| 1. |
- El-Alti, Leila, 1986, et al.
(författare)
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Person Centered Care and Personalized Medicine: Irreconcilable Opposites or Potential Companions?
- 2019
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Ingår i: Health Care Analysis. - : Springer Science and Business Media LLC. - 1065-3058 .- 1573-3394. ; 27:1, s. 45-59
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Tidskriftsartikel (refereegranskat)abstract
- In contrast to standardized guidelines, personalized medicine and person centered care are two notions that have recently developed and are aspiring for more individualized health care for each single patient. While having a similar drive toward individualized care, their sources are markedly different. While personalized medicine stems from a biomedical framework, person centered care originates from a caring perspective, and a wish for a more holistic view of patients. It is unclear to what extent these two concepts can be combined or if they conflict at fundamental or pragmatic levels. This paper reviews existing literature in both medicine and related philosophy to analyze closer the meaning of the two notions, and to explore the extent to which they overlap or oppose each other, in theory or in practice, in particular regarding ethical assumptions and their respective practical implications.
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| 3. |
- Kesarimangalam, Sriram, 1983, et al.
(författare)
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High diversity of bla NDM-1 -encoding plasmids in Klebsiella pneumoniae isolated from neonates in a Vietnamese hospital
- 2022
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 1872-7913 .- 0924-8579. ; 59:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The carbapenemase-encoding gene blaNDM-1 has been reported in Vietnam during the last 10 years, and blaNDM-producing Enterobacteriaceae are now silently and rapidly spreading. A key factor behind dissemination of blaNDM-1 is plasmids, mobile genetic elements that commonly carry antibiotic resistance genes and spread via conjugation. The diversity of blaNDM-1-encoding plasmids from neonates at a large Vietnamese hospital was characterized in this study. Methods: 18 fecal Klebsiella pneumoniae and Klebsiella quasipneumoniae isolates collected from 16 neonates at a large pediatric hospital in Vietnam were studied using optical DNA mapping (ODM) and next-generation sequencing (NGS). Plasmids carrying the blaNDM-1 gene were identified by combining ODM with Cas9 restriction. The plasmids in the isolates were compared to investigate whether the same plasmid was present in different patients. Results: Although the same plasmid was found in some isolates, ODM confirmed that there were at least 10 different plasmids encoding blaNDM-1 among the 18 isolates, thus indicating wide plasmid diversity. The ODM results concur with the NGS data. Interestingly, some isolates had two distinct plasmids encoding blaNDM-1 that could be readily identified with ODM. The coexistence of different plasmids carrying the same blaNDM-1 gene in a single isolate has rarely been reported, probably because of limitations in plasmid characterization techniques. Conclusions: The plasmids encoding the blaNDM-1 gene in this study cohort were diverse and may represent a similar picture in Vietnamese society. The study highlights important aspects of the usefulness of ODM for plasmid analysis.
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| 4. |
- Leandro-Garcia, Luis J., et al.
(författare)
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Genome-wide association study identifies ephrin type A receptors implicated in paclitaxel induced peripheral sensory neuropathy
- 2013
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Ingår i: Journal of Medical Genetics. - : BMJ Publishing Group Ltd. - 0022-2593 .- 1468-6244. ; 50:9, s. 599-605
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Tidskriftsartikel (refereegranskat)abstract
- Background Peripheral neuropathy is the dose limiting toxicity of paclitaxel, a chemotherapeutic drug widely used to treat solid tumours. This toxicity exhibits great inter-individual variability of unknown origin. The present study aimed to identify genetic variants associated with paclitaxel induced neuropathy via a whole genome approach. less thanbrgreater than less thanbrgreater thanMethods A genome-wide association study (GWAS) was performed in 144 white European patients uniformly treated with paclitaxel/carboplatin and for whom detailed data on neuropathy was available. Per allele single nucleotide polymorphism (SNP) associations were assessed by Cox regression, modelling the cumulative dose of paclitaxel up to the development of grade 2 sensory neuropathy. less thanbrgreater than less thanbrgreater thanResults The strongest evidence of association was observed for the ephrin type A receptor 4 (EPHA4) locus (rs17348202, p=1.0x10(-6)), and EPHA6 and EPHA5 were among the top 25 and 50 hits (rs301927, p=3.4x10(-5) and rs1159057, p=6.8x10(-5)), respectively. A meta-analysis of EPHA5-rs7349683, the top marker for paclitaxel induced neuropathy in a previous GWAS (r(2)=0.79 with rs1159057), gave a hazard ratio (HR) estimate of 1.68 (p=1.4x10(-9)). Meta-analysis of the second hit of this GWAS, XKR4-rs4737264, gave a HR of 1.71 (p=3.1x10(-8)). Imputed SNPs at LIMK2 locus were also strongly associated with this toxicity (HR=2.78, p=2.0x10(-7)). less thanbrgreater than less thanbrgreater thanConclusions This study provides independent support of EPHA5-rs7349683 and XKR4-rs4737264 as the first markers of risk of paclitaxel induced neuropathy. In addition, it suggests that other EPHA genes also involved in axonal guidance and repair following neural injury, as well as LIMK2 locus, may play an important role in the development of this toxicity. The identified SNPs could form the basis for individualised paclitaxel chemotherapy.
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| 6. |
- Kurland, Lisa, 1960-, et al.
(författare)
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Polymorphisms in the angiotensinogen and angiotensin II type 1 receptor gene are related to change in left ventricular mass during antihypertensive treatment : results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial
- 2002
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 20:4, s. 657-663
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Our aim was to determine if gene polymorphisms in the renin-angiotensin-aldosterone system (RAAS) were related to the degree of change in left ventricular hypertrophy (LVH) during antihypertensive treatment. METHODS AND RESULTS: Patients with essential hypertension and echocardiographically diagnosed LVH were included in a double-blind study to receive treatment with either the angiotensin II type 1 receptor (AT1-receptor) antagonist irbesartan (n = 41), or the beta-1 adrenergic receptor blocker atenolol (n = 43) as monotherapy for 3 months. The angiotensinogen T174M and M235T, the angiotensin-converting enzyme I/D, the AT1-receptor A1166C and the aldosterone synthase (CYP11B2) -344 C/T polymorphisms were analysed and related to the change in left ventricular mass (LVM). Patients with the angiotensinogen 174 TM genotype treated with irbesartan responded with the greatest reduction in LVM (-23 +/- 31SD g/m2 for TM and +0.5 +/- 18 g/m2 for TT, P = 0.005), independent of blood pressure reduction. Both the angiotensinogen 235 T-allele (P = 0.02) and the AT1-receptor 1166 AC genotype responded with the greatest reduction in LVM when treated with irbesartan (-0.1 +/- 19 g/m2 for AA and -18 +/- 30 g/m2 for AC, P = 0.02), independent of blood pressure reduction. These polymorphisms were not associated with the change in LVM during treatment with atenolol. DISCUSSION: The angiotensinogen T174M and M235T and the AT1-receptor A1166C polymorphisms were related to the change in LVH during antihypertensive treatment with an AT1-receptor antagonist; of these angiotensinogen T174M was the most powerful. This highlights the role of the RAAS for left ventricular hypertrophy and the potential of pharmacogenetics as a tool for guidance of antihypertensive therapy.
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| 7. |
- Tajsharghi, Homa, 1968, et al.
(författare)
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Myosin storage myopathy associated with a heterozygous missense mutation in MYH7.
- 2003
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Ingår i: Annals of neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 54:4, s. 494-500
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Tidskriftsartikel (refereegranskat)abstract
- Myosin constitutes the major part of the thick filaments in the contractile apparatus of striated muscle. MYH7 encodes the slow/beta-cardiac myosin heavy chain (MyHC), which is the main MyHC isoform in slow, oxidative, type 1 muscle fibers of skeletal muscle. It is also the major MyHC isoform of cardiac ventricles. Numerous missense mutations in the globular head of slow/beta-cardiac MyHC are associated with familial hypertrophic cardiomyopathy. We identified a missense mutation, Arg1845Trp, in the rod region of slow/beta-cardiac MyHC in patients with a skeletal myopathy from two different families. The myopathy was characterized by muscle weakness and wasting with onset in childhood and slow progression, but no overt cardiomyopathy. Slow, oxidative, type 1 muscle fibers showed large inclusions consisting of slow/beta-cardiac MyHC. The features were similar to a previously described entity: hyaline body myopathy. Our findings indicate that the mutated residue of slow/beta-cardiac MyHC is essential for the assembly of thick filaments in skeletal muscle. We propose the term myosin storage myopathy for this disease.
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| 8. |
- Sandin, Linnea, et al.
(författare)
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Beneficial effects of increased lysozyme levels in Alzheimer’s disease modelled in Drosophila melanogaster
- 2016
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Ingår i: The FEBS Journal. - : John Wiley & Sons. - 1742-464X .- 1742-4658. ; 283:19, s. 3508-3522
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Tidskriftsartikel (refereegranskat)abstract
- Genetic polymorphisms of immune genes that associate with higher risk to develop Alzheimer’s disease (AD) have led to an increased research interest on the involvement of the immune system in AD pathogenesis. A link between amyloid pathology and immune gene expression was suggested in a genome-wide gene expression study of transgenic amyloid mouse models. In this study, the gene expression of lysozyme, a major player in the innate immune system, was found to be increased in a comparable pattern as the amyloid pathology developed in transgenic mouse models of AD. A similar pattern was seen at protein levels of lysozyme in human AD brain and CSF, but this lysozyme pattern was not seen in a tau transgenic mouse model. Lysozyme was demonstrated to be beneficial for different Drosophila melanogaster models of AD. In flies that expressed Aβ1-42 or AβPP together with BACE1 in the eyes, the rough eye phenotype indicative of toxicity was completely rescued by coexpression of lysozyme. In Drosophila flies bearing the Aβ1-42 variant with the Arctic gene mutation, lysozyme increased the fly survival and decreased locomotor dysfunction dose dependently. An interaction between lysozyme and Aβ1-42 in the Drosophila eye was discovered. We propose that the increased levels of lysozyme, seen in mouse models of AD and in human AD cases, were triggered by Aβ1-42 and caused a beneficial effect by binding of lysozyme to toxic species of Aβ1-42, which prevented these from exerting their toxic effects. These results emphasize the possibility of lysozyme as biomarker and therapeutic target for AD.
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| 9. |
- Chen, Yun, 1966, et al.
(författare)
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Neonatal losartan treatment suppresses renal expression of molecules involved in cell-cell and cell-matrix interactions
- 2004
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Ingår i: Journal of the American Society of Nephrology. - : Lippincott Williams & Wilkins. - 1046-6673 .- 1533-3450. ; 15:5, s. 1232-43
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Tidskriftsartikel (refereegranskat)abstract
- Lack of neonatal angiotensin II type 1 receptor (AT(1)) stimulation produces renal abnormalities characterized by papillary atrophy and impaired urinary concentrating ability, but the mechanisms involved are still unclear. DNA microarray was used to identify genes that are differentially expressed in renal medulla in response to neonatal treatment with AT(1) receptor antagonist losartan (30 mg/kg per d), which commenced within 24 h after birth. The data showed that losartan treatment for 48 h downregulated 68 genes, approximately 30% of which encode various components of cytoskeleton and cytoskeleton-associated proteins, extracellular matrix, and enzymes involved in extracellular matrix maturation or turnover. With the use of immunohistochemistry and Western immunoblot, the microarray data were confirmed and it was demonstrated that losartan suppressed renal expression of syndecan 2, alpha-smooth muscle actin, MHC class II, and leukocyte type 12-lipoxygenase by day 4. In addition, losartan inhibited medullary expression of integrin alpha6 and caused relocalization of integrins alpha6 and alpha3. Moreover, losartan inhibited cell proliferation in medullary tubules by day 9, as detected by Ki-67 immunostaining. This study provides new data supporting the contention that a lack of AT(1) receptor stimulation results in abnormal matrix assembly, disturbed cell-cell and cell-matrix interactions, and subsequent abnormal tubular maturation. Moreover, regulation of the expression of leukocyte type 12-lipoxygenase and alpha-smooth muscle actin by the renin-angiotensin system in the immature kidney adds new knowledge toward the understanding of renal vascular development.
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| 10. |
- Franks, P. W., et al.
(författare)
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Technological readiness and implementation of genomic-driven precision medicine for complex diseases
- 2021
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 290:3, s. 602-620
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Forskningsöversikt (refereegranskat)abstract
- The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment - genomic-driven precision medicine (GDPM) - may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data.
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