[The use of intermittent pneumatic compression for critical limb ischaemia without vascular surgery reconstruction]. / Intermitterende pneumatisk kompressions-behandling ved underekstremitetsiskæmi uden kirurgiske behandlingstilbud.

Patients with critical limb ischaemia, without possibility for vascular surgery reconstruction, are a high selected population with a wide scale occurrence of co-morbidity and mortality. We outline the use of intermittent pneumatic compression (IPC) to these patients. Impact on both wound healing and cost-effectiveness concerning IPC use are recently shown. The overriding purpose of IPC use is to decrease the frequency of major and to lower the extent of ischaemic rest pain. IPC equipment is currently available around the country, but is not often used on the indication critical limb ischaemia.

Markers of inflammation in relation to long-term cardiovascular mortality in patients with lower-extremity peripheral arterial disease.

BACKGROUND: Elevated levels of inflammatory mediators reflect vascular inflammation, and play a significant role in the genesis of atherosclerosis, plaque instability and rupture. METHODS AND MATERIAL: Plasma α-defensin and serum high sensitivity C reactive protein (hs-CRP) levels were examined in 463 patients with lower-extremity peripheral arterial disease (PAD). The relationships between inflammatory markers and lethal outcome were examined by Cox regression, and receiver operating characteristic (ROC) analysis. RESULTS: Overall, 126 patients died, hereof 59 of cardiovascular causes. The patients with chronic critical limb ischemia (CLI) at baseline had significantly higher α-defensin and hs-CRP levels compared with patients with intermittent claudication (IC). For patients with IC, the relative risk for cardiovascular mortality was three times higher in patients within the upper tertile of α-defensin concentration (>162 µg/l), when compared with those in the two lower tertiles (HR 3.04 95% CI 1.26-7.32). The multivariable model revealed that IC-patients with high α-defensin and high hs-CRP concentration had more than 5 times higher risk for cardiovascular mortality than those with either high α-defensin or high hs-CRP alone, and low α-defensin or low hs-CRP concentrations (HR 5.16, 95% CI 1.78-14.8). Area under the ROC curve for combined use of high values of α-defensin and hs-CRP was 0.71 (95% CI 0.57-0.85). The addition of α-defensin or hs-CRP to conventional risk factors significantly improved the accuracy of risk prediction model for cardiovascular mortality. No associations were found among α-defensin, hs-CRP, and lethal outcome for patients with CLI. CONCLUSIONS: Combined analysis of α-defensin and hs-CRP, adds prognostic information with regard to the long-term cardiovascular prognosis among patients with IC.

Higher cystatin C level predicts long-term mortality in patients with peripheral arterial disease.

AIMS: Cystatin C and cathepsins could play a role in different processes and stages of the atherosclerotic disease. We aimed to investigate the relationship of cystatin C, and cathepsins L, and S, to lethal outcome in patients with peripheral arterial disease (PAD). METHODS AND RESULTS: We studied 378 patients with established PAD. Cox regression was used to assess relationships between serum cystatin C or cathepsins L and S, and time to lethal outcome. The role of cystatin for prognosis of cardiovascular death was assessed with c-statistic, and net reclassification improvement (NRI). Patients with cystatin C levels above 1 mg/l (fifth quintile) had a significantly increased adjusted risk for all-cause and cardiovascular mortality compared to patients with cystatin C levels below or equal to 1 mg/l (hazard ratios (HR) 2.2, 95% CI 1.22-4.12, and HR 3.2, 95% CI 1.39-7.59, respectively). Furthermore, high cystatin C levels were related with higher all-cause (adjusted HR 2.99, 95% CI 1.31-6.85) and cardiovascular mortality (adjusted HR 4.36, 95% CI 1.07-18.8) among PAD patients without renal impairment. Although the addition of cystatin C to conventional risk factors improved the accuracy of risk prediction model for cardiovascular mortality (0.72-0.79; p=0.03), it did not reclassify a substantial proportion of patients to risk categories (NRI=0.12, p=0.128). CONCLUSIONS: Higher cystatin C levels independently predicted 5 years all-cause, and cardiovascular death in PAD patients. However, a small improvement in discrimination with the addition of cystatin C to conventional risk factors, and no improvement in reclassification of risk categories suggest that clinical usefulness of cystatin C for predicting cardiovascular mortality in PAD population might be modest.

The Viborg Vascular (VIVA) screening trial of 65-74 year old men in the central region of Denmark: study protocol.

BACKGROUND: Screening for abdominal aortic aneurysm (AAA) of men aged 65-74 years reduces the AAA-related mortality and is generally considered cost effective. Despite of this only a few national health care services have implemented permanent programs. Around 10% of men in this group have peripheral arterial disease (PAD) defined by an ankle brachial systolic blood pressure index (ABI) below 0.9 resulting in an increased mortality-rate of 25-30%. In addition well-documented health benefits may be achieved through primary prophylaxis by initiating systematic cholesterol-lowering, smoking cessation, low-dose acetylsalicylic acid (aspirins), exercise, a healthy diet and blood-pressure control altogether reducing the increased risks for cardiovascular disease by at least 20-25%. The benefits of combining screening for AAA and PAD seem evident; yet they remain to be established. The objective of this study is to assess the efficacy and the cost-effectiveness of a combined screening program for AAA, PAD and hypertension. METHODS: The Viborg Vascular (VIVA) screening trial is a randomized, clinically controlled study designed to evaluate the benefits of vascular screening and modern vascular prophylaxis in a population of 50,000 men aged 65-74 years. Enrolment started October 2008 and is expected to stop in October 2010. The primary outcome is all-cause mortality. The secondary outcomes are cardiovascular mortality, AAA-related mortality, hospital services related to cardiovascular conditions, prevalence of AAA, PAD and potentially undiagnosed hypertension, health-related quality of life and cost effectiveness. Data analysis by intention to treat. RESULTS: Major follow-up will be performed at 3, 5 and 10 years and final study result after 15 years. TRIAL REGISTRATION: ClinicalTrials.gov NCT00662480.

Association of serum adiponectin with risk for cardiovascular events in patients with peripheral arterial disease.

OBJECTS: Adiponectin exerts anti-atherogenic and anti-inflammatory properties and may be important as a biomarker for cardiovascular disease (CVD). We examined whether serum adiponectin was linked with future cardiovascular events or all-cause death in patients with peripheral arterial disease (PAD). METHODS: The study prospectively included 468 patients (58% male) with symptomatic PAD. Serum total adiponectin was determined by an in-house immunoassay. We used Cox regression, adjusted for age, gender, BMI, systemic hypertension, smoking status, diabetes mellitus, previous myocardial infarction (MI), ankle-brachial index (ABI), symptoms of leg ischemia, total cholesterol, and use of beta-blockers (BAB) and angiotensin-converting enzyme (ACE) inhibitors to assess possible relationship between serum adiponectin and time to first non-fatal cardiovascular event, and all-cause death. RESULTS: During the median follow-up of 3.5 years, 215 new cases of non-fatal cardiovascular events and 97 all-cause deaths were detected. Adjusted Cox-regression analysis showed that a 1mg/l increase in serum adiponectin was associated with a decrease in the risk of non-fatal cardiovascular events to 0.68, (95% CI 0.47-0.99) in men, but not in women (HR 0.96 95% CI 0.55-1.70). The relative risk of adverse non-fatal cardiovascular events was 77% higher in male patients within the lower adiponectin tertile, when compared with those in the higher tertile (95% CI 1.05-2.97). Moreover, serum adiponectin was the only significant independent predictor of non-fatal cardiovascular events for men with severe PAD (HR=0.37, 95% CI, 0.16-0.89; p=0.026), whereas previous MI (p=0.92) and ABI (p=0.08) failed to reach statistical significance in the multivariable model. We did not obtain any significant associations between serum adiponectin and all-cause mortality. Multivariable model revealed that age and previous MI were independently associated with risk for all-cause death. CONCLUSIONS: Lower levels of serum adiponectin were significantly associated with an increased risk for future non-fatal cardiovascular events in men with symptomatic PAD, but not in women.

Proteomic identification of differentially expressed proteins in aortic wall of patients with ruptured and nonruptured abdominal aortic aneurysms.

OBJECTIVE: To compare the basic proteomic composition of abdominal aortic aneurysm (AAA) wall tissue in patients with nonruptured and ruptured aneurysms. METHODS: A proteomic approach with two-dimensional gel electrophoresis (2D-PAGE) and mass spectrometry (MS) was used to identify differentially expressed proteins in AAA tissue from nine patients with nonruptured and eight patients with ruptured AAA. Computerized image analysis was used to detect protein spots. Differentially expressed protein spots were in-gel digested and identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Western blot analysis was used to confirm differential expression. RESULTS: Seven differentially expressed proteins were detected among 745 protein spots, selecting spots whose average relative volumes differed more than twofold between the nonruptured and the ruptured group. Four protein spots were up-regulated in the ruptured group, and three were down-regulated. Five of the spots were identified. Among the upregulated spots, No. 605 was identified as peroxiredoxin-2. The up-regulation was confirmed by Western blotting. No. 381 was identified as an actin fragment. Two spots, Nos. 719 and 499, could not be identified. Among the down-regulated protein spots, No. 130 contained two peptides; one reliably determined peptide, FEDGVLDPDYPR, is found in vitronectin. Another peptide, QIDNPDYK, was borderline significant and found in calreticulin. The down-regulation of vitronectin was confirmed by Western blotting. Spot Nos. 193 and 199 both contained peptides from albumin with actin also present in No. 199. CONCLUSION: The identified proteins suggest that the aortic wall of ruptured aneurysms responds to a stressful condition and that proteolytic degradation of the cytoskeleton and connective tissue may be part of the response.

Completeness and positive predictive value of registration of upper limb embolectomy in the Danish National Vascular Registry.

OBJECTIVE: TO EVALUATE COMPLETENESS AND POSITIVE PREDICTIVE VALUE OF THE DANISH NATIONAL VASCULAR REGISTRY REGARDING REGISTRATION OF THE SURGICAL PROCEDURES: embolectomy of brachial, ulnar, or radial artery. STUDY DESIGN AND SETTINGS: The study was based on first-time embolectomies in the brachial, ulnar, or radial artery performed in Denmark from January 1, 1990 to December 31, 2002. The data were primarily retrieved from the Danish National Vascular Registry and secondarily from the Danish National Registry of Patients. Medical records were retrieved using a standardized form. RESULTS: In total, 1433 incident cases of first-time embolectomy were found in both registries. The positive predictive value of the registration was 97.5% (95% confidence interval [CI]; 96.4-98.4). The degree of completeness was 86.5% (95% CI; 84.3-88.5). For the registration period from 1990 till 1996 the degree of completeness was 78.2% (95% CI; 74.4-81.7), and from 1997 till 2002 it was 93.8% (95% CI; 91.6-95.7). CONCLUSION: The completeness and positive predictive value of registration of embolectomy in the upper limb in the Danish National Vascular Registry was 86.5% and 97.5%, respectively. This registry can be a valuable tool for epidemiological research and quality-monitoring.

Low-dose aspirin may prevent growth and later surgical repair of medium-sized abdominal aortic aneurysms.

Experimental data suggest that aspirin-induced platelet inhibition may retard growth of abdominal aortic aneurysms. In this article, whether low-dose aspirin use is associated with reduced aneurysm progression and subsequent need for surgery is examined. In this observational cohort study within a screening trial, 148 patients with small aneurysms (maximum diameter 30-48 mm) annually are followed. Patients were referred for surgery when the aneurysmal diameter exceeded 50 mm. Median follow-up time was 6.6 years. Among patients whose abdominal aortic aneurysms were initially 40 to 49 mm in size, the abdominal aortic aneurysm expansion rate for low-dose aspirin users compared with nonusers was 2.92 mm/y versus 5.18 mm/y (difference 2.27 mm/y, 95% CI, 0.42-4.11). No difference in expansion rates and risk ratios for operative repair was found for patients with abdominal aortic aneurysms <40 mm. For medium-sized abdominal aortic aneurysms, low-dose aspirin may prevent abdominal aortic aneurysm growth and need for subsequent repair, but residual confounding cannot be excluded.

[Cost-benefit analysis of population screening for abdominal aortic aneurism, based on five-year results of a randomised hospital-based screening trial]. / Nytteomkostningsanalyse af populationsscreening for abdominalt aortaaneurisme baseret på fem års resultater af en randomiseret hospitalsbaseret screeningsundersøgelse--sekundaerpublikation.

The lethality of ruptured abdominal aortic aneurysm (AAA) is 80-95% compared to 5-6% after elective surgery. However, AAA seldom causes symptoms before rupture. From 1994 to 1998, 12,639 men aged 64-73, from Viborg County, were randomised 1:1 for an invitation to an ultrasonographic scan or for controls. There were 75% fewer emergency operations (P < 0.001), and 67% lower AAA-specific mortality in the screening group (P = 0.002). The costs were 6,221 pounds sterling (4,034-13,782) per saved living year, expected to decrease to about 1,860 pounds sterling after 10 years. Screening of Danish men, aged 65-73, is recommended.

[Performing major upper abdominal operations in a low-volume hospital: is it possible?]. / Større kirurgiske indgreb i øvre abdomen ved et mellemstort sygehus. Går det an?

INTRODUCTION: The outcomes of cardio-oesophageal resection, gastric resection, total gastrectomy and Whipple's operation in a low-volume hospital over a decade are presented. MATERIALS AND METHODS: Thirty-seven patients were followed for five years after a cardio-oesophageal resection, 21 after a Billroth II resection, 15 after total gastrectomy and 28 after a Whipple's operation. Mortality and morbidity rates, post-operative in-hospital period and long-term survival were measured. RESULTS: Cardio-oesophageal resection: The morbidity rate was 19%, the mortality rate was 11%, and the median post-operative stay in hospital was 11 days. The five-year survival rate based on death from cancer was 37% and from all causes 32%. Gastric resection and gastrectomy: The morbidity rate was 14%, the mortality rate was 3%, and the median post-operative period in hospital was 9 days after gastric resection and 11 days after gastrectomy. The five-year survival rate based on death from was cancer 55% and from all causes 37%. Whipple's procedure: The morbidity rate was 17%, the mortality rate was 4% and the median post-operative stay in hospital was 10 days. The survival rate based on death from cancer was 77% and from all causes was 54% after five years for cancer of the ampulla of Vater, and 27% and 31% after three years for pancreatic head carcinoma. CONCLUSION: Major gastric and pancreatic operations can be performed in a low-volume hospital with satisfactory results.

Screening for abdominal aortic aneurysms: single centre randomised controlled trial.

OBJECTIVE: To determine whether screening Danish men aged 65 or more for abdominal aortic aneurysms reduces mortality. DESIGN: Single centre randomised controlled trial. SETTING: All five hospitals in Viborg County, Denmark. PARTICIPANTS: All 12,639 men born during 1921-33 and living in Viborg County. In 1994 we included men born 1921-9 (64-73 years). We also included men who became 65 during 1995-8. INTERVENTIONS: Men were randomised to the intervention group (screening by abdominal ultrasonography) or control group. Participants with an abdominal aortic aneurysm > 5 cm were referred for surgical evaluation, and those with smaller aneurysms were offered annual scans. OUTCOME MEASURES: Specific mortality due to abdominal aortic aneurysm, overall mortality, and number of planned and emergency operations for abdominal aortic aneurysms. RESULTS: 4860 of 6333 men were screened (attendance rate 76.6%). 191 (4.0% of those screened) had abdominal aortic aneurysms. The mean follow-up time was 52 months. The screened group underwent 75% (95% confidence interval 51% to 91%) fewer emergency operations than the control group. Deaths due to abdominal aortic aneurysms occurred in nine patients in the screened group and 27 in the control group. The number needed to screen to save one life was 352. Specific mortality was significantly reduced by 67% (29% to 84%). Mortality due to non-abdominal aortic aneurysms was non-significantly reduced by 8%. The benefits of screening may increase with time. CONCLUSION: Mass screening for abdominal aortic aneurysms in Danish men aged 65 or more reduces mortality.

Serum antibodies against Chlamydia pneumoniae outer membrane protein cross-react with the heavy chain of immunoglobulin in the wall of abdominal aortic aneurysms.

BACKGROUND: Chlamydia pneumoniae (Cp) has been demonstrated in arteries and abdominal aortic aneurysms (AAAs). However, the validity of the methods used is questioned, and antibiotic treatment trials have thus far shown disappointing results. Nevertheless, antibodies against the Cp outer membrane proteins (OMPs) have been associated with progression of atherosclerosis and AAAs. The aim of this study was to detect Cp OMPs in the wall of AAA patients by use of purified serum antibodies directed against Cp OMP and to assess potential cross-reacting proteins in AAA walls. METHODS AND RESULTS: Seventeen patients undergoing infrarenal AAA repair were studied. Full AAA thickness tissue was collected from the anterior wall of the aneurysm. Anti-OMP was extracted from seropositive AAA patients by use of an ELISA kit (Labsystems). Analysis was performed by use of 2D polyacrylamide gel electrophoresis, immunoblotting, and mass spectrometric protein identification. OMP antigens were not detected in 16 of 17 AAA walls. However, 3 major AAA proteins cross-reacted with anti-OMP. The proteins were all identified as heavy chains of human immunoglobulin. CONCLUSIONS: We could not find evidence of Cp OMP in 16 of 17 AAA walls, but instead, all samples showed a strong cross-reaction between Cp OMP antibodies and human immunoglobulin. This might indicate that AAA is an autoimmune disease, perhaps triggered by an initial Cp infection.

Macrophage migration inhibitory factor is associated with aneurysmal expansion.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine released mainly from macrophages and activated lymphocytes. Both atherosclerosis and abdominal aortic aneurysm (AAA) are inflammatory diseases tightly linked to the function of these cells. The correlation and contribution of MIF to these human diseases remain unknown, although a recent rabbit study showed expression of this cytokine in atherosclerotic lesions. MATERIAL AND METHODS: MIF immunohistochemistry was performed on tissue sections from five normal aortas, seven atherosclerotic carotids, and six AAAs. A group of 112 men with small AAAs (defined as 3 to 5 cm) was recruited at the time of diagnosis, had serum samples taken, and was followed annually for 1 to 5 years (mean, 2.9 years) and referred for surgery if the AAA exceeded 5 cm in diameter. Of this study group, 98 had serum MIF measured with an enzyme-linked immunosorbent assay and 61 had detectable levels. RESULTS: In human atherosclerotic and aneurysmal lesions, MIF protein colocalized in macrophages, endothelial cells, and smooth muscle cells, but normal arteries had negligible MIF expression. Furthermore, serum-MIF levels correlated significantly with annual expansion rate (r = 0.28; P =.005), persisting after adjustment for initial AAA size, smoking habits, diastolic blood pressure, ankle blood pressure index, and age. After exclusion of 38 cases with MIF levels below the detection limit, initial AAA size was also significantly correlated with the MIF levels (r = 0.42; P =.001), persisting after adjustment for similar confounders, and the correlation coefficient with expansion rate increased to 0.42 (P =.001). CONCLUSION: Highly expressed MIF in macrophages, endothelial cells, and smooth muscle cells in lesions from atherosclerosis and AAA and significant association between serum MIF level and AAA initial size and AAA expansion rate in a group of patients with AAA suggest a potential involvement of this proinflammatory cytokine in the pathogenesis of these cardiovascular diseases.

[Hospital costs and benefits of screening for abdominal aortic aneurysm. Results from a randomized screening trial]. / Hospitalsomkostninger og nytte af screening for abdominalt aortaaneurisme. Resultater fra en randomiseret screeningsundersøgelse.

INTRODUCTION: The hospital costs and benefits of screening older males for abdominal aortic aneurysms (AAA) are unknown. MATERIAL AND METHODS: In 1994, a hospital-based screening trial of 12,658 65-73-year-old males in the County of Viborg, Denmark, was started. AAA > 5 cm were referred for surgery. The remaining AAA were offered annual control scans. Those with aortic ectasia (def.: 2.5-2.9 cm) were rescreened at 5-year intervals. AAA-operations and deaths of AAA at hospital were registered. Finally, costs of screening, surveillance, and treatment were registered. Data on causes of death outside hospitals could not be obtained. RESULTS: The attendance rate was 76%, of whom 191 (4.0%) had AAA. The average observation time was 5.13 years. 60 in the screened and 41 in the control group were operated (P = 0.06), 7 and 27 were operated as an emergency (P < 0.001), and 6 and 19 died at the hospitals due to AAA (p = 0.009). The costs per scan were 83.50 DKK, 81,400 DKK per elective operation (71,485 DKK after screening), and 117,000 DKK for an emergency operation. The costs per prevented hospital death were 67,855 DKK or approx. 7,540 DKK per life year saved (1 GBP = 12 DKK). DISCUSSION: Screening older males for AAA in Denmark seems very cost-effective and reduces hospital mortality of AAA by 68% and probably the overall AAA-specific mortality by 73%.

A review of macrolide treatment of atherosclerosis and abdominal aortic aneurysms.

Seroepidemiological studies have shown an association between Chlamydia pneumoniae and atherosclerosis, the risk of acute myocardial infarction and abdominal aortic aneurysms (AAA). Several studies have detected C. pneumoniae in atherosclerotic lesions from coronary and carotid arteries, in AAA, and in sclerotic aortic valves. However, culturing of C. pneumoniae is difficult and has seldomly succeeded from atherosclerotic lesions. Thus, the pathogenicity is unknown, and the significance of detecting the organism is unresolved. Nevertheless, in a large observational study comparing the risk of cardiovascular events among recipients of macrolide versus pencillins, macrolide treatment reduced the risk of such events after relevant adjustment. Furthermore, in two out of three minor randomized clinical trials were patients with ischaemic heart disease were randomized into antibiotic treated and placebo groups, a significant reduction in serious end-points were noticed in patients receiving macrolide. Similarly, two other minor randomized trials showed that macrolide treatment inhibited growth of small AAA. Macrolide therapy thus seems potential to improve the outcome of severe ischaemic heart disease, and growth of AAA. If true, it not known whether this is transient because of macrolide's non-specific anti-inflammatory effect or latent infection, or permanent because of eradicating C. pneumoniae organisms. In order to clarify this, large and long term randomized trials are needed, as well as diagnostic methods that can differentiate between individuals who are or are not infected with C. pneumoniae. The latter are needed in order to clarify the impact of the presence of C. pneumoniae and to avoid overconsumption of antimicrobials, which can result in serious ecological problems.

Development and validation of QoL5 for clinical databases. A short, global and generic questionnaire based on an integrated theory of the quality of life.

OBJECTIVE: To develop and validate a short, global, and generic quality of life (QoL) questionnaire for clinical databases. The construct validity and item weighting of existing questionnaires are increasingly questioned. DESIGN: Cross-sectional population study. SUBJECT: 2460 Danes aged 18-88 years, randomly selected through the Danish Central Person Registry. INTERVENTIONS: Ten questions covering the spectrum of the integrative theory of QoL together with the Nottingham Health Profile (NHP), Sickness Impact Profile (SIP), and self-estimated QoL questionnaire were sent by mail. A test-retest study of 50 people was conducted after one month. MAIN OUTCOME MEASURES: Construct and criterion validity, reliability, and sensitivity. RESULTS: QoL5 correlations with SIP, NHP, Self-estimated QoL were 0.37, 0.52, and 0.76, respectively, and increased among those who were unwell. Cronbach's alpha was 0.69. All correlations in Siegel's test were over 0.6, and the test-retest correlation was 0.82. Only 12 respondents in each group will be needed to detect a difference of 10% in the QoL score between two groups. CONCLUSIONS: QoL5 is a valid global and generic QoL measurement. Despite the use of only five questions, internal consistency and sensitivity were acceptable. So a relevant and practical outcome measurement is available for clinical databases.

[Reduction of the expansion rate of small abdominal aortic aneurysms with roxithromycin. Results from a randomized controlled trial]. / Haemning af små abdominale aortaaneurismers ekspansion med roxithromycin. Resultater fra et randomiseret klinisk kontrolleret forsøg.

INTRODUCTION: Macrolide treatment has been reported to reduce the risk of recurrent ischaemic heart disease. The influence of a macrolide on the expansion rate of small abdominal aortic aneurysms (AAA) is unknown at present. The aim of this study was to investigate the effect of roxithromycin on the expansion rate of small AAA. MATERIALS AND METHODS: A total of 92 patients with a small AAA were recruited from two populations. One population consisted of 6.339 men aged 65-73 years who were offered participation in a mass screening programme for AAA at the local hospital. From this population 66 subjects were recruited. The remaining 26 were recruited from among 49 subjects diagnosed at interval screening for an initial aortic diameter between 25 mm and 29 mm. The patients were randomized to receive either oral roxithromycin 300 mg once daily for 28 days or matching placebo, and followed for a mean of 1.5 years. RESULTS: During the first year the mean annual expansion rate of AAA was reduced by 44% in the macrolid group (1.56 mm/year) compared to 2.80 mm/year after placebo (p = 0.02). During the second year the difference was only 5%. Multiple linear regression analysis showed that roxithromycin treatment and initial AAA size were significantly related to AAA expansion when adjusted for smoking, diastolic blood pressure, and IgA level > or = 20. The logistic regression analysis confirmed a significant difference in expansion rates above 2 mm annually between the intervention and placebo groups, OR = 0.09 (95% CI: 0.01-0.83). DISCUSSION: In comparison to placebo, roxithromycin 300 mg daily for four weeks reduced the expansion rate of AAA.

Members of the nuclear factor 1 family reduce the transcriptional potential of the nuclear receptor LXRalpha promoter.

Expression of the LXRalpha nuclear receptor in liver is predicted to affect cholesterol and lipid metabolism. Here we show that a short fragment from the LXRalpha gene promoter spanning the region from -144 to +43 relative to the mRNA initiation site can drive transcription of a reporter gene. Under basal conditions, in vitro DNase I footprinting demonstrated interaction between nuclear proteins and an NF1 recognition site in close vicinity to the transcriptional initiation. Both supershift, mutational analyses in EMSA and transfections provided evidence that the NF1 (nuclear factor I) transcription factor interacts with the LXRalpha promoter. All four members of the NF1 family were found to suppress the transcriptional activity indicating a general inhibitory effect on LXRalpha expression. A similar regulation by NF1 was also observed when using a fragment from the LXRalpha promoter extending up to position -3033 therefore giving the inhibitory effect of NF1 a significant impact on LXRalpha gene expression.