| 139451. |
- Persson, Anna, et al.
(författare)
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Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure ( COPE): A Pilot Study in Alcohol-dependent Women
- 2017
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Ingår i: Journal of addiction medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 1932-0620 .- 1935-3227. ; 11:2, s. 119-125
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Posttraumatic stress disorder (PTSD) and substance use disorders are highly comorbid. Effective treatments are largely lacking. This pilot study evaluated the safety and feasibility of a novel intervention, Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE), in preparation for a randomized controlled trial. Methods: Twenty-two treatment-seeking women with current DSM-IV-TR PTSD and alcohol dependence (AD) were recruited. Participants received COPE. Safety and feasibility were evaluated, as were efficacy-related outcomes: PTSD and depression symptom severity, alcohol use, craving, and dependence severity. Results: No adverse events occurred. COPE was implemented in routine clinical practice. Among the assessed women, 95.8% were eligible to participate. Treatment attendance and completion were higher than in previous studies. Post treatment, all efficacy-related outcomes, including PTSD and depression symptom severity, alcohol use, craving, and dependence severity, were significantly reduced. Conclusions: COPE was safe and feasible to use. Concerns that trauma-focused, exposure-based therapy might promote relapse in this population appear unwarranted. Our findings provide initial evidence suggestive of COPE efficacy for comorbid PTSD and AD in women. These results provide a strong rationale for investigating the efficacy of COPE for comorbid PTSD and AD in women in a randomized controlled trial.
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| 139452. |
- Persson, AK, et al.
(författare)
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Correlational analysis for identifying genes whose regulation contributes to chronic neuropathic pain
- 2009
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Ingår i: Molecular pain. - : SAGE Publications. - 1744-8069. ; 5, s. 7-
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Tidskriftsartikel (refereegranskat)abstract
- Nerve injury-triggered hyperexcitability in primary sensory neurons is considered a major source of chronic neuropathic pain. The hyperexcitability, in turn, is thought to be related to transcriptional switching in afferent cell somata. Analysis using expression microarrays has revealed that many genes are regulated in the dorsal root ganglion (DRG) following axotomy. But which contribute to pain phenotype versus other nerve injury-evoked processes such as nerve regeneration? Using the L5 spinal nerve ligation model of neuropathy we examined differential changes in gene expression in the L5 (and L4) DRGs in five mouse strains with contrasting susceptibility to neuropathic pain. We sought genes for which the degree of regulation correlates with strain-specific pain phenotype. Results In an initial experiment six candidate genes previously identified as important in pain physiology were selected for in situ hybridization to DRG sections. Among these, regulation of the Na+ channel α subunit Scn11a correlated with levels of spontaneous pain behavior, and regulation of the cool receptor Trpm8 correlated with heat hypersensibility. In a larger scale experiment, mRNA extracted from individual mouse DRGs was processed on Affymetrix whole-genome expression microarrays. Overall, 2552 ± 477 transcripts were significantly regulated in the axotomized L5DRG 3 days postoperatively. However, in only a small fraction of these was the degree of regulation correlated with pain behavior across strains. Very few genes in the “uninjured” L4DRG showed altered expression (24 ± 28). Conclusion Correlational analysis based on in situ hybridization provided evidence that differential regulation of Scn11a and Trpm8 contributes to across-strain variability in pain phenotype. This does not, of course, constitute evidence that the others are unrelated to pain. Correlational analysis based on microarray data yielded a larger “look-up table” of genes whose regulation likely contributes to pain variability. While this list is enriched in genes of potential importance for pain physiology, and is relatively free of the bias inherent in the candidate gene approach, additional steps are required to clarify which transcripts on the list are in fact of functional importance.
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| 139453. |
- Persson, Anna
(författare)
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CYP2C19 and brain development : implications for susceptibility to anxiety in a transgenic mouse model
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The cytochrome P450-2C19 enzyme is involved in the metabolism of about 10 % of all drugs used today and displays high genetic polymorphism, causing absent, decreased or elevated enzyme activity that divides the population into different metabolic phenotypes. CYP2C19 enzymatic activity is also highly influenced by different substances including drugs and in vivo studies have shown that estradiol and 17α-ethinylestradiol, commonly used in hormone replacement therapy and oral contraceptives, decreased CYP2C19 mediated metabolism in vivo in humans. We investigated by which mechanisms this inhibition is mediated and found that the estrogens at rather high concentrations competitively inhibit CYP2C19 activity, but more importantly, at low clinically relevant concentrations caused a decreased gene transcription through a novel estrogen responsive element half-site in the CYP2C19 promoter region. Such estrogen CYP2C19 interactions are important to consider during drug development. Recently is was described by our laboratory that subjects lacking functional CYP2C19 enzyme had lower depressive symptoms based on analyses of a large twin cohort. To investigate CYP2C19’s potential effect on behavior and brain function a transgenic mouse model expressing the human CYP2C19 gene was characterized. We found that CYP2C19 is expressed in the developing fetal but not in adult brain. Newborn pups homozygous for the CYP2C19 gene insert display high neonatal lethality and severe brain malformations with complete commissural agenesis and a severely reduced hippocampus. Hemizygous mice (CYP2C19Tg-Hem) showed less extensive phenotypes, thus survived and were characterized at 7 (adolescent) and 15 weeks (young adult) of age. CYP2C19Tg-Hem mice display increased stress sensitivity and anxiety-like behavior, which was more pronounced in young adult mice. Furthermore, a smaller hippocampal formation was seen at both ages as measured by manual outlining of brain sections and confirmed in adult mice by magnetic resonance imaging. The CYP2C19Tg-Hem mice hippocampal formation furthermore displayed an increased neuronal activation, or c-fos expression, after acute stress. This might be explained by the drastic reduction of immature neurons and the reduced number of GABAergic interneurons observed in the dentate gyrus of the hippocampus in the CYP2C19 transgenic mice. The results indicate that CYP2C19 expression during brain development increases the susceptibility to develop anxiety-related disorders later in life. This is interesting since, as mentioned above, absence of CYP2C19 enzyme is protective against depressive symptoms in humans, a phenotype displaying high comorbidity with anxiety disorders. Since the pathophysiology behind major depressive disorder and anxiety disorders is still mostly unknown, the model presented could be used for the investigation of factors important in the pathogenesis of these disorders and might also be used in the development of novel anxiolytic drugs.
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| 139454. |
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| 139455. |
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| 139456. |
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| 139457. |
- Persson, Asa E, et al.
(författare)
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The mutagenic effect of ultraviolet-A1 on human skin demonstrated by sequencing the p53 gene in single keratinocytes.
- 2002
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Ingår i: Photodermatology, Photoimmunology & Photomedicine. - : Wiley. - 0905-4383 .- 1600-0781. ; 18:6, s. 287-293
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sun exposure is accepted as the major risk factor for developing skin cancer, the most common cancer in the western world. Ultraviolet-B (UV-B) radiation is considered the causative agent, but recently several findings suggest a role also for ultraviolet-A (UV-A) radiation. Repeated suberythemal doses of ultraviolet-A1 (UV-A1) on healthy human skin induce an increase of p53 immunoreactive cells in epidermis, which may indicate cell cycle arrest and/or occurrence of p53 mutations.METHODS: We have investigated the possible mutagenic effect of UV-A1 on skin by sequencing exons 4-11 and adjacent intron sequence of the p53 gene in immunoreactive single cells from three healthy individuals. Previously unexposed buttock skin was irradiated three times a week for 2 weeks with physiological fluences (40 J/cm2) of UV-A1. Punch biopsies were taken before and at different time-points after the exposure, and from these single p53 immunoreactive cells were isolated by using laser-assisted microdissection.RESULTS: Three mutations--all being indicative of oxidative damage and most likely related to UV-A exposure--were found among the 37 single cells from exposed skin, whereas no mutations were found in the 22 single cells taken before exposure.CONCLUSIONS: The findings indicate a mutagenic effect of low-dose UV-A1 on healthy human skin, which further demonstrates the importance of considering UV-A when taking protective measures against skin cancer.
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| 139458. |
- Persson, Anita, 1971, et al.
(författare)
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Effect of surgery on cardiac structure and function in mild primary hyperparathyroidism.
- 2011
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Ingår i: Clinical endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 74:2, s. 174-180
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Tidskriftsartikel (refereegranskat)abstract
- Context The cardiovascular (CV) risk profile is worsened in primary hyperparathyroidism (PHPT), and CV mortality is related to serum calcium levels. It is unknown whether CV mortality is increased in the most common form of PHPT and whether the increased CV risk is reversible after surgery. Objective To investigate reversibility of echocardiographic variables in patients with mild PHPT who were randomized to observation without surgery or operation, and followed for 2years. Design/Setting/Patients Forty-nine patients (mean age 63±7years, 8 men) who had performed the 2-year visit in a randomized study on mild PHPT (serum calcium at baseline 2·65±0·09mm) (observation) vs 2·67±0·06mm (surgery) and where echocardiography had been performed, participated in the study. Results Calcium and parathyroid hormone (PTH) levels were normalized following surgery and were stable in the observation group. PTH levels at baseline were highly correlated with ventricular mass. Detailed echocardiography revealed a minor and borderline significant treatment effect of surgery on left ventricular mass index (LVMI) compared to observation (P=0·066) and a significant 11% reduction in diastolic dimension of the interventricular septum (IVSd-mean) in the surgery group (P<0·01), with no alterations in the observation group. Conclusions Based on detailed echocardiographic measures over a 2-year observation period, we found only minor differences between the two groups. However, the potential treatment effect on LVMI and the within-group differences in IVSd-mean suggest that longer follow-up may yield larger and clinically important differences.
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| 139459. |
- Persson, A., et al.
(författare)
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EPOS trial: The effect of air filtration through a plasma chamber on the incidence of surgical site infection in orthopaedic surgery: A study protocol of a randomised, double-blind, placebo-controlled trial
- 2022
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction There is controversy regarding the importance of air-transmitted infections for surgical site infections (SSIs) after orthopaedic surgery. Research has been hindered by both the inability in blinding the exposure, and by the need for recruiting large enough cohorts. The aim of this study is to investigate whether using a new form of air purifier using plasma air purification (PAP) in operating rooms (ORs) lowers the SSI rate or not. Methods and analysis Multicentre, double-blind, cluster-randomised, placebo-controlled trial conducted at seven hospitals in 2017-2022. All patients that undergo orthopaedic surgery for minimum 30 min are included. Intervention group: patients operated in OR with PAP devices turned on. Control group: patients operated in OR with PAP devices turned off. Randomisation: each OR will be randomised in periods of 4 weeks, 6 weeks or 8 weeks to either have the devices on or off. Primary outcome: any SSI postoperatively defined as a composite endpoint of any of the following: use of isoxazolylpenicillin, clindamycin or rifampicin for 2 days or more, International Classification of Diseases codes or Nordic Medico-Statistical Committee codes indicating postoperative infection. In a second step, we will perform a chart review on those patients with positive indicators of SSI to further validate the outcome. Secondary outcomes are described in the Methods section. Power: we assume an SSI rate of 2%, an SSI reduction rate of 25% and we need approximately 45 000 patients to attain a power of 80% at a significance level of 0.05. Ethics and dissemination The study is approved by the Swedish Ethical Review Authority. The interim analysis results from the study will be presented only to the researchers involved unless the study thereafter is interrupted for whatever reason. Publication in a medical journal will be presented after inclusion of the last patient. Trial registration number NCT02695368. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.
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| 139460. |
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