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30251.
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30252.
  • Ström, Susanne (författare)
  • Optimisation of human embryonic stem cell derivation and culture : towards clinical quality
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • For clinical grade human embryonic stem cell (hESC) lines, a robust derivation and culture system without any substances having animal origin would be optimal. The general aims of these studies have been to gradually improve our hESC derivation and cultures. The first step towards clinical quality was the use of human foreskin fibroblasts instead of mouse embryonic fibroblasts to support the undifferentiated growth of the pluripotent stem cells. This was followed by replacing foetal calf serum as a supplement in the culture medium with the commercially available Serum Replacement, first in the cultures and later also for the derivation of new hESC lines. The immunosurgery generally used for isolation of the inner cell mass (ICM) involves animal serum and complement. We have been able to replace the surgical method with a mechanical procedure for the isolation of the inner cell mass, and this gives better results. We have also evaluated whether the morphology of the embryos donated to stem cell research has an impact on derivation success. We have carried out statistical analyses on the early cleavage rate, morphological score of the embryo at cleavage stage and the score for the ICM and the trophectoderm at the time for isolation of the ICM. We have shown that there is no correlation between the morphology and derivation success. All embryos donated for stem cell research should be used for isolation in an attempt to derive new hESC lines. Even embryos with no visible ICM have generated pluripotent hESCs. In the final study we have been able to culture hESCs on a human recombinant laminin, LN-511, for more than 20 passages (four months) in a well-defined medium devoid of any animal-derived components. The use of a well-defined system is most important in understanding the pluripotent state and being able to direct the differentiation in the desired direction for clinical applications in the future. We have taken hESC research from a culture system that depended on several animal-derived components to a totally xeno-free system. We hope that these improved culture procedures can be used for the development of cell lineages for use in therapeutic purposes.
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30253.
  • Strömberg, Anna, et al. (författare)
  • Bone marrow derived cells in adult skeletal muscle tissue in humans
  • 2013
  • Ingår i: Skeletal Muscle. - : Springer Science and Business Media LLC. - 2044-5040. ; 3:1, s. 12-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:During the past decade, several animal studies have demonstrated that in addition to local cells, cells from the bone marrow (BM) possess the ability to contribute to regeneration of injured skeletal muscle tissue. In addition, in mice, regular physical activity has been displayed to be a sufficient stimulus for BM-derived cell contribution to the muscle, indicating that this is part of the ongoing physiological remodeling of skeletal muscle. However, whether BM-derived cells participate in human skeletal muscle remodeling is not known. To this end, we analyzed the incorporation of BM-derived cells in healthy human skeletal muscle in women transplanted with male BM.METHODS:Skeletal muscle biopsies were obtained from the m. vastus lateralis of women transplanted with male donor hematopoietic stem cells 6 to 12 years earlier. Healthy women served as controls. Immunohistochemical staining for skeletal muscle fibers, satellite cells (SCs) or endothelial cells (ECs) combined with fluorescent in situ hybridization (FISH) of X and Y chromosomes was used to identify cells of BM origin within the biopsies. Three dimensional confocal imaging was performed to demonstrate colocalization of Y chromosome and DAPI within muscle fibers. To further investigate whether BM-derived cells incorporate into the SC niche, myoblasts were extracted from the biopsies from the transplanted women, cultured, and analyzed using XY FISH and immunocytochemistry.RESULTS:Three dimensional confocal imaging indisputably demonstrated colocalization of Y chromosome and DAPI within muscle fibers. Some Y chromosomes were found within centrally located nuclei. No Y chromosomes were detected in CD56+ SCs in the tissue sections nor in the myoblasts cultured from the extracted SCs. Y chromosome+ ECs were found in all sections from the transplanted subjects. No Y chromosomes were found in the skeletal muscle biopsies obtained from healthy control women.CONCLUSIONS:We demonstrate that BM-derived cells contribute to skeletal muscle fibers and ECs. Our results support that BM contribution to skeletal muscle occurs via direct fusion to muscle fibers, and that the contributing cells derive from the hematopoietic lineage. Thus, the present findings encourage further studies of the importance of this process for the physiological adaptation occurring throughout life.
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30254.
  • Strömberg, Cecilia (författare)
  • Aspects of treatment of common bile duct stones
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Gallstone disease is a major cause of morbidity and at least 10 000 cholecystectomies are performed annually in Sweden. At the time of surgery about 5-15% of the patients also have common bile duct stones (CBDS). Introduction of new techniques like Endoscopic Retrograde CholangioPancreatography (ERCP) and laparoscopy have changed the treatment for these patients. Aims: To analyze how CBDS has been treated in Sweden 1965-2009 and to calculate mortality connected to the different procedures, to assess the risk of malignancy after ERCP in benign disease and identify risk factors for death within 90 days. To evaluate the short term clinical outcome and identify risk-factors for failure in laparoscopic transcystic common bile duct exploration (LTCE). Methods: Data on all patients with an in-patient procedure code of common bile duct exploration or ERCP 1965- 2009 were collected from the Swedish Hospital Discharge Register and those with a diagnosis of malignancy in the bile ducts, liver or pancreas were excluded. The outcome death was identified by cross-linkage to the Registry of Causes of Death and readmission in the Swedish Hospital Discharge Register. For assessment of cancer risk a cohort study of all patients in Sweden having had an ERCP before the end of 2003 without a diagnosis of malignancy at the time of the procedure or within two years after it was performed. To calculate mortality and analyze risk-factors for death after ERCP a case-control study based on the population of Stockholm 1990-2003 was performed. Cases were defined as patients having died within 90 days of the procedure and controls were randomly chosen among those who did not die. Data were collected prospectively on patients having a cholecystectomy at S:t Göran’s Hospital 1994-2002, in 155 patients a LTCE were attempted and the outcome analyzed. Results: The Swedish Hospital Discharge Registry contained records of 126 885 procedures for treatment of common bile duct stones in 110 119 individuals, without a diagnosis of malignancy at the time of the procedure, during 1965-2009. The 90-day mortality was 0.24 % after open surgery, 0.90% after ERCP, 0.67% after combined procedures and 0% after laparoscopic surgery. After adjustment for confounding factors, mainly age and comorbidity, in the multivariate analyses there was no significant difference in mortality between open surgery and ERCP. The risk of malignancy in the bile ducts alone and in the bile ducts, liver and pancreas together was significantly elevated in the cohort of individuals having had an ERCP before 2003, irrespective of if an ES was performed or not. The risk of malignancy diminished with increasing follow-up time. Patients ever having had a cholecystectomy had a significantly lower risk of the studied malignancies. In Stockholm County during 1990-2003 the 90-day mortality after ERCP was 1.6%. Advanced age, severe comorbidity, high complexity of the procedure and the occurrence of a complication were associated to death within 90 days, whereas a previous cholecystectomy or the simultaneous performance of an endoscopic sphincterotomy reduced the risk. An attempt of transcystic CBD exploration with complete stone clearance in the 155 patients at S:t Göran’s Hospital could be fulfilled in 85 %. The median operating time was 184 minutes (range 89-384 minutes) and the median postoperative hospital stay was one day. There was a significant 3-fold increase in risk of failure of clearance of the bile ducts among patients with stones of >5 mm compared to patients with stones ≤5 mm. Conclusions: Common bile duct stones were mainly treated endoscopically. ERCP and open surgery were associated with a similar mortality after adjustment for confounding factors. Laparoscopic treatment was chosen in younger and healthier patients, probably with a less severe disease, and no 90-day mortality was recorded. The risk of malignancy in the bile ducts, liver or pancreas was elevated after ERCP in benign disease. However, ES did not seem to affect this risk. Old age and comorbidity were the main risk factors for death after ERCP but a complex procedure or the occurrence of a complication also seemed to increase short term mortality. The performance of a sphincterotomy may decrease the risk of death, possibly by facilitating adequate drainage. Previous cholecystectomy may also decrease the risk of dying after ERCP. Laparoscopic transcystic exploration of the CBD had a high frequency of stone clearance and low morbidity in the present study. Moreover, large stones were a risk factor for failure in stone clearance.
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30255.
  • Strömberg, Cecilia, et al. (författare)
  • Possible mortality reduction by endoscopic sphincterotomy during endoscopic retrograde cholangiopancreatography : a population-based case-control study.
  • 2012
  • Ingår i: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 0930-2794 .- 1432-2218. ; 26:5, s. 1369-76
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is widely used for young patients, but ERCP and endoscopic sphincterotomy in particular are reported to be associated with increased complication and mortality rates. This study aimed to calculate mortality and to identify risk factors for death within 90 days after ERCP for nonmalignant disease.METHODS: From the Swedish Hospital Discharge Registry, the authors identified all individuals in Stockholm County who had undergone in-patient ERCP during 1990-2003. Among these individuals, they excluded those recorded in the Swedish Cancer Registry as having a diagnosis of malignancy in the liver, pancreas, or bile ducts. Cases, defined as patients who had died within 90 days after the procedure, were identified by cross-linkage to the causes of death registry. Control subjects were randomly sampled from the same cohort. The medical records were studied to discern risk factors for death after ERCP.RESULTS: The mortality rate was 1.6%. Advanced age, severe comorbidity, high complexity of the procedure, and occurrence of a complication were associated with death within 90 days, whereas a previous cholecystectomy or the simultaneous performance of an endoscopic sphincterotomy reduced the risk.CONCLUSIONS: Old age and comorbidity are the main risk factors for death after ERCP, but a complex procedure or the occurrence of a complication also seems to increase short-term mortality. The performance of a sphincterotomy may reduce the risk of death, possibly by facilitating adequate drainage. A previous cholecystectomy also may decrease the risk of death after ERCP.
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30256.
  • Strömberg de Sousa Soares, Ranja (författare)
  • Depression in primary care : detection, description and mortality
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Aims: The aims of these studies were to explore the prevalence and severity of depression among unscheduled drop-in patients in primary care and to identify possible cues to depression in the consultation. Further aims were to analyze the association between depression and psychosocial stressors and lifestyle factors from a gender perspective and to evaluate the usefulness of the Gotland Male Depression Scale (GS) in screening for depression among men. A final aim was to analyze the long term mortality rate (MR) and the standardized mortality rate among the patients who had been diagnosed as having a major depressive disorder (MDD). Background: Depression is a common diagnosis in primary care, but had been reported to remain undetected in half of the consultations, especially among men despite the fact that men had higher rates of suicide. Detecting and diagnosing patients with depression in primary care is essential since depression reduces quality of life, functioning level, work ability and possibly also life expectancy. Patients and Methods: Patients visiting two primary care physicians’ drop-in clinics were screened using the Beck Depression Inventory (BDI) with a cut-off value of ≥ 10 and the men were screened also with the GS with a cut-off value of ≥ 13. A two-step screening method was used among patients aged 18–75 years visiting two primary care physicians’ drop-in clinics in opportunistic and targeted screenings. Patients with screening scores above the cut-off values were interviewed by the physicians at a repeat visit and the DSM-IV criteria for major depressive disorder (MDD) were applied. Severity of depression was measured with the Montgomery-Åsberg Depression Rating Scale (MADRS). The study population consisted of 404 patients (men n=235, women n=169) categorised as depressed (n=124) or non-depressed (n= 280). Their socio-demographic data, lifestyle and psychosocial stressors were obtained from a questionnaire. Symptoms mentioned at the screening visit were examined from the medical charts and categorised as somatic or mental. Twelve years after inclusion, the causes of death for the depressed patients were obtained from the National Cause of Death Register. Mortality data regarding the non-depressed patients were obtained from the Swedish National Register and data from the Life Tables Statistics Sweden were used to calculate standardised mortality rates (SMRs). The screenings among men with GS and BDI were compared, as were the outcomes from the opportunistic and targeted screenings. Differences between depressed and non-depressed men and women regarding socio-demographic and clinical data were analysed. The odds ratios (ORs) with 95% confidence intervals (95% CI) for being depressed were calculated for the psychosocial stressors and lifestyle factors. Multiple logistic regression modelling was used to obtain the main effect models separately for men and women for the risk factors for depression. Differences in the MRs between the depressed and the non-depressed patients were calculated as well as their SMRs. As a reference for comparison the SMRs in the Swedish population in the same age and in the same time period were calculated. Cox regression was applied to calculate the hazard ratios (HRs) for the mortality rate during the 12-year follow-up period for the depressed and the non-depressed patients in relation to the explanatory variables. Main results: The prevalence of depression was 25% among women and 11% among men. The severity of depression was mild or moderate and severe depression was very rare. Mentioning a mental symptom was a cue to detect depression among women but not consistently among men. The proportions as depressed patients were higher from the targeted screenings than from the opportunistic screenings. Screening with GS did not detect more depressed men than BDI. Smoking was associated with depression only among men. Three psychosocial stressors were equally associated with depression among the men and the women: being dissatisfied with family situation, being very stressed and perceiving poor physical health, and the ORs in the main effect models varied from 3.1 (95% CI 1.4–6.6) up to 22.4 (95% CI 5.8–86.8). Dissatisfaction with one’s working situation was also associated with depression: in men OR 13.2 (95% CI 4.7–37.5) and in women: OR 32.5 (95% CI 4.1–254.7). The MR among the depressed men was significantly higher than among the non-depressed. The SMRs among depressed men and women did not differ from those in the general Swedish population. Conclusions: The prevalence and severity of depression was comparable to that in other primary care settings. Depressed women had often mentioned mental symptoms. Questions about family and working situation, feeling very stressed and feelings about one’s physical health could be used as risk indicators for depression in clinical practice for both men and women. Moreover, the long-term follow-up underlines the importance of finding patients with depression and thoroughly examine them also regarding their somatic health.
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30257.
  • Strömberg, Ella, et al. (författare)
  • Oral status, oral hygiene habits and caries risk factors in home-dwelling elderly dependent on moderate and substantial supportive care for daily living.
  • 2012
  • Ingår i: Community Dentistry and Oral Epidemiology. - : Wiley. - 1600-0528 .- 0301-5661. ; 40:3, s. 221-229
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract – Objectives: Elderly people with disabilities have an increased risk of developing oral diseases as compared with the healthy elderly. The aim of this study was to investigate oral hygiene habits, clinical variables related to oral self-care and caries risk in elderly individuals living at home with moderate and substantial needs of home care. Methods: A random sample of 151 elderly people with moderate needs and 151 with substantial needs of home care were examined. Data concerning general health, social conditions and oral hygiene habits were collected using a questionnaire. Data showing the prevalence of caries, plaque scores and gingival bleeding were obtained through clinical examinations. Results: Elderly subjects with substantial needs of home nursing had more active caries (P < 0.01) and more often gingival bleeding (P < 0.05), as compared with elderly people with moderate needs. Forty-nine per cent of the elderly with moderate needs performed acceptable self-care, as compared with 25% of the individuals with substantial needs. Good self-care was associated with women, low plaque scores, less bleeding and less caries. Factors increasing the risk of having caries were low saliva secretion, high plaque scores and a large number of fillings, while having a dentist and good oral hygiene habits increased the chance of not developing caries. Conclusions: Good oral hygiene habits were associated with less prevalence of plaque and oral disease in the elderly irrespective of extent of needs of home nursing. However, the elderly with moderate needs more often performed good self-care, indicating that the possibilities of strengthening self-care and learning new routines are better when functions are less affected.
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30258.
  • Strömberg, Ranja, et al. (författare)
  • Psychosocial stressors and depression at a Swedish primary health care centre. A gender perspective study.
  • 2011
  • Ingår i: BMC Family Practice. - : Springer Science and Business Media LLC. - 1471-2296. ; 12, s. 120-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Psychosocial stress may account for the higher prevalence of depression in women and in individuals with a low educational background. The aim of this study was to analyse the association between depression and socio-demographic data, psychosocial stressors and lifestyle circumstances from a gender perspective in a relatively affluent primary care setting.METHODS: Patients, aged 18- 75 years, visiting a drop-in clinic at a primary care health centre were screened with Beck's Depression Inventory (BDI). The physicians used also targeted screening with BDI. A questionnaire on socio-demographic data, psychosocial stressors and use of alcohol and tobacco was distributed. Among patients, who scored BDI ≥ 10, DSM-IV-criteria were used to diagnose depression. Of the 404 participants, 48 men and 76 women were diagnosed with depression. The reference group consisted of patients with BDI score <10, 187 men and 93 women. Age-adjusted odds ratios (ORs) with 95% confidence intervals (CI) as being depressed were calculated for the psychosocial stressors and lifestyle circumstances, separately for men and women. Multiple logistic regression analyses were used to determine the age-adjusted main effect models for men and women.RESULTS: The same three psychosocial stressors: feeling very stressed, perceived poor physical health and being dissatisfied with one's family situation were associated with depression equally in men and women. The negative predictive values of the main effect models in men and women were 90.7% and 76.5%, respectively. Being dissatisfied with one's work situation had high ORs in both men and women. Unemployment and smoking were associated with depression in men only.CONCLUSIONS: Three questions, frequently asked by physicians, which involve patient's family and working situation as well as perceived stress and physical health, could be used as depression indicators in early detection of depression in men and women in primary health care.
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30259.
  • Strömqvist, Björn, et al. (författare)
  • X-Stop Versus Decompressive Surgery For Lumbar Neurogenic Intermittent Claudication: A Randomized Controlled Trial With 2 Years Follow-Up.
  • 2013
  • Ingår i: Spine. - 0362-2436 .- 1528-1159. ; 38:17
  • Tidskriftsartikel (refereegranskat)abstract
    • ABSTRACT: Study Design. Prospective randomized controlled study.Objective. To compare the outcome of indirect decompression by means of the X-Stop implant to conventional decompression in patients with neurogenic intermittent claudication due to lumbar spinal stenosis.Summary of Background Data. Decompression is the golden standard for lumbar spinal stenosis nowadays but afflicted with complications and a certain number of dissatisfied patients. Interspinous implants have been on the market for more than 10 years but no prospective study comparing its outcome to decompression has been performed.Methods. After power calculation 100 patients were included, 50 in X-Stop group and 50 in decompression group. Patients with symptomatic one- or two-level lumbar spinal stenosis and neurogenic claudication relieved on flexion were included. X-Stop operations were performed under local anaesthesia.Mean Patient Age. 69 (49-89) years, male/female distribution 56/44. Minimal dural sac area was in all cases except two ≤ 80 mm.Non-Inferiority Hypothesis. Six, 12, and 24 months follow-up. Intention-to-treat (ITT) as well as As-Treated (AT) analyses.Primary Outcome Measure. Zürich Claudication Questionnaire. Secondary outcome measures: VAS pain, SF-36, complications and re-operations.Results. Patients in both groups improved significantly regarding primary and secondary outcome measures. The results were similar at 6, 12 and 24 months and at no time point any statistical difference between the two types of surgery could be identified. Three patients (6%) in the decompression group had further surgery, compared to 13 patients (26%) in the X-Stop group (p = 0.04). Results were identical in ITT and AT analysis.Conclusion. For spinal stenosis with neurogenic claudication, decompressive surgery as well as X-Stop are rewarding procedures. Similar results were achieved in both groups, however, with a higher number of re-operations in the X-Stop group. Patients having X-Stop removal and decompression experienced results similar to those randomized to primary decompression.
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30260.
  • Strömqvist, Johan, et al. (författare)
  • A modified FCCS procedure applied to Ly49A-MHC class Icis-interaction studies in cell membranes
  • 2011
  • Ingår i: Biophysical Journal. - : Elsevier. - 0006-3495 .- 1542-0086. ; 101:5, s. 1257-1269
  • Tidskriftsartikel (refereegranskat)abstract
    • The activity of natural killer (NK) cells is regulated by a fine-tuned balance between activating and inhibitory receptors. Dual-color fluorescence cross-correlation spectroscopy (FCCS) was used to directly demonstrate a so-called cis-interaction between a member of the inhibitory NK cell receptor family Ly49 (Ly49A), and its ligand, the major histocompatibility complex (MHC) class I, within the plasma membrane of the same cell. By a refined FCCS model, calibrated by positive and negative control experiments on cells from the same lymphoid cell line, concentrations and diffusion coefficients of free and interacting proteins could be determined on a collection of cells. Using the intrinsic intercellular variation of their expression levels for titration, it was found that the fraction of Ly49A receptors bound in cis increase with increasing amounts of MHC class I ligand. This increase shows a tendency to be more abrupt than for a diffusion limited three dimensional bimolecular reaction, which most likely reflects the two-dimensional confinement of the reaction. For the Ly49A- MHC class I interaction it indicates that within a critical concentration range the local concentration level of MHC class I can provide a distinct regulation mechanism of the NK cell activity.
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