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2.
Eur Heart J Open ; 2(6): oeac069, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36600882

ABSTRACT

Aims: End-stage renal disease (ESRD) treated by chronic hemodialysis (HD) is associated with poor cardiovascular (CV) outcomes, with no available evidence-based therapeutics. A multiplexed proteomic approach may identify new pathophysiological pathways associated with CV outcomes, potentially actionable for precision medicine. Methods and results: The AURORA trial was an international, multicentre, randomized, double-blind trial involving 2776 patients undergoing maintenance HD. Rosuvastatin vs. placebo had no significant effect on the composite primary endpoint of death from CV causes, nonfatal myocardial infarction or nonfatal stroke. We first compared CV risk-matched cases and controls (n = 410) to identify novel biomarkers using a multiplex proximity extension immunoassay (276 proteomic biomarkers assessed with OlinkTM). We replicated our findings in 200 unmatched cases and 200 controls. External validation was conducted from a multicentre real-life Danish cohort [Aarhus-Aalborg (AA), n = 331 patients] in which 92 OlinkTM biomarkers were assessed. In AURORA, only N-terminal pro-brain natriuretic peptide (NT-proBNP, positive association) and stem cell factor (SCF) (negative association) were found consistently associated with the trial's primary outcome across exploration and replication phases, independently from the baseline characteristics. Stem cell factor displayed a lower added predictive ability compared with NT-ProBNP. In the AA cohort, in multivariable analyses, BNP was found significantly associated with major CV events, while higher SCF was associated with less frequent CV deaths. Conclusions: Our findings suggest that NT-proBNP and SCF may help identify ESRD patients with respectively high and low CV risk, beyond classical clinical predictors and also point at novel pathways for prevention and treatment.

3.
Scand J Surg ; 110(1): 86-92, 2021 Mar.
Article in English | MEDLINE | ID: mdl-31537176

ABSTRACT

BACKGROUND AND AIMS: Long-term prospective data on patient-reported outcome after surgical treatment of pelvic ring injuries are scarce. This study aimed at describing results at 5 years post-surgery using validated outcome measures. PATIENTS AND METHODS: Patients admitted for surgical treatment of pelvic ring injuries were prospectively included and asked to report their outcome at 1, 2 and 5 years post-surgery using two patient-reported outcome measures: the generic Short-Form 36 and the condition-specific pelvic discomfort index. Data were evaluated using mixed-effects linear models. RESULTS: There were 108 patients (68 males and 40 females), mean age 38 years. Injury type according to the AO/OTA-classification was B-type in 68 patients and C-type in 40 patients. No domain of the Short-Form 36 reached norm values at 5 years post-surgery. Females reported a worse outcome than males concerning general health (p < 0.01) at 5 years. Recovery of physical function (p < 0.01), mental health (p = 0.04), and pain (p = 0.01) was observed for males at 5 years compared to earlier assessments, while females on the contrary described more pain at this time-point (p = 0.03). Mean pelvic discomfort index at 5 years was 27, indicating moderate residual pelvic discomfort overall. Males reported less pelvic discomfort than females at 5 years (p = 0.02) and improved when compared to results at 2 years (p = 0.02), while females did not. Influence of age, fracture type, and presence of associated injuries on patient-reported outcome was limited. CONCLUSION: Surgically treated pelvic ring injuries are associated with long-standing negative effects on patient-reported outcome. Males report a better outcome than females at 5 years post-surgery.


Subject(s)
Fractures, Bone/surgery , Patient Reported Outcome Measures , Pelvic Bones/injuries , Pelvic Bones/surgery , Adult , Female , Fracture Fixation, Internal , Humans , Male , Pain Measurement , Prospective Studies , Quality of Life
4.
Bioconjug Chem ; 24(10): 1721-32, 2013 Oct 16.
Article in English | MEDLINE | ID: mdl-23981119

ABSTRACT

In the current work we characterize the uptake mechanism of two NickFect family members, NF51 and NF1, related to the biological activity of transfected plasmid DNA (pDNA). Both vectors condense pDNA into small negatively charged nanoparticles that transfect HeLa cells with equally high efficacy and the delivery is mediated by SCARA3 and SCARA5 receptors. NF1 condenses DNA into less homogeneous and less stable nanoparticles than NF51. NF51/pDNA nanoparticles enter the cells via macropinocytosis, while NF1/pDNA complexes use clathrin- or caveolae-mediated endocytosis and macropinocytosis. Analysis of separated endosomal compartments uncovered lysomotropic properties of NF51 that was also proven by cotransfection with chloroquine. In summary we characterize how radical modifications in peptides, such as introducing a kink in the structure of NF51 or including extra negative charge by phospho-tyrosine substitution in NF1, resulted in equally high efficacy for gene delivery, although this efficacy is achieved by using differential transfection pathways.


Subject(s)
DNA/administration & dosage , Peptides/chemistry , Plasmids/administration & dosage , Transfection , Clathrin/metabolism , DNA/chemistry , DNA/genetics , Endocytosis , HeLa Cells , Humans , Nanoparticles/chemistry , Peptides/chemical synthesis , Peptides/metabolism , Plasmids/chemistry , Plasmids/genetics
5.
Arch Environ Occup Health ; 68(3): 145-52, 2013.
Article in English | MEDLINE | ID: mdl-23566321

ABSTRACT

This study investigated self-image and coping ability in a group of patients with symptoms from indoor environment. A follow-up questionnaire was sent to 239 patients previously referred with nonspecific building-related symptoms at University Hospital in Umeå, Sweden. One hundred seventy-four women and 14 men answered and the patient group rated their self-image as more spontaneous, more positive, and less negative than a control group. The patient group rated higher on the cognitive scale in the Coping Resources Inventory (CRI) than the control group. The female patients had an increased risk of not being able to work associated with a low score on negative self-image. The authors conclude that certain personality traits may be potential risk factors that increase the probability of encountering and experiencing stressful work situations. The resulting stress may increase workers' susceptibility to indoor environment exposure.


Subject(s)
Adaptation, Psychological , Occupational Diseases/psychology , Self Concept , Sick Building Syndrome/psychology , Adult , Case-Control Studies , Female , Follow-Up Studies , Humans , Male , Occupational Diseases/epidemiology , Personality , Risk Assessment , Risk Factors , Sick Building Syndrome/epidemiology , Surveys and Questionnaires , Sweden/epidemiology
6.
Article in English | MEDLINE | ID: mdl-24404405

ABSTRACT

Typically, genome-wide association studies consist of regressing the phenotype on each SNP separately using an additive genetic model. Although statistical models for recessive, dominant, SNP-SNP, or SNP-environment interactions exist, the testing burden makes an evaluation of all possible effects impractical for genome-wide data. We advocate a two-step approach where the first step consists of a filter that is sensitive to different types of SNP main and interactions effects. The aim is to substantially reduce the number of SNPs such that more specific modeling becomes feasible in a second step. We provide an evaluation of a statistical learning method called "gradient boosting machine" (GBM) that can be used as a filter. GBM does not require an a priori specification of a genetic model, and permits inclusion of large numbers of covariates. GBM can therefore be used to explore multiple GxE interactions, which would not be feasible within the parametric framework used in GWAS. We show in a simulation that GBM performs well even under conditions favorable to the standard additive regression model commonly used in GWAS, and is sensitive to the detection of interaction effects even if one of the interacting variables has a zero main effect. The latter would not be detected in GWAS. Our evaluation is accompanied by an analysis of empirical data concerning hair morphology. We estimate the phenotypic variance explained by increasing numbers of highest ranked SNPs, and show that it is sufficient to select 10K-20K SNPs in the first step of a two-step approach.

7.
Clin Pharmacol Ther ; 87(5): 572-8, 2010 May.
Article in English | MEDLINE | ID: mdl-20375999

ABSTRACT

Well-characterized genes that affect warfarin metabolism (cytochrome P450 (CYP) 2C9) and sensitivity (vitamin K epoxide reductase complex 1 (VKORC1)) explain one-third of the variability in therapeutic dose before the international normalized ratio (INR) is measured. To determine genotypic relevance after INR becomes available, we derived clinical and pharmacogenetic refinement algorithms on the basis of INR values (on day 4 or 5 of therapy), clinical factors, and genotype. After adjusting for INR, CYP2C9 and VKORC1 genotypes remained significant predictors (P < 0.001) of warfarin dose. The clinical algorithm had an R(2) of 48% (median absolute error (MAE): 7.0 mg/week) and the pharmacogenetic algorithm had an R(2) of 63% (MAE: 5.5 mg/week) in the derivation set (N = 969). In independent validation sets, the R(2) was 26-43% with the clinical algorithm and 42-58% when genotype was added (P = 0.002). After several days of therapy, a pharmacogenetic algorithm estimates the therapeutic warfarin dose more accurately than one using clinical factors and INR response alone.


Subject(s)
Genetic Variation/genetics , International Normalized Ratio/standards , Systems Integration , Warfarin/administration & dosage , Aged , Aryl Hydrocarbon Hydroxylases/genetics , Cohort Studies , Cytochrome P-450 CYP2C9 , Dose-Response Relationship, Drug , Female , Genotype , Humans , International Normalized Ratio/methods , Male , Middle Aged , Mixed Function Oxygenases/genetics , Pharmacogenetics/methods , Vitamin K Epoxide Reductases , Warfarin/pharmacokinetics
8.
Nucleic Acids Res ; 38(13): 4296-312, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20338882

ABSTRACT

The retinoic acid receptor-related orphan receptor (ROR) alpha has been demonstrated to regulate lipid metabolism. We were interested in the ROR alpha 1 dependent physiological functions in skeletal muscle. This major mass organ accounts for approximately 40% of the total body mass and significant levels of lipid catabolism, glucose disposal and energy expenditure. We utilized the strategy of targeted muscle-specific expression of a truncated (dominant negative) ROR alpha 1 Delta DE in transgenic mice to investigate ROR alpha 1 signaling in this tissue. Expression profiling and pathway analysis indicated that ROR alpha influenced genes involved in: (i) lipid and carbohydrate metabolism, cardiovascular and metabolic disease; (ii) LXR nuclear receptor signaling and (iii) Akt and AMPK signaling. This analysis was validated by quantitative PCR analysis using TaqMan low-density arrays, coupled to statistical analysis (with Empirical Bayes and Benjamini-Hochberg). Moreover, westerns and metabolic profiling were utilized to validate the genes, proteins and pathways (lipogenic, Akt, AMPK and fatty acid oxidation) involved in the regulation of metabolism by ROR alpha 1. The identified genes and pathways were in concordance with the demonstration of hyperglycemia, glucose intolerance, attenuated insulin-stimulated phosphorylation of Akt and impaired glucose uptake in the transgenic heterozygous Tg-ROR alpha 1 Delta DE animals. In conclusion, we propose that ROR alpha 1 is involved in regulating the Akt2-AMPK signaling pathways in the context of lipid homeostasis in skeletal muscle.


Subject(s)
Muscle, Skeletal/metabolism , Nuclear Receptor Subfamily 1, Group F, Member 1/metabolism , AMP-Activated Protein Kinases/metabolism , Acetyl-CoA Carboxylase/metabolism , Animals , Blood Glucose , Cell Line , Fatty Acids/biosynthesis , Gene Expression Profiling , Glucose Intolerance/metabolism , Humans , Insulin/pharmacology , Liver X Receptors , Mice , Mice, Transgenic , Muscle, Skeletal/enzymology , Nuclear Receptor Subfamily 1, Group F, Member 1/genetics , Nuclear Receptor Subfamily 1, Group F, Member 1/physiology , Orphan Nuclear Receptors/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Sequence Deletion , Signal Transduction , Sterol Regulatory Element Binding Protein 1/metabolism , Trans-Activators/metabolism , Transcription Factors
9.
Int J Obes (Lond) ; 34(3): 524-36, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20029376

ABSTRACT

OBJECTIVE: The Ski gene regulates skeletal muscle differentiation in vitro and and in vivo. In the c-Ski overexpression mouse model there occurs marked skeletal muscle hypertrophy with decreased adipose tissue mass. In this study, we have investigated the underlying molecular mechanisms responsible for the increased skeletal muscle and decreased adipose tissue mass in the c-Ski mouse. APPROACH: Growth and body composition analysis (tissue weights and dual energy X-ray absorptiometry) coupled with skeletal muscle and white adipose gene expression and metabolic phenotyping in c-Ski mice and wild-type (WT) littermate controls was performed. RESULTS: The growth and body composition studies confirmed the early onset of accelerated body growth, with increased lean mass and decreased fat mass in the c-Ski mice. Gene expression analysis in skeletal muscle from c-Ski mice compared with WT mice showed significant differences in myogenic and lipogenic gene expressions that are consistent with the body composition phenotype. Skeletal muscle of c-Ski mice had significantly repressed Smad1, 4, 7 and myostatin gene expression and elevated myogenin, myocyte enhancer factor 2, insulin-like growth factor-1 receptor and insulin-like growth factor-2 expression. Strikingly, expression of the mRNAs encoding the master lipogenic regulators, sterol-regulatory enhancer binding protein 1c (SREBP1c), and the nuclear receptor liver X-receptor-alpha, and their downstream target genes, SCD-1 and FAS, were suppressed in skeletal muscle of c-Ski mice, as were the expressions of other nuclear receptors involved in adipogenesis and metabolism, such as peroxisome proliferator-activated receptor-gamma, glucocorticoid receptor and retinoic acid receptor-related orphan receptor-alpha. Transfection analysis demonstrated Ski repressed the SREBP1c promoter. Moreover, palmitate oxidation and oxidative enzyme activity was increased in skeletal muscle of c-Ski mice. These results suggest that the Ski phenotype involves attenuated lipogenesis, decreased myostatin signalling, coupled to increased myogenesis and fatty acid oxidation. CONCLUSION: Ski regulates several genetic programs and signalling pathways that regulate skeletal muscle and adipose mass to influence body composition development, suggesting that Ski may have a role in risk for obesity and metabolic disease.


Subject(s)
Body Composition/genetics , DNA-Binding Proteins/genetics , Lipogenesis/genetics , Muscle, Skeletal/physiology , Proto-Oncogene Proteins/genetics , Animals , Body Composition/physiology , DNA-Binding Proteins/physiology , Fatty Acids/metabolism , Gene Silencing , Growth/physiology , Mice , Mice, Transgenic , Myostatin/metabolism , Proto-Oncogene Proteins/physiology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sterol Regulatory Element Binding Protein 1/metabolism , Thinness/genetics , Thinness/metabolism
10.
N Engl J Med ; 360(8): 753-64, 2009 Feb 19.
Article in English | MEDLINE | ID: mdl-19228618

ABSTRACT

BACKGROUND: Genetic variability among patients plays an important role in determining the dose of warfarin that should be used when oral anticoagulation is initiated, but practical methods of using genetic information have not been evaluated in a diverse and large population. We developed and used an algorithm for estimating the appropriate warfarin dose that is based on both clinical and genetic data from a broad population base. METHODS: Clinical and genetic data from 4043 patients were used to create a dose algorithm that was based on clinical variables only and an algorithm in which genetic information was added to the clinical variables. In a validation cohort of 1009 subjects, we evaluated the potential clinical value of each algorithm by calculating the percentage of patients whose predicted dose of warfarin was within 20% of the actual stable therapeutic dose; we also evaluated other clinically relevant indicators. RESULTS: In the validation cohort, the pharmacogenetic algorithm accurately identified larger proportions of patients who required 21 mg of warfarin or less per week and of those who required 49 mg or more per week to achieve the target international normalized ratio than did the clinical algorithm (49.4% vs. 33.3%, P<0.001, among patients requiring < or = 21 mg per week; and 24.8% vs. 7.2%, P<0.001, among those requiring > or = 49 mg per week). CONCLUSIONS: The use of a pharmacogenetic algorithm for estimating the appropriate initial dose of warfarin produces recommendations that are significantly closer to the required stable therapeutic dose than those derived from a clinical algorithm or a fixed-dose approach. The greatest benefits were observed in the 46.2% of the population that required 21 mg or less of warfarin per week or 49 mg or more per week for therapeutic anticoagulation.


Subject(s)
Algorithms , Anticoagulants/administration & dosage , Aryl Hydrocarbon Hydroxylases/genetics , Mixed Function Oxygenases/genetics , Pharmacogenetics , Warfarin/administration & dosage , Adolescent , Adult , Aged , Aged, 80 and over , Child , Cohort Studies , Cytochrome P-450 CYP2C9 , Dose-Response Relationship, Drug , Female , Genotype , Humans , International Normalized Ratio , Least-Squares Analysis , Male , Middle Aged , Polymorphism, Single Nucleotide , Vitamin K Epoxide Reductases , Young Adult
11.
Ann Rheum Dis ; 68(11): 1746-53, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19019891

ABSTRACT

OBJECTIVES: To confirm and define the genetic association of STAT4 and systemic lupus erythematosus (SLE), investigate the possibility of correlations with differential splicing and/or expression levels, and genetic interaction with IRF5. METHODS: 30 tag SNPs were genotyped in an independent set of Spanish cases and controls. SNPs surviving correction for multiple tests were genotyped in five new sets of cases and controls for replication. STAT4 cDNA was analysed by 5'-RACE PCR and sequencing. Expression levels were measured by quantitative PCR. RESULTS: In the fine mapping, four SNPs were significant after correction for multiple testing, with rs3821236 and rs3024866 as the strongest signals, followed by the previously associated rs7574865, and by rs1467199. Association was replicated in all cohorts. After conditional regression analyses, two major independent signals, represented by SNPs rs3821236 and rs7574865, remained significant across the sets. These SNPs belong to separate haplotype blocks. High levels of STAT4 expression correlated with SNPs rs3821236, rs3024866 (both in the same haplotype block) and rs7574865 but not with other SNPs. Transcription of alternative tissue-specific exons 1, indicating the presence of tissue-specific promoters of potential importance in the expression of STAT4, was also detected. No interaction with associated SNPs of IRF5 was observed using regression analysis. CONCLUSIONS: These data confirm STAT4 as a susceptibility gene for SLE and suggest the presence of at least two functional variants affecting levels of STAT4. The results also indicate that the genes STAT4 and IRF5 act additively to increase the risk for SLE.


Subject(s)
Interferon Regulatory Factors/genetics , Lupus Erythematosus, Systemic/genetics , STAT4 Transcription Factor/genetics , Adult , Alternative Splicing , Case-Control Studies , Child , Gene Expression Regulation , Genetic Predisposition to Disease , Genotype , Humans , Lupus Erythematosus, Systemic/blood , Polymorphism, Single Nucleotide , RNA, Messenger/genetics , STAT4 Transcription Factor/blood
12.
Dig Liver Dis ; 40(5): 355-60, 2008 May.
Article in English | MEDLINE | ID: mdl-18291729

ABSTRACT

BACKGROUND AND STUDY AIMS: Intestinal metaplasia, especially type III intestinal metaplasia is considered to be a precursor of gastric cancer and because of this it is suggested that these patients should be followed up by gastroscopy. Our aim was to find out the prevalence of intestinal metaplasia and its subtypes, the appearance of intestinal metaplasia in different parts of the stomach, and the correlation of intestinal metaplasia with other histological and endoscopic findings. PATIENTS AND METHODS: A total of 505 consecutive patients, with a mean age+/-S.D. of 54+/-16 years, had two biopsies taken from the antrum, two from the corpus, and, in 272 cases, two from the angulus of the stomach during routine upper gastrointestinal endoscopy. Histological specimens were examined according to the updated Sydney system and the ones with incomplete intestinal metaplasia were further stained for sulphomucin visualisation to divide these into types II and III. RESULTS: The overall prevalence of intestinal metaplasia was 19%. The prevalence of type III intestinal metaplasia was 2.8%, type II intestinal metaplasia was 4.4%, and complete intestinal metaplasia was 11%. Intestinal metaplasia was found most frequently in the antrum and also in the angulus. There was no type III intestinal metaplasia in the corpus. Intestinal metaplasia was found more frequently in patients with atrophic gastritis than in other patients (p < 0.01). The patients with type III intestinal metaplasia were older than the patients without intestinal metaplasia (mean age of 73 versus 51 years). None of the patients with a totally normal appearing stomach in upper gastrointestinal endoscopy had type II or type III intestinal metaplasia. CONCLUSION: The relatively high overall prevalence of intestinal metaplasia was found in patients referred for gastroscopy in a region of low prevalence of Helicobacter pylori infection and low incidence of gastric cancer. Intestinal metaplasia was most often found in the antrum and angulus. Type III intestinal metaplasia was more prevalent in older patients and intestinal metaplasia was more frequently found in patients with atrophic gastritis. Normal appearing endoscopic finding seems to exclude type II and III intestinal metaplasia.


Subject(s)
Intestinal Neoplasms/epidemiology , Intestines/pathology , Stomach Neoplasms/epidemiology , Stomach/pathology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Biopsy , Endoscopy, Gastrointestinal , Female , Finland/epidemiology , Humans , Intestinal Neoplasms/pathology , Male , Metaplasia/epidemiology , Metaplasia/pathology , Middle Aged , Neoplasm Staging , Prevalence , Prognosis , Retrospective Studies , Risk Factors , Sex Distribution , Stomach Neoplasms/pathology
13.
Int Arch Occup Environ Health ; 81(7): 805-12, 2008 Jul.
Article in English | MEDLINE | ID: mdl-17924130

ABSTRACT

OBJECTIVES: The aim of this study was to describe and analyse the medical and social prognoses of patients with non-specific building-related symptoms. METHODS: A follow-up questionnaire focusing on current medical and social status, care, treatment, other actions taken and personality traits was sent to 239 patients with non-specific building-related symptoms assessed during the period between 1986 and 1998 at University Hospital in Umeå, Sweden. The response rate was 79%. RESULTS: Fatigue, irritation of the eyes, and facial erythema were the most common weekly symptoms reported at follow-up. As females constituted 92% of the respondents, statistical analyses were restricted to women. The level and severity of symptoms decreased over time, although nearly half of the patients claimed that symptoms were more or less unchanged after 7 years or more, despite actions taken. Twenty-five percent of the patients were on the sick-list, and 20% drew disability pension due to persistent symptoms at follow-up. The risk of having no work capabilities at follow-up was significantly increased if the time from onset to first visit at the hospital clinic was more than 1 year. This risk was also significantly higher if the patient at the first visit had five or more symptoms. All risk assessments were adjusted for length of follow-up. Symptoms were often aggravated by different situations in everyday life. CONCLUSIONS: Long-lasting symptoms aggravated by environmental factors exist within this group of patients. The results support that early and comprehensive measures for rehabilitation are essential for the patients.


Subject(s)
Sick Building Syndrome/physiopathology , Sick Leave/statistics & numerical data , Adult , Female , Follow-Up Studies , Humans , Male , Medical Records , Middle Aged , Prognosis , Rehabilitation, Vocational , Sick Building Syndrome/epidemiology , Surveys and Questionnaires , Sweden/epidemiology
14.
Article in English | MEDLINE | ID: mdl-16261950

ABSTRACT

AIM: Several studies have shown a negative correlation between cancer and atopy-related diseases. There are also a few reports of a positive relationship. We wanted to further evaluate these relationships in a prospective study. SUBJECTS AND METHODS: The incidence of malignant diseases among adult patients with atopy-related diseases (asthma, rhinitis, urticaria, eczema etc; n = 13811), who had been skin prick tested in 1976-1999 was compared with the incidence in the general population. Expected cancer incidence from the date of skin prick testing up to 1999 was obtained from cause-, sex-, calendar-year-, and 5-year-age-group specific incidence rates for the county. These rates were calculated from cancer incidence and population counts obtained from the Swedish Cancer Register. The 95% confidence intervals (CIs) for cause-specific standardized incidence ratios (SIRs) were calculated. Skin prick tests were performed with Dermatophagoides pteronyssinus, horse, dog, cat, timothy, mugwort, birch, and Cladosporium. Patients having one or several positive skin prick test reactions (> or = 2+) were regarded as atopics. RESULTS: 119 cases of cancer occurred among 6224 atopic individuals (SIR 1.0) compared with 216 cases (SIR 0.94, CI 0.82-1.08) among 6358 non-atopics. There was a slight excess of Hodgkin's lymphoma cases among atopic men (SIR 4.03, 95% CI 1-10.3), and of non Hodgkin lymphoma cases among atopic women (SIR 4.52, 95% CI 1.23-11.6). However, a large number of comparisons were made which can have caused random findings. CONCLUSIONS: The results showed no associations between atopy or allergic symptoms, and subsequent cancer risk, but supported the theory that type-I allergy is not related to cancer risk.


Subject(s)
Hypersensitivity, Immediate/diagnosis , Hypersensitivity, Immediate/epidemiology , Neoplasms/epidemiology , Skin Tests , Adolescent , Adult , Asthma/diagnosis , Asthma/epidemiology , Dermatitis, Atopic/diagnosis , Dermatitis, Atopic/epidemiology , Female , Follow-Up Studies , Hodgkin Disease/epidemiology , Humans , Incidence , Lymphoma, Non-Hodgkin/epidemiology , Male , Middle Aged , Prospective Studies , Rhinitis, Allergic, Perennial/diagnosis , Rhinitis, Allergic, Perennial/epidemiology , Risk Factors , Sex Distribution , Sweden/epidemiology , Urticaria/diagnosis , Urticaria/epidemiology
15.
Community Dent Oral Epidemiol ; 33(6): 427-37, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16262610

ABSTRACT

OBJECTIVES: In Sweden, many patients with symptoms allegedly caused by their dental materials have exchanged their restorations, but the effects of the exchange have been insufficiently investigated. Therefore, the aim of the study was to describe the change in health over time for these patients and the hypothesis was that the patients could be divided based on their symptoms and that the ability to recover differs between these groups. Furthermore, we also examined if other factors such as replacement of dental restorative materials and follow-up time had any impact on the perceived health status. METHODS: A questionnaire was sent to 614 patients who had been referred to the School of Dentistry, Umeå, Sweden, with symptoms allegedly caused by dental restorative materials. The response rate was 55%. RESULTS: The risk of having any further complaints was higher for patients with complex symptoms (P = 0.03) and these patients had exchanged their restorations to a significantly larger extent than the others (P = 0.03). The remaining complaints was more frequent among men (P = 0.02). Exchange of dental restorative materials had no significant impact on the ability to recover completely. However, the patients who had exchanged their restorations completely perceived a significantly larger alleviation of their symptoms than the others (P < 0.01), although the frequency of most of the symptoms had increased. CONCLUSIONS: Patients with complex symptoms had a more unfavorable long-term prognosis concerning persistent complaints than those with localized symptoms only. Furthermore, the results indicate that the patients might experience health improvements after removal of their dental restorative materials. The reason for this improvement, however, is unclear. Further analyses regarding other possible explanations than the 'odontological/medical' are needed.


Subject(s)
Dental Materials/adverse effects , Dental Restoration, Permanent/adverse effects , Health Status , Mouth Diseases/etiology , Self-Assessment , Somatoform Disorders/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Dental Restoration, Permanent/psychology , Female , Humans , Logistic Models , Male , Middle Aged , Mouth Diseases/psychology , Prognosis , Retreatment , Somatoform Disorders/psychology , Surveys and Questionnaires , Sweden
16.
Endoscopy ; 37(6): 532-6, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15933925

ABSTRACT

BACKGROUND AND STUDY AIMS: The incisura angularis is considered to be a typical site for Helicobacter pylori colonization, glandular atrophy, intestinal metaplasia, gastric ulcer, and gastric carcinoma. Our aim was to clarify whether it is necessary to biopsy the incisura angularis routinely during gastroscopy, in addition to obtaining biopsies of the corpus and antrum. PATIENTS AND METHODS: A total of 272 consecutive patients, with a mean age +/- SD of 53.8 +/- 15.5 years, had two biopsies taken from the angulus, two from the antrum, and two from the corpus of the stomach during routine upper gastrointestinal endoscopy. Histological specimens were examined according to the updated Sydney System for the classification and grading of gastritis. RESULTS: Of the 272 patients, 11 (4.0 %) showed chronic inflammation in the angulus biopsy only. Similarly, the angulus was the only biopsy site which showed neutrophil polymorph infiltration (or "activity") in two patients (0.7 %), intestinal metaplasia in 13 patients (4.7 %), atrophy in three patients (1.1 %), and H. pylori colonization in one patient (0.4 %). Dysplasia (intraepithelial neoplasia) was not found in any of the biopsied sites in any of the 272 patients. H. pylori was found in 39 of the 272 patients (14 %). Of the 272 patients, 120 patients showed abnormalities at the incisura angularis, 101 having gastropathy or erosions, and only 19 showing more specific macroscopic changes, the main ones being ulcer, ulcer scarring, and atrophy. Of the 152 patients with a normal-looking mucosa at the angulus, only six (3.9 %) showed the histological changes of chronic inflammation in the angulus alone. Similarly, the angulus was the only biopsy site which showed neutrophil polymorph infiltration in one patient (1/152, 0.7 %), and intestinal metaplasia in five patients (5/152, 3.3 %). Atrophy and H. pylori colonization were not seen exclusively at the angulus in any of the patients with a macroscopically normal-looking angulus. CONCLUSION: Based on our data, routine biopsy of the incisura angularis would provide little additional clinical information to that obtainable from antrum and corpus biopsies.


Subject(s)
Gastric Mucosa/pathology , Gastroscopy , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy/methods , Diagnosis, Differential , Female , Gastritis, Atrophic/pathology , Humans , Male , Metaplasia/pathology , Middle Aged , Precancerous Conditions/pathology , Reproducibility of Results
17.
Pharmacogenomics J ; 5(4): 262-70, 2005.
Article in English | MEDLINE | ID: mdl-15883587

ABSTRACT

We report a novel combination of factors that explains almost 60% of variable response to warfarin. Warfarin is a widely used anticoagulant, which acts through interference with vitamin K epoxide reductase that is encoded by VKORC1. In the next step of the vitamin K cycle, gamma-glutamyl carboxylase encoded by GGCX uses reduced vitamin K to activate clotting factors. We genotyped 201 warfarin-treated patients for common polymorphisms in VKORC1 and GGCX. All the five VKORC1 single-nucleotide polymorphisms covary significantly with warfarin dose, and explain 29-30% of variance in dose. Thus, VKORC1 has a larger impact than cytochrome P450 2C9, which explains 12% of variance in dose. In addition, one GGCX SNP showed a small but significant effect on warfarin dose. Incorrect dosage, especially during the initial phase of treatment, carries a high risk of either severe bleeding or failure to prevent thromboembolism. Genotype-based dose predictions may in future enable personalised drug treatment from the start of warfarin therapy.


Subject(s)
Anticoagulants/administration & dosage , Carbon-Carbon Ligases/genetics , Mixed Function Oxygenases/genetics , Polymorphism, Single Nucleotide , Warfarin/administration & dosage , Adult , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Dose-Response Relationship, Drug , Female , Haplotypes , Humans , Male , Middle Aged , Regression Analysis , Vitamin K Epoxide Reductases , Warfarin/therapeutic use
18.
Int Arch Occup Environ Health ; 77(8): 538-42, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15538619

ABSTRACT

OBJECTIVES: The aim of the present study was to measure coping resources and self-image in patients with visual display terminal (VDT)-related skin symptoms and hypersensitivity to electricity (HE). METHODS: From 1980 to 1998, 350 patients with electrical sensitivity were registered. The patients were subdivided into two groups: patients with skin symptoms evoked by VDTs, television screens, and fluorescent-light tubes and patients with so-called hypersensitivity to electricity with multiple symptoms evoked by exposure to different electrical environments. A questionnaire was sent to all patients and contained the coping resources inventory (CRI) and the structural analysis of social behaviour (SASB) in order for us to measure coping resources and self-image, respectively. The CRI and SASB scores were compared with those of control groups. Two hundred and fifty respondents (73%) returned the questionnaire, 200 (78.5% women) in the VDT group and 50 (62% women) in the HE group. RESULTS: The patient group rated high on the CRI spiritual/philosophical scale and high on the SASB spontaneous, positive and negative clusters but low on the controlled cluster. The female patients scored high on the CRI emotional scale. The VDT group rated lower than the controls on the SASB controlled cluster and higher on both the positive and negative cluster. The HE group scored higher than the control group on the SASB spontaneous and positive clusters. The women in the HE group scored higher on the CRI cognitive and CRI total scale than the VDT group and control group and higher on the CRI emotional scale than the controls. The women in the HE group rated higher than both the women in the VDT and control groups on the SASB spontaneous and positive clusters. CONCLUSIONS: The deviant self-image found in these patients, especially the female HE patients, support the view that VDT and HE symptoms can be stress related. In the clinic, a trustful alliance should be established with the patient in order for a more realistic view to be achieved of the capacity.


Subject(s)
Adaptation, Psychological , Computer Terminals , Dermatitis, Occupational/psychology , Electricity/adverse effects , Self Concept , Analysis of Variance , Dermatitis, Occupational/etiology , Female , Humans , Male , Middle Aged , Occupational Exposure/adverse effects , Sex Factors , Stress, Psychological/complications , Surveys and Questionnaires
19.
Article in English | MEDLINE | ID: mdl-15160445

ABSTRACT

AIM: The main aim of the study was to describe the differences between some Northern countries regarding what foods, according to the patients, elicit hypersensitivity symptoms. METHODS: At the participating clinics, patients with a history of food hypersensitivity (n = 1139) were asked to fill in a questionnaire in which 86 different foodstuffs were listed. Skin-prick tests (SPT) were performed with common inhalant allergens. RESULTS: The foods that were reported as eliciting symptoms differed between countries. In Russia, Estonia, and Lithuania; citrus fruits, chocolate, honey, apple, hazelnut, strawberry, fish, tomato, egg, and milk were most often reported as causes of hypersensitivity. In Sweden and Denmark; birch pollen (BP) related foods, such as nuts, apple, pear, kiwi, stone fruits, and carrot were the most common causes. In all countries, children, more often than adults, had symptoms of allergic reaction to citrus fruits, tomato, strawberry, milk, egg, and fish. Most patients (95%) reported hypersensitivity to several foodstuffs (median: eight foods). The most common symptoms were oral allergy syndrome and urticaria. Severe symptoms were most common with fish, shellfish, nuts, and milk. Slight symptoms were most common with rice, coriander, poppy seed, lingonberry, corn, caraway red currant, and fig. Earlier well-known correlations, such as that between BP sensitization and some fruits and vegetables, as well as that between mugwort and some spices, were conoborated. Positive correlations were found between self-reported hypersensitivity to crustaceans and SPT with horse. A negative correlation was seen between hypersensitivity to crustaceans and SPT with BP. CONCLUSIONS: The foodstuffs that often are reported to cause food hypersensitivity, differ between Sweden/Denmark on one side and the Baltic States and Russia on the other. BP-related foods dominate in Scandinavia, whereas some mugwort-related foods are of more importance in Russia and the Baltic States.


Subject(s)
Food Hypersensitivity/diagnosis , Food Hypersensitivity/epidemiology , Patient Participation , Adolescent , Adult , Aged , Aged, 80 and over , Allergens/pharmacology , Child , Child, Preschool , Denmark/epidemiology , Estonia/epidemiology , Female , Health Surveys , Humans , Incidence , Lithuania/epidemiology , Male , Middle Aged , Patch Tests , Risk Factors , Russia/epidemiology , Surveys and Questionnaires , Sweden/epidemiology
20.
J Investig Allergol Clin Immunol ; 13(3): 149-54, 2003.
Article in English | MEDLINE | ID: mdl-14635463

ABSTRACT

BACKGROUND: According to a few case reports, kissing can induce symptoms due to food allergy. OBJECTIVE: We wanted to investigate the occurrence of kiss-induced allergic symptoms and other social inconveniences among patients with self-reported food hypersensitivity. METHODS: A questionnaire was answered by 1139 patients (1-84 years old, mean age 29 years, 393 males and 746 females) who considered themselves to be food allergic. RESULTS: 12% of the patients experienced allergic symptoms when in close contact with (e.g., kissing) a person who had eaten a nontolerated food prior to the contact. Some case histories suggested that the symptoms only appeared if the food intake had occurred immediately before the kiss. In addition, the questionnaires showed that 55% had problems in daily life finding tolerable food, 44% were afraid of a severe reaction from eating nontolerated food, 13% could experience symptoms when sitting beside a person who was eating such a food, and 17% could experience symptoms in the kitchen when someone else was preparing such food. CONCLUSIONS: What other people eat can influence the quality of life of food-allergic patients.


Subject(s)
Food Hypersensitivity/etiology , Hypersensitivity, Immediate/etiology , Lip , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Child , Child, Preschool , Cohort Studies , Female , Food Hypersensitivity/diagnosis , Food Hypersensitivity/epidemiology , Humans , Hypersensitivity, Immediate/epidemiology , Incidence , Male , Middle Aged , Population Surveillance , Risk Assessment , Severity of Illness Index , Sexual Behavior , Sweden/epidemiology
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