| 1. |
- Arvidsson, Sandra, 1986-, et al.
(författare)
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Enlarged cross-sectional area in peripheral nerves in Swedish patients with hereditary V30M transthyretin amyloidosis
- 2023
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Ingår i: Annals of Medicine. - : Taylor & Francis Group. - 0785-3890 .- 1365-2060. ; 55:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In hereditary transthyretin amyloidosis (ATTRv), two different fibrillar forms causing the amyloid deposition, have been identified, displaying substantially cardiac or neuropathic symptoms. Neuropathic symptoms are more frequent in early-onset patients, whereas late-onset patients, besides cardiac symptoms, seem to develop carpal tunnel syndrome, more often. With ultrasonography (US) of peripheral nerves, it is possible to distinguish structural changes, and enlarged cross-sectional area (CSA). The main purpose of this study was, for the first time, to elucidate US of peripheral nerves in Swedish ATTRv patients at an early stage of the disease, and to evaluate possible early enlarged CSA.Material and methods: This prospective study included first visit data of 13 patients, aged 30–88 years, of which 11 with late-onset age. All had a positive V30M mutation. Eight men and six women (aged 28–74 years) served as controls.Results: Significantly enlarged CSA was seen in ATTRv patients for the tibial nerve at the ankle (p =.001), the sural nerve (p <.001), the peroneal nerve at the popliteal fossa (p =.003), and the ulnar nerve at the middle upper arm (p =.007).Conclusion: US of peripheral nerves could be a valuable tool in disease evaluation and could facilitate monitoring of disease progression.
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| 2. |
- Hawkins, Philip N., et al.
(författare)
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Evolving landscape in the management of transthyretin amyloidosis
- 2015
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Ingår i: Annals of Medicine. - : Informa UK Limited. - 0785-3890 .- 1365-2060. ; 47:8, s. 625-638
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Forskningsöversikt (refereegranskat)abstract
- Transthyretin (TTR) amyloidosis (ATTR amyloidosis) is a multisystemic, multigenotypic disease resulting from deposition of insoluble ATTR amyloid fibrils in various organs and tissues. Although considered rare, the prevalence of this serious disease is likely underestimated because symptoms can be non-specific and diagnosis largely relies on amyloid detection in tissue biopsies. Treatment is guided by which tissues/organs are involved, although therapeutic options are limited for patients with late-stage disease. Indeed, enthusiasm for liver transplantation for familial ATTR amyloidosis with polyneuropathy was dampened by poor outcomes among patients with significant neurological deficits or cardiac involvement. Hence, there remains an unmet medical need for new therapies. The TTR stabilizers tafamidis and diflunisal slow disease progression in some patients with ATTR amyloidosis with polyneuropathy, and the postulated synergistic effect of doxycycline and tauroursodeoxycholic acid on dissolution of amyloid is under investigation. Another therapeutic approach is to reduce production of the amyloidogenic protein, TTR. Plasma TTR concentration can be significantly reduced with ISIS-TTRRx, an investigational antisense oligonucleotide-based drug, or with patisiran and revusiran, which are investigational RNA interference-based therapeutics that target the liver. The evolving treatment landscape for ATTR amyloidosis brings hope for further improvements in clinical outcomes for patients with this debilitating disease.
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| 3. |
- Möllsten, Anna, et al.
(författare)
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Glu298Asp and NOS4ab polymorphisms in diabetic nephropathy.
- 2006
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Ingår i: Annals of Medicine. - : Informa UK Limited. - 0785-3890 .- 1365-2060. ; 38:7, s. 522-528
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- BACKGROUND AND AIMS: The risk of diabetic nephropathy (DN) increases with increase in intraglomerular pressure, which may partly be regulated by nitric oxide (NO). NO-production can be affected by polymorphisms in the endothelial NO-synthase gene (NOS3), hyperglycaemia and smoking. We therefore studied association between DN and two polymorphisms in NOS3, Glu298Asp and NOS4ab, in Caucasian type 1 diabetes (T1D) patients. PATIENTS AND METHODS: A total of 1510 Finnish and Swedish T1D patients were included in a cross-sectional case-control study. Incipient DN was defined as an albumin excretion rate (AER) of 20-200 microg/min (n = 336). Overt DN = AER>200 microg/min or renal replacement therapy (n = 619). All patients with DN were considered as cases. The controls were T1D patients with diabetes duration 20 years, AER<20 microg/min and without antihypertensive treatment (n = 555). The genetic markers studied were a 27 bp repeat (NOS4ab) and Glu298Asp (rs1799983). RESULTS: Age at onset of diabetes, male sex, duration of diabetes, HbA1c, blood pressure and smoking were assessed as possible confounders in the logistic regression analysis, which showed that homozygosity for the Glu-allele of the Glu298Asp-polymorphism was independently associated with increased risk of DN (OR = 1.46; 95% CI = 1.12-1.91). The variables smoking (OR = 2.13; 95% CI = 1.63-2.78), male sex (OR = 1.61; 95% CI = 1.23-2.10), HbA1c (OR per % increase above upper limit of the normal reference range = 1.02; 95% CI = 1.02-1.03), systolic (OR = 1.05; 95% CI = 1.04-1.06) and diastolic blood pressure (OR = 1.04; 95% CI = 1.02-1.05) also significantly and independently increased the risk of DN when taking age at diabetes onset and diabetes duration into account. The NOS4 a-allele was not associated with DN. CONCLUSIONS: The Glu/Glu-genotype of the NOS3 Glu298Asp polymorphism may increase the risk of developing DN independently of other known risk factors.
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| 4. |
- Norlin, Jenny M., et al.
(författare)
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Health-related quality of life in patients with generalized pustular psoriasis–a Swedish register study
- 2024
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Ingår i: Annals of Medicine. - : Taylor & Francis. - 0785-3890 .- 1365-2060. ; 56:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Real-world data on health-related quality of life (HRQoL) in generalized pustular psoriasis (GPP) are scarce and studies have been restricted in terms of instruments used for assessments. Objective: To assess generic and dermatology-specific HRQoL of patients with GPP compared with patients with plaque psoriasis using real-world data from the Swedish National Register for Systemic Treatment of Psoriasis. Methods: Cross-sectional data from 2006 to 2021 including 7041 individuals with plaque psoriasis without GPP and 80 patients with GPP, of which 19% also had plaque psoriasis. Total scores for the EuroQol-5 Dimensions (EQ-5D) and Dermatology Life Quality Index (DLQI), as well as degree of severity within the instruments’ dimensions/questions, were compared between patient groups. Results: EQ-5D scores were significantly (p < .01) lower (worse) in patients with GPP (mean [standard deviation (SD)] 0.613 [0.346]) vs. patients with plaque psoriasis (mean [SD] 0.715 [0.274]), indicating lower generic HRQoL of patients with GPP. Significantly (p < .01) higher (worse) total DLQI scores were observed for patients with GPP (mean [SD] 10.6 [8.9]) compared with patients with plaque psoriasis (mean [SD] 7.7 [7.1]), with proportionally more patients with GPP having severe (20% vs. 16%) and very severe (17% vs. 8%) problems. The worsened scores for GPP vs. plaque psoriasis were consistent across EQ-5D dimensions and DLQI questions. Conclusions: Individuals with GPP have a considerable impairment in both generic and dermatology-specific HRQoL. The HRQoL was significantly worse in individuals with GPP compared to individuals with plaque psoriasis. The significant HRQoL impairment of GPP shows the potential value of better healthcare interventions for this multisystem disease.
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| 5. |
- Norlin, Jenny M., et al.
(författare)
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Health-related quality of life in patients with palmoplantar pustulosis : a Swedish register study
- 2024
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Ingår i: Annals of Medicine. - : Taylor & Francis Group. - 0785-3890 .- 1365-2060. ; 56:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Real-world data on health-related quality of life (HRQoL) in palmoplantar pustulosis (PPP) are scarce and few studies have analysed the generic HRQoL.Objectives: To assess HRQoL using the generic EQ-5D instrument and the Dermatology Life Quality Index (DLQI) instrument in PPP compared to plaque psoriasis.Methods: Cross-sectional data from PsoReg, the Swedish National Registry for Systemic Treatment of Psoriasis (2006–2021), were examined. The study included 306 patients with PPP, out of which 22% had concomitant plaque psoriasis (n = 68), and 7041 patients with plaque psoriasis only. EQ-5D and DLQI were compared between patients with PPP and patients with plaque psoriasis, overall and stratified by sex. A subgroup analysis compared outcomes for patients with PPP vs. patients with severe plaque psoriasis (Psoriasis Area and Severity Index ≥10). Multiple regression analyses were performed to control for potential confounders (age, sex, comorbidities, lifestyle factors).Results: Patients with PPP were to a larger extent female (79% vs. 37%, p < .01) and older (mean [SD] age 59.9 [11.9] vs. 50.7 [16.0] years, p < .01) than patients with plaque psoriasis. EQ-5D values were significantly lower (worse) in patients with PPP (mean [SD] 0.622 [0.309]) compared to patients with plaque psoriasis (mean [SD] 0.715 [0.274]). No significant difference was observed compared to patients with severe plaque psoriasis (p = .237). DLQI was comparable in PPP and plaque psoriasis patients (p = .117). In the regression analyses, PPP only and PPP with plaque psoriasis were associated with lower EQ-5D values of 0.065 (p < .01) and 0.061 points (p < .10) compared to plaque psoriasis patients.Conclusions: PPP had a substantial negative impact on patients’ generic and dermatology-specific HRQoL. Patients with PPP were worse off in terms of generic HRQoL compared with patients with plaque psoriasis when controlling for the impact of potential confounders.
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| 6. |
- Partonen, Timo, et al.
(författare)
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Three circadian clock genes Per2, Arnt1, and Npas2 contribute to winter depression
- 2007
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Ingår i: Annals of Medicine. - New York : Informa Healthcare. - 0785-3890 .- 1365-2060. ; 39:3, s. 229-238
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Tidskriftsartikel (refereegranskat)abstract
- Background. Multiple lines of evidence suggest that the circadian clock contributes to the pathogenesis of winter depression or seasonal affective disorder (SAD). We hypothesized that sequence variations in three genes, including Per2, Arntl, and Npas2, which form a functional unit at the core of the circadian clock, predispose to winter depression.Methods. In silico analysis of the biological effects of allelic differences suggested the target single-nucleotide polymorphisms (SNPs) to be analyzed in a sample of 189 patients and 189 matched controls. The most relevant SNP in each gene was identified for the interaction analysis and included in the multivariate assessment of the combined effects of all three SNPs on the disease risk.Results. SAD was associated with variations in each of the three genes in gene-wise logistic regression analysis. In combination analysis of variations of Per2, Arntl, and Npas2, we found additive effects and identified a genetic risk profile for the disorder. Carriers of the risk genotype combination had the odds ratio of 4.43 of developing SAD as compared with the remaining genotypes, and of 10.67 as compared with the most protective genotype combination.Conclusion. Variations in the three circadian clock genes Per2, Arntl, and Npas2 are associated with the disease, supporting the hypothesis that the circadian clock mechanisms contribute to winter depression.
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