Summary
APC-resistance is the most common hereditary condition associated with venous thrombosis. It is in a majority of cases due to a single point mutation in the factor V gene (FVR506Q). Currently ...used functional APC-resistance tests have 85-90% sensitivity and specificity for the FVR506Q mutation. A modified test which includes predilution of patient plasma in factor V depleted plasma has increased the sensitivity and specificity for the factor V mutation. However, neither the original nor the modified APC-resistance test have been evaluated in patients with acute thrombotic events. We have therefore used the original and the modified APC-resistance tests in 220 patients with clinically suspected acute deep venous thrombosis and in 278 healthy controls. The FVR506Q mutation was determined in all patients. The patients were classified as either DVT (deep venous thrombosis)-negative or DVT-positive depending on the outcome of contrast phlebography. In individuals with normal factor V genotype, the original APC-resistance test gave significantly lower APC-ratio values both in DVT-positive and DVT-negative patients than in healthy controls. The specificity of the original APC-resistance test for the FVR506Q mutation in controls and in DVT-negative and DVT-positive patients were 85%, 54% and 28%, respectively, when a cut off APC-ratio of 3.2 which insured 100% sensitivity was used. Using the modified APC-resistance test, essentially no difference in APC-ratios between patients with normal factor V genotype and healthy controls with normal factor V genotype was observed. The modified APC-resistance test had a specificity for the FVR506Q mutation of 98.8% at an APC-ratio cut off of 2.1 which ensured 100% sensitivity. The original APC-resistance test gave lower APC-ratios in women than in men and in patients with acute thrombosis as compared to controls. In conclusion, the modified APC-resistance test is highly sensitive and specific for the FVR506Q mutation. This test can be used in clinical practice as an easy to perform screening test for the FVR506Q allele. Moreover, the test performs equally well in patients with acute suspected venous thrombosis as in healthy controls.
Venous thromboembolism (VTE) and arterial thrombosis have been thought to result from two different mechanisms. Recent data indicate that the two diseases may share some common risk factors, such as ...the activity of inflammation on haemostasis. In this population-based study we explored whether raised levels of inflammation-sensitive plasma markers (ISPs) increase the risk for venous thromboembolism. Measurements of five ISPs (fibrinogen, haptoglobin, ceruloplasmin, α1-antitrypsin and orosomucoid) were performed in 6,068 subjects from “the Malmö Preventive Study”. These apparently healthy men from the city of Malmö in Sweden, were included in the study between 1974 and 1982 and followed up until 2008. We calculated the hazard ratio (HR) for VTE in relation to the number of raised ISPs as well as individual ISPs in the fourth quartile. Mean follow-up time was 26.2 years. Out of the cohort (n = 6,068), 398 (6.6 %) had a venous thromboembolism during the follow-up. The number of raised ISPs was significantly associated with age, BMI and smoking. Age, BMI and diabetes mellitus type 2 were also significant risk factors for developing a VTE (HR = 1.05 with
p
< 0.01 and 95 % CI 1.01–1.08, HR = 1.10 with
p
< 0.001 and 95 % CI 1.06–1.14 and HR = 1.78 with
p
< 0.05 and 95 % CI 1.13–2.81, respectively). Incidence of venous thromboembolism was not significantly related to number of raised inflammatory proteins (
p
for trend = 0.37) or any of the individual ISPs. Age and BMI is significantly associated with the risk for developing VTE. Incidence of VTE was not associated with any of the inflammatory proteins.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Evidence suggests an increased risk of cardiovascular (CV) diseases, including acute coronary syndrome (ACS), in idiopathic inflammatory myopathies (IIM). The aim of this study was to investigate the ...risk of ACS in an incident IIM cohort compared to the general Swedish population.
A cohort of 655 individuals with incident IIM and 6813 general population comparators were identified from national registries. IIM subjects were diagnosed from 2002 to 2011. Followup started at IIM diagnosis and corresponding date in the general population. ACS, CV comorbidities, and CV risk factors were defined using International Classification of Diseases codes. Incidence rates including 95% CI were calculated. Cox proportional hazards models were used to compare the risk of ACS in patients with IIM and the general population. The competing risk of death was accounted for using competing risk regression models.
The incidence rate of ACS in IIM was higher than in the general population, particularly within the first year of diagnosis and in older individuals. The overall ACS incidence rate in IIM was 15.6 (95% CI 11.7-20.4) per 1000 person-years, with an HR of 2.4 (95% CI 1.8-3.2) compared with the general population. When accounting for the competing risk of death, the risk of ACS in IIM remained increased with a cumulative incidence of 7% at 5 years compared to 3.3% in the general population.
IIM individuals are at higher risk of ACS, particularly within the first year after diagnosis.
Experimental studies have established that the sulfated glycosaminoglycans heparan sulfate and chondroitin sulfate act as co-receptors of cytokines and growth factors that drive the malignant cell ...phenotype and the remodelling of the surrounding tumor stroma. However, the clinical relevance of these studies remains ill-defined. The present study investigates the significance of chondroitin sulfate expression in malignant cells and the stroma, respectively, of tumors from two independent cohorts of breast cancer patients (cohort I: 144 patients, 130 evaluable samples; cohort II: 498 patients, 469 evaluable samples; ER-positive patients ~86% in both cohorts). Kaplan-Meier analysis and Cox proportional hazards modelling were used to assess the relationship between chondroitin sulfate and recurrence-free and overall survival. High chondroitin sulfate expression in malignant cells was shown to predict shorter recurrence-free survival (P=0.007, cohort I; P=0.024, cohort II) and overall survival (cohort I: P=0.044; cohort II: P<0.001) in both cohorts. In multivariate analysis, high chondroitin sulfate in malignant cells was shown to be an independent, predictive factor of poor overall survival (cohort I: hazard ratio 2.28: 95% confidence interval 1.08-4.81, P=0.031; cohort II: hazard ratio 1.71: 95% confidence interval 1.23-2.38, P=0.001). However, chondroitin sulfate in the stroma showed no correlation with known markers of tumor aggressiveness or with clinical outcome in either cohort. Our data suggest that high chondroitin sulfate expression in malignant cells is associated with an adverse outcome in patients with primary breast cancer, supporting the idea of a functional and potentially targetable role of chondroitin sulfate in tumor disease.
Abstract
Background
Youth unemployment remains at a high stable level in many countries making it a public health problem of importance. The aim was to examine the short-term effect of unemployment ...at a young age (aged 17–29 years) on self-reported binge drinking and alcohol-related problems.
Methods
We used data from a cross-sectional national study that took place in 2013, with a follow-up in 2014. A sample of young adults aged 17–29 years (n = 1188, response rate of 46.3%) that completed both surveys served as the study sample in the current study. The same self-reported questionnaire, consisting of questions regarding their alcohol habits and sociodemographic information, was used on both occasions. Information on the outcomes of binge drinking and alcohol-related harm were obtained from the 2014 survey. From the 2013 survey, information on individual and family level covariates were collected. Odds ratios (ORs) with 95% confidence intervals (CIs) with employed individuals as the reference group were estimated by logistic regression analysis.
Results
At baseline, results indicate that employed individuals reported the greatest prevalence of weekly binge drinking. In the fully adjusted models, unemployment appeared to be associated with an increased risk of alcohol-related problems (OR 1.37, 95% CI 0.77–2.45); however, this was not the case for weekly binge drinking (OR 0. 94, 95% CI 0.45–1.96).
Conclusion
Unemployment at a young age may be a risk factor for later alcohol-related problems. Thus, targeting youth unemployment could be one element in an effective health policy aimed at reducing rates of alcohol use disorders.
Full text
Available for:
NUK, OILJ, UL, UM, UPUK, VSZLJ
Abstract Introduction To evaluate the risk for recurrence after first venous thromboembolism (VTE) among patients with or without Factor V Leiden (FVL) mutation. Materials and Methods A prospective ...population based study of 1465 consecutive unselected VTE patients was performed at Skåne University Hospital 1998–2008. The VTE was objectively verified and the patients answered questionnaire and left blood samples for evaluation. Results Out of 1465 patients (72149% men and 74451% women) thrombophilia data were available for 1267, and FVL mutation was found in heterozygous form in 339 (27). The homozygous form and prothrombin mutation (PTM) were much less common. Patients were followed during 4.8 ± 2.3 years (total 6133 patient years) and recurrence after first VTE (evaluated in 1108 patients) occurred in 131 (12%, 95%CI 10–14%), where of 49(37%) had heterozygous FVL mutation and 57(44%) were without thrombophilia. The remaining 25(19%) patients had either PTM, FVL in homozygous form, compound PTM/FVL or unknown thrombophilia status. Having FVL mutation in heterozygous form significantly increased the risk for VTE recurrence (odds ratio 2.4 (95 %CI 1.6–3.6; p < 0.01). In a Kaplan-Meier analysis the FVL group also differed significantly (p < 0.01) from the other patients concerning time to recurrence (almost 25% vs. 10% after 8 years). Conclusions FVL mutation in heterozygous form is common among VTE patients and significantly increases the risk for VTE recurrence.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
So far, two thioredoxin proteins, DHD and Trx-2, have been biochemically characterized in Drosophila melanogaster. Here, with the cloning and characterization of TrxT we describe an additional ...thioredoxin with testis-specific expression. TrxT and dhd are arranged as a gene pair, transcribed in opposite directions and sharing a 471 bp regulatory region. We show that this regulatory region is sufficient for correct expression of the two genes. This gene pair makes a good model for unraveling how closely spaced promoters are differentially regulated by a short common control region. Both TrxT and DHD proteins are localized within the nuclei in testes and ovaries, respectively. Use of a transgenic construct expressing TrxT fused to Enhanced Yellow Fluorescent Protein reveals a clear association of TrxT with the Y chromosome lampbrush loops ks-1 and kl-5 in primary spermatocytes. The association is lost in the absence of the Y chromosome. Our results suggest that nuclear thioredoxins may have regulatory functions in the germline.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Background/Objectives
Obesity is the main risk factor for obstructive sleep apnoea, commonly occurring in females who are overweight after menopause. We aimed to study the effect of a ...palaeolithic diet on sleep apnoea in females with overweight after menopause from the population.
Methods
Seventy healthy, non-smoking females with a mean age of 60 years and a mean BMI of 33 kg/m
2
were randomised to a palaeolithic diet or to a control low-fat diet according to Nordic Nutritional Recommendations, for 2 years. The apnoea-hypopnoea index was measured and daytime sleepiness was estimated during the intervention.
Results
The mean apnoea-hypopnoea index at baseline was 11.6 (95% CI 8.6–14.5). The mean weight loss was 7.2 kg (95% CI 5.3–9.2 kg) in the palaeolithic diet group and 3.9 kg in the control group (95% CI 1.9–5.9 kg);
p
< 0.021 for the group difference. The reduction in weight corresponded to a reduction in the apnoea-hypopnoea index in the palaeolithic diet group (
r
= 0.38,
p
= 0.034) but not in the control group (
r
= 0.08,
p
= 0.69). The apnoea-hypopnoea index was reduced in the palaeolithic diet group when the weight was reduced by more than 8 kg. Daytime sleepiness according to the Epworth Sleepiness Scale score and the Karolinska Sleepiness Scale score was unaffected by dietary group allocation.
Conclusions
A substantial decrease in body weight of 8 kg was needed to achieve a reduction in sleep apnoea in this small trial of women who are overweight after menopause. The palaeolithic diet was more effective for weight reduction than a control low-fat diet and the reduction in sleep apnoea was related to the degree of weight decrement within this diet group.
Trial registration
Clinicaltrials.gov: NCT00692536.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
You have reached the maximum number of search results that are displayed.
For better performance, the search offers a maximum of 1,000 results per query (or 50 pages if the option 10/page is selected).
Consider using result filters or changing the sort order to explore your results further.
PDF
