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Östermalm, Sweden

Bitar M.S.,Kuwait University | Abdel-Halim S.M.,Danderyd Hospital | Al-Mulla F.,Kuwait University
American Journal of Physiology - Endocrinology and Metabolism | Year: 2013

A heightened state of oxidative stress and senescence of fibroblasts constitute potential therapeutic targets in nonhealing diabetic wounds. Here, we studied the underlying mechanism mediating diabetes-induced cellular senescence using in vitro cultured dermal fibroblasts and in vivo circular wounds. Our results demonstrated that the total antioxidant capacity and mRNA levels of thioredoxinreductase and glucose-6-phosphate dehydrogenase as well as the ratio of NADPH/NADP were decreased markedly in fibroblasts from patients with type 2 diabetes (DFs). Consistent with this shift in favor of excessive reactive oxygen species, DFs also displayed a significant increase in senescenceassociated β-galactosidase activity and phospho-γ-histone H2AX (pH2AX) level. Moreover, the ability of PDGF to promote cell proliferation/migration and regulate the phosphorylation-dependent activation of Akt and ERK1/2 appears to be attenuated as a function of diabetes. Mechanistically, we found that diabetes-induced oxidative stress upregulated caveolin-1 (Cav-1) and PTRF expression, which in turn sequestered Mdm2 away from p53. This process resulted in the activation of a p53/p21-dependent pathway and the induction of premature senescence in DFs. Most of the aforementioned oxidative stress and senescence-based features observed in DFs were recapitulated in a 10-day-old diabetic wound. Intriguingly, we confirmed that the targeted depletion of Cav-1 or PTRF using siRNAor Vivo-Morpholino antisense-based gene therapy markedly inhibited diabetes/oxidative stress-induced premature senescence and also accelerated tissue repair in this disease state. Overall, our data illuminate Cav-1/PTRF-1 as a key player of a novel signaling pathway that may link a heightened state of oxidative stress to cellular senescence and impaired wound healing in diabetes. © 2013 the American Physiological Society.


Sommerfeld D.K.,Danderyd Hospital | Sommerfeld D.K.,Karolinska Institutet | Gripenstedt U.,Karolinska Institutet | Welmer A.-K.,Karolinska University Hospital
American Journal of Physical Medicine and Rehabilitation | Year: 2012

The objective of this study was to present an overview of the prevalence of spasticity after stroke as well as of test instruments and treatments. Recent studies show that spasticity occurs in 20%-30% of all stroke victims and in less than half of those with pareses. Although spasticity may occur in paretic patients after stroke, muscle weakness is more likely to be the reason for the pareses. Spasticity after stroke is more common in the upper than the lower limbs, and it seems to be more common among younger than older people. To determine the nature of passive stretch, electromyographic equipment is needed. However, the Modified Ashworth Scale, which measures the sum of the biomechanical and neural components in passive stretch, is the most common instrument used to grade spasticity after stroke. Treatment of spasticity with physiotherapy is recommended, although its beneficial effect is uncertain. The treatment of spasticity with botulinum toxin in combination with physiotherapy is suggested to improve functioning in patients with severe spasticity. A task-specific approach rather than a neurodevelopmental approach in assessing and treating a patient with spasticity after stroke seems to be preferred. Copyright © 2012 Lippincott Williams & Wilkins.


Zwedberg S.,Karolinska Institutet | Zwedberg S.,Karolinska University Hospital | Blomquist J.,Danderyd Hospital | Sigerstad E.,Karolinska University Hospital
Midwifery | Year: 2015

Objective: to explore midwives' experiences and perceptions of skin-to-skin contact between mothers and their healthy full-term infants immediately and during the first day after caesarean section. Design: qualitative interviews with semi-structured questions. Setting and participants: eight midwives at three different hospitals in Stockholm participated in the study. All participants provided care for mothers and their newborn infants after caesarean birth. Analysis: transcribed material was analysed and interpreted using qualitative content analysis. The analysis yielded the theme 'fighting an uphill battle'. Findings: skin-to-skin contact was considered to be important, and something that midwives strove to implement as a natural element of postnatal care. However, in daily practice, midwives experienced many obstacles to such care, such as lack of knowledge among parents and other professionals about the benefits of skin-to-skin contact, the mother's condition after the caesarean section, and other organisational difficulties (e.g. collaboration with other professionals, lack of time). Introducing more skin-to-skin care was a challenge for the midwives, who sometimes felt both dismissed and disappointed when they tried to communicate the benefits of this type of care. Conclusion: skin-to-skin contact is not prioritised because many health care practitioners are unaware of its positive effects, and their care reflects this lack of knowledge. There is a need for education among all health care practitioners involved in caesarean procedures. Another difficulty is that many parents are unaware of the benefits of skin-to-skin contact. Maternity outpatient clinics need to inform parents about the benefits of such care, so mothers will understand the importance of skin-to-skin contact. © 2014 Elsevier Ltd.


Kiessling A.,Danderyd Hospital
Education for health (Abingdon, England) | Year: 2014

BACKGROUND: The healthcare system is complex and the education of medical and nursing students is not always a priority within it. However, education offered at the point of care provides students with opportunities to apply knowledge, and to develop the necessary skills and attitudes needed to practice their future profession. The major objective of this study was to identify students' views of generic aspects of the healthcare environment that influences their progress towards professional competence.METHODS: We collected free text answers of 75 medical students and 23 nursing students who had completed an extensive questionnaire concerning their learning in clinical wards. In order to obtain richer data and a deeper understanding, we also interviewed a purposive sample of students. Qualitative content analysis was conducted.RESULTS: We identified three themes: (1) How management, planning and organising for learning enabled content and learning activities to relate to the syllabus and workplace, and how this management influenced space and resources for supervision and learning; (2) Workplace culture elucidated how hierarchies and communication affected student learning and influenced their professional development and (3) Learning a profession illustrated the importance of supervisors' approaches to students, their enthusiasm and ability to build relationships, and their feedback to students on performance.DISCUSSION: From a student perspective, a valuable learning environment is characterised as one where management, planning and organising are aligned and support learning. Students experience a professional growth when the community of practice accepts them, and competent and enthusiastic supervisors give them opportunities to interact with patients and to develop their own responsibilities.


Leander K.,Karolinska Institutet | Blomback M.,Karolinska Institutet | Wallen H.,Danderyd Hospital | He S.,Karolinska Institutet
Thrombosis and Haemostasis | Year: 2012

We assessed whether abnormality of haemostasis measured by a newly developed global method is associated with risk of a first myocardial infarction (MI). The global markers Coagulation activation profile (Cp), Fibrinolysis activation profile (Fp) and sum of fibrin optical density over time (Fibrin OD- sum) were determined in plasma from 800 MI cases and 1,123 controls included in the Stockholm Heart Epidemiology Program. Clotlysis time (CLT) was also determined based on raw data of fibrin OD from the global assay. Odds ratios (OR) of MI with 95% confidence intervals (CI) were calculated using logistic regression. A Fp value <10 th percentile value in controls was significantly associated with increased MI risk; OR after multivariate adjustments for conventional cardiovascular risk factors 1.66 (95% CI 1.22-2.27). For an abnormally long CLT (>90 th percentile value in controls) the adjusted OR of MI was 2.62 (95% CI 1.87-3.66) and for a high Fibrin OD-sum value (>90 th percentile in controls) it was 1.86 (95% CI 1.37-2.53). A high Cp value was not significantly associated with MI. In conclusion, we found that abnormal haemostasis in platelet-poor plasma, reflected either as an attenuated fibrinolytic capacity or the resulting increase of fibrin formation, was associated with increased MI risk. © Schattauer 2012.

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