umu.sePublications
Change search
Refine search result
1 - 37 of 37
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Anan, Intissar
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Bång, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Lundgren, Hans-Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wixner, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Westermark, Per
    A case report of osteoarthritis associated with hereditary transthyretin amyloidosis ATTRV30M2019In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 26, p. 29-30Article in journal (Refereed)
  • 2.
    Arvidsson, Sandra
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wikström, Gerhard
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Right ventricular involvement in transthyretin amyloidosis2018In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 25, no 3, p. 160-166Article in journal (Refereed)
    Abstract [en]

    Background: The extent of right ventricular (RV) involvement in transthyretin amyloidosis (ATTR) is unknown.

    Objectives: This study sought to establish the degree of RV involvement in ATTR amyloidosis, and compare findings with RV involvement in hypertrophic cardiomyopathy (HCM).

    Methods: Forty-two patients with ATTR amyloidosis and echocardiographic evidence of cardiac amyloidosis (cardiac ATTR), 19 ATTR patients with normal left ventricular (LV) wall thickness (non-cardiac ATTR), 25 patients with diagnosed HCM and 30 healthy controls were included in this study. Echocardiographic measurements for conventional parameters, as well as RV global and segmental strain, were recorded.

    Results: When comparing RV structure and function between cardiac ATTR amyloidosis and HCM patients, only segmental strain differed between the two groups. In cardiac ATTR amyloidosis, we found an RV apex-to-base strain gradient with highest deformation in the apex. This pattern was reversed in patients with HCM.

    Conclusions: RV involvement is common in cardiac ATTR patients. The present study also detected an RV apical sparing pattern in patients with ATTR cardiomyopathy, similar to what has previously been described for the left ventricle in these patients. This pattern was not seen in HCM patients. Further studies are needed to assess the clinical importance of these findings.

  • 3. Berk, John L
    et al.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sekijima, Yoshiki
    Yamashita, Taro
    Heneghan, Michael
    Zeldenrust, Steven R
    Ando, Yukio
    Ikeda, Shu-ichi
    Gorevic, Peter
    Merlini, Giampaolo
    Kelly, Jeffrey W
    Skinner, Martha
    Bisbee, Alice B
    Dyck, Peter J
    Obici, Laura
    The diflunisal trial: study accrual and drug tolerance2012In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 19, no S1, p. 37-38Article in journal (Refereed)
    Abstract [en]

    Familial amyloidotic polyneuropathy (FAP) is a protein folding disorder that induces neuropathy and cardiomyopathy, leading to death within 7-15 years after onset of clinical disease. In vitro, small ligands binding the thyroid hormone docking site stabilize tetrameric transthyretin, inhibiting amyloid fibril formation. We undertook a randomized, placebo-controlled clinical trial to determine whether diflunisal, a well-known non-steroidal anti-inflammatory drug (NSAID) alters neurologic disease progression in FAP. We enrolled 130 subjects with wide age and FAP mutation representation. To date, few recognized complications of NSAIDs have occurred in the study cohort. Data collection will be completed by November 2012.

  • 4. Buxbaum, Joel
    et al.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Serum transthyretin levels in Swedish TTR V30M carriers2010In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 17, no 2, p. 83-85Article in journal (Refereed)
    Abstract [en]

    Serum transthyretin (TTR) levels have been reported to be reduced in Portuguese and Japanese patients with TTR V30M familial amyloidotic polyneuropathy and pre-symptomatic carriers of the allele as well as in the carriers of a number of other mutant TTRs. The only published report of serum TTR levels in Swedish TTR V30M carriers suggested that serum TTR levels were elevated in a small number of cases. Since Swedish V30M carriers have a lower degree of clinical penetrance than those from other countries we wished to determine if the reportedly elevated serum TTR concentrations and the lower clinical penetrance were part of a pathologic process that differed between the Swedish carriers and those of other ethnic groups. We compared the serum TTR levels, as determined by ELISA, in 42 documented Swedish TTR V30M carriers with 16 control individuals from the same geographic area in northern Sweden. Serum TTR concentrations in the controls were statistically significantly higher than in the TTR V30M carriers, which were in the same range as those in African-Americans carrying the TTR V122I allele. Thus, Swedish TTR V30M carriers have the same reduction in serum TTR as do other ethnic groups carrying the same or other TTR mutations.

  • 5.
    Gustavsson, Sandra
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Grönlund, Christer
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Can echocardiography and ECG discriminate hereditary transthyretin V30M amyloidosis from hypertrophic cardiomyopathy?2015In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 22, no 3, p. 163-170Article in journal (Refereed)
    Abstract [en]

    Objective: Hereditary transthyretin (ATTR) amyloidosis with increased left ventricular wall thickness could easily be misdiagnosed by echocardiography as hypertrophic cardiomyopathy (HCM). Our aim was to create a diagnostic tool based on echocardiography and ECG that could optimise identification of ATTR amyloidosis. Methods: Data were analysed from 33 patients with biopsy proven ATTR amyloidosis and 30 patients with diagnosed HCM. Conventional features from ECG were acquired as well as two dimensional and Doppler echocardiography, speckle tracking derived strain and tissue characterisation analysis. Classification trees were used to select the most important variables for differentiation between ATTR amyloidosis and HCM. Results: The best classification was obtained using both ECG and echocardiographic features, where a QRS voltage >30 mm was diagnostic for HCM, whereas in patients with QRS voltage <30 mm, an interventricular septal/posterior wall thickness ratio (IVSt/PWt) >1.6 was consistent with HCM and a ratio <1.6 supported the diagnosis of ATTR amyloidosis. This classification presented both high sensitivity (0.939) and specificity (0.833). Conclusion: Our study proposes an easily interpretable classification method for the differentiation between HCM and increased left ventricular myocardial thickness due to ATTR amyloidosis. Our combined echocardiographic and ECG model could increase the ability to identify ATTR cardiac amyloidosis in clinical practice.

  • 6.
    Heldestad, Victoria
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Obayashi, Konen
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nordh, Erik
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Comparison of quantitative sensory testing and heart rate variability in Swedish Val30Met ATTR2011In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 18, no 4, p. 183-190Article in journal (Refereed)
    Abstract [en]

    Patients with transthyretin amyloidosis (ATTR) polyneuropathy, a hereditary fatal disease, often report defects in both thermal perception and autonomic nervous system function as their first clinical symptoms. While elevated thermal perception thresholds (TPT) for cold and warmth only recently have been shown as an early marker of small nerve fiber dysfunction in these patients, heart rate variability (HRV) has frequently been used to quantify autonomic neuropathy. The main purpose with this report was to elucidate a possible relationship between estimates of HRV and TPT in a selected group of early and late-onset Swedish Val30Met ATTR patients. The results show significantly more pronounced elevation of TPT in early compared to late-onset patients. Significant correlations between HRV and TPT were found among late-onset cases, indicating a possible relationship between loss of thin nerve fibers in somatic and autonomic nerves, while generally no such relationships were found among early-onset cases. This observation emphasizes the importance of testing both HRV and TPT to ensure optimal early detection of neuropathic changes in an as wide as possible range of small nerve fibers in suspected ATTR patients. This is of particular importance as the phenotype of the ATTR disease varies between groups with different age of onset.

  • 7.
    Hellman, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Regional differences and similarities of FAP in Sweden2012In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 19, no S1, p. 53-54Article in journal (Refereed)
    Abstract [en]

    Marked differences in phenotype in familial amyloid polyneuropathy (FAP) populations have been noted between but also within FAP populations. Initially, it was believed that patients with FAP, caused by the TTR V30M mutation, shared the same founder. However, recent studies have clearly shown that the V30M mutation in Sweden occurred spontaneously later in time than that in Portugal. The Swedish FAP-population's phenotype differs between various areas within northern Sweden. Thus the age at onset is in average 20 years earlier in Skelleftea than in Pitea areas, a distance of only 60 km. Age at onset appears also to have an impact on complications of the disease. Late-onset cases often develop a cardiomyopathy, especially male patients. Mitochondrial haplotype distribution has been noted to differ between early- and late- onset patients in the Swedish population. Mitochondrial function is one possible factor contributing to the differences seen both between and within populations.

  • 8.
    Henein, Michael Y.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Response: Atrial impairment in transthyretin cardiac amyloidosis: an early marker of cardiac involvement and a prognostic factor2018In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 25, no 2, p. 136-136Article in journal (Refereed)
  • 9.
    Henein, Michael Y.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Arvidsson, Sandra
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Pilebro, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Westermark, Per
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Reduced left atrial myocardial deformation irrespective of cavity size: a potential cause for atrial arrhythmia in hereditary transthyretin amyloidosis2018In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 25, no 1, p. 46-53Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cardiac amyloidosis (CA) is a myocardial disease and commonly under-diagnosed condition. In CA patients, atrial fibrillation might occur in the absence of left atrial (LA) enlargement.

    OBJECTIVES: The aim of this study is to assess LA size and function, and its relationship with atrial arrhythmia in patients with hereditary transthyretin amyloidosis (ATTR).

    METHODS: Forty-six patients with confirmed ATTR amyloidosis on abdominal biopsy were studied. Assessment with 2D echocardiography and 2D strain showed 31 patients had increased LV wall thickness (LVWT) (septal thickness >12 mm), and 15 had normal LVWT. In addition to conventional measurements, LV and LA global longitudinal strain (GLS%) and strain rate (SR) were obtained. Western blot analysis was done to assess fibril type. ATTR patients with increased LVWT were compared with 23 patients with hypertrophic cardiomyopathy (HCM) and 31 healthy controls. ATTR amyloidosis patients also underwent 24 hour Holter monitoring to determine the presence of atrial arrhythmia.

    RESULTS: Atrial deformation during atrial systole was reduced in ATTR amyloidosis patients with increased LVWT independent of LA size and in contrast to HCM. Twenty of the ATTR amyloidosis patients (54%) had ECG evidence of significant atrial arrhythmic events. LA strain rate, during atrial systole, was the only independent predictor of atrial arrhythmia (β = 3.28, p = .012).

    CONCLUSION: In ATTR cardiomyopathy with increased LVWT, LA myocardial function is abnormal, irrespective of atrial cavity size. Reduced LA myocardial SR during atrial systole, irrespective of cavity volume, E/e' and LV deformation, is also a strong predictor for atrial arrhythmic events.

  • 10.
    Hörnsten, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Pennlert, Johanna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Jensen, Steen M
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Heart complications in familial transthyretin amyloidosis: impact of age and gender.2010In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 17, no 2, p. 63-68Article in journal (Refereed)
    Abstract [en]

    Heart arrhythmia is common in Swedish patients with familial amyloidotic polyneuropathy (FAP), as well as cardiomyopathy. We investigated the relationship between Holter ECG and echocardiographic findings in 108 FAP patients, with particular focus on age and gender differences. Female patients were younger than male patients at symptom onset (p < 0.01). Only 4 of 39 patients with septal hypertrophy were females. Regression analysis showed that age of onset, gender and duration of disease were significantly related with intraventricular septum (IVS) thickness. Sixty-five patients (25 females) presented with abnormal 24-h ECG recordings. IVS thickness was not significantly related to conduction disturbances or the presence of ventricular arrhythmia (VA). However, IVS thickness and atrial dimension were both related to increased rate of supraventricular arrhythmia (SVA). Male gender was clearly associated with more pronounced septal thickness of the heart. Conduction disturbances were not related to IVS thickness, indicating that the distribution and extent of infiltration of the heart by amyloid are heterogeneous and related to gender and age of onset. These findings highlight the necessity of 24-h ECGs to detect conduction disturbances, due to their occurrence in the absence of echocardiographic evidence of amyloid deposition in the myocardium.

  • 11.
    Hörnsten, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jensen, Steen M
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Outcome of heart rate variability and ventricular late potentials after liver transplantation for familial amyloidotic polyneuropathy2008In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 15, no 3, p. 187-195Article in journal (Refereed)
    Abstract [en]

    Reduced heart rate variability (HRV) is common in familial amyloidotic polyneuropathy (FAP), as well as cardiac arrhythmias. We examined the effects of liver transplantation (LTx) on 24-h HRV and ventricular late potentials. Twenty-one liver-transplanted FAP patients underwent Holter-ECG recordings and signal average electrocardiography recordings (SAECG) before and after LTx. Mean follow-up time after LTx was 21.7 months. Three patients had marked increased HRV after LTx, but this was in all cases caused by the development of subtle atrial arrhythmia and did not reflect an improvement in the cardiac autonomic control. In total, ten patients were excluded from analysis of HRV because of arrhythmia. Spectral analysis of HRV showed no significant differences before and after LTx in the remaining 11 patients. Positive late potentials were found in 33% of patients before LTx and this proportion was unchanged after LTx. Reduced HRV and positive late potentials are common in Swedish FAP patients, and remain stable, at least within the short term after transplantation. If an increase of HRV after transplantation is observed, it should raise the suspicion that the patient has developed subtle atrial arrhythmia.

  • 12.
    Hörnsten, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olofsson, Bert-Ove
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Arrhythmia - a pitfall in tests of cardiac autonomic function after liver transplantation for familial amyloidotic polyneuropathy: a long-term follow-up of Swedish patients2012In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 19, no 2, p. 81-86Article in journal (Refereed)
    Abstract [en]

    Liver transplantation (LT) is a potentially curative treatment for hereditary transthyretin amyloidosis, of which familial amyloid polyneuropathy (FAP) is the most common form in Sweden. This study investigated the long-term development in heart rate variability (HRV) after LT in Swedish FAP patients. HRV was analyzed before LT, and during a first (<40 months) and a second (>40 months) follow-up recording after transplantation, respectively. Power spectrum analysis was performed on 2-min sequences in the supine position and after passive tilt, after careful identification of patients with arrhythmia. Data were obtained from 33 patients, but 18 patients had developed cardiac arrhythmia or were pacemaker-treated (4 before LT and 14 after LT) and three patients had not performed the first follow-up recording. In the remaining 12 patients, HRV decreased between the pretransplant evaluation and the first follow-up, thereafter no significant changes were found. In conclusion, our study showed that the progressive development of cardiac arrhythmias after LT is a major pitfall when assessing cardiac autonomic function in FAP patients, especially in patients older than 40 years. In the minority of patients with sinus rhythm in all recordings, cardiac autonomic modulation remained stable after transplantation and no improvement was noted.

  • 13. Ihse, Elisabet
    et al.
    Rapezzi, Claudio
    Merlini, Giampaolo
    Benson, Merrill D.
    Ando, Yukio
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ikeda, Shu-ichi
    Lavatelli, Francesca
    Obici, Laura
    Quarta, Candida C.
    Leone, Ornella
    Jono, Hirofumi
    Ueda, Mitsuharu
    Lorenzini, Massimiliano
    Liepnieks, Juris
    Ohshima, Toshinori
    Tasaki, Masayoshi
    Yamashita, Taro
    Westermark, Per
    Amyloid fibrils containing fragmented ATTR may be the standard fibril composition in ATTR amyloidosis2013In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 20, no 3, p. 142-150Article in journal (Refereed)
    Abstract [en]

    The clinical phenotype of familial ATTR amyloidosis depends to some extent on the particular mutation, but differences exist also within mutations. We have previously described that two types of amyloid fibril compositions exist among Swedish ATTRV30M amyloidosis patients, one consisting of a mixture of intact and fragmented ATTR (type A) and one consisting of mainly intact ATTR (type B). The fibril types are correlated to phenotypic differences. Patients with ATTR fragments have a late onset and develop cardiomyopathy, while patients without fragments have an early onset and less myocardial involvement. The present study aimed to determine whether this correlation between fibril type and phenotype is valid for familial ATTR amyloidosis in general. Cardiac or adipose tissues from 63 patients carrying 29 different TTR non-V30M mutations as well as 13 Japanese ATTRV30M patients were examined. Fibril type was determined by western blotting and compared to the patients' age of onset and degree of cardiomyopathy. All ATTR non-V30M patients had a fibril composition with ATTR fragments, except two ATTRY114C patients. No clear conclusions could be drawn about a phenotype to fibril type correlation among ATTR non-V30M patients. In contrast, Japanese ATTRV30M patients showed a similar correlation as previously described for Swedish ATTRV30M patients. This study shows that a fibril composition with fragmented ATTR is very common in ATTR amyloidosis, and suggests that fibrils composed of only full-length ATTR is an exception found only in a subset of patients.

  • 14. Janunger, T
    et al.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Holmgren, G
    Lövheim, O
    Ohlsson, P I
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Tashima, K
    Heart failure caused by a novel amyloidogenic mutation of the transthyretin gene: ATTR Ala45Ser.2000In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 7, no 2, p. 137-40Article in journal (Refereed)
    Abstract [en]

    Cardiac failure in transthyretin (TTR) amyloidosis patients has been shown to be caused by different mutations in the TTR gene. In the present case, a 73-year-old man from Northern Sweden was evaluated for heart failure. Amyloid deposits were found in subcutaneous fat and in intestinal biopsies. The presence of a variant form of TTR was detected in the plasma by electrospray ionisation mass spectrometry (ESI-MS). The mutation was located by single-strand conformation polymorphism (SSCP) analysis of the TTR gene where a band shift was seen in exon 2. Direct sequencing of exon 2 revealed a single base-pair substitution (G1724T). This transversion results in an amino acid substitution at codon 45, alanine to serine (ATTR Ala45Ser). Mass spectrometry analysis excluded that the variant is a polymorphism, since no similar shift in molecular weight has been present in more than 200 control samples. Congo red and immunostaining of duodenum biopsy specimens confirmed the presence of systemic ATTR amyloidosis, and clinical examination, including echocardiography, found evidence of a restrictive cardiomyopathy. He had 10 years previously been operated for a bilateral carpal tunnel syndrome, but otherwise no symptoms were present that could be attributed to his systemic amyloidosis. No axonal polyneuropathy was noted at nerve conduction studies. This novel mutation is the second amyloidogenic TTR mutation found in the Swedish population.

  • 15.
    Jonsén, Elisabeth
    et al.
    Umeå University, Faculty of Medicine, Nursing.
    Suhr, O B
    Tashima, K
    Athlin, E
    Early liver transplantation is essential for familial amyloidotic polyneuropathy patients' quality of life.2001In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 8, no 1, p. 52-7Article in journal (Refereed)
    Abstract [en]

    Nineteen patients, who had undergone liver transplantation for familial amyloidotic polyneuropathy, had answered a quality of life questionnaire including 61 questions on somatic and mental symptoms, social aspects of life, confidence and satisfaction before, one year, and two years after transplantation. We found that patient satisfaction was generally good two years or more after the transplantation. Most of the patients were very or quite satisfied with the result. All of them had the drive to go on and felt hopeful about the future. However, on the second follow-up, 37% of the patients noted that they felt more insecure in their everyday life and there was a significant difference between the two assessments. The diarrhea score became worse between one and two years after the transplantation and was closely related to the duration of the gastrointestinal symptoms and to the duration of the disease before transplantation. The mental symptoms also increased significantly between the evaluations and this related to the severity of the somatic symptoms. Our conclusion is that liver transplantation should be performed before advanced somatic symptoms start to develop in order to improve the patients' chances of a good quality of life following liver transplantation.

  • 16. Kawaji, Takahiro
    et al.
    Ando, Yukio
    Ando, Eiko
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Tanihara, Hidenobu
    Transthyretin-related vitreous amyloidosis in different endemic areas.2010In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 17, no 3-4, p. 105-108Article in journal (Refereed)
    Abstract [en]

    Background: to investigate the vitreous opacity in patients with familial amyloidotic polyneuropathy (FAP) in two major endemic areas, Japan and Sweden. Methods: we obtained clinical data for 90 patients with vitreous opacity that was associated with FAP amyloidogenic transthyretin (ATTR) Val30Met; 18 Japanese patients and 72 Swedish patients. We reviewed medical records at Kumamoto University Hospital in Japan and Umeå University Hospital in Sweden. We evaluated the characteristics of the patients, systemic and ocular histories, clinical findings and treatment. RESULTS: swedish patients were significantly older at the onset of vitreous opacity (mean age 67.8 years) than were Japanese patients (47.6 years). A similar age difference was found for the onset of polyneuropathy. In addition, Swedish patients without polyneuropathy were significantly older (74.1 years) at the onset of vitreous opacity than those with polyneuropathy (64.6 years). A significant difference in the occurrence of vitreous opacity as the only manifestation of FAP was seen for Swedish patients (35%) compared with Japanese patients (6%). CONCLUSIONS: swedish FAP ATTR Val30Met patients appeared to develop vitreous opacity later and more frequently compared with Japanese patients.

  • 17.
    Lindhagen-Persson, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Vestling, M
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Reixach, N
    Division of Rheumatology Research, W.M. Keck Autoimmune Disease Center, The Scripps Research Institute, La Jolla, CA, USA.
    Olofsson, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Formation of cytotoxic transthyretin is not dependent on inter-molecular disulphide bridges commonly found within the amyloid form2008In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 15, no 4, p. 240-245Article in journal (Refereed)
    Abstract [en]

    Familial amyloidotic polyneuropathy (FAP) is linked to destabilising point mutations in the human plasma protein transthyretin (TTR). Consistent with similar amyloid disorders, low molecular weight TTR oligomers have been shown to exert the major cytotoxic effect. The amyloid structure of TTR contains non-native inter-molecular disulphide linkages via the cysteine at position 10 (Cys10). Moreover, substitution of Cys10 in a mouse model for TTR-amyloidosis abolishes TTR deposits, indicating an important role of Cys10 in FAP pathogenesis. However, the role of disulphide bridges in TTR cytotoxicity has not been elucidated. By probing Cys10Ser TTR variants to the human neuroblastoma SH-SY5Y cell line, we have addressed this question, and our results clearly show that formation of an inter-molecular disulphide bridge is not a pre-requisite for TTR cytotoxicity. This finding suggests that prevention of inter-molecular TTR disulphide bridges as a therapeutic intervention will not impair the cytotoxic potential of TTR.

  • 18.
    Marberg, Therese
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Söderberg, Karin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wixner, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Self-reported gastrointestinal symptoms are more common in liver transplanted transthyretin amyloidosis patients than in healthy controls and in patients transplanted for end-stage liver disease2019In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 26, p. 47-48Article in journal (Refereed)
  • 19.
    Morozova-Roche, Ludmilla
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Strengthening the positions of Scandinavian science in research on neurodegenerative and age-dependent amyloid diseases2010In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 17, no 1, p. 39-Article in journal (Refereed)
  • 20.
    Norgren, Nina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olsson, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nyström, Hanna
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ericzon, Bo Goran
    de Tayrac, Marie
    Genin, Emmanuelle
    Plante-Bordeneuve, Violaine
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Gene expression profile in hereditary transthyretin amyloidosis: differences in targeted and source organs2014In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 21, no 2, p. 113-119Article in journal (Refereed)
    Abstract [en]

    Introduction: Hereditary transthyretin amyloidosis (ATTR) is a genetic disease caused by a point mutation in the TTR gene that causes the liver to produce an unstable TTR protein. The most effective treatment has been liver transplantation in order to replace the variant TTR producing liver with one that produces only wild-type TTR. ATTR amyloidosis patients' livers are reused for liver sick patients, i.e. the Domino procedure. However, recent findings have demonstrated that ATTR amyloidosis can develop in the recipients within 7-8 years. The aim of this study was to elucidate how the genetic profile of the liver is affected by the disease, and how amyloid deposits affect target tissue. Methods: Gene expression analysis was used to unravel the genetic profiles of Swedish ATTR V30M patients and controls. Biopsies from adipose tissue and liver were examined. Results and Conclusions: ATTR amyloid patients' gene expression profile of the main source organ, the liver, differed markedly from that of the controls, whereas the target organs' gene expression profiles were not markedly altered in the ATTR amyloid patients compared to those of the controls. An impaired ER/protein folding pathway might suggest ER overload due to mutated TTR protein.

  • 21. Nyhlin, N
    et al.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    el-Salhy, M
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ando, Y
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Endocrine cells in the upper gastrointestinal tract in relation to gastrointestinal dysfunction in patients with familial amyloidotic polyneuropathy.1999In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 6, no 3, p. 192-8Article in journal (Refereed)
    Abstract [en]

    Gastrointestinal (GI) dysfunction is a common complication of familial amyloidotic polyneuropathy (FAP). In previous reports, a decreased content of small and large intestinal endocrine cells has been found in patients with FAP and it has been suggested that this may contribute to the development of GI disturbances. The aim of the present study was to investigate the endocrine cell content in the stomach and duodenum of FAP patients, and to correlate the findings with gastric emptying. Fifteen patients with FAP were included in the study. Twenty-eight subjects with macroscopically and histologically normal mucosa were used as controls for endocrine cell contents and 14 healthy subjects for gastric scintigraphy. The endocrine cells were identified by immunohistochemistry and quantified with image analysis. Gastric emptying time was detected by scintigraphy and endoscopy. The number of chromogranin A-immunoreactive (IR) cells was reduced in all investigated parts of the GI tract except bulbus duodeni. Gastrin/CCK cell content was reduced in duodenum, but tended to be increased in antrum of the stomach (P = 0.07). Otherwise, the content of all other endocrine cells types in the upper GI tract was reduced compared with controls. A correlation with malnutrition was found for gastric inhibitory polypeptide and secretin cell content in bulbus duodeni. Gastric scintigraphy disclosed delayed gastric emptying of solid food, but the finding was not correlated to the decreased content of neuroendocrine cells. The severity of endocrine cell depletion was not correlated to duration of GI disturbances. The present study showed that the endocrine cells of the stomach are affected in FAP patients and that the abnormalities in the upper GI endocrine cells occur early during the course of the disease.

  • 22.
    Obayashi, K
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karlsson, Marcus
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Okamoto, S
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ando, Y
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hemodynamic responses after tilt reversal in FAP2011In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 18, no Suppl 1, p. 161-163Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to evaluate hemodynamic responses after tilt reversal in familial amyloid polyneuropathy (FAP). Systolic blood pressure (BP) and heart rate variability (HRV) were analyzed in the baseline, 70-degree upright position, and after tilt reversal in 10 patients with FAP and 14 healthy controls. Maximum systolic BP after tilt reversal was increased in FAP as compared to baseline (BP overshoot), whereas controls showed a significantly lower BP overshoot. In all states, all HRV parameters were significantly lower than those of the controls. In a linear regression analysis adjusted for age, we found a significant inverse relation between BP overshoot and HRV in all three states. Five patients presented atrial arrhythmia precluding HRV analysis: four of those presented BP overshoots 12 mmHg. BP overshoot may be a useful marker to assess the progression of cardiac autonomic dysfunction, especially since heart arrhythmia in many patients with FAP prevents HRV analysis.

  • 23.
    Okamoto, Sadahisa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Zhao, Ying
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Backman, Christer
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Ericzon, Bo-Göran
    Center for Surgical Sciences, Karolinska Institute, Karolinska University Hospital, Huddinge, Sweden.
    Wijayatunga, Priyantha
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Development of cardiomyopathy after liver transplantation in Swedish hereditary transthyretin amyloidosis (ATTR) patients2011In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 18, no 4, p. 200-205Article in journal (Refereed)
    Abstract [en]

    Background: Recent studies of liver transplanted (LTx) familial amyloidotic polyneuropathy (FAP) patients have shown a progression of cardiomyopathy in some patients after LTx, but knowledge of the underlying factors remains limited.

    Methods: Seventy-five patients, who had undergone LTx from 1996 to 2008, were included. They had all been examined by echocardiography 1-16 months before LTx. Fifty-four had been re-examined 7-34 months, and forty-two 36-137 months after LTx.

    Results: A significant increase in interventricular septum (IVS) thickness occurred after LTx (p < 0.01), particularly in males (p = 0.002) and late onset patients (p = 0.003). The development of post-LTx cardiomyopathy was related to patient's age at onset of the disease, male gender and pre-LTx IVS thickness. On multivariate regression analysis, however, age at onset was the only significant predictor for the development of cardiomyopathy (odds ratio = 1.14, 95% confident interval 1.01-1.30, p = 0.04).

    Conclusion: An increase of IVS thickness can be observed in FAP patients after LTx. Age at onset of the disease is the main predictor for increased IVS thickness and for the development of cardiomyopathy after liver transplantation.

  • 24.
    Olsson, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jonasson, Jenni
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Cederquist, Kristina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Frequency of the transthyretin Val30Met mutation in the northern Swedish population2014In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 21, no 1, p. 18-20Article in journal (Other academic)
    Abstract [en]

    By genotyping a large number of samples from the Northern Sweden Health and Disease Study cohort, a carrier frequency could be determined for the Skelleftea and Lycksele populations. A previous study of the amyloidogenic transthyretin mutation TTRV30M in Northern Sweden's endemic area has shown a large variation in carrier frequency and penetrance of the trait within the area. However, the estimations have been based on a small sample size within the different regions in the area and therefore, the wide variation in TTRV30M carrier frequency observed between the Lycksele and Skelleftea populations are uncertain. Based on a total of 3460 samples, the estimated overall carrier frequency in the two regions was 1.82% with a carrier frequency in the Skelleftea and Lycksele population of 1.63% and 2.02%, respectively. Thus, the previously reported extremely high frequency in the Lycksele region compared to that of the Skelleftea region could not be substantiated. However, it does not change the previous finding of a surprisingly higher carrier frequency in the population from endemic area of Northern Sweden compared to that reported from endemic areas in Portugal.

  • 25. Stangou, Arie J
    et al.
    Lobato, Luisa
    Zeldenrust, Steven
    Rela, Mohamed
    Portmann, Bernard
    Linke, Reinhold P
    Conceicao, Isabel
    Otto, Gerd
    Wilczek, Henryk
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Azoulay, Daniel
    Grateau, Gilles
    Picken, Maria
    O'Grady, John
    Heaton, Nigel
    Ericzon, Bo-Göran
    Benson, Merrill D
    Solid organ transplantation for non-TTR hereditary amyloidosis: report from the 1st International Workshop on the Hereditary Renal Amyloidoses2012In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 19, no S1, p. 81-84Article in journal (Refereed)
    Abstract [en]

    Fibrinogen A alpha-chain (AFib) and apolipoprotein AI (AApoAI) amyloidosis due to variants in the AFib and ApoAI genes are the most common types of hereditary amyloidosis in Europe and the United States. Liver is the exclusive source of the aberrant amyloidogenic protein in AFib and responsible for supplying approximately half of the circulating variant ApoAI. Nephrotic syndrome and renal impairment due to renal amyloidosis are common disease manifestations; however, recent research provides evidence to support a more diverse and systemic disease phenotype, which in turn has implications in the management of the hereditary amyloidoses with solid organ transplantation and, in particular, liver transplantation.

  • 26.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Commentary to Isabel Conceicao et al. early diagnosis through targeted follow-up of identified carriers of TTR gene mutations2019In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 26, no 1, p. 1-2Article in journal (Other academic)
  • 27.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Response: concerning "late early and late onset" ATTR Val30Met patients2019In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818Article in journal (Refereed)
  • 28.
    Suhr, Ole B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Åhlström Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Rydh, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Gastric emptying before and after liver transplantation for familial amyloidotic polyneuropathy, Portuguese type (Val30Met).2003In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 10, no 2, p. 121-6Article in journal (Refereed)
    Abstract [en]

    Liver transplantation is an accepted treatment of familial amyloidotic polyneuropathy (FAP), Portuguese type (Val30Met), and the outcome so far seems promising. Gastric retention with nausea and vomiting are common complications of the disease, and may interfere with immuno-suppression therapy and prolong recovery after liver transplantation. The aim of this study was to assess the frequency of gastric retention in FAP patients and to evaluate the impact liver transplantation has on gastric emptying. Twenty-two patients, who had undergone liver transplantation, and had been re-examined for gastric retention after the procedure, were included in the study. Gastric emptying was recorded by scintigraphy after the ingestion of a 99m-technetium (99mTc)-labelled meal (omelette). The half-time (T50) of the emptying phase was calculated. Gastrointestinal symptoms before and after transplantation were recorded, and the majority of patients were also subjected to an upper endoscopic examination, where the presence of solid residual in the stomach was regarded as consistent with gastric retention. A high frequency of gastric retention was noted among the patients both before and after transplantation, and no significant improvement for the group was noted, even though decreased gastric emptying was noted for patients with a duration of the disease for less that 4 years. Patients who improved their nutritional status after transplantation had a faster gastric emptying than those who deteriorated. From our findings it can be concluded that gastric retention is a common complication of FAP and that gastric emptying in patients with longstanding disease (> or = 4 years) is unchanged after liver transplantation.

  • 29.
    Suhr, Ole B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Andersen, Oluf
    Aronsson, Thomas
    Jonasson, Jenni
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Kalimo, Hannu
    Lundahl, Christer
    Lundgren, Hans-Eric
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Melberg, Atle
    Nyberg, Johan
    Olsson, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Sandberg, Arne
    Westermark, Per
    Report of five rare or previously unknown amyloidogenic transthyretin mutations disclosed in Sweden.2009In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 16, no 4, p. 208-214Article in journal (Refereed)
    Abstract [en]

    The number of amyloidogenic transthyretin (TTR) mutations described in the literature is more than 100. However, for several mutations, the phenotype has been described in a few individuals only; thus, the knowledge of the clinical course and the outcome after therapeutical interventions such as liver transplantation is limited. We describe the phenotype associated with five rare amyloidogenic TTR mutations that lately were discovered in Sweden: ATTR Val30Leu, Ala45Ser, Leu55Gln, Gly57Arg and Tyr69His of which ATTR Gly57Arg is previously unknown. The symptoms at onset differed, but cardiomyopathy and peripheral neuropathy were observed in all except the ATTR Tyr69His mutation. Likewise, carpal tunnel syndrome was found or had been present in all cases except the case with the ATTR Val30Leu mutation. The phenotype of the ATTR Tyr69His mutation was characterised by oculo-meningeal symptoms with seizures and a steadily progressing dementia, symptoms rarely found in ATTR amyloidosis, but similar to those previously described for this mutation, where all cases appear to originate from one Swedish family. Two patients with the ATTR Leu55Gln and Ala45Ser mutations have been subjected to liver transplantation, but echocardiographic examination has revealed an increasing cardiomyopathy after transplantation in both cases, the ATTR Leu55Gln patient succumbed 2 years after transplantation from progressive disease.

  • 30.
    Suhr, Ole B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ericzon, Bo-Göran
    Selection of hereditary transthyretin amyloid patients for liver transplantation: the Swedish experience2012In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 19, no S1, p. 78-80Article in journal (Refereed)
    Abstract [en]

    Liver transplantation (LTx) is currently an accepted treatment for hereditary transthyretin amyloidosis (h-ATTR). However, to optimize the outcome, careful selection of patients is required, since increased mortality compared with that found for nontransplanted historical controls are observed for several groups of h-ATTR patients. We have noted that malnourished patients and patients with a late onset of the disease especially in combination with findings of cardiomyopathy are at risk for an increased mortality and morbidity. Recently detection of different types of amyloid fibrils that appears to be related to the phenotype of the patient may facilitate patient selection for LTx.

  • 31.
    Suhr, Ole B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Olofsson, Bert-Ove
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Backman, Christer
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Myocardial hypertrophy and function are related to age at onset in familial amyloidotic polyneuropathy.2006In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 13, no 3, p. 154-159Article in journal (Refereed)
  • 32.
    Suhr, Ole B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Wixner, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Pilebro, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lundgren, Hans-Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    The Swedish landscape of hereditary ATTR amyloidosis2017In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 24, no 1, p. 93-94Article in journal (Refereed)
    Abstract [en]

    Northern Sweden is a well-known clustering area for hereditary transthyretin (TTR) amyloid (ATTR) amyloidosis caused by the Val30Met mutation. However, several additional mutations have been found in the Swedish population, of which many, such as the Ala45Ser, Gly57Arg and His88Arg mutations, have not been reported outside of Sweden to the best of our knowledge. We aim to give an overview of the various mutations found in the Swedish population.

  • 33. Westermark, Per
    et al.
    Nowak, Greg
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ericzon, Bo-Goran
    Domino liver transplantation: full-length transthyretin in donor and recipient patients with ATTR Val30Met amyloidosis2017In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 24, p. 128-129Article in journal (Refereed)
  • 34.
    Wiklund, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Kadkhodaee, Amir
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Andersson, Kennet
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Normal scores of deep breathing tests: beware of dysrhythmia in transthyretin amyloidosis2018In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 25, no 1, p. 54-61Article in journal (Refereed)
    Abstract [en]

    Background: The heart rate (HR) response to paced deep breathing (DB) is a common test of cardiac autonomic function, where high heart rate variability (HRV) is considered to reflect normal autonomic function. We evaluated the DB test in patients with hereditary transthyretin amyloid (ATTRm) amyloidosis, where autonomic dysregulation and atrial arrhythmias are common.Methods: Paced DB was performed during one minute (six breaths/min) in 165 recordings in adult ATTRm amyloidosis patients with the TTR Val30Met mutation, 42 hypertrophic cardiomyopathy (HCM) patients and 211 healthy subjects. HRV was scored by traditional DB indices and by a novel regularity index, estimating the fraction of the HRV that was coherent with the breathing pattern.Results: Twenty per cent of ATTRm amyloidosis patients presented with age-adjusted HRV scores within normal limits but poor regularity due to subtle atrial arrhythmias and cardiac conduction disturbances. Forty-seven per cent of ATTRm amyloidosis patients presented with HRV scores below normal limits, whereas HCM patients presented with higher HRV than ATTRm amyloidosis patients.Conclusions: Reduced HRV is common in ATTRm amyloidosis patients during DB, however, autonomic function cannot be evaluated in patients presenting with the combination of normal scores and low regularity, since their HR responses often reflects dysrhythmias.

  • 35.
    Wixner, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Obayashi, Konen
    Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
    Ando, Yukio
    Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Loss of gastric interstitial cells of Cajal in patients with hereditary transthyretin amyloidosis2013In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 20, no 2, p. 99-106Article in journal (Refereed)
    Abstract [en]

    Background: Hereditary transthyretin (TTR) amyloidosis is a systemic neuropathic disorder caused by TTR gene mutations. Gastrointestinal complications are common and the underlying mechanisms remain unclear. The interstitial cells of Cajal (ICC) function as pacemaker cells in the gastrointestinal tract and are important for gastrointestinal motility. The aim of this study was to investigate the densities of gastric ICC and nerves in patients with TTR amyloidosis compared to non-amyloidosis controls.

    Methods: Antral wall autopsy specimens from 11 Japanese ATTR V30M patients and 10 controls were analyzed with immunohistochemistry and computerized analysis. Antibodies to c-Kit and TMEM16A were used to assess ICC and an antibody to PGP 9.5 was used to assess nervous tissue. The study was approved by a Japanese ethical committee.

    Results: The densities of c-Kit-immunoreactive (IR) ICC were significantly lower in the circular and longitudinal muscle layers of patients compared to controls (p = 0.004 for both). Equivalent results were found for TMEM 16A-IR ICC. There were no significant differences in PGP 9.5-IR cells in the circular or longitudinal muscle layers between patients and controls (p = 0.173 and 0.099, respectively).

    Conclusions: A loss of gastrointestinal ICC may be an important factor for the digestive disturbances in hereditary TTR amyloidosis.

  • 36.
    Wixner, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Pilebro, Bjorn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lundgren, Hans-Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Olsson, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Effect of doxycycline and ursodeoxycholic acid on transthyretin amyloidosis2017In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 24, no 1, p. 78-79Article in journal (Refereed)
    Abstract [en]

    Doxycycline has been shown to disrupt transthyretin amyloid (ATTR) fibrils [1] and tauro-ursodeoxycholic acid (TUDCA) has been shown to reduce TTR toxic aggregates in mice [2]. Further, in 2010 Cardoso et al. showed that a combined doxycycline/TUDCA treatment had a synergistic effect, decreasing ATTR deposition. Ursodeoxycholic acid (UDCA) is a bile acid used for the treatment of certain cholestatic syndromes with an efficacy similar to that of TUDCA. Based on this knowledge, we wanted to explore if treatment with doxycycline and UDCA (Dox/Urso) would prevent disease progression in ATTR amyloidosis. UDCA was selected since TUDCA is not available in Sweden.

  • 37.
    Wixner, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Westermark, Per
    Ihse, Elisabet
    Pilebro, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lundgren, Hans-Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    The Swedish open-label diflunisal trial (DFNS01) on hereditary transthyretin amyloidosis and the impact of amyloid fibril composition2019In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 26, p. 39-40Article in journal (Refereed)
1 - 37 of 37
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf