Meredith I.T.,MonashHeart |
Meredith I.T.,Southern Health |
Verheye S.,Ziekenhuis Netwerk Antwerpen Middelheim |
Weissman N.J.,MedStar Research Institute |
And 16 more authors.
EuroIntervention | Year: 2013
Aims: The EVOLVE FHU trial demonstrated non-inferiority of six-month late loss with two dose formulations of SYNERGY, a novel bioabsorbable polymer everolimus-eluting stent (EES) compared with the durable polymer PROMUS Element (PE) EES. The current analysis describes the six-month IVUS and clinical results through two years from the EVOLVE FHU trial. Methods and results: EVOLVE recruited 291 patients from 29 centres. At six months, IVUS-assessed in-stent net volume obstruction was 3.40±5.06% for PROMUS Element (PE) vs. 2.68±4.60% for SYNERGY (p=0.34) and 3.09±4.29% for SYNERGY 1/2 dose (p=0.68 vs. PE). There were no significant differences between groups for any other measured IVUS parameter including resolved, persistent, and late-acquired incomplete stent apposition (ISA). At two years, target lesion failure (TLF) was 6.1% for PE vs. 5.5% for SYNERGY (p=0.87) and 5.2% for SYNERGY 1/2 dose (p=0.81). There were no significant differences between groups for cardiac death, repeat revascularisation, MI or stent thrombosis through two years. Conclusions: At six months, everolimus delivered from an ultrathin bioabsorbable abluminal polymer resulted in equivalent net volume obstruction and ISA compared with a permanent polymer EES. There were no significant differences between PE and either SYNERGY stent for any major cardiac endpoint through two years. Clinical trials number: NCT01135225. © Europa Digital and Publishing 2013. All rights reserved.
Bjursell M.K.,Karolinska Institutet |
Blom H.J.,VU University Amsterdam |
Cayuela J.A.,Sahlgrenska University Hospital |
Engvall M.L.,Karolinska Institutet |
And 16 more authors.
American Journal of Human Genetics | Year: 2011
Four inborn errors of metabolism (IEMs) are known to cause hypermethioninemia by directly interfering with the methionine cycle. Hypermethioninemia is occasionally discovered incidentally, but it is often disregarded as an unspecific finding, particularly if liver disease is involved. In many individuals the hypermethioninemia resolves without further deterioration, but it can also represent an early sign of a severe, progressive neurodevelopmental disorder. Further investigation of unclear hypermethioninemia is therefore important. We studied two siblings affected by severe developmental delay and liver dysfunction. Biochemical analysis revealed increased plasma levels of methionine, S-adenosylmethionine (AdoMet), and S-adenosylhomocysteine (AdoHcy) but normal or mildly elevated homocysteine (Hcy) levels, indicating a block in the methionine cycle. We excluded S-adenosylhomocysteine hydrolase (SAHH) deficiency, which causes a similar biochemical phenotype, by using genetic and biochemical techniques and hypothesized that there was a functional block in the SAHH enzyme as a result of a recessive mutation in a different gene. Using exome sequencing, we identified a homozygous c.902C>A (p.Ala301Glu) missense mutation in the adenosine kinase gene (ADK), the function of which fits perfectly with this hypothesis. Increased urinary adenosine excretion confirmed ADK deficiency in the siblings. Four additional individuals from two unrelated families with a similar presentation were identified and shown to have a homozygous c.653A>C (p.Asp218Ala) and c.38G>A (p.Gly13Glu) mutation, respectively, in the same gene. All three missense mutations were deleterious, as shown by activity measurements on recombinant enzymes. ADK deficiency is a previously undescribed, severe IEM shedding light on a functional link between the methionine cycle and adenosine metabolism. © 2011 The American Society of Human Genetics.
Al Sayegb S.,Karolinska Institutet |
Filen T.,Academic Hospital of Uppsala |
Johansson M.,Falu lasarett |
Sandstrom S.,Karolinska University Hospital |
And 2 more authors.
Scandinavian Journal of Pain | Year: 2013
Background and purpose: This case of a 42 year old woman with lower extremity Complex Regional Pain Syndrome (CRPS) after a twisting injury of the ankle, effectively treated with the addition of mirror therapy to a rehabilitation programme, prompted a literature review of both CRPS and mirror therapy. Mirror therapy is a newer adjunct to other forms of pain control and functional restoration for treatment of CRPS as well as other difficult clinical problems. This was a required group project as part of a university based course in chronic pain for healthcare workers. Materials and methods: The PubMed database up to September 26, 2012 was reviewed using four search word groups: "CRPS mirror therapy", "mirror CRPS", "reflex sympathetic dystrophy OR Complex Regional Pain Syndrome AND mirror" and "reflex sympathetic dystrophy OR Complex Regional Pain Syndrome AND mirror. +. RCT". Nine studies from PubMed met the criteria that this working group had chosen for inclusion in the analysis of mirror therapy as treatment. These references were supplemented by others on CRPS in order to generate an adequate review of both the syndrome CRPS and mirror therapy itself. Some references were specific for mirror therapy in the treatment of CRPS but others described mirror therapy for the treatment of phantom limb pain, brachial plexus avulsion pain, for physical rehabilitation of stroke related paresis and for rehabilitation after hand surgery. Results: Criteria for the diagnosis of CRPS including the International Association for the Study of Pain criteria and the Budapest criteria are reviewed with an emphasis on the specificity and sensitivity of the various criteria for clinical and research purposes. The signs and symptoms of CRPS are a part of the criteria review.The main treatment strategy for CRPS is physical rehabilitation for return of function and mirror therapy is one of many possible strategies to aid in this goal.The patient in this case report had failed many of the adjunctive therapies and rehabilitation had been unsuccessful until the addition of mirror therapy. She then could progress with physical rehabilitation and return to a more normal life. Mirror therapy techniques are briefly described as part of a discussion of its success with relationship to signs and symptoms as well as to the duration of CRPS (and other syndromes). Some discussion of the theories of the central effects of both CRPS and phantom limb pain and how these are affected by mirror therapy is included.An analysis of the 9 most relevant articles plus a critique of each is present in table form for review. Conclusions: There appears to be a clear indication for the use of mirror therapy to be included in the multidisciplinary treatment of CRPS types 1 and 2 with a positive effect on both pain and motor function. There is also evidence that mirror therapy can be helpful in other painful conditions such as post stroke pain and phantom limb pain. Implications: CRPS is often overlooked as an explanation for obscure pain problems. Prompt diagnosis is essential for effective treatment. Mirror therapy is a newer technique, easy to perform and can be a useful adjunct to aid physical rehabilitation and decrease pain in this population. Much further prospective research on mirror therapy in CRPS is ongoing and is needed to systematize the technique, to clarify the effects and to define the place of this therapy in the multidisciplinary management of CRPS. © 2013 Scandinavian Association for the Study of Pain.
PubMed | Helmholtz Center Munich, Karolinska Institutet, Oregon Health And Science University, Irccs Foundation Neurological Institute C Besta and 9 more.
Type: Journal Article | Journal: American journal of human genetics | Year: 2016
SQSTM1 (sequestosome 1; also known as p62) encodes a multidomain scaffolding protein involved in various key cellular processes, including the removal of damaged mitochondria by its function as a selective autophagy receptor. Heterozygous variants in SQSTM1 have been associated with Paget disease of the bone and might contribute to neurodegeneration in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Using exome sequencing, we identified three different biallelic loss-of-function variants in SQSTM1 in nine affected individuals from four families with a childhood- or adolescence-onset neurodegenerative disorder characterized by gait abnormalities, ataxia, dysarthria, dystonia, vertical gaze palsy, and cognitive decline. We confirmed absence of the SQSTM1/p62 protein in affected individuals fibroblasts and found evidence of a defect in the early response to mitochondrial depolarization and autophagosome formation. Our findings expand the SQSTM1-associated phenotypic spectrum and lend further support to the concept of disturbed selective autophagy pathways in neurodegenerative diseases.
Geijer M.,Skåne University Hospital |
Lindqvist U.,Uppsala University |
Husmark T.,Falu Lasarett |
Alenius G.-M.,Umeå University |
And 3 more authors.
Journal of Rheumatology | Year: 2015
Objective. To describe early radiographic findings in patients from the Swedish psoriatic arthritis (SwePsA) registry, progression of destruction, correlations with clinical disease variables, and predictors of destruction. Methods. Hand and foot radiographs were available for 72 of 197 SwePsA patients followed for 5 years. Clinical data were collected according to the SwePsA protocol. Results. Disease characteristics and clinical improvement were similar in men and women. Radiographic abnormalities were more pronounced in men. Total Wassenberg radiographic score at baseline was 0 in 45% of men and 51% of women. One man and one woman had a score > 10. At 5 years, total score was 0 in 14% of men and 40% of women (p = 0.018); 17% of men and 7% of women had scores > 10. Mean total scores for men and women had increased. Baseline erythrocyte sedimentation rate was associated with baseline total radiographic score. In men, swollen joint count was positively, and in women tender joint count negatively, correlated to total radiographic score. After 5 years, only male scores, mainly hand scores, significantly correlated with 28-joint Disease Activity Score and Disease Activity Index for Psoriatic Arthritis scores, swollen joint count, and dactylitis. Achieving remission or minimal disease activity after 5 years protected against structural damage, mainly in men. Conclusion. Radiographic progression in early PsA was generally slow but substantial. Male sex appears to be a risk factor for early radiographic damage while the presence of baseline radiographic damage and dactylitis developing during followup seem to predict further destruction. Hand and foot radiograph scoring cannot be substituted with clinical signs. The Journal of Rheumatology Copyright © 2015. All rights reserved.
Nagtegaal I.D.,Radboud University Nijmegen |
Tot T.,Falu Lasarett |
Jayne D.G.,St James University Hospital |
McShane P.,University of Leeds |
And 6 more authors.
Journal of Clinical Oncology | Year: 2011
Purpose: New editions of the TNM staging system for colorectal cancer have been subject to extensive criticism. In the current study, we evaluate each edition of TNM and analyze stage migration caused by the different versions. Patients and Methods: Two independent test populations were used: participants derived from a randomized surgical trial from the United Kingdom (n = 455) and patients from a population-based series from Sweden (n = 505). All slides from these patient cases were reviewed with special attention for the presence of tumor deposits. Tumor deposits were classified according to the fifth, sixth, and seventh editions of TNM and correlated with prognosis. Results: Every change in edition of TNM led to a stage migration of between 33% and 64% in patients with tumor deposits. Reproducibility was best in the fifth edition of TNM. The prognostic value of the seventh edition was best only when all tumor deposits irrespective of size or contour were included as lymph nodes. The prognostic value of the fifth edition was better than that of the sixth. Conclusion: We demonstrate there is a place for tumor deposits in the staging of patients with colorectal cancer. However, many questions remain about their definition and the reproducibility and use of this category in special situations, such as after neoadjuvant treatment. These should be the subject of additional research before use as a factor in TNM staging. This work demonstrates the necessity of testing modifications before their introduction. © 2011 by American Society of Clinical Oncology.
Klint M.,Uppsala University |
Hadad R.,Örebro University |
Christerson L.,Uppsala University |
Lore B.,Falu Lasarett |
And 7 more authors.
Clinical Microbiology and Infection | Year: 2011
In 2006, a new variant of Chlamydia trachomatis (nvCT) was discovered in Sweden that was not detectable with Abbott m2000 (Abbott) and Amplicor/COBAS Amplicor/TaqMan48 (Roche). The proportion of nvCT was 20-64% of the detected Chlamydia cases in counties using Abbott/Roche test systems. Although the ProbeTec system from Becton Dickinson (BD) could detect nvCT, the proportion of nvCT in counties using BD was 7-19%. The objective of the current study was to follow the nvCT proportions from 2007 to 2009 in two counties that used Roche and had introduced test systems able to detect nvCT in late 2006. The nvCT was also followed in two counties that used BD, and in all four counties the effect of nvCT on the serotype distribution of C. trachomatis wild-type strains was analysed. A total of 2576 specimens positive for C. trachomatis were collected in the four counties at three time points, and analysed for nvCT and serotype E. The proportion of nvCT declined significantly in the two counties using Roche, from 65% and 48% in 2007 to 24% for both counties in 2009 (p<0.001). The nvCT proportion increased in Norrbotten county, which used BD, from 9% in 2007 to 19% in 2009 (p0.03). In Uppsala county, which also used BD but was surrounded by counties using detection systems from Roche, the proportion of nvCT declined from 24% in 2007 to 18% in 2009 (p<0.03). No major difference in the level of serotype E was seen. The proportion of nvCT seems to rapidly converge in the Swedish counties after the selective diagnostic advantage for nvCT has been lost in the Abbott/Roche counties. © 2010 The Authors. Clinical Microbiology and Infection © 2010 European Society of Clinical Microbiology and Infectious Diseases.
Jahns A.C.,Umeå University |
Killasli H.,Karolinska Institutet |
Nosek D.,Umeå University |
Lundskog B.,Umeå University |
And 4 more authors.
APMIS | Year: 2014
Hidradenitis suppurativa (acne inverse) (HS) is a chronic skin disease primarily affecting hair follicles. The aetiology of HS is unknown, but infection is believed to play some role. This retrospective study investigated the microbial colonization directly in skin appendices in HS skin samples. Archival samples from 27 patients with HS were screened by immunofluorescence labelling with monoclonal and polyclonal antibodies against Gram-positive bacteria, Propionibacterium acnes and Propionibacterium granulosum. Fluorescence in situ hybridization was used for further species identification of Staphylococcus spp. Overall, 17 patients (63%) were found positive for bacterial colonization. Of these, 15 showed colonization in hair follicles and/or sinus tracts. The most commonly identified bacteria were DAPI labelled coccoids that were seen in 71% of the positive patients in the form of biofilms and microcolonies. P. acnes was found as biofilms in hair follicles of two patients. Staphylococcus aureus and coagulase-negative staphylococci were not detected in any sample. The results of this study indicate a common bacterial presence in HS skin lesions. Bacterial biofilms are not uncommon and their pathogenic role needs further evaluation. © 2014 APMIS.
PubMed | Enkopings Lasarett, Falu Lasarett, Karolinska University Hospital, Lund University and 4 more.
Type: Case Reports | Journal: European journal of medical genetics | Year: 2015
In 2005 we reported the first case of transthyretin His88Arg (p. His108Arg) amyloidosis, a mutation characterised by cardiomyopathy. Six additional gene carriers of whom five have clinical symptoms of disease have now been identified in Sweden, and we have been able to identify a possible founder and to characterise the Swedish phenotype of the transthyretin (TTR) His88Arg mutation. Genealogical studies of church records were used to identify the individuals with the disease and their families. Routine clinical investigations of neurological and heart manifestation of the disease were utilised. We found that genealogically all seven individuals were related and originated from the same region in Sweden. Amyloid deposits were demonstrated in biopsies and the TTR His88Arg mutation was identified in all patients. Patients had a late onset disease ( 50 years of age) and all exhibited a severe amyloid cardiomyopathy. A pronounced peripheral axonal neuropathy was with certainty demonstrated in one patient only, who also was operated for a magnetic resonance confirmed spinal stenosis, however, without any effect on his neurological symptoms. Five of the patients had carpal tunnel syndrome. The first reported case is now deceased from cardiac failure. One patient has had a sequential heart and liver transplantation. One gene carrier had no symptoms or findings of disease on latest evaluation at the age of 44.the Swedish TTRHis88Arg patients all have a common Swedish founder. Cardiomyopathy with heart failure, as well as carpal tunnel syndrome and spinal stenosis were early signs of disease; but peripheral neuropathy was present in one patient before symptoms of cardiomyopathy so the phenotypical presentation of this mutation is variable.
Anagrius C.,Falu lasarett |
Lore B.,Falu lasarett |
Jensen J.S.,Statens Serum Institute
PLoS ONE | Year: 2013
Objectives: To evaluate therapy for Mycoplasma genitalium infection with doxycycline or azithromycin 1 g compared to five days of azithromycin (total dose 1.5 g). Methods: A retrospective case study was performed among patients attending the STD-clinic in Falun, Sweden 1998-2005. All patients with a positive PCR test for M. genitalium were routinely offered a test of cure (toc). Response to doxycycline for 9 days, azithromycin 1 g single dose and extended azithromycin (500 mg on day 1 followed by 250 mg o.d. for 4 days) was determined. In patients with treatment failure after azithromycin, macrolide resistance was monitored before and after treatment. Furthermore, the rate of macrolide resistance was monitored for positive specimens available from 2006-2011. Results: The eradication rate after doxycycline was 43% (48% for women and 38% for men), for azithromycin 1 g 91% (96% for women and 88% for men) and for extended azithromycin 99% (100% for women and 93% for men). Macrolide resistance developed in 7/7 examined (100%) of those testing positive after azithromycin 1 g, but in none of those treated with extended azithromycin. Macrolide resistance before treatment increased from 0% in 2006 and 2007 to 18% in 2011. Conclusions: These findings confirm the results from other studies showing that doxycycline is inefficient in eradicating M. genitalium. Although azithromycin 1 g was not significantly less efficient than extended dosage, it was associated with selection of macrolide resistant M. genitalium strains and should not be used as first line therapy for M. genitalium. Monitoring of M. genitalium macrolide resistance should be encouraged. © 2013 Anagrius et al.