| 1. |
- Chang, Ya-Ting, et al.
(author)
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Versican accumulates in vascular lesions in pulmonary arterial hypertension
- 2016
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In: PULMONARY CIRCULATION. - : Wiley. - 2045-8932 .- 2045-8940. ; 6:3, s. 347-359
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Journal article (peer-reviewed)abstract
- Pulmonary arterial hypertension (PAH) is a lethal condition for which there is no effective curative pharmacotherapy. PAH is characterized by vasoconstriction, wall thickening of pulmonary arteries, and increased vascular resistance. Versican is a chondroitin sulfate proteoglycan in the vascular extracellular matrix that accumulates following vascular injury and promotes smooth-muscle cell proliferation in systemic arteries. Here, we investigated whether versican may play a similar role in PAH. Paraffin-embedded lung sections from patients who underwent lung transplantation to treat PAH were used for immunohistochemistry. The etiologies of PAH in the subjects involved in this study were idiopathic PAH, scleroderma, and congenital heart disease (atrial septal defect) with left-to-right shunt. Independent of the underlying etiology, increased versican immunostaining was observed in areas of medial thickening, in neointima, and in plexiform lesions. Western blot of lung tissue lysates confirmed accumulation of versican in patients with PAH. Double staining for versican and CD45 showed only occasional colocalization in neointima of high-grade lesions and plexiform lesions. In vitro, metabolic labeling with [S-35] sulfate showed that human pulmonary artery smooth-muscle cells (hPASMCs) produce mainly chondroitin sulfate glycosaminoglycans. In addition, hypoxia, but not cyclic stretch, was demonstrated to increase both versican messenger RNA expression and protein synthesis by hPASMCs. Versican accumulates in vascular lesions of PAH, and the amount of versican correlates more with lesion severity than with underlying etiology or inflammation. Hypoxia is a possible regulator of versican accumulation, which may promote proliferation of pulmonary smooth-muscle cells and vascular remodeling in PAH.
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| 2. |
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| 3. |
- Ericson-Lidman, Eva, 1960-
(author)
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The complicated struggle to be a support : meanings of being a co-worker, supervisor and closely connected to a person developing burnout
- 2008
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Doctoral thesis (other academic/artistic)abstract
- The overall aim of this thesis is to illuminate meanings of being a co-worker, supervisor and closely connected to a person developing burnout, and to describe perceptions of signs preceding burnout. The thesis comprises four papers and is based on qualitative data. In papers I and II, the data material consisted of interviews with 15 female coworkers of a person developing burnout, in paper III, interviews with 12 supervisors to care providers suffering from burnout, and in paper IV, interviews on two occasions with 5 people closely connected to a person developing burnout. Thematic content analysis (I) and phenomenological-hermeneutic method (II, III, IV) was used to analyse/interpret the interview text. The findings show that the coworkers retrospectively recalled different signs preceding their workmate’s burnout. They describe that their workmate was struggling to manage alone and was showing self-sacrifice. Co-workers also describe that their workmates were struggling to achieve unattainable goals and were becoming distanced and isolated. Finally, the co-workers describe that their workmates were showing signs of falling apart (I). Meanings of being a female co-worker to a person developing burnout are struggling, on the one hand to understand and help the person with symptoms of burnout, and on the other to manage one’s own work. This burdensome situation means that the co-workers are filled with contradictory and frustrating feelings and when the workmate is finally sick-listed, troubled conscience arise in the coworkers (II). Meanings of being a supervisor for care providers suffering from burnout are struggling to help the care provider continue to work, but being responsible for the unit, the supervisors are forced to ensure that the work is carried out. As the situation proceeds, supervisors are trapped in a predicament, unable to help and feeling inadequate. When the care provider is sick-listed, feelings of self-blame arise. When the time comes for rehabilitation the supervisors are once again caught between conflicting demands in a seemingly impossible mission (III). Meanings of being closely connected to a person suffering from burnout are putting one’s life on hold in order to help the person, striving to stand by to the person developing burnout, regardless of one’s own needs. Those closely connected are saving the face of the person developing burnout in order to protect them from stress. As the situation proceeds, those closely connected carry the burden alone in this strained situation and sometimes they are treated with disrespect by the person developing burnout, a situation which reveals their own suffering. Striving to find recuperation engenders troubled conscience. This situation reveals a huge need for support for those closely connected to a person developing burnout (IV). The comprehensive understanding is that meanings of being a co-worker, supervisor and closely connected to a person developing burnout are, on the one hand, a complicated struggle to support the person and on the other to shoulder a heavy burden. They try to do everything they can to help and support the person developing burnout (II-IV), these attempts, however, do not seem to reach through (I-IV). Co-workers describe signs that something is the matter (I), but they (co-workers, supervisors and those closely connected) do not understand what is happening (IIIV). This burdensome situation is full of conflict for those involved, torn between the complicated struggle to support the person developing burnout and to manage this burdensome situation. Faced with their own shortcomings, troubled conscience arises. The comprehensive understanding of the four papers (I-IV) are discussed and reflected on with the help of social support theories and the ideas of the Danish philosopher Lögstrup’s thoughts about the ethical demand.
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| 4. |
- Hederos, Carl-Axel, et al.
(author)
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Comparison of clinically diagnosed asthma with parental assessment of children's asthma in a questionnaire
- 2007
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In: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 18:2, s. 135-141
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Journal article (peer-reviewed)abstract
- Epidemiological evaluations of the prevalence of asthma are usually based on written questionnaires (WQs) in combination with validation by clinical investigation. In the present investigation, we compared parental assessment of asthma among their preschool children in response to a WQ with the corresponding medical records in the same region. An International Study of Asthma and Allergies in Childhood (ISAAC)-based WQ was answered by 75% of the parents of 6295 children aged 1–6 yr. Clinically diagnosed asthma, recorded in connection with admissions to the hospital or a visit to any of the outpatient clinics in the same region, were analysed in parallel. Finally, a complementary WQ was sent to the parents of children identified as asthmatic by either or both of this approaches. In response to the WQ 5.9% were claimed to suffer from asthma diagnosed by a doctor. According to the medical records, the prevalence of clinically diagnosed asthma was 4.9%. The estimated prevalence among children requiring treatment for their asthma was 4.4%. The sensitivity of the WQ was 77%, the specificity 97.5%. In the 1–2 yr age group the sensitivity was only 22%. This WQ was able to identify 54% of the children with a medical record of asthma. Forty percent of the children claimed by their parents to be asthmatic had no medical record of asthma. An ISAAC-based parentally completed WQ provided an acceptable estimation of the prevalence of asthma in children 2–6 yr of age, although only half of the individual patients identified in this manner are the same as those identified clinically.
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| 5. |
- Ketelhuth, D. F., et al.
(author)
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Identification of a danger-associated peptide from apolipoprotein B100 (ApoBDS-1) that triggers innate proatherogenic responses
- 2011
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In: Circulation. - Stockholm : Karolinska Institutet, Dept of Medicine, Solna. - 1524-4539 .- 0009-7322. ; 124:22
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Journal article (peer-reviewed)abstract
- BACKGROUND: Subendothelial deposited low-density lipoprotein particles are a known inflammatory factor in atherosclerosis. However, the causal components derived from low-density lipoprotein are still poorly defined. Apolipoprotein B100 (ApoB100) is the unexchangeable protein component of low-density lipoprotein, and the progression of atherosclerosis is associated with immune responses to ApoB100-derived peptides. In this study, we analyzed the proinflammatory activity of ApoB100 peptides in atherosclerosis. METHODS AND RESULTS: By screening a peptide library of ApoB100, we identified a distinct native peptide referred to as ApoB100 danger-associated signal 1 (ApoBDS-1), which shows sequence-specific bioactivity in stimulation of interleukin-8, CCL2, and interleukin-6. ApoBDS-1 activates mitogen-activated protein kinase and calcium signaling, thereby effecting the expression of interleukin-8 in innate immune cells. Ex vivo stimulation of carotid plaques with ApoBDS-1 enhances interleukin-8 and prostaglandin E release. Furthermore, we demonstrated that ApoBDS-1-positive peptide fragments are present in atherosclerotic lesions using immunoassays and that low-molecular-weight fractions isolated from plaque show ApoBDS-1 activity inducing interleukin-8 production. CONCLUSIONS: Our data show that ApoBDS-1 is a previously unrecognized peptide with robust proinflammatory activity, contributing to the disease-promoting effects of low-density lipoprotein in the pathogenesis of atherosclerosis.
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| 6. |
- Kornfält Isberg, Helena, et al.
(author)
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Different antibiotic regimes in men diagnosed with lower urinary tract infection - a retrospective register-based study
- 2020
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In: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 38:3, s. 291-299
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Journal article (peer-reviewed)abstract
- Objective To compare the proportion of therapy failure, recurrence and complications within 30 days after consultation between men diagnosed with lower urinary tract infection (UTI) treated with narrow-spectrum antibiotics (nitrofurantoin or pivmecillinam) and broad-spectrum antibiotics (fluoroquinolones or trimethoprim or trimethoprim/sulfamethoxazole). Design A retrospective cohort study based on data derived from electronic medical records between January 2012 and December 2015. Setting Primary health care and hospital care in five different counties in Sweden. Patients:A total of 16,555 men aged between 18 and 79 years diagnosed with lower UTI. Main outcome measures Treatment with narrow-spectrum antibiotics was compared with broad-spectrum antibiotics regarding therapy failure, recurrence and complications within 30 days. Results The median age of included men was 65 IQR (51-72) years. Narrow-spectrum antibiotics were prescribed in 8457 (40%) and broad-spectrum antibiotics in 12,667 (60%) cases, respectively. Therapy failure was registered in 192 (0.9%), recurrence in 1277 (6%) and complications in 121 (0.6%) cases. Therapy failure and recurrence were more common in patients treated with narrow-spectrum antibiotics and trimethoprim (p < 0.001), but no such difference could be detected regarding complications. Conclusion There was no difference in incidence of complications within 30 days between men treated with narrow- or broad-spectrum antibiotics. Patients prescribed broad-spectrum antibiotics had lower odds of reconsultation because of therapy failure and recurrence. From current data, treatment with narrow-spectrum antibiotics seems to be an optimal choice regarding preventing complications when treating men with lower UTI.
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| 7. |
- Lundstrom, Ulrika Hahn, et al.
(author)
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Surgical versus endovascular intervention for vascular access thrombosis : a nationwide observational cohort study
- 2022
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In: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 37:9, s. 1742-1750
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Journal article (peer-reviewed)abstract
- Background There is no consensus whether an arteriovenous (AV) access thrombosis is best treated by surgical or endovascular intervention. We compared the influence of surgical versus endovascular intervention for AV access thrombosis on access survival using real-life data from a national access registry. Methods We included patients from the Swedish Renal Access Registry (SRR-Access) with a working AV access undergoing surgical or endovascular intervention for their first thrombosis between 2008 and 2020. The primary outcome was the risk of access abandonment (secondary patency at 30, 60, 90 and 365 days). Secondary outcomes were time to next intervention and 30-day mortality. Access characteristics were obtained from the SRR-Access and patient characteristics were collected from the Swedish Renal Registry. Outcomes were assessed with multivariable logistic regression and Cox proportional hazards regression models adjusted for demographics, clinical and access-related variables. Results A total of 904 patients with AV access thrombosis (54% arteriovenous fistula, 35% upper arm access) were included, with a mean age of 62 years, 60% were women, 75% had hypertension and 33% had diabetes. Secondary patency was superior after endovascular intervention versus surgical (85% versus 77% at 30 days and 76% versus 69% at 90 days). The adjusted odds of access abandonment within 90 days and 1 year were higher in the surgical thrombectomy group {odds ratio (OR) 1.44 [95% confidence interval (CI) 1.05-1.97] and OR 1.25 (0.94-1.66), respectively}. Results were consistent in the long-term analysis. There was no significant difference in time to next intervention or mortality, and results were consistent within subgroups. Conclusions Endovascular intervention was associated with a small short- and long-term benefit as compared with open surgery in haemodialysis patients with AV access thrombosis.
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| 8. |
- Rystedt, Karin, et al.
(author)
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Effects of penicillin V on the faecal microbiota in patients with pharyngotonsillitis-an observational study
- 2022
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In: JAC - Antimicrobial Resistance. - : OXFORD UNIV PRESS. - 2632-1823. ; 5:1
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Journal article (peer-reviewed)abstract
- Background The intestinal microbiota functions as a reservoir of antibiotic resistance. Objectives To evaluate penicillin V (phenoxymethylpenicillin) effects on the faecal microbiota with focus on beta-lactam resistance. Methods We included 31 primary care patients with group A streptococcal pharyngotonsillitis treated with penicillin V for 5 (800 mg x 4) or 10 days (1000 mg x 3). Twenty-nine patients contributed with three faecal swab samples each. The faecal specimens were collected at the start of penicillin V treatment, after the last dose and at follow-up 7-9 days after completed treatment. Samples were inoculated semiquantitatively on selective screening agar plates to study beta-lactam resistance, species shifts among Enterobacterales and enterococci, and colonization with Candida spp. and Clostridioides difficile. Representative colonies were identified using MALDI-TOF. Results were analysed by non-parametric statistical methods. Results An increase in the proportion of patients colonized with ampicillin-resistant Enterobacterales, from 52% to 86% (P = 0.007), and Enterobacterales with decreased susceptibility to third-generation cephalosporins, from 32% to 52% (P = 0.034), was observed between the first and second samples. This increase was no longer significant at follow-up. New colonization with ampicillin-resistant Enterobacterales species and non-Enterobacterales Gram-negative species was observed, and persisted at follow-up. Conclusions Following treatment with penicillin V, we observed decreased susceptibility to ampicillin and third-generation cephalosporins, and prolonged colonization with non-Escherichia coli Gram-negative species. These findings challenge the perception that penicillin V has limited ecological effect on the intestinal microbiota, and emphasizes the importance of avoiding even narrow-spectrum antimicrobials when possible.
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| 9. |
- Wallengren, Joanna, et al.
(author)
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Urtikaria och angioödem.
- 2009
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In: Allergi och astma. - 9789144029962 ; , s. 381-398
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Book chapter (peer-reviewed)
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| 10. |
- Widhe, Mona, et al.
(author)
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A multicenter study on children with Lyme Neuroborreliosis : Up-regulation of Borrelia-specific IL-4 and IFN-γ secreting cells in cerebrospinal fluid and blood
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Other publication (other academic/artistic)abstract
- The clinical course and outcome of several infectious diseases are dependent on the type of immune response elicited against the pathogen. As suggested by animal models the interleukin (IL)-4 and interferon (IFN)-γ responses seem to play a role in Lyme borreliosis. In adults with neuroborreliosis (NB), a type 1 like response with high production of Borrelia-specific IFN-γ, but no IL-4, in the cerebrospinal fluid (CSF) and blood has been reported. Since children have a more benign course of NB than adults, we wanted to investigate type 1 and type 2 like responses in children with NB. CSF and blood were collected from children during the acute stage of 'confirmed NB' (n=34), 'possible NB' (n=30) and 'non-NB' (n=10). The number of Borrelia-speciflc IL-4 and IFN-γ producing cells was measured by ELISPOT. Borrelia-specific secretion of both IL-4 and IFN-γ was increased in CSF in confirmed (p<0.05) and possible (p<0,01) NB, compared with non-NB. Furthermore, children with NB had significantly higher Borrelia-speciflc IL-4 secretion in cerebrospinal fluid than an adult reference material with NB (p<0,05). There were no differences in cytokine secretion in relation to onset or recovery of neurological symptoms. Since IL-4 is known to down-regulate the pro-inflammatory and possibly hannful. effects of prolonged IFN-γ responses, the observed prominent IL-4 response in the CNS-compartment might contribute to the more benign disease course seen in children with Lyme NB.
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