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1.
Acta Derm Venereol ; 104: adv34879, 2024 Mar 04.
Article En | MEDLINE | ID: mdl-38436430

Syphilis is currently a treatable disease, with a low incidence in most developed countries, although the prevalence has increased recently, especially among men-who-have-sex-with-men. In many of the least developed countries, however, syphilis is still a major health problem, although the problem is not comparable to the desperate situation worldwide less than 80 years ago. At that time, and for many centuries previously, syphilis dramatically affected the lives and health of individuals and threatened the well-being of many societies. This review examines the aetiology, transmission, and many manifestations of syphilis from a historical perspective, emphasizing morbidity, treatment, psychosocial and cultural manifestations, as well as ethical issues uncovered in the clinical search for knowledge about the manifestations of the disease.


Sexual and Gender Minorities , Syphilis , Male , Humans , Penicillins/adverse effects , Homosexuality, Male , Pandemics , Syphilis/diagnosis , Syphilis/drug therapy , Syphilis/epidemiology
2.
Article En | MEDLINE | ID: mdl-36316740

BACKGROUND: Many similarities exist between borderline personality disorder (BPD) and attention-deficit/hyperactivity disorder (ADHD), more so in women than in men. People with comorbid ADHD and BPD represent a subgroup of BPD patients with distinct symptom expression and, consequently, a different prognosis. We used Swedish national high quality registers to assess whether such comorbidity is related to increased mortality risk. The study focused on women with BPD because they are more likely than men to be clinically diagnosed with BPD and present a higher mortality risk, especially for unnatural causes of death, including suicide. FINDINGS: In a cohort of 15 847 women diagnosed with BPD a subsequent clinical diagnosis of ADHD did not influence the overall risk of mortality, including suicide. CONCLUSIONS: Women with comorbid ADHD and BPD have a similar mortality risk as those only diagnosed with BPD.

3.
BJPsych Open ; 6(5): e95, 2020 Aug 25.
Article En | MEDLINE | ID: mdl-32838831

BACKGROUND: People with a personality disorder have a higher mortality and reduced life expectancy than the general population. Childbearing is thought to have a protective effect on morbidity and mortality. Yet, there are no studies on whether childbearing is related to a lower mortality among women with personality disorder. AIMS: This study examined associations between childbearing and mortality among women with personality disorder. Our hypothesis was that parity would be associated with lower mortality. METHOD: This register-based cohort study included 27 412 women treated for personality disorder in in-patient or specialised out-patient care between 1990 and 2015. We used nationwide population-based registers to obtain information on sociodemographics, child delivery, healthcare use and mortality. Mortality risk estimates were calculated as hazard ratios (HRs) with 95% CIs using Cox regression. Adjustments were made for year of birth, educational level, age at diagnosis, comorbidity and severity of personality disorder. RESULTS: Nulliparous women had a nearly twofold increased mortality risk (adjusted HR = 1.78, 95% CI 1.50-2.12) compared with parous women and over twofold mortality risk (adjusted HR = 2.29, 95% CI 1.72-3.04) compared with those giving birth after their first personality disorder diagnosis. Those giving birth before their first personality disorder diagnosis had a 1.5-fold higher risk of mortality than those giving birth after their first personality disorder diagnosis (adjusted HR = 1.48, 95% CI 1.06-2.07). There was a threefold risk of suicide in nulliparous women compared with those giving birth after their first personality disorder diagnosis (adjusted HR = 2.90, 95% CI 1.97-4.26). CONCLUSIONS: Childbearing history should be an integral part of the clinical evaluation of women with personality disorder.

4.
Burns ; 45(6): 1367-1374, 2019 09.
Article En | MEDLINE | ID: mdl-31378623

OBJECTIVE: A history of psychiatric disorders is more common among patients who have had burns than in the general population. To try and find out the scale of the problem we have assessed self-reported symptoms of anxiety and depression after a burn. METHODS: Consecutive patients with burns measuring more than 10% total body surface area or duration of stay in hospital of seven days or more were included. Personal and clinical details about the patients were extracted from the database at each center. Data were collected from the Hospital Anxiety and Depression Scale, as well as Health-Related Quality of Life (HRQoL; Short Form-36, SF-36) and questionnaires about socioeconomic factors. All results were obtained 12 and 24 months after the burn, and compared with those from a reference group. RESULTS: A total of 156 patients responded to the questionnaires. Mean (SD) age and TBSA (%) were 46 (16.4) years and 23.6 (19.2) %, respectively. There were no differences in incidence between the burn and reference groups in anxiety or depression either 12 or 24 months after the burn. Those who reported higher anxiety and depression scores also had consistently poorer HRQoL as assessed by the SF-36. CONCLUSION: Seen as a group, people who have had burns report anxiety and depression the same range as a reference group. Some patients, however, express more anxiety and depression, and concomitantly poorer HRQoL. These patients should be identified, and offered additional support.


Anxiety/psychology , Burns/psychology , Depression/psychology , Quality of Life/psychology , Adult , Asthma/epidemiology , Burns/epidemiology , Comorbidity , Female , Follow-Up Studies , Humans , Hypersensitivity/epidemiology , Male , Mental Disorders/epidemiology , Middle Aged , Nervous System Diseases/epidemiology , Surveys and Questionnaires , Unemployment/psychology
5.
J Psychiatr Res ; 83: 29-36, 2016 12.
Article En | MEDLINE | ID: mdl-27552531

OBJECTIVE: The influence of psychopathology on suicide method has revealed different distributions among different psychiatric disorders. However, evidence is still scarce. We hypothesized that having a diagnosis of personality disorder (PD) affect the suicide method, and that different PD clusters would influence the suicide method in different ways. In addition, we hypothesized that the presence of psychiatric and somatic co-morbidity also affects the suicide method. METHOD: We examined 25,217 individuals aged 15-64 who had been hospitalized in Sweden with a main diagnosis of PD the years 1987-2013 (N = 25,217). The patients were followed from the date of first discharge until death or until the end of the follow-up period, i.e. December 31, 2013, for a total of 323,508.8 person-years, with a mean follow up time of 11.7 years. The SMR, i.e. the ratio between the observed number of suicides and the expected number of suicides, was used as a measure of risk. RESULTS: Overall PD, different PD-clusters, and comorbidity influenced the suicide method. Hanging evidenced highest SMR in female PD patients (SMR 34.2 (95% CI: 29.3-39.8)), as compared to non-PD patients and jumping among male PD patients (SMR 24.8 (95% CI: 18.3-33.6)), as compared to non PD-patients. Furthermore, the elevated suicide risk was related to both psychiatric and somatic comorbidity. CONCLUSION: The increased suicide risk was unevenly distributed with respect to suicide method and type of PD. However, these differences were only moderate and greatly overshadowed by the overall excess suicide risk in having PD. Any attempt from society to decrease the suicide rate in persons with PD must take these characteristics into account.


Cause of Death , Personality Disorders/epidemiology , Personality Disorders/psychology , Self-Injurious Behavior/epidemiology , Suicide/psychology , Suicide/statistics & numerical data , Adolescent , Adult , Age Distribution , Comorbidity , Female , Humans , Longitudinal Studies , Male , Mental Disorders/epidemiology , Middle Aged , Retrospective Studies , Risk Factors , Sweden , Young Adult
6.
Burns ; 42(8): 1781-1788, 2016 Dec.
Article En | MEDLINE | ID: mdl-27341954

BACKGROUND: Chronic pain after burn can have severe physical and psychological effects on former patients years after the initial injury. Although the issue of pain after burn has gained increased attention over the past years, prospective, longitudinal studies are scarce. Our aim was to prospectively investigate consecutive burn patients for pain severity over time and to evaluate the prevalence and characteristics of post-burn pain to 2-7 years after the burn. As an additional aim, the effects of burn and individual-related factors, especially health-related Quality of Life (HRQoL), were investigated. METHOD: Sixty-seven consecutive burn patients were assessed during acute care at 3, 6, 12 and 24 months, as well as at 2-7 years post-burn. HRQoL, symptoms of post-traumatic stress disorder (PTSD) and other psychiatric disorders were investigated. During the interviews that took place 2-7 years after the injury (mean 4.6±1.9 years), current chronic post-burn pain was assessed using the Brief Pain Inventory-Short Form (BPI-SF). RESULTS: One-third of the patients still reported pain 2-7 years after the injury. Pain severity and interference with daily life were mainly mild to moderate though they were found to be associated with significantly lower HRQoL. Chronic pain after burn was associated with both burn- and individual-related factors. In logistic regression analysis HRQoL at 3 and 12 months and symptoms of PTSD at 12 months were independent factors in predicting chronic pain after burn. CONCLUSION: Pain after burn becomes a chronic burden for many former burn patients and decreases HRQoL. A novel finding in this study was that HRQoL assessed early after burn was a predictor for the development of chronic pain. This finding may help to predict future pain problems and serve as an indicator for pain preventive measures.


Burns/psychology , Chronic Pain/psychology , Health Status , Quality of Life/psychology , Stress Disorders, Post-Traumatic/psychology , Activities of Daily Living , Adult , Body Surface Area , Burns/epidemiology , Burns/physiopathology , Chronic Pain/epidemiology , Female , Humans , Length of Stay/statistics & numerical data , Logistic Models , Longitudinal Studies , Male , Middle Aged , Stress Disorders, Post-Traumatic/epidemiology , Surveys and Questionnaires , Sweden/epidemiology , Trauma Severity Indices
7.
Anticancer Res ; 36(5): 2131-7, 2016 May.
Article En | MEDLINE | ID: mdl-27127114

BACKGROUND: Tumor stroma is similar to the connective tissue of chronic inflammation. The extracellular matrix of tumors is formed by cancer-associated fibroblasts that also modulate the inflammatory response. MATERIALS AND METHODS: We studied the ability of oral keratinocytes (NOK) and oral squamous cell carcinoma cells (SCC) to induce an innate immune response in fibroblasts. Co-cultures with fibroblasts in collagen gels and keratinocytes in inserts were used. Pentraxin 3 (PTX3) was used as an indicator of an innate immune response. RESULTS: SCC and NOK up-regulated fibroblast mRNA expression and protein release of PTX3. mRNA levels were more pronounced in cultures with malignant cells. The induction of PTX3 was abrogated by an interleukin-1 receptor antagonist CONCLUSION: Keratinocytes have the capacity to induce an interleukin-1-dependent innate immune response by fibroblasts in vitro. This could be important for subsequent fibroblast modulation of the inflammatory reaction in non-malignant and malignant disease processes.


Carcinoma, Squamous Cell/pathology , Head and Neck Neoplasms/pathology , Keratinocytes/pathology , Mouth/cytology , C-Reactive Protein/metabolism , Carcinoma, Squamous Cell/metabolism , Cell Line, Tumor , Coculture Techniques , Fibroblasts/metabolism , Fibroblasts/pathology , Head and Neck Neoplasms/metabolism , Humans , Interleukin-1alpha/biosynthesis , Keratinocytes/metabolism , Mouth/metabolism , Receptors, Interleukin-1/biosynthesis , Serum Amyloid P-Component/metabolism , Squamous Cell Carcinoma of Head and Neck
8.
Int Wound J ; 13(3): 372-81, 2016 Jun.
Article En | MEDLINE | ID: mdl-25185742

Cell migration requires spatiotemporal integration of signals that regulate cytoskeletal dynamics. In response to a migration-promoting agent, cells begin to polarise and extend protrusions in the direction of migration. These cytoskeletal rearrangements are orchestrated by a variety of proteins, including focal adhesion kinase (FAK) and the Rho family of GTPases. CCN2, also known as connective tissue growth factor, has emerged as a regulator of cell migration but the mechanism by which CCN2 regulates keratinocyte function is not well understood. In this article, we sought to elucidate the basic mechanism of CCN2-induced cell migration in human keratinocytes. Immunohistochemical staining was used to demonstrate that treatment with CCN2 induces a migratory phenotype through actin disassembly, spreading of lamellipodia and re-orientation of the Golgi. In vitro assays were used to show that CCN2-induced cell migration is dependent on FAK, RhoA and Cdc42, but independent of Rac1. CCN2-treated keratinocytes displayed increased Cdc42 activity and decreased RhoA activity up to 12 hours post-treatment, with upregulation of p190RhoGAP. An improved understanding of how CCN2 regulates cell migration may establish the foundation for future therapeutics in fibrotic and neoplastic diseases.


Cell Movement , Actins , Cell Polarity , Connective Tissue Growth Factor , Focal Adhesion Protein-Tyrosine Kinases , Guanine Nucleotide Exchange Factors , Humans , Keratinocytes , Repressor Proteins , cdc42 GTP-Binding Protein
9.
Br J Psychiatry ; 207(4): 339-45, 2015 Oct.
Article En | MEDLINE | ID: mdl-26159601

BACKGROUND: Although personality disorders are associated with increased overall mortality, less is known about cause of death and personality type. AIMS: To determine causes of mortality in ICD personality disorders. METHOD: Based on data from Swedish nationwide registers, individuals admitted to hospital with a primary diagnosis of personality disorder between 1987 and 2011 were followed with respect to mortality until 31 December 2011. Standardised mortality ratios (SMRs) with 95% confidence intervals and underlying causes of death were calculated. RESULTS: All-cause SMRs were increased, overall and in all clusters, for natural as well as unnatural causes of death. The overall SMR was 6.1 in women and 5.0 in men, as high as previously reported for anorexia nervosa, with higher rates in cluster B and mixed/other personality disorders. The SMR for suicide was 34.5 in women and 16.0 in men for cluster B disorders. Somatic and psychiatric comorbidity increased SMRs. CONCLUSIONS: The SMR was substantially increased for all personality disorder clusters. Thus, there was an increased premature mortality risk for all personality disorders, irrespective of category.


Cause of Death/trends , Hospitalization/statistics & numerical data , Personality Disorders/mortality , Suicide/statistics & numerical data , Adolescent , Adult , Comorbidity , Female , Humans , Male , Middle Aged , Risk Factors , Sweden/epidemiology , Young Adult
10.
Anticancer Res ; 35(6): 3253-65, 2015 Jun.
Article En | MEDLINE | ID: mdl-26026085

BACKGROUND: While carcinoma-associated fibroblasts (CAFs) support tumorigenesis, normal tissue fibroblasts suppress tumor progression. Mechanisms behind conversion of fibroblasts into a CAF phenotype are largely unrevealed. MATERIALS AND METHODS: Transwell co-cultures with fibroblasts in collagen gels and squamous-cell carcinoma (SCC) cells or normal oral keratinocytes (NOKs) in inserts. Differences in fibroblast global gene expression were analyzed using Affymetrix arrays and subsequent functional annotation and cluster analysis, as well as gene set enrichment analysis were performed. RESULTS: There were 52 up-regulated and 30 down-regulated transcript IDs (>2-fold, p<0.05) in fibroblasts co-cultured with SCC compared to NOKs. Functional analysis demonstrated an enrichment of collagen-related genes. There were similarities with gene sets reflecting a non-specific, innate-type response with activation of both interferon pathways and connective tissue turnover. CONCLUSION: There were distinct differences in fibroblast gene expression between the co-culture types. Many were in genes related to an innate-type of response and to connective tissue turnover.


Carcinoma, Squamous Cell/genetics , Cell Transformation, Neoplastic/genetics , Fibroblasts/pathology , Head and Neck Neoplasms/genetics , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Coculture Techniques , Fibroblasts/metabolism , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms/pathology , Humans , Keratinocytes/pathology , Neoplasm Proteins/biosynthesis
11.
J Burn Care Res ; 36(3): 405-13, 2015.
Article En | MEDLINE | ID: mdl-25162945

Years after injury, pruritus is a common and severe problem for many burn patients. However, its characteristics and consequences are often only partially described. The authors therefore performed a prospective detailed examination of burn- and individual-related factors and considered those in relation to pruritus severity. Sixty-seven consecutive burn patients were assessed during acute care, and at 3 and 12 months postburn regarding preburn psychiatric disorders, health-related quality of life, post traumatic stress disorder, and personality traits. Postburn pruritus was subsequently assessed 2 to 7 years postburn using the Questionnaire for Pruritus Assessment. Fifty-one individuals, 76% of the participants, reported burn pruritus any time after the burn. Thirty-three individuals, 49% of the participants, reported ongoing pruritus the last 2 months. Information on the characteristics of pruritus was obtained from 32 of these individuals. Most perceived pruritus as bothersome or annoying and as present every day, 16 (50%) were considered to have severe pruritus, and 11 (34 %) scratched themselves to the point of bleeding. In logistic regressions, this was independently related to TBSA full-thickness burn and health-related quality of life at 3 months, and to TBSA full thickness burn and the personality trait impulsiveness, respectively. About half of the previous burn patients experienced ongoing pruritus on an average of 4.5 years after injury, and half of them had severe pruritus. Scratching oneself to the point of bleeding is linked both to a certain personality and to pruritus. It is suspected that many patients are left without access to the best available treatment.


Burns/epidemiology , Pruritus/epidemiology , Survivors/statistics & numerical data , Adult , Burns/psychology , Comorbidity , Disease Progression , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prevalence , Pruritus/psychology , Severity of Illness Index , Surveys and Questionnaires , Survivors/psychology , Sweden/epidemiology , Young Adult
12.
Disabil Rehabil ; 37(6): 534-40, 2015.
Article En | MEDLINE | ID: mdl-24963942

PURPOSE: Personality disorders (PDs) are associated with significant distress, disability, and cause great difficulties in life. PDs have been suggested to influence adaptation after major burns, but the potential relationship has not been fully elucidated. This study aimed to describe the prevalence of PDs in 107 patients with major burn injury, and to identify the impact of PDs on perceived patient outcome assessed as health-related quality of life (HRQoL) one year after burn. METHODS: One burn-specific instrument (Burn Specific Health Scale-Brief (BSHS-B)) and two generic instruments (EuroQol Five Dimensions and Short Form 36 Health Survey) were used, and Psychiatric Axis I and II disorders were assessed one year post burn. RESULTS: This study identified an above normal prevalence of PDs among individuals afflicted by burn, and participants with PD had a significantly larger lifetime burden of Axis I disorders compared to participants without PD. Participants with PDs scored significantly lower than those without PD in the BSHS-B domain Skin involvement, and the effect of having a PD was related to the subscale Treatment regimens. There was no relationship between the presence of PD and generic HRQoL. CONCLUSIONS: An implication of these observations is that special rehabilitation efforts including more tailored interventions must be offered to these patients to ensure that the obstacles they perceive to caring for themselves in this respect are eliminated. IMPLICATIONS FOR REHABILITATION: This study identified an above normal prevalence of PDs among individuals afflicted by burn and these individuals reported poor burn-specific health-related quality of life. The identification of difficulties with compliance and endurance regarding daily skin care may cause negative consequences for optimal rehabilitation and underscore the importance of offering more tailored interventions in rehabilitation. Inflexible behavioral patterns related to the PD diagnosis imply the need for communication strategies by the rehabilitation team, which include flexibility, creativity, and diplomacy. There is a need for further research focusing on identifying the factors that facilitate the individual's own ability to take action and have control.


Burns/psychology , Burns/rehabilitation , Personality Disorders/complications , Quality of Life , Adult , Aged , Aged, 80 and over , Female , Health Status , Health Surveys , Humans , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Regression Analysis , Surveys and Questionnaires , Young Adult
13.
BJPsych Open ; 1(1): 54-55, 2015 Jun.
Article En | MEDLINE | ID: mdl-27703723

SUMMARY: Personality disorders (PDs) are associated with increased overall mortality. In patients hospitalised with a principal diagnosis of PD, this is observed for all clusters and for natural as well as unnatural causes of death. Data from Swedish nationwide registers were used to assess whether this was also true for the majority of patients diagnosed with PDs not severe enough to lead to hospitalisation. There was an increased mortality in all clusters, and for natural as well as unnatural death, also in patients treated as out-patients only, although not to the same extent as in those hospitalised. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

14.
J Burn Care Res ; 35(3): 243-50, 2014.
Article En | MEDLINE | ID: mdl-23666385

A severe burn not only affects the patients, but may also have a great impact on the lives of family members. It is known that family members of patients with burns experience psychological distress, but health-related quality of life (HRQoL) has not been studied in this group. The aim was to study predictors of HRQoL in family members of patients with burns. Forty-four family members of adult patients treated in a burn center, between 2000 and 2007, completed questionnaires during care, and at 3, 6, and 12 months after injury. HRQoL was assessed with the EuroQol 5D (EQ-5D), which consists of the dimensions: mobility, self-care, usual activities, pain, and anxiety/depression. The questionnaire generates an EQ-5D index and a visual analog scale (VAS) score. Overall, the EQ-5D index was similar to that of the general population. A slight improvement in HRQoL was found in the VAS scores and in the anxiety/depression dimension over time. In regression models, HRQoL was primarily predicted by earlier life events, symptoms of post-traumatic stress disorder, and HRQoL, assessed during the patients' hospitalization. In summary, HRQoL assessed with VAS scores increased slightly during the first year postburn, and early screening for life events and psychological symptoms, and HRQoL might be useful in identifying family members in need of support.


Burns/psychology , Family/psychology , Stress Disorders, Post-Traumatic/psychology , Stress, Psychological/epidemiology , Surveys and Questionnaires , Adult , Burns/diagnosis , Burns/therapy , Family Relations , Female , Humans , Injury Severity Score , Linear Models , Longitudinal Studies , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Prospective Studies , Sex Factors , Socioeconomic Factors , Stress Disorders, Post-Traumatic/physiopathology , Stress, Psychological/etiology , Sweden , Young Adult
15.
J Surg Res ; 185(2): e109-19, 2013 Dec.
Article En | MEDLINE | ID: mdl-24079812

BACKGROUND: CCN2 (previously known as connective tissue growth factor) is a multifunctional matricellular protein that has numerous effects on cell life and cell interactions with the connective tissue. Although the importance of CCN2 for the fibrotic process in wound healing has been well studied, the involvement of CCN2 in keratinocyte function has not yet been explored. Therefore, the aim of the present study was to investigate the role of CCN2 in the epidermis during wound healing. MATERIALS AND METHODS: Immunohistochemistry was done on sections from full-thickness porcine wounds. The effect of CCN2 on the migration of cultured human keratinocytes exposed to scratch wounds, the effect on phosphorylation of extracellular signal-related kinases (ERK), and the effect of adding inhibitors to the ERK/mitogen-activated protein kinase pathway to human keratinocytes were studied. RESULTS: The CCN2 protein was transiently expressed in vivo at the leading keratinocyte edge during re-epithelialization of full-thickness porcine wounds. In vitro, exogenous addition of CCN2 to human keratinocyte cultures regulated keratinocyte migration and resulted in phosphorylation of ERK. The addition of inhibitors of ERK/mitogen-activated protein kinase counteracted the effect of CCN2 on migration. CONCLUSIONS: CCN2 was transiently expressed at the leading keratinocyte edge in vivo. The biologic importance of this was supported in vitro, because CCN2 regulated human keratinocyte migration through activation of the Ras-mitogen-activated protein kinase kinase-ERK signal transduction pathway.


Cell Movement/physiology , Connective Tissue Growth Factor/metabolism , Keratinocytes/metabolism , MAP Kinase Signaling System/physiology , Wound Healing/physiology , Wounds and Injuries/metabolism , Animals , Cell Proliferation , Cells, Cultured , Epidermal Cells , Epidermis/injuries , Epidermis/metabolism , Female , Fluorescent Antibody Technique , Humans , In Vitro Techniques , Mitogen-Activated Protein Kinases/metabolism , Sus scrofa , Wounds and Injuries/pathology , ras Proteins/metabolism
16.
Exp Cell Res ; 319(19): 2938-46, 2013 Nov 15.
Article En | MEDLINE | ID: mdl-23988606

BACKGROUND: CCN2, (a.k.a. connective tissue growth factor and CTGF) has emerged as a regulator of cell migration. While the importance of CCN2 for the fibrotic process in wound healing has been well studied, the effect of CCN2 on keratinocyte function is not well understood. In this study, we investigated the mechanism behind CCN2-driven keratinocyte adhesion and migration. MATERIALS AND METHODS: Adhesion assays were performed by coating wells with 10 µg/ml fibronectin (FN) or phosphate-buffered saline (PBS). Keratinocytes were seeded in the presence or absence of 200 ng/ml CCN2, 5 mmol/l ethylenediaminetetraacetic acid, 10 mmol/l cations, 500 µl arginine-glycine-aspartic acid (RGD), 500 µM arginine-glycine-glutamate-serine (RGES), and 10 µg/ml anti-integrin blocking antibodies. Migration studies were performed using a modified Boyden chamber assay. Quantitative PCR was used to study the effect of CCN2 on integrin subunit mRNA expression. To block intracellular pathways, keratinocytes were pretreated with 20 µM PD98059 (MEK-1 inhibitor) or 20 µM PF573228 (FAK inhibitor) for 60 min prior the addition of CCN2. Western blot was used to measure CCN2, p-ERK1/2, and ERK1/2. RESULTS: CCN2 enhanced keratinocyte adhesion to fibronectin via integrin α5ß1. The addition of anti-integrin α5ß1 antibodies reduced CCN2-mediated keratinocyte migration. In addition, CCN2 regulated mRNA and protein expression of integrin subunits α5 and ß1. CCN2 activated the FAK-MAPK signaling pathway, and pretreatment with MEK1-specific inhibitor PD98059 markedly reduced CCN2-induced keratinocyte migration. CONCLUSIONS: Our results demonstrate that CCN2 enhances keratinocyte adhesion and migration through integrin α5ß1 and activation of the FAK-MAPK signaling cascade.


Cell Movement/physiology , Connective Tissue Growth Factor/metabolism , Integrin alpha5beta1/metabolism , Keratinocytes/metabolism , Cell Adhesion/physiology , Cells, Cultured , Connective Tissue Growth Factor/genetics , Fibronectins/metabolism , Humans , Integrin alpha5beta1/genetics , Keratinocytes/cytology , Phosphorylation/physiology , Signal Transduction/physiology
17.
Anticancer Res ; 33(8): 3113-8, 2013 Aug.
Article En | MEDLINE | ID: mdl-23898067

BACKGROUND: To investigate possible differences in the effects of soluble factors from oral squamous cell carcinoma (SCC) cells (UT-SCC-87) and normal oral keratinocytes (NOK) on fibroblast expression of genes involved in tumor stroma turnover. MATERIALS AND METHODS: Transwell co-cultures with fibroblasts in collagen gels, and SCC cells or NOK in inserts were carried out. Fibroblast gene expression was measured with real-time polymerase chain reaction (PCR). RESULTS: The expression of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) was up-regulated in co-cultures with SCC cells but not with NOK. In contrast, both SCC cells and NOK regulated matrix metalloproteinase-1 (MMP1) and -3, and tissue inhibitor of metalloproteinases-2 (TIMP2) and -3 to a similar extent, while MMP2 and TIMP1 were largely unaffected. Interleukin 1 alpha (IL1α) up-regulated both MMP1 and MMP3 and down-regulated PAI-1, TIMP2 and -3. CONCLUSION: SCC and NOK regulate fibroblast expression of genes involved in tumor stroma turnover differentially in vitro. These observations may contribute to a better understanding of the mechanisms behind extracellular matrix turnover in tumors.


Carcinoma, Squamous Cell/metabolism , Head and Neck Neoplasms/metabolism , Keratinocytes/metabolism , Plasminogen Activator Inhibitor 1/metabolism , Urokinase-Type Plasminogen Activator/metabolism , Adult , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Coculture Techniques , Female , Fibroblasts/metabolism , Fibroblasts/pathology , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Humans , Keratinocytes/pathology , Male , Plasminogen Activator Inhibitor 1/genetics , Squamous Cell Carcinoma of Head and Neck , Urokinase-Type Plasminogen Activator/genetics
18.
J Trauma Acute Care Surg ; 74(5): 1321-6, 2013 May.
Article En | MEDLINE | ID: mdl-23609285

BACKGROUND: The Burn Specific Health Scale Brief (BSHS-B), which is the only multidimensional measure to evaluate burn-specific aspects of health status, has previously been validated in several languages across the world. However, the stability of the underlying construct was not cross-culturally evaluated. The current study reports on measurement invariance across two samples of Swedish- and Dutch- speaking patients with burns. METHODS: In a prospective study, 231 and 275 Swedish and Dutch-Belgian patients with burns, completed the BSHS-B at 9 or 12 months, respectively, after burn. Using a multigroup confirmatory factor analysis, measurement invariance across languages (Swedish and Dutch) was tested. RESULTS: The results of the confirmatory factor analysis in the total sample revealed that the scale structure for the earlier reported three-factor structure and the original nine-factor structure was adequate. However, an eight-factor structure in which hand function and simple abilities were merged provided the best fit. This structure was used to test measurement invariance across the two language groups. The two-group outcomes testing measurement invariance across Swedish- and Dutch-speaking patients indicated a stable, configural invariance. CONCLUSION: The BSHS-B seems to function uniformly across both language groups. The BSHS-B can be used to compare cross-cultural results in both countries.


Burns/psychology , Adult , Cross-Cultural Comparison , Factor Analysis, Statistical , Female , Humans , Male , Middle Aged , Netherlands , Prospective Studies , Quality of Life/psychology , Reproducibility of Results , Surveys and Questionnaires/standards , Sweden
19.
J Trauma Acute Care Surg ; 74(3): 855-61, 2013 Mar.
Article En | MEDLINE | ID: mdl-23425748

BACKGROUND: The plasma concentration of natriuretic peptide type B (BNP) or NT-proBNP (P-BNP or P-NT-proBNP) reflects cardiac load. In intensive care unit settings and in chronic inflammation, it is also affected by non-heart-related mechanisms. It has been suggested to be a marker of hydration after severe burns and to predict outcome in critically ill patients, but results are contradictory. We therefore measured P-NT-proBNP after severe burns and related it to injury related variables and to organ dysfunction. METHODS: Fifty consecutive patients with a burn size greater than 10% were studied for the first 2 weeks. P-NT-proBNP changes were analyzed in relation to burn size, age, changes in body weight, C-reactive protein in plasma, and organ function assessed as Sequential Organ Failure Assessment (SOFA) scores RESULTS: P-NT-proBNP showed large day-to-day and between patient variations. Daily change in body weight correlated with P-NT-proBNP only on Day 2, when maximum mobilization of edema occurred. Thereafter, P-NT-proBNP correlated with C-reactive protein in plasma as well as with SOFA scores. Burn size correlated with maximal weight change, which in turn correlated with both time for and value of maximum P-NT-proBNP. Maximal P-NT-proBNP was related to mortality and correlated better with SOFA score on Day 14 compared with age and burn size. In linear regressions, together with age at injury and total body surface area, P-NT-proBNP assessed on Days 3 to 8 was an independent predictor for every subsequent SOFA score measured one or more days later up to Day 14. CONCLUSION: P-NT-proBNP exhibited considerable interindividual and day-to-day variations. Values were related to mortality, burn size, water accumulation, posttraumatic response, and organ function. Maximum P-NT-proBNP correlated stronger with length of stay and with organ function on Day 14, compared with age and burn size. High values in Days 3 through 8 were also independent predictors of subsequent organ function up to 2 weeks after injury. LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level III.


Burn Units , Burns/blood , Natriuretic Peptide, Brain/blood , Adolescent , Adult , Burns/diagnosis , Burns/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Prognosis , Retrospective Studies , Sweden/epidemiology , Trauma Severity Indices , Young Adult
20.
J Adv Nurs ; 69(2): 384-93, 2013 Feb.
Article En | MEDLINE | ID: mdl-22509932

AIM: To report a study of predictors of psychological symptoms in family members of patients with burns. BACKGROUND: Family members are important as a source of social support for patients undergoing prolonged rehabilitation. Little is known about psychological symptoms of family members of patients with burns, especially in the long term. DESIGN: The design of the study was prospective and longitudinal. METHODS: Forty-four family members of adult patients treated in a burn centre between 2000-2007 completed questionnaires during care and at 3, 6, and 12 months after injury. Psychological symptoms were assessed with the Hospital Anxiety and Depression Scale. Predictors for anxiety and depression were explored in regression analyses. RESULTS: The mean scores indicated normal to mild symptoms in general. Moderate and severe symptom levels during care and at 12 months were demonstrated on the anxiety subscale by 15/44 and 5/39, respectively, and on the depression subscale by 5/44 and 0/39 of the family members, respectively. In the final regression models, the primary predictor was psychological symptoms at the previous assessment. Other predictors were previous life events, age, and the coping strategy avoidance. CONCLUSION: Family members of patients with burns demonstrate normal to mild levels of psychological symptoms that decrease over time. One-third show moderate to severe anxiety symptoms during care and may benefit from counselling. Previous symptoms predict later symptoms, indicating that screening with a validated instrument is useful. The results provide guidance for nurses in assessing and planning adequate interventions for family members.


Anxiety Disorders/etiology , Burns/psychology , Depressive Disorder/etiology , Family/psychology , Adaptation, Psychological , Adolescent , Adult , Aged , Aged, 80 and over , Burns/nursing , Counseling , Female , Humans , Male , Middle Aged , Prospective Studies , Stress, Psychological/etiology , Young Adult
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