| 1. |
- Fu, Michael, 1963, et al.
(författare)
-
Adherence to optimal heart rate control in heart failure with reduced ejection fraction : insight from a survey of heart rate in heart failure in Sweden (HR-HF study)
- 2017
-
Ingår i: Clinical Research in Cardiology. - : SPRINGER HEIDELBERG. - 1861-0684 .- 1861-0692. ; 106:12, s. 960-973
-
Tidskriftsartikel (refereegranskat)abstract
- Despite that heart rate (HR) control is one of the guideline-recommended treatment goals for heart failure (HF) patients, implementation has been painstakingly slow. Therefore, it would be important to identify patients who have not yet achieved their target heart rates and assess possible underlying reasons as to why the target rates are not met. The survey of HR in patients with HF in Sweden (HR-HF survey) is an investigator-initiated, prospective, multicenter, observational longitudinal study designed to investigate the state of the art in the control of HR in HF and to explore potential underlying mechanisms for suboptimal HR control with focus on awareness of and adherence to guidelines for HR control among physicians who focus on the contributing role of beta-blockers (BBs). In 734 HF patients the mean HR was 68 +/- 12 beats per minute (bpm) (37.2% of the patients had a HR > 70 bpm). Patients with HF with reduced ejection fraction (HFrEF) (n = 425) had the highest HR (70 +/- 13 bpm, with 42% > 70 bpm), followed by HF with preserved ejection fraction and HF with mid-range ejection fraction. Atrial fibrillation, irrespective of HF type, had higher HR than sinus rhythm. A similar pattern was observed with BB treatment. Moreover, non-achievement of the recommended target HR (< 70 bpm) in HFrEF and sinus rhythm was unrelated to age, sex, cardiovascular risk factors, cardiovascular diseases, and comorbidities, but was related to EF and the clinical decision of the physician. Approximately 50% of the physicians considered a HR of > 70 bpm optimal and an equal number considered a HR of > 70 bpm too high, but without recommending further action. Furthermore, suboptimal HR control cannot be attributed to the use of BBs because there was neither a difference in use of BBs nor an interaction with BBs for HR > 70 bpm compared with HR < 70 bpm. Suboptimal control of HR was noted in HFrEF with sinus rhythm, which appeared to be attributable to physician decision making rather than to the use of BBs. Therefore, our results underline the need for greater attention to HR control in patients with HFrEF and sinus rhythm and thus a potential for improved HF care.
|
|
| 2. |
- Shev, S, et al.
(författare)
-
Second-generation hepatitis C Elisa antibody tests confirmed by the four-antigen recombinant immunoblot assay correlate well with hepatitis C viremia and chronic liver disease in Swedish blood donors
- 1993
-
Ingår i: Vox Sanguinis. - 1423-0410. ; 65:1, s. 32-37
-
Tidskriftsartikel (refereegranskat)abstract
- Seventy-three Swedish blood donors (52 men, 21 women; median age 36 years) repeatedly reactive for hepatitis C antibodies (anti-HCV C-100-3) were tested with a second-generation (2nd-gen) anti-HCV Elisa and a 4-band recombinant immunoblot assay (RIBA 2). These results were correlated to serum alanine aminotransferase (S-ALAT), liver morphology and viremia as detected by 'nested' polymerase chain reaction (PCR) based on primers from a 5'-noncoding sequence of the HCV genome. Thirty-five of 46 (76%) donors with positive 2nd-gen Elisa tests confirmed by RIBA 2 were PCR positive whereof 27 had histological findings compatible with chronic persistent hepatitis (CPH) and 7 had chronic active hepatitis (CAH). Ten of 56 (18%) 2nd-gen Elisa-positive donors were RIBA 2 negative (or indeterminate) and none of these had chronic hepatitis nor were PCR positive. Seventeen of 73 (23%) donors were 1st-gen Elisa positive but 2nd-gen Elisa negative. All of these were PCR negative and only 1 (6%) had chronic hepatitis (CPH). An elevated S-ALAT level (reference < 0.7 mu kat/l) was found in 26 2nd-gen Elisa and RIBA 2-positive donors of which 18 had CPH and 7 had CAH and all 25 were PCR positive. A normal S-ALAT level was found in 9 of 34 (26%) donors with chronic hepatitis (all had CPH) and positive PCR. We have found that blood donors with positive 2nd-gen anti-HCV Elisa tests confirmed by RIBA-2 and especially with a concomitant elevated S-ALAT are highly likely to be viremic as demonstrated by PCR and to have chronic hepatitis.
|
|
| 3. |
- Bestas, Burcu, et al.
(författare)
-
Splice-correcting oligonucleotides restore BTK function in X-linked agammaglobulinemia model
- 2014
-
Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 124:9, s. 4067-4081
-
Tidskriftsartikel (refereegranskat)abstract
- X-linked agammaglobulinemia (XLA) is an inherited immunodeficiency that results from mutations within the gene encoding Bruton's tyrosine kinase (BTK). Many XLA-associated mutations affect splicing of BTK pre-mRNA and severely impair B cell development. Here, we assessed the potential of antisense, splice-correcting oligonucleotides (SCOs) targeting mutated BTKtranscripts for treating XLA. Both the SCO structural design and chemical properties were optimized using 2'-O-methyl, locked nucleic acid, or phosphorodiamidate morpholino backbones. In order to have access to an animal model of XLA, we engineered a transgenic mouse that harbors a BAC with an authentic, mutated, splice-defective human BTK gene. BTK transgenic mice were bred onto a Btk knockout background to avoid interference of the orthologous mouse protein. Using this model, we determined that BTK-specific SCOs are able to correct aberrantly spliced BTK in B lymphocytes, including pro-B cells. Correction of BTK mRNA restored expression of functional protein, as shown both by enhanced lymphocyte survival and reestablished BTK activation upon B cell receptor stimulation. Furthermore, SCO treatment corrected splicing and restored BTK expression in primary cells from patients with XLA. Together, our data demonstrate that SCOs can restore BTK function and that BTK-targeting SCOs have potential as personalized medicine in patients with XLA.
|
|
| 4. |
- Hansson, J., et al.
(författare)
-
Monitoring of kindreds with hereditary predisposition for cutaneous melanoma and dysplastic nevus syndrome: results of a Swedish preventive program
- 2007
-
Ingår i: J Clin Oncol. ; 25:19, s. 2819-2824
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate a program initiated in 1987 by the Swedish Melanoma Study Group aiming to provide preventive surveillance to kindreds with hereditary cutaneous melanoma and dysplastic nevus syndrome. PATIENTS AND METHODS: Overall, 2,080 individuals belonging to 280 melanoma families were followed for 14 years between 1987 and 2001 at 12 participating centers. Data were registered in a central database. RESULTS: Among 1,912 skin lesions excised during follow-up, 41 melanomas were removed in 32 individuals. Of these, 15 (37%) were in situ melanomas and 26 (63%) invasive melanomas. The median tumor thickness of invasive melanomas was 0.5 mm. Ulceration was absent in 24 of 26 invasive melanomas (92%) and 12 (46%) lacked vertical growth phase. Compared with melanomas in the general Swedish population, the melanomas identified in these kindreds during follow-up had better prognostic characteristics. All melanomas except one were diagnosed in families with two or more first-degree relatives with melanoma. Diagnosis of melanoma occurred in three of eight kindreds with germline CDKN2A mutations, supporting that families with such mutations are at increased risk for melanoma development. Of the 32 individuals who developed melanoma during follow-up, 21 (66%) had had at least one previously diagnosed melanoma. CONCLUSION: This study shows that a coordinated program aimed at detecting and offering skin surveillance in kindreds with hereditary cutaneous melanoma results in a low incidence of melanomas during the follow-up period and that the tumors that do arise have favorable prognostic characteristics.
|
|
| 5. |
- Mansson, A., et al.
(författare)
-
Neutral third party versus treating institution for evaluating quality of life after radical cystectomy
- 2004
-
Ingår i: Eur Urol. - 0302-2838. ; 46:2, s. 195-9
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the possible impact of a neutral third party on the patients' responses to health-related quality of life (HRQL) instruments. METHODS: 119 patients operated at the Department of Urology in Lund with radical cystectomy and continent urinary tract reconstruction (continent cutaneous diversion or orthotopic bladder substitution) for locally advanced bladder cancer were included in the study. They were randomly divided in two groups, similar with regard to gender, age, length of follow-up, and type of reconstruction. The EORTC instruments QLQ-C30 and QLQ-BLM30 were sent to the patients. One group; "Lund patients", received the instruments from the Department of Urology in Lund, while the other group; "Stockholm patients", received the instruments from a neutral third party, i.e. "The Project Health and Well-Being" at the Karolinska Institutet in Stockholm. RESULTS: Response rates were high in both groups, 59 out of 60 among Lund patients and 57 out of 59 among Stockholm patients. There were statistically significantly more bowel problems reported in the Stockholm patients than in the Lund patients (p<0.05) in the QLQ-C30 instrument. Regarding type of reconstruction, the Stockholm patients with continent cutaneous diversion scored higher for constipation than the Lund patients (p<0.05), and the Stockholm patients with bladder substitution scored lower for emotional functioning and higher for dyspnoea and economical problems than the Lund patients (p<0.05. There were no statistically significant differences between the Lund patients and the Stockholm patients in the QLQ-BLM30 instrument. CONCLUSION: Though few factors differed between the two groups, the results may indicate that different results are obtained when a study is totally administered and analyzed by a neutral third party as compared with the surgeon or his or her institution. Larger studies are needed to further test this hypothesis.
|
|
| 6. |
- Liedberg, Fredrik, et al.
(författare)
-
Diagnostic delay and prognosis in invasive bladder cancer
- 2003
-
Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 37:5, s. 396-400
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To study diagnostic delay in invasive bladder cancer in a population-based material with long-term follow-up, and to evaluate whether delay in diagnosis affects the risk of bladder cancer death. Material and Methods: In a previous study, 177 patients with invasive bladder cancer (T1-T4) diagnosed in 1988 were investigated with regard to diagnostic delay. A review of all available clinical records was performed. In the present study, causes of death for these patients were registered over a 12-year follow-up period, and the impact of diagnostic delay on bladder cancer death was studied by means of survival analysis. Results: The median diagnostic delay in the material was 144 days. When the patients were stratified into groups with diagnostic delays of 0-3, 3-6, 6-12 and >12 months, those with T1 tumours in the two groups with a diagnostic delay of <6 months showed a trend towards a decreased risk of bladder cancer death. In contrast, in patients with muscle-invasive disease, a significantly increased risk of bladder cancer death was noted for those with a diagnostic delay of <6 months. Conclusion: A trend towards better prognosis was found for patients with T1 tumours with a shorter diagnostic delay. The poor prognosis of patients with muscle-invasive disease and a short diagnostic delay suggests aggressive behaviour of the tumour and may explain the worse prognosis in these patients.
|
|
| 7. |
- C. Lin, Yin, et al.
(författare)
-
A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate
- 2010
-
Ingår i: Nature Immunology. - : Nature Publishing Group. - 1529-2908 .- 1529-2916. ; 11:7, s. 635-U109
-
Tidskriftsartikel (refereegranskat)abstract
- It is now established that the transcription factors E2A, EBF1 and Foxo1 have critical roles in B cell development. Here we show that E2A and EBF1 bound regulatory elements present in the Foxo1 locus. E2A and EBF1, as well as E2A and Foxo1, in turn, were wired together by a vast spectrum of cis-regulatory sequences. These associations were dynamic during developmental progression. Occupancy by the E2A isoform E47 directly resulted in greater abundance, as well as a pattern of monomethylation of histone H3 at lysine 4 (H3K4) across putative enhancer regions. Finally, we divided the pro-B cell epigenome into clusters of loci with occupancy by E2A, EBF and Foxo1. From this analysis we constructed a global network consisting of transcriptional regulators, signaling and survival factors that we propose orchestrates B cell fate.
|
|
| 8. |
- Hammar, L, et al.
(författare)
-
Lewis phenotype of erythrocytes and Leb-active glycolipid in serum of pregnant women
- 1981
-
Ingår i: Vox Sanguinis. - 1423-0410. ; 40:1, s. 27-33
-
Tidskriftsartikel (refereegranskat)abstract
- In an attempt to provide an explanation for the previously reported effect of pregnancy on the Lewis phenotype of erythrocytes, the level of Leb-active glycolipid in serum was compared with the reactions of erythrocytes, using samples obtained from 73 nonpregnant women, 74 women at the time of delivery, and 2 women at weekly intervals during their pregnancy. In this Swedish population, the frequency of the Le(a--b-) blood group increased from 11% in nonpregnant women to 36% in women at the time of delivery. Among Le(a--b+) women of all ABO groups, those who were A1 most often became (Leb-) during pregnancy. The change in phenotype occurred as early as the 24th week of gestation; the Leb antigen was again detectable within 6 weeks after delivery. The concentration of Leb glycolipid in serum, as measured by radioimmunoassay, decreased only slightly during pregnancy. The repartition of glycolipids, secondary to the increased ratio of lipoprotein to red cell mass that occurs during pregnancy, may account for the relative lack of Lewis glycolipid on erythrocytes.
|
|
| 9. |
- Klinth, J, et al.
(författare)
-
Cardiotonic bipyridine amrinone slows myosin-induced actin filament sliding at saturating [MgATP]
- 2003
-
Ingår i: Journal of Muscle Research and Cell Motility. - 0142-4319. ; 24:1, s. 15-32
-
Tidskriftsartikel (refereegranskat)abstract
- Previously reported effects of amrinone on skeletal muscle function suggest that the drug reduces the rate constant of myosin cross-bridge dissociation. We have used the in vitro motility assay to further elucidate the mechanism underlying this effect and to aid these studies a new, improved,. lament tracking software was developed in the Matlab(TM) environment. The experiments were carried out at 30degreesC using heavy meromyosin from fast rabbit muscle and rhodamine-phalloidin labeled actin. laments. A slowing effect of amrinone on. lament sliding velocity at 1 mM MgATP was observed at drug concentrations >0.3 mM. This effect showed signs of saturation at the highest drug concentrations (1-2 mM) that could be readily tested. The sliding velocity exhibited hyperbolic dependence on [ MgATP] with a V-max of 7.2 +/- 0.9 mum/s and a K-M of 0.18 +/- 0.02 mM. Amrinone (1 mM) reduced V-max by 32 +/- 5% (P < 0.01) and K-M by 42 &PLUSMN; 8% (P < 0.05; n = 4). These results are accounted for in the most straightforward way by a model where amrinone acts directly on the actomyosin system and reduces the rate constant of MgADP release. Such a well-defined effect on the myosin cross-bridge cycle makes the drug a potentially useful pharmacological tool for further studies of myosin function both in vitro and in the ordered. lament array of a living muscle fiber.
|
|
| 10. |
- Kumar, Parvin, et al.
(författare)
-
Physical exercise is associated with a reduction in plasma levels of fractalkine, TGF-beta 1, eotaxin-1 and IL-6 in younger adults with mobility disability
- 2022
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:2
-
Tidskriftsartikel (refereegranskat)abstract
- Mobility disability (MD) refers to substantial limitations in life activities that arise because of movement impairments. Although MD is most prevalent in older individuals, it can also affect younger adults. Increasing evidence suggests that inflammation can drive the development of MD and may need to be targeted for MD prevention. Physical exercise has anti-inflammatory properties and has been associated with MD prevention. However, no studies to date have examined whether exercise interventions affect the peripheral inflammatory status in younger adults with MD. To this end, we used blood samples from young and middle-aged adults with MD (N = 38; median age = 34 years) who participated in a 12-week intervention that included aerobic and resistance exercise training. A pre-post assessment of inflammatory biomarkers was conducted in plasma from two timepoints, i.e., before the exercise trial and at follow-up (3-7 days after the last exercise session). We successfully measured 15 inflammatory biomarkers and found that exercise was associated with a significant reduction in levels of soluble fractalkine, transforming growth factor beta 1 (TGF-beta 1), eotaxin-1 and interleukin (IL) 6 (corrected alpha = 0.004). We also found significant male-specific effects of exercise on (i) increasing IL-16 and (ii) decreasing vascular endothelial growth factor-A (VEGF-A). In line with our results, previous studies have also found that exercise can reduce levels of TGF-beta 1, eotaxin-1 and IL-6. However, our finding that exercise reduces plasma levels of fractalkine in younger adults with MD, as well as the sex-dependent findings, have not been previously reported and warrant replication in larger cohorts. Given the suggested role of inflammation in promoting MD development, our study provides additional support for the use of physical exercise as a treatment modality for MD.
|
|
