Improved one-year survival after acute myocardial infarction in Icelandbetween 1986 and 1996.

During the last decade the treatment of patients with acute myocardial infarction (AMI) has changed dramatically. In order to evaluate the overall impact of these changes on mortality and morbidity, we collected data on all patients hospitalized for AMI in Reykjavik, Iceland, during the calendar years of 1986 and 1996. Demographical characteristics of AMI patients did not change significantly between study periods. One-year mortality decreased from 26.3 to 19.7% (p < 0.05). Patients discharged with aspirin or beta-antagonists as well as those who received thrombolytic therapy had decreased 1-year mortality both years. Patients discharged with diuretics, digoxin or antiarrhythmics had increased 1-year mortality. We conclude that the 25% reduction in 1-year mortality is partially due to changes in therapy.     

A genetic contribution to inflammatory bowel disease in Iceland: a genealogic approach.

BACKGROUND AND AIMS: Both genetic and environmental factors play a role in the development of Crohn's disease (CD) and ulcerative colitis (UC), collectively known as inflammatory bowel disease (IBD). The aim of this study was to estimate the genetic component in IBD in Iceland. METHODS: A population-based sample, representing everyone diagnosed with IBD in Iceland from 1950 to 1996, was studied using a computerized population-wide genealogic database. The relationships among the patients were analyzed by calculating the kinship coefficient and the relative risk. RESULTS: The kinship coefficients for the patients were significantly greater than the mean kinship coefficient for the controls ( P < 10 -6 ). The risk ratio for siblings of IBD, UC, and CD patients was 5.0 ( P < 0.001), 5.9 ( P < 0.001), and 4.1 ( P = 0.033), respectively. The cross-risk ratio for siblings of UC patients developing CD (or vice versa) was 2.6 ( P = 0.015). CONCLUSIONS: The results indicate that the IBD patients are more closely related than the controls, which strongly supports the involvement of a genetic component in the development of IBD in Icelandic patients. We find that the increase in risk for relatives of UC probands to develop UC, or relatives of CD probands to develop CD, is greater than the increase in risk for relatives of UC probands to develop CD, or relatives of CD probands to develop UC.     

Subclinical intestinal inflammation: an inherited abnormality in Crohn's disease relatives?

BACKGROUND & AIMS: One approach to unraveling the genetics of complex inherited disease, such as Crohn's disease, is to search for subclinical disease markers among unaffected family members. We assessed the possible presence, prevalence, and inheritance pattern of subclinical intestinal inflammation in apparently healthy relatives of patients with Crohn's disease. METHODS: A total of 49 patients with Crohn's disease, 16 spouses, and 151 (58%) of 260 available first-degree relatives underwent a test for intestinal inflammation (fecal calprotectin concentration). The mode of inheritance was assessed from 36 index patients (by variance component analysis) when more than 50% of relatives were studied. RESULTS: Fecal calprotectin concentrations in patients with Crohn's disease (47 mg/L; confidence interval [CI], 27-95 mg/L) and relatives (11 mg/L; CI, 9-14 mg/L) differed significantly (P < 0.0001) from controls (4 mg/L; CI, 3-5 mg/L), whereas that of the spouses did not (4 mg/L; CI, 3-6 mg/L; P > 0.5). Fecal calprotectin concentration was increased in 49% of all relatives studied. The increased fecal calprotectin concentration among the relatives of the 36 index patients had an inheritance pattern that was most consistent with an additive inheritance pattern. CONCLUSIONS: There is a high prevalence of subclinical intestinal inflammation in first-degree relatives of patients with Crohn's disease that conforms best to an additive inheritance pattern. The genetic basis for this abnormality may represent a risk factor for Crohn's disease.     

Leukotriene B4 and C4 generation by human leukocytes after ex vivo stimulation with Ca-ionophore and opsonized zymosan in children with atopic asthma

The ex vivo release of leukotriene B₄ (LTB₄) and leukotriene C₄ (LTC₄) from leukocytes was evaluated after stimulation with both Ca-ionophore (Ca-I) and opsonized zymosan (OZ) in children with atopic asthma. Twenty-seven patients with asthma of varying severity were evaluated and divided into three groups: 1) moderate to severe asthma using inhaled steroids and symptom-free for the last 3 weeks (n = 8), 2) mild asthma with sporadic symptoms, only using inhaled pVagonists < 3 times/week (n = 8), and 3) acute asthmatic attacks admitted to hospital (n = 11). A group of children without atopic disease or any other known disease served as controls (n = 15). Total serum IgE levels were significantly increased in the children with asthma compared with the control group. LTC₄ production was only significantly increased in the group of children with moderate to severe asthma after stimulation with Ca-I, when compared with controls. In the same group, a trend towards increased LTC₄ production after stimulation with OZ was found. LTB₄ was not significantly increased in any patient group compared with the control group. A significant correlation between LTC₄ production after stimulation with Ca-I, but not OZ, and the relative blood eosinophil count was found in all subjects. LTC₄ generation per eosinophilic cell after stimulation with Ca-I or OZ was not statistically different in any patient group compared with the controls. We conclude that the increased leukotriene (LT) levels found after the stimulation of peripheral white blood cells sampled from atopic children with asthma are mainly the result of increased numbers of LT-producing cells, rather than due to increased releasability from these cells.     

Translation,data quality,reliability, validity and responsiveness of the Norwegian version of the Effective Musculoskeletal Consumer Scale (EC-17)

Background  

The Effective Musculoskeletal Consumer Scale (EC-17) is a self-administered questionnaire for evaluating self-management interventions that empower and educate people with rheumatic conditions. The aim of the study was to translate and evaluate the Norwegian version of EC-17 against the necessary criteria for a patient-reported outcome measure, including responsiveness to change.     

Effects of a 5-lipoxygenase-activating protein inhibitor on biomarkers associated with risk of myocardial infarction: a randomized trial

Context  Myocardial infarction (MI) is the leading cause of death in the world. Variants in the 5-lipoxygenase–activating protein (FLAP) gene are associated with risk of MI. Objective  To determine the effect of an inhibitor of FLAP on levels of biomarkers associated with MI risk. Design, Setting, and Patients  A randomized, prospective, placebo-controlled, crossover trial of an inhibitor of FLAP (DG-031) in MI patients who carry at-risk variants in the FLAP gene or in the leukotriene A₄ hydrolase gene. Of 268 patients screened, 191 were carriers of at-risk variants in FLAP (87%) or leukotriene A₄ hydrolase (13%). Individuals were enrolled in April 2004 and were followed up by designated cardiologists from a university hospital in Iceland until September 2004. Interventions  Patients were first randomized to receive 250 mg/d of DG-031, 500 mg/d of DG-031, 750 mg/d of DG-031, or placebo. After a 2-week washout period, patients received DG-031 if they had received placebo first or placebo if they had received DG-031 first. Treatment periods lasted for 4 weeks. Main Outcome Measures  Changes in levels of biomarkers associated with risk of MI. Results  In response to 750 mg/d of DG-031, production of leukotriene B₄ was significantly reduced by 26% (95% confidence interval [CI], 10%-39%; P = .003) and myeloperoxidase was significantly reduced by 12% (95% CI, 2%-21%; P = .02). The higher 2 doses of DG-031 produced a nonsignificant reduction in C-reactive protein (16%; 95% CI, –2% to 31%; P = .07) at 2 weeks. However, there was a more pronounced reduction (25%; 95% CI, 5%-40%; P = .02) in C-reactive protein at the end of the washout period that persisted for another 4 weeks thereafter. The FLAP inhibitor DG-031 was well tolerated and was not associated with any serious adverse events. Conclusion  In patients with specific at-risk variants of 2 genes in the leukotriene pathway, DG-031 led to significant and dose-dependent suppression of biomarkers that are associated with increased risk of MI events.      

Analysis of 76Br-BrdU in DNA of brain tumors after a PET study does not support its use as a proliferation marker

76Br-bromodeoxyuridine has previously been suggested as a PET tracer to characterize proliferation potential. However, in animal studies a large fraction of the tissue radioactivity is due to 76Br-bromide, which remains extracellular for extensive periods and contributes significantly to the level of radioactivity. The present project aimed at investigating whether in human brain tumors, sufficient amounts of 76Br-bromodeoxyuridine would be incorporated into DNA, to motivate further attempts with this tracer. Eight patients with brain tumors: 3 meningiomas, 2 astrocytoma grade IV, 1 astrocytoma oligodendroglioma grade II-IV and 2 metastases, were examined with PET and 76Br-BrdU on three occasions: immediately after injection of the tracer, at 4-6, and at 18-20 hours after administration. After the first PET study, diuresis was introduced and maintained for about 12 hours. About 20 hours after tracer administration, 200 mg/m(2) bromodeoxyuridine was administered to 7 patients median 5.8 (range 1-22) hours prior to operation allowing the immunohistochemical analysis of the proliferation potential. During the operation, tumor samples were taken and radioactivity in DNA extracted and measured. The uptake of radioactivity was higher in the tumors than in brain parenchyma. However, in the operative samples only 1-27% (average: 9%) of the radioactivity was found in the DNA fraction. The plasma radioactivity remained high throughout the study with only minimal signs of elimination by the diuresis. 76Br-BrdU is extensively metabolized to 76Br-bromide, and only a minor fraction of the radioactivity is found in the DNA fraction, making it unlikely that this tracer can be used for assessment of proliferation potential.