates in patients older than 45 years, with severe liver fibrosis or pretreatment viraemia above 400 000 IU/mL were strongly associated with slower second phase declines of HCV RNA. Genotype 2/3 infections responded more rapidly than genotype 1, reaching week 4 negativity (RVR) in 59%vs 22%. We conclude that baseline response predictors such as age, fibrosis and viral load were well reflected by the early viral kinetics as assessed by repeated HCV RNA quantifications. The kinetic patterns and the high relapse rate in genotype 2/3 patients without RVR suggest that this group might benefit from treatment durations longer than 24 weeks.
  •  
43.
  • Lindh, Magnus, 1960, et al. (författare)
  • IL28B polymorphisms determine early viral kinetics and treatment outcome in patients receiving peginterferon/ribavirin for chronic hepatitis C genotype 1
  • 2011
  • Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 18:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Single nucleotide polymorphisms (SNPs) upstream of IL28B predict the outcome of treatment in chronic hepatitis C virus (HCV) infection, but their impact on viral kinetics and relation to other predictors are not well known. Here, two SNPs, rs12979860 and rs8099917, were analysed and related to early viral kinetics during treatment in 110 patients with HCV genotype 1 infection. The reduction of HCV RNA after 7days of therapy was more pronounced (P<0.0001) in patients with CC(rs12979860) or TT(rs8099917) than in patients carrying TT(rs12979860) or GG(rs8099917), respectively. The two SNPs were in linkage disequilibrium (d' =1, r2 = 0.44), but CC(rs12979860) was less common (43% vs. 71%) than TT(rs8099917). Patients carrying both CC(rs12979860) and TT(rs8099917) genotypes achieved lower levels of HCV RNA at week 4 than those with CT or TT at rs12979860 and TT(rs8099917) (P=0.0004). The viral elimination was significantly influenced by rs12979860 independently of baseline viral load, age or fibrosis. This translated into high rates of sustained viral response (SVR) among patients carrying CC(rs12979860) despite the presence of high viral load at baseline (SVR 74%), high age (SVR 79%) or severe liver fibrosis (SVR 83%). We conclude that the IL28B variability influences the antiviral efficiency of interferon/ribavirin therapy and has a strong impact on SVR, independently of traditional response predictors. A combined assessment of these SNPs in conjunction with other response predictors may better predict outcome in difficult-to-treat patients.
  •  
44.
  • Lindh, Magnus, 1960, et al. (författare)
  • Interleukin 28B Gene Variation at rs12979860 Determines Early Viral Kinetics During Treatment in Patients Carrying Genotypes 2 or 3 of Hepatitis C Virus
  • 2011
  • Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 203:12, s. 1748-1752
  • Tidskriftsartikel (refereegranskat)abstract
    • Single-nucleotide polymorphisms upstream of the interleukin 28B (interferon lambda 3) gene (IL28B) strongly influence treatment efficacy in patients carrying hepatitis C virus (HCV) of genotype 1. In patients receiving 12 or 24 weeks of interferon-ribavirin therapy for infection with genotype 2 or 3 (n = 341), we found that rs12979860 strikingly determined the first phase of viral elimination (P < .001). In patients treated for 24 weeks, rs12979860 also predicted the rate of sustained virologic response (P = .02), especially among those with high baseline HCV RNA levels (P = .002) or older than 45 years (P = .01). Patients carrying CCrs12979860 had higher baseline HCV RNA levels (P < .001) and did not, when treated for 12 weeks, achieve sustained virologic response more often than those carrying CTrs1297986 or TTrs1297986. The results indicate that IL28B gene testing may identify patients carrying genotype 2 or 3 who could benefit from extended treatment.
  •  
45.
  • Lisinski, Alexander, 1989, et al. (författare)
  • Impact of chosen cutoff on response rate differences between selective serotonin reuptake inhibitors and placebo
  • 2022
  • Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Response defined as a 50% reduction in the sum score of the Hamilton Depression Rating Scale (HDRS-17-sum) is often used to assess the efficacy of antidepressants. Critics have, however, argued that dichotomising ratings with a cutoff close to the median may lead to scores clustering on either side, the result being inflation of miniscule drug-placebo differences. Using pooled patient-level data sets from trials of three selective serotonin reuptake inhibitors (SSRIs) (citalopram, paroxetine and sertraline) (n = 7909), and from similar trials of duloxetine (n = 3478), we thus assessed the impact of different cutoffs on response rates. Response criteria were based on (i) HDRS-17-sum, (ii) the sum score of the HDRS-6 subscale (HDRS-6-sum) and (iii) the depressed mood item. The separation between SSRI and placebo with respect to response rates increased when HDRS-17-sum was replaced by HDRS-6-sum or depressed mood as effect parameter and was markedly dependent on SSRI dose. With the exception of extreme cutoff values, differences in response rates were largely similar regardless of where the cutoff was placed, and also not markedly changed by the exclusion of subjects close to the selected cutoff (e.g., +/- 10%). The observation of similar response rate differences between active drugs and placebo for different cutoffs was corroborated by the analysis of duloxetine data. In conclusion, the suggestion that using a cutoff close to the median when defining response has markedly overestimated the separation between antidepressants and placebo may be discarded.
  •  
46.
  • Lisinski, Alexander, 1989, et al. (författare)
  • Item-based analysis of the effects of duloxetine in depression: a patient-level post hoc study
  • 2020
  • Ingår i: Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 1740-634X .- 0893-133X. ; 45:3, s. 553-560
  • Tidskriftsartikel (refereegranskat)abstract
    • Oft-cited trial-level meta-analyses casting doubt on the usefulness of antidepressants have been based on re-analyses of to what extent the active drug has outperformed placebo in reducing the sum score of the Hamilton Depression Rating Scale (HDRS-17-sum) in clinical trials. Recent studies, however, suggest patient-level analyses of individual HDRS items to be more informative when assessing the efficacy of an antidepressant. To shed further light on both symptom-reducing and symptom-aggravating effects of a serotonin and noradrenaline reuptake inhibitor, duloxetine, when used for major depression in adults, we hence applied this approach to re-analyse data from 13 placebo-controlled trials. In addition, using patient-level data from 28 placebo-controlled trials of selective serotonin reuptake inhibitors (SSRIs), the response profile of duloxetine was compared to that of these drugs. Duloxetine induced a robust reduction in depressed mood that was not dependent on baseline severity and not caused by side-effects breaking the blind. A beneficial effect on depressed mood was at hand already after one week; when outcome was assessed using HDRS-17-sum as effect parameter, this early response was however masked by a concomitant deterioration with respect to adverse event-related items. No support for a suicide-provoking effect of duloxetine was obtained. The response profile of duloxetine was strikingly similar to that of the SSRIs. We conclude that the use of HDRS-17-sum as effect parameter underestimates the true efficacy and masks an early effect of duloxetine on core symptoms of depression. No support for major differences between duloxetine and SSRIs in clinical profile were obtained.
  •  
47.
  • Lundgren, Pia, 1967, et al. (författare)
  • National cohort of infants born before 24 gestational weeks showed increased survival rates but no improvement in neonatal morbidity
  • 2022
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 111:8, s. 1515-1525
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim To describe survival and neonatal morbidities in infants born before 24 weeks of gestation during a 12-year period. Methods Data were retrieved from national registries and validated in medical files of infants born before 24 weeks of gestation 2007-2018 in Sweden. Temporal changes were evaluated. Results In 2007-2018, 282 live births were recorded at 22 weeks and 460 at 23 weeks of gestation. Survival to discharge from hospital of infants born alive at 22 and 23 weeks increased from 20% to 38% (p = 0.006) and from 45% to 67% (p < 0.001) respectively. Caesarean section increased from 12% to 22% (p = 0.038) for infants born at 22 weeks. Neonatal morbidity rates in infants alive at 40 weeks of postmenstrual age (n = 399) were unchanged except for an increase in necrotising enterocolitis from 0 to 33% (p = 0.017) in infants born at 22 weeks of gestation. Bronchopulmonary dysplasia was more common in boys than girls, 90% versus 82% (p = 0.044). The number of infants surviving to 40 weeks doubled over time. Conclusion Increased survival of infants born before 24 weeks of gestation resulted in increasing numbers of very immature infants with severe neonatal morbidities likely to have a negative impact on long-term outcome.
  •  
48.
  • Ly, Helena-Jamin, et al. (författare)
  • A prediction model could foresee adequate height response in children eligible for growth hormone treatment
  • 2022
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 111:2, s. 346-353
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim Prediction models may be useful in accurately identifying children who will benefit from growth hormone (GH) treatment. We aimed to validate the Gothenburg prediction model for this purpose. Methods The study included prepubertal children with GH deficiency who started treatment with GH during 2004-2016 at Queen Silvia Children's Hospital, Gothenburg, based on a first-year growth prediction of >= 0.7 SDS in height according to the Gothenburg prediction model on a GH dose of 33 mu g/kg/day. Observed heights retrieved from medical charts were compared with predicted heights. Results The study included 121 patients (64% boys) with at least one year of data after the start of GH treatment. The median (range) GH dose was 30 (10-43) mu g/kg/day for the first year and age at start of treatment was 5.32 (3-11.8) years. The model correctly excluded poor responders resulting in 119/121 (98%) patients having a height gain of at least >= 0.5 SDS in a year. However, the model underestimated relatively low predictions and overestimated relatively high predictions, with a residual standard deviation of 0.31 SDS. Conclusion By using a validated prediction model for GH in a clinical context, unnecessarily treating short children with an expected poor height outcome can be avoided.
  •  
49.
  • Martner, Anna, 1979, et al. (författare)
  • Transient and durable T cell reactivity after COVID-19
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 119:30
  • Tidskriftsartikel (refereegranskat)abstract
    • This study analyzed whole blood samples (n = 56) retrieved from 30 patients at 1 to 21 (median 9) mo after verified COVID-19 to determine the polarity and duration of antigen-specific T cell reactivity against severe acute respiratory syndrome coronavirus 2-derived antigens. Multimeric peptides spanning the entire nucleocapsid protein triggered strikingly synchronous formation of interleukin (IL)-4, IL-12, IL-13, and IL-17 ex vivo until similar to 70 d after confirmed infection, whereafter this reactivity was no longer inducible. In contrast, levels of nucleocapsid-induced IL-2 and interferon-gamma remained stable and highly correlated at 3 to 21 mo after infection. Similar cytokine dynamics were observed in unvaccinated, convalescent patients using whole-blood samples stimulated with peptides spanning the N-terminal portion of the spike 1 protein. These results unravel two phases of T cell reactivity following natural COVID-19: an early, synchronous response indicating transient presence of multipolar, antigen-specific T helper (T-H) cells followed by an equally synchronous and durable T(H)1-like reactivity reflecting long-lasting T cell memory.
  •  
50.
  • Mossberg, Natalia, et al. (författare)
  • Leukocyte oxygen radical production determines disease severity in the recurrent Guillain-Barré
  • 2010
  • Ingår i: Journal of Inflammation. - : Springer Science and Business Media LLC. - 1476-9255. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The recurrent Guillain-Barré syndrome (RGBS) is characterized by at least two GBS episodes with intervening remission. In a previous study of monophasic GBS, we reported that the magnitude of oxygen radical production ("respiratory burst”) in peripheral blood leukocytes was inversely correlated to disease severity. The present study sought to establish a similar correlation in patients with RGBS. Methods: Oxygen radical production in leukocytes was induced by formyl-Met-Leu-Phe (fMLF), Trp-Lys-Tyr-Met-Val- Met-NH2 (WKYMVM), or phorbol myristate acetate (PMA) and assessed by quantifying superoxide anion formed by the leukocyte NADPH oxidase. Results: Disease severity, assessed using the MRC score, was negatively correlated to superoxide anion production triggered by fMLF or WKYMVM (p = 0.001 and 0.002, respectively; n = 10). Superoxide anion production also was significantly lower in RGBS patients with incomplete recovery after stimulation with fMLF (p = 0.004) or WKYMVM (p = 0.003). Conclusion: We conclude that a lower respiratory burst in leukocytes is strongly associated with a severe course of RGBS
  •  
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