| 1. |
- Dalin, Frida, 1984-, et al.
(författare)
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Clinical and immunological characteristics of Autoimmune Addison's disease : a nationwide Swedish multicenter study
- 2017
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 379-389
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.
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| 2. |
- Milberg, Anna, et al.
(författare)
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Patients Sense of Security During Palliative Care-What Are the Influencing Factors?
- 2014
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Ingår i: Journal of Pain and Symptom Management. - : Elsevier. - 0885-3924 .- 1873-6513. ; 48:1, s. 45-55
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT:Having a sense of security is vitally important to patients who have a limited life expectancy.OBJECTIVES:We sought to identify the factors associated with patients' sense of security during the palliative care period.METHODS:We recruited 174 adult patients (65% of those eligible) from six palliative home care units. The relationship between the patients' sense of security during palliative care and individual factors was evaluated in a stepwise procedure using the generalized linear model (ordinal multinomial distribution and logit link).RESULTS:Respondents' ratings of their sense of security ranged from 1 (never) to 6 (always), with a mean value of 4.6 (SD 1.19). Patients with lower feelings of security experienced higher stress; more worry about personal finances; lower feelings of self-efficacy; a lower sense of security with the palliative care provided (lower ratings on subscales of care interaction); mastery; prevailed own identity; higher symptom intensity (especially depression, anxiety, and lack of well-being); lower health-related quality of life; lower attachment anxiety and avoidance; less support from family, relatives, and friends; lower comfort for those closest to them; and more often had gynecological cancer. Six variables (mastery, nervousness and stress, gynecological cancer, self-efficacy, worrying about personal finances, and avoidance) were selected in building the stepwise model.CONCLUSION:These findings stress the importance of palliative care services in supporting dying patients' sense of security through symptom management with a wide scope and through supporting the patients' sense of mastery, identity, and perception of a secure care interaction and also through attention to the family members' situation.
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| 3. |
- Conway, Marie C, et al.
(författare)
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Maternal and child FADS genotype as determinants of cord blood long chain polyunsaturated fatty acid (LCPUFA) concentrations in the Seychelles Child Development Study
- 2021
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Ingår i: British Journal of Nutrition. - 1475-2662. ; 126:11, s. 1687-1697
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Tidskriftsartikel (refereegranskat)abstract
- Optimal maternal long chain polyunsaturated fatty acid (LCPUFA) status is essential for the developing foetus. The fatty acid desaturase (FADS) genes are involved in the endogenous synthesis of LCPUFA. The minor allele of various FADS single nucleotide polymorphisms (SNPs) have been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of arachidonic acid (AA) and docosahexaenoic acid (DHA). There is limited research on the influence of FADS genotype on cord PUFA status. The current study investigated the influence of maternal and child genetic variation in FADS genotype on cord blood PUFA status in a high fish-eating cohort. Cord blood samples (n=1088) collected from the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Of those with cord PUFA data available, maternal (n=1062) and child (n=916), FADS1 (rs174537, rs174561), FADS2 (rs174575), and FADS1-FADS2 (rs3834458) were determined. Regression analysis determined that maternal minor allele homozygosity was associated with lower cord blood concentrations of docosahexaenoic acid (DHA) and the sum of EPA+DHA. Lower cord blood AA concentrations were observed in children who were minor allele homozygous for rs3834458 (β=0.075; p=0.037). Children who were minor allele carriers for rs174537, rs174561, rs174575 and rs3834458 had a lower cord blood AA:LA ratio (p<0.05 for all). Both maternal and child FADS genotype were associated with cord LCPUFA concentrations, and therefore, the influence of FADS genotype was observed despite the high intake of preformed dietary LCPUFA from fish in this population.
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| 4. |
- Eriksdotter-Jönhagen, Maria, et al.
(författare)
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Encapsulated cell biodelivery of nerve growth factor to the Basal forebrain in patients with Alzheimer's disease.
- 2012
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 33:1, s. 18-28
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Tidskriftsartikel (refereegranskat)abstract
- Degeneration of cholinergic neurons in the basal forebrain correlates with cognitive decline in patients with Alzheimer's disease (AD). Targeted delivery of exogenous nerve growth factor (NGF) has emerged as a potential AD therapy due to its regenerative effects on the basal forebrain cholinergic neurons in AD animal models. Here we report the results of a first-in-man study of encapsulated cell (EC) biodelivery of NGF to the basal forebrain of AD patients with the primary objective to explore safety and tolerability.
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| 5. |
- Ferreira, Daniel, et al.
(författare)
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Brain changes in Alzheimer's disease patients with implanted encapsulated cells releasing nerve growth factor
- 2015
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 43, s. 1059-1072
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Tidskriftsartikel (refereegranskat)abstract
- © 2015-IOS Press and the authors. New therapies with disease-modifying effects are urgently needed for treating Alzheimer's disease (AD). Nerve growth factor (NGF) protein has demonstrated regenerative and neuroprotective effects on basal forebrain cholinergic neurons in animal studies. In addition, AD patients treated with NGF have previously shown improved cognition, EEG activity, nicotinic binding, and glucose metabolism. However, no study to date has analyzed brain atrophy in patients treated with NGF producing cells. In this study we present MRI results of the first clinical trial in patients with AD using encapsulated NGF biodelivery to the basal forebrain. Six AD patients received the treatment during twelve months. Patients were grouped as responders and non-responders according to their twelve-months change in MMSE. Normative values were created from 131 AD patients from ADNI, selecting 36 age-and MMSE-matched patients for interpreting the longitudinal changes in MMSE and brain atrophy. Results at baseline indicated that responders showed better clinical status and less pathological levels of cerebrospinal fluid (CSF) Aβ1-42. However, they showed more brain atrophy, and neuronal degeneration as evidenced by higher CSF levels of T-tau and neurofilaments. At follow-up, responders showed less brain shrinkage and better progression in the clinical variables and CSF biomarkers. Noteworthy, two responders showed less brain shrinkage than the normative ADNI group. These results together with previous evidence supports the idea that encapsulated biodelivery of NGF might have the potential to become a new treatment strategy for AD with both symptomatic and disease-modifying effects.
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| 6. |
- Gliga, Anda R., et al.
(författare)
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Exposure to Mild Steel Welding and Changes in Serum Proteins With Putative Neurological Function—A Longitudinal Study
- 2020
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Ingår i: Frontiers in Public Health. - : Frontiers Media SA. - 2296-2565. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Welders are exposed to high levels of metal particles, consisting mainly of iron and manganese (Mn) oxide. Metal particles, especially those containing Mn can be neurotoxic. In this exploratory study, we evaluated associations between welding and expression of 87 putative neurology-related proteins in serum in a longitudinal approach. The study cohort from southern Sweden included welders working with mild steel (n = 56) and controls (n = 67), all male and non-smoking, which were sampled at two timepoints (T1, T2) 6-year apart. Observed associations in the longitudinal analysis (linear mixed models) were further evaluated (linear regression models) in another cross-sectional sample which included welders (n = 102) and controls (n = 89) who were sampled only once (T1 or T2). The median respirable dust levels for welders after adjusting for respiratory protection was at T1 0.6 (5–95 percentile: 0.2–4.2) and at T2 0.5 (0.1–1.8) mg/m3. The adjusted median respirable Mn concentration was at T2 0.049 mg/m3 (0.003–0.314) with a Spearman correlation between adjusted respirable dust and respirable Mn of rS = 0.88. We identified five neurology-related proteins that were differentially expressed in welders vs. controls in the longitudinal sample, of which one (nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1; NMNAT1) was also differentially expressed in the cross-sectional sample. NMNAT1, an axon-protective protein linked to Alzheimers disease, was upregulated in welders compared with controls but no associations were discerned with degree of exposure (welders only: years welding, respirable dust, cumulative exposure). However, we identified five additional proteins that were associated with years welding (GCSF, EFNA4, CTSS, CLM6, VWC2; welders only) both in the longitudinal and in the cross-sectional samples. We also observed several neurology-related proteins that were associated with age and BMI. Our study indicates that low-to-moderate exposure to welding fumes is associated with changes in circulating levels of neurology-related proteins.
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| 7. |
- Karami, Azadeh, et al.
(författare)
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Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:11, s. 1316-1328
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The extensive loss of central cholinergic functions in Alzheimer's disease (AD) brain is linked to impaired nerve growth factor (NGF) signaling. The cardinal cholinergic biomarker is the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), which has recently been found in cerebrospinal fluid (CSF). The purpose of this study was to see if EC-NGF therapy will alter CSF levels of cholinergic biomarkers, ChAT, and acetylcholinesterase. Method: Encapsulated cell implants releasing NGF (EC-NGF) were surgically implanted bilaterally in the basal forebrain of six AD patients for 12 months and cholinergic markers in CSF were analyzed. Results: Activities of both enzymes were altered after 12 months. In particular, the activity of soluble ChAT showed high correlation with cognition, CSF tau and amyloid-beta, in vivo cerebral glucose utilization and nicotinic binding sites, and morphometric and volumetric magnetic resonance imaging measures. Discussion: A clear pattern of association is demonstrated showing a proof-of-principle effect on CSF cholinergic markers, suggestive of a beneficial EC-NGF implant therapy.
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| 8. |
- Taj, Tahir, et al.
(författare)
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Effect of welding fumes on the cardiovascular system: a six-year longitudinal study
- 2021
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Ingår i: Scandinavian Journal of Work Environment & Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 47:1, s. 52-61
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Tidskriftsartikel (refereegranskat)abstract
- Objective This study investigated whether low-to-moderate exposure to welding fumes is associated with adverse effects on the cardiovascular system. Methods To test this, we performed a longitudinal analysis of 78 mild steel welders and 96 controls; these subjects were examined twice, six years apart (ie, timepoints 1 and 2). All subjects (male and non-smoking at recruitment) completed questionnaires describing their health, work history, and lifestyle. We measured their blood pressure, endothelial function (by EndoPAT), and risk markers for cardiovascular disease [low-density lio-protein (LDL), homocysteine, C-reactive protein]. Exposure to welding fumes was assessed from the responses to questionnaires and measurements of respirable dust in their breathing zones adjusted for use of respiratory protection equipment. Linear mixed-effect regression models were used for the longitudinal analysis. Results Median respirable dust concentrations, adjusted for respirable protection, of the welders were 0.7 (5-95 percentile range 0.2-4.2) and 0.5 (0.1-1.9) mg/m 3 at timepoints 1 and 2, respectively. Over the six-year period, welders showed a statistically significant increase in systolic [5.11 mm Hg, 95% confidence interval (CI) 1.92-8.31] and diastolic (3.12 mm Hg, 95% CI 0.74-5.5) blood pressure compared with controls (multi-variable adjusted mixed effect models). Diastolic blood pressure increased non-significantly by 0.22 mm Hg (95% CI-0.02-0.45) with every additional year of welding work. No consistent significant associations were found between exposure and endothelial function, LDL, homocysteine, or C-reactive protein. Conclusion Exposure to welding fumes at low-to-moderate levels is associated with increased blood pressure, suggesting that reducing the occupational exposure limit (2.5 mg/m(3) for inorganic respirable dust in Sweden) is needed to protect cardiovascular health of workers.
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| 9. |
- Wahlberg, Jeanette, 1969-, et al.
(författare)
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Altered Chemokine Th1/Th2 Balance in Addison's Disease: Relationship with Hydrocortisone Dosing and Quality of Life
- 2014
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Ingår i: Hormone and Metabolic Research. - : Georg Thieme Verlag KG. - 0018-5043 .- 1439-4286. ; 46:1, s. 48-53
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Tidskriftsartikel (refereegranskat)abstract
- The adrenalitis found in autoimmune Addison’s disease (AAD) is considered having a Th1-driven pathogenesis. Circulating Th1- and Th2-associated chemokines responsible for the trafficking of leukocytes to inflammatory sites are markers for the Th1/Th2 balance. The aim of the study was to assess if the same daily hydrocortisone dose of 30 mg given in either 2 or 4 doses to patients with AAD could affect the Th1/Th2 balance of circulating chemokines.Fifteen patients (6 women) with AAD were included in this randomised, placebo controlled, double blind cross-over study. Samples for chemokines, Th1-associated (CXCL10, CXCL11) and Th2-associated (CCL17, CCL22), were drawn 5 times during a 24-h period at the end of each treatment period and analysed with Luminex. Seven control subjects did the same diurnal blood sampling once. Subjects with AAD had higher median diurnal levels of the Th1-associated chemokines than controls, CXCL10 [43 (33–56) pg/ml vs. 22 (19–34) pg/ml, p<0.01] and CXCL11 [37 (29–48) pg/ml vs. 16 (9–24) pg/ml, p<0.001], whereas no significant difference was found regarding the Th2-related chemokines. Similar chemokine levels were found when the same hydrocortisone dose of 30 mg was divided in 2 or 4 doses. Levels of CXCL11 correlated negatively with scores of SF-36 domains (high score indicate better health) of General Health (GH) and total score for Physical Component Summary (PCS), and these negative correlations were most pronounced at 04:00 h on the 2-dose regimen. Patients with AAD have a dominant Th1 chemokine profile that partially correlates to reduced quality of life.
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| 10. |
- Wahlberg, Patrik, 1966-, et al.
(författare)
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Kernels and multiple windows for estimation of the Wigner-Ville spectrum of Gaussian locally stationary processes
- 2007
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Ingår i: IEEE Transactions on Signal Processing. - Piscataway : IEEE Press. - 1053-587X .- 1941-0476. ; 55:1, s. 73-84
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Tidskriftsartikel (refereegranskat)abstract
- This paper treats estimation of the Wigner-Ville spectrum (WVS) of Gaussian continuous-time stochastic processes using Cohen's class of time-frequency representations of random signals. We study the minimum mean square error estimation kernel for locally stationary processes in Silverman's sense, and two modifications where we first allow chirp multiplication and then allow nonnegative linear combinations of covariances of the first kind. We also treat the equivalent multitaper estimation formulation and the associated problem of eigenvalue-eigenfunction decomposition of a certain Hermitian function. For a certain family of locally stationary processes which parametrizes the transition from stationarity to nonstationarity, the optimal windows are approximately dilated Hermite functions. We determine the optimal coefficients and the dilation factor for these functions as a function of the process family parameter.
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