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Biomedical subjects

M Leinonen

Publications and source records attributed to M Leinonen.

At least 19 recordsLinked to original sources
PubMed2004

Treatment of acute Chlamydia pneumoniae infection with telithromycin in C57BL/6J mice.

OBJECTIVES: The efficacy of telithromycin, a new ketolide antibiotic, was investigated in the treatment of acute Chlamydia pneumoniae infection in a mouse model. METHODS: C57BL/6J mice were inoculated intranasally, and the effects of three different doses of telithromycin (25, 50 and 100 mg/kg) were assessed after 5 and 10 days of treatment. Lungs for culture, PCR, histopathology, and blood for serum samples were collected immediately after each treatment period and at 3 weeks post-inoculation. C. pneumoniae-specific antibodies were analysed, and the effect of treatment was assessed by culture, detection of C. pneumoniae DNA and determination of histopathological inflammatory changes in mouse lungs. RESULTS: Culture negativity in the lungs was achieved with the higher doses, 50 and 100 mg/kg, after 10 days of treatment. C. pneumoniae DNA was not totally eradicated with the treatments, but the groups treated with 50 and 100 mg/kg doses for 10 days had the lowest DNA positivity rates (10%) 3 weeks after the inoculation. In lung histopathology, the efficacy of telithromycin on inflammatory changes was also dose-dependent: higher doses were more effective in reducing the inflammatory reaction. Overall, the 25 mg/kg dose had a weaker effect compared with the others. CONCLUSIONS: Telithromycin had both time- and dose-dependent effects on the eradication of chlamydia and on reducing infection-induced inflammatory changes in mouse lungs.

Acute Disease↗
PubMed2004

Heat shock protein 60 autoimmunity and early lipid lesions in cholesterol-fed C57BL/6JBom mice during Chlamydia pneumoniae infection.

Chronic Chlamydia pneumoniae infection and autoimmunity to heat shock protein 60 (Hsp60) have both been documented to be associated with atherosclerosis. Herein, we studied the effects of C. pneumoniae infection and a diet with a low-cholesterol supplement on the development of autoantibodies to mouse Hsp60 and early lipid lesions in the aortic valve of C57BL/6JBom mice. In addition, pulmonary infection was investigated. C57BL/6JBom mice were given one to three C. pneumoniae inoculations and fed either a regular diet or a diet enriched with 0.2% cholesterol. Autoantibody responses against mouse Hsp60 developed in both diet groups when the mice were infected with C. pneumoniae and in uninfected mice fed a cholesterol-enriched diet. C. pneumoniae infections increased subendothelial foam cell accumulation in mice on a 0.2% cholesterol-enriched diet (p = 0.022), without apparent hypercholesterolemia. These in vivo data suggest that autoantibodies against mouse Hsp60 develop as a consequence of cholesterol feeding and repeated C. pneumoniae infections. Further, infectious burden increased early lipid lesions in C57BL/6JBom mice fed a cholesterol-enriched diet.

Animals↗
PubMed2004

Streptococcus pneumoniae in nasopharyngeal secretions of healthy children: comparison of real-time PCR and culture from STGG-transport medium.

Precise methods for the detection of Streptococcus pneumoniae are needed for predicting the consequences of pneumococcal conjugate vaccines on nasopharyngeal carriage. In this study, 400 nasopharyngeal swab samples from children were analyzed using a real-time pneumolysin (ply)-PCR method. The specimens were originally collected into STGG-transport medium and cultured in 1999, after which they were stored at -80 degrees C until analyzed by real-time PCR in 2001. The sensitivities of real-time PCR and culture methods were also studied by analyzing 10-fold dilutions of a pneumococcal broth culture using both methods. Of the 400 nasopharyngeal swab samples, 158 (40%) were positive in culture and 276 (69%) by real-time PCR. A minor part (4%) of the culture-positive samples remained negative by PCR. There was a trend between the quantity of genome equivalents detected by PCR and the number of colonies found in culture. When analyzing 10-fold dilutions of a pneumococcal broth culture, a higher number of genome equivalents were detected using real-time PCR than the number of colonies detected by culture. Quantitative real-time PCR provides feasible means for quantifying pneumococcal carriage. Further studies are needed to confirm that positive PCR findings really indicate the presence of viable pneumococcus in nasopharyngeal specimens.

Bacterial Proteins↗
PubMed2004

Type-specific enzyme immunoassay for detection of pneumococcal capsular polysaccharide antigens in nasopharyngeal specimens.

We developed a new competitive EIA method for the demonstration of pneumococcal capsular polysaccharides from respiratory samples. The pediatric types 4, 6B, 9V, 14, 18C, 19F and 23F were selected for this study, because these capsular polysaccharides were included in the first heptavalent pneumococcal conjugate vaccines, which were used in the Finnish Otitis Media Vaccine Trial. Sensitivity of the EIA tests for purified polysaccharide antigens varied between 5 and 100 ng/ml, depending on the type. The assays performed well in 100 nasopharyngeal samples (NPS) samples processed through an enrichment culture, with an almost 100% sensitivity compared with routine culture. The method appeared type-specific, except that EIA for 6B capsule also detected 6A. The method is applicable for type-specific identification of pneumococcus in carriage studies.

Antibodies, Bacterial↗
PubMed2004

Association between Chlamydia trachomatis antibodies and subfertility in the Northern Finland Birth Cohort 1966 (NFBC 1966), at the age of 31 years.

The objective of this study was to assess the serological association between previous Chlamydia trachomatis infection and subfertility in a general population sample. A nested case (n = 493)-control (n = 986) study in a population-based birth cohort consisting of 12,058 live births from the year 1966 was conducted. The analysis was restricted to those 6007 cohort members who replied to a postal inquiry and participated in a health examination including blood samples at the age of 31 years. The presence of C. trachomatis-specific serum IgG antibodies was screened by a synthetic peptide-based enzyme-linked immunosorbent assay. All the positive sera were further tested by the microimmunofluorescence method using immunotype pools and individual immunotypes of C. trachomatis as antigens. An association was found between the detection of immunotype-specific C. trachomatis antibodies and subfertility both in men and women. The results of the present study confirm the serological association between past C. trachomatis infections and subfertility in male or female partners of the couple in the population-based sample.

Adult↗
PubMed2004

Antibodies to Chlamydia trachomatis heat shock proteins Hsp60 and Hsp10 and subfertility in general population at age 31.

PROBLEM: To assess the association between antibodies to Chlamydia trachomatis heat shock proteins 60 and 10 (Hsp60 and Hsp10) and subfertility in a general population sample. METHOD OF STUDY: A nested case (n = 146)-control (n = 278) study in a population-based birth cohort. Serum immunoglobulin (Ig)G and IgA antibodies against C. trachomatis Hsp60 and Hsp10, explanatory factors, were measured by enzyme immunoassay, using recombinant proteins as antigens. The main outcome variable was subfertility (time to pregnancy > or =12 months). RESULTS: The prevalence and medians of serum IgA antibodies to Hsp60 and Hsp10 were significantly higher in the female partners of subfertile couple than in their fertile controls. On the contrary, among male partners of subfertile couple, especially among smokers serum antibody levels to Hsp antigens were lower than in the controls. CONCLUSION: The results indicate a serological association of antibodies to chlamydial Hsp antigens with female subfertility in a population-based sample.

Adult↗
PubMed2003

The tolerability and efficacy of entacapone over 3 years in patients with Parkinson's disease.

The long-term safety and efficacy of the catechol-O-methyltransferase (COMT) inhibitor entacapone was investigated in a 3-year open-label extension of the 6-month double-blind placebo-controlled Nordic (NOMECOMT) study. After a wash-out following this study, 132 patients with Parkinson's disease (PD) experiencing motor fluctuations treated with levodopa/dopa decarboxylase (DDC) inhibitor received additional therapy with entacapone 200 mg, administered with each dose of levodopa. The most common adverse events (AEs) were insomnia (30%), dizziness (20%), nausea (20%), aggravated parkinsonism (17%) and hallucinations (14%). Only 19 (14%) patients discontinued because of AEs. Most dopaminergic AEs occurred shortly after initiation of entacapone, and these could be managed by levodopa down-adjustment. The mean duration of benefit of a single dose of levodopa increased significantly from 2.1 to 2.8 h (P < 0.01) at 3 months and remained prolonged for the whole study. At the end of the study, the mean daily dose of levodopa was significantly decreased from baseline (from 737 to 696 mg; P < 0.05). The patients' global assessment indicated that 69% of patients improved when given entacapone and this proportion was maintained until the end of the study (64%). There was a significant worsening of disability upon withdrawal of entacapone. In conclusion, entacapone given in combination with levodopa, has a good long-term safety profile and a sustained beneficial effect in patients with PD with motor fluctuations.

Aged↗
PubMed2002

Detection of Streptococcus pneumoniae DNA by using polymerase chain reaction and microwell hybridization with Europium-labelled probes.

The present paper describes a novel modification of polymerase chain reaction (PCR) for the detection of Streptococcus pneumoniae DNA in clinical specimens. PCR was based on the detection of a 209-base pair segment of the S. pneumoniae pneumolysin gene. For the demonstration of the amplification product, microwell hybridization with a Europium-labelled oligonucleotide probe complementary to a biotinylated strand of the PCR product was performed, and the presence of the PCR product was monitored by time-resolved fluorescence (TRF) of the Europium chelate. The sensitivity of the assay for purified S. pneumoniae DNA was 50 fg DNA corresponding to 20 genome equivalents of S. pneumoniae DNA. The efficiency of the hybridization step was monitored by using known amounts of synthetic target oligonucleotides as standards. Sensitivity of 3 x 10(8) molecules per individual reaction well was achieved with a 30-min attachment time and a 3-h hybridization time. Detection of PCR-amplified products by the microwell hybridization technique and TRF was compared to agarose gel electrophoresis in 50 middle ear fluid samples obtained from children with acute otitis media. The agarose gel and TRF detection methods identified all culture-positive samples, but both were also positive for 55% of the culture-negative samples. The results suggest that the detection of amplified PCR products by microwell hybridization using Europium-labelled oligonucleotides is a reliable method for the demonstration of the pneumolysin gene fragment. Furthermore, the method is suitable for automation and, thus, for testing high numbers of samples. The clinical significance of the PCR findings remains to be studied.

Bacteriological Techniques↗
PubMed2002

Evaluation of gene-technological and conventional methods in the identification of Streptococcus pneumoniae.

To find reliable methods able to identify the "difficult" Streptococcus pneumoniae isolates, an in-house polymerase chain reaction (PCR) for pneumolysin gene (Ply-PCR) and a commercial RNA hybridisation test (AccuProbe) were evaluated. Selected isolates of suspected pneumococci, sent for confirmation of identification and for serotyping, were classified into four groups based on their optochin sensitivity and capsule reaction. All isolates in Group 1, which consisted of 24 typical, optochin-sensitive, encapsulated pneumococcal strains, were positive in the Ply-PCR and AccuProbe tests. In Group 2, which consisted of 25 optochin-sensitive, but unencapsulated pneumococcal strains, all the isolates were positive in the Ply-PCR test, and 23 were positive in the AccuProbe test. In Group 3, which consisted of 15 atypical, optochin-resistant but encapsulated pneumococci, 12 of the isolates were positive in the Ply-PCR and 12 in the AccuProbe test, and 11 of these 12 strains were positive in both tests. In Group 4, which consisted of 36 equivocal optochin-resistant, unencapsulated isolates, 15 strains were positive in the Ply-PCR test and 8 strains in the AccuProbe test. As a conclusion, the Ply-PCR and AccuProbe tests identified similarly typical optochin-sensitive pneumococci, but gave partly controversial results about atypical pneumococci. Thus, they did not reliably help in the identification of suspected pneumococcal isolates lacking the conventional characteristics of pneumococcus.

Bacterial Capsules↗
PubMed2002

Efficacy and safety of entacapone in Parkinson's disease patients with suboptimal levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (Celomen study).

OBJECTIVES: To determine the efficacy and safety of the catechol-O-methyltransferase (COMT) inhibitor entacapone, used as an adjunct to levodopa, in Parkinson's disease (PD) patients. PATIENTS AND METHODS: In this parallel group, randomized, double-blind study, 301 PD patients, the majority with motor fluctuations, received entacapone (200 mg) or placebo with each daily dose of standard or controlled-release (CR) levodopa. The 24-week treatment period was followed by 2 weeks of entacapone withdrawal. Efficacy was determined by home diaries ('on' and 'off' times), Unified Parkinson's Disease Rating Scale (UPDRS) and changes in levodopa dosage, and safety by adverse-event inquiry, vital signs, electro cardiography (ECG) and laboratory tests. RESULTS: In the total population, the UPDRS activities of daily living and motor scores were significantly improved (P < 0.05) by entacapone vs placebo. In fluctuating patients, 'on' time increased (1.7 h) and 'off' time decreased (1.5 h) significantly more with entacapone than with placebo (0.5 and 0.6 h, respectively; P < 0.05), and the daily levodopa dose was reduced by 54 mg with entacapone and increased by 27 mg with placebo (P < 0.05). Entacapone benefit was lost on withdrawal. Entacapone efficacy was comparable between patients using CR and standard levodopa preparations. Increased dyskinesias (entacapone 34%, placebo 26%) and nausea (10 and 5%, respectively), mostly occurring shortly after treatment initiation, were generally managed by reducing the levodopa dose. Diarrhoea (entacapone 8%, placebo 4%) was seldom severe. There were no differences in vital signs, ECG or laboratory results. CONCLUSION: Entacapone is an effective and safe levodopa extender and enhancer, improving the symptomatic efficacy of levodopa in PD and adding to the patients' benefit.

Aged↗
PubMed2002

Enterovirus, mycoplasma and other infections as predictors for myocardial infarction.

OBJECTIVES: To study antibodies against five infectious agents for their prediction of major coronary events in men with and without evidence of coronary heart disease at baseline. DESIGN: A case-control study nested within a prospective population study. SUBJECTS: The study cases included 441 men 45-64 years old with nonfatal myocardial infarction or coronary death within a mean follow-up time of 10 years. A total of 165 men had already signs of heart disease at baseline, whilst 276 were apparently healthy at the beginning of the study. Two controls for each case were matched for age, heart disease status and place of residence. Antibodies against enterovirus, Mycoplasma pneumoniae, Chlamydia pneumoniae, cytomegalovirus and adenovirus were determined. RESULTS: Men without reported baseline heart disease, but not those with heart disease, showing the highest quartile of antibodies to enterovirus and mycoplasma or increased levels of immune complex-bound antibodies to chlamydia had a significantly higher risk of coronary events than men with lower level of antibodies. The increased risk demonstrated in men with high levels of antibodies to enterovirus and mycoplasma remained significant after adjustment for other antibodies, acute-phase reactant and conventional risk factors. Serological evidence of infection by multiple agents was also significantly associated with coronary events. CONCLUSIONS: Serological evidence for several infectious agents is associated with the risk of coronary heart disease, but only in men without baseline history of heart disease.

Acute-Phase Reaction↗
PubMed2002

Chlamydia pneumoniae inhibits apoptosis in human epithelial and monocyte cell lines.

Chlamydia pneumoniae is an obligate intracellular pathogen with a tendency to cause persistent infections that has been associated with many chronic conditions such as asthma and coronary artery disease. However, its immunopathogenic mechanisms are poorly understood. When aiming to study the impact of C. pneumoniae infection on host cell apoptosis, we found that epithelial infected (HL) cells and macrophages (U937-line) were resistant to staurosporine and tumour necrosis factor (TNF)-alpha-induced physiological apoptosis 48, 72 or 120 h post-infection, as determined by flow cytometry, DNA fragmentation assay and fluorescence microscopy. The antiapoptotic influence was observed even at a late stage of the chlamydial life cycle and was dependent on the chlamydial protein synthesis. The mechanisms involved blockage of mitochondrial cytochrome c release and caspase 3 activation. We also found that during a persistent C. pneumoniae infection induced in vitro by penicillin treatment of cell cultures, the inhibition of apoptosis was extended for up to 120 h of follow-up post-infection and was restricted to the cells carrying chlamydial inclusions. Our findings suggest that inhibition of apoptosis may be one of the pathogenetic mechanisms by which C. pneumoniae infection can mediate the development of chronic diseases.

Apoptosis↗
PubMed2002

Effect of acute Chlamydia pneumoniae infection on lipoprotein metabolism in NIH/S mice.

Chlamydia pneumoniae is a well-known cause of respiratory infections, globally. Chronic C. pneumoniae infection has been associated with atherosclerosis. The aim of the present study was to investigate the effects of acute C. pneumoniae infection on serum lipid levels and some regulatory proteins/enzymes in NIH/S mice. Female mice (n=30) were intranasally infected with 5.3*10(5) inclusion forming units (IFU) of C. pneumoniae and control mice (n = 30) were inoculated with buffer. Six uninoculated mice at day 0 and then six mice from each group 3, 6, 9, 14 and 20 days post-inoculation were killed and serum samples were collected for analysis. Successful infection was confirmed by IgG response to C. pneumoniae and positive Chlamydia cultivation from the lungs. Serum triglycerides and total cholesterol, as well as the activities of hepatic lipase (HL), lecithin-cholesterol acyltransferase (LCAT) and phospholipid transfer protein (PLTP) and the concentration of lipopolysaccharide-binding protein (LBP) were analyzed. In C. pneumoniae infected mice, a minor change in triglyceride (corrected p-value 0.020) levels was observed 9 days post-infection (p.i.). LCAT activity declined remarkably, and the lowest activities were measured on day 9 p.i. (67% from the baseline value). HL and PLTP activities did not differ from those in the control group during the whole experimental period. There was a 2.5-fold increase in the serum LBP concentration owing to the C. pneumoniae infection 9 days p.i. The data indicate that acute C. pneumoniae infection, although clinically almost asymptomatic, causes small, transient changes in serum total lipids and some key proteins involved in lipoprotein metabolism in mice.

Acute Disease↗
PubMed2001

Microbial etiology of community-acquired pneumonia in the adult population of 4 municipalities in eastern Finland.

To determine the etiology of community-acquired pneumonia in the adult population of a defined area, specific antibody responses in paired serum samples, levels of circulating pneumococcal immune complexes in serum samples, and pneumococcal antigen in urine were measured. Samples (304 paired serum samples and 300 acute urine samples) were obtained from 345 patients > or =15 years old with community-acquired, radiologically confirmed pneumonia, which comprised all cases in the population of 4 municipalities in eastern Finland during 1 year. Specific infecting organisms were identified in 183 patients (including 49 with mixed infection), as follows: Streptococcus pneumoniae, 125 patients; Haemophilus influenzae, 12; Moraxella catarrhalis, 8; chlamydiae, 37 (of which, Chlamydia pneumoniae, 30); Mycoplasma pneumoniae, 30; and virus species, 27. The proportion of patients with pneumococcal infections increased and of those with Mycoplasma infections decreased with age, but for each age group, the etiologic profile was similar among inpatients and among outpatients. S. pneumoniae was the most important etiologic agent. The annual incidence of pneumococcal pneumonia per 1000 inhabitants aged > or =60 years was 8.0.

Adolescent↗
PubMed2001

Infectious etiologies in acute exacerbation of COPD.

Acute exacerbation (AE) is a frequent episode during the prolonged chronic course of chronic obstructive pulmonary disease (COPD), which entails significant morbidity and mortality. The purpose of this study was to determine the frequency distribution of infectious etiologies in these episodes. Two hundred forty hospitalizations for AECOPD were included in a prospective, purely serologically based study. Paired sera were obtained for each of the hospitalizations and were tested using immunofluorescence or EIA methods to identify 13 different pathogens. Only significant changes in antibody titers were considered diagnostic. The mean age ( +/- SD) of the patients was 66.8 +/- 9.0 years and 179 (84%) were males. In 175 (72.9%) hospitalizations at least one infectious etiology was identified. In 117 (48.8%) hospitalizations at least one of 7 viral etiologies was identified. In 72 (30.0%) hospitalizations at least one of the following atypical bacteria was identified: Legionella spp. in 40 (16.7%), Mycoplasma pneumoniae in 34 (14.2%), and Coxiella burnetii in a single hospitalization. In 58 (24.2%) hospitalizations at least one classic bacterial etiology was found: Streptococcus pneumoniae in 48 (20.0%), Hemophilus influenzae in 10 (4.2%) and Moraxella catarrhalis in 9 (3.8%). More than one etiology was found in 72 (30.0%) hospitalizations. There were no significant differences in the etiologic distribution when the patients were classified by severity of airway obstruction or the clinical type of the exacerbation. We conclude that in most cases of hospitalization due to AECOPD the infectious etiology is viral or atypical bacteria and is classic bacteria in only a minority of cases. More than one etiologic cause can be identified in a third of the cases. The frequency distribution of the etiologies is not associated with the severity of airway obstruction or the clinical type of the exacerbation. The results of our study suggest that atypical bacteria should be covered in antibiotic regimens recommended for AECOPD. This issue should be addressed in future studies.

Adult↗
PubMed2001

Twelve-month safety of entacapone in patients with Parkinson's disease.

The safety of entacapone combined with levodopa and a dopadecarboxylase (DDC) inhibitor was tested in a 12-month double-blind study of 326 patients with idiopathic Parkinson's disease (PD). The study population represented 'typical' PD outpatients, including patients with varying disease severity and with various concomitant medications. Two-thirds of the patients were randomized to receive 200 mg of entacapone with each of 2--10 daily levodopa doses, and one-third to receive placebo. All entacapone patients were included in the safety evaluation of adverse events (AEs), vital signs, ECG, and laboratory parameters. Entacapone was well tolerated with a discontinuation rate due to AEs of 14% compared with 11% with placebo (NS). As expected, due to dopaminergic enhancement, dyskinesia was more frequent as an AE with entacapone than with placebo. Dryness of mouth, urine discoloration and diarrhoea were more frequent non-dopaminergic AEs with entacapone than with placebo. Entacapone had no adverse effects on hepatic enzyme activity, ECG or haemodynamic parameters, and there was no evidence of any toxicity. As an indication of levodopa enhancement with entacapone, patients taking 5--10 doses of levodopa, most likely representing predominantly fluctuating patients, showed a significant decrease in their mean daily levodopa dose of 94 mg in the entacapone group compared with a decrease of 39 mg in the placebo group (P < 0.01). The interval between the first two morning doses of levodopa increased by 17% with entacapone, whereas with placebo no extension was observed (P < 0.05). Despite levodopa dose reduction, efficacy of entacapone was maintained. As further evidence of efficacy, Parkinsonian symptoms markedly worsened in all patients after withdrawal of entacapone. We conclude that entacapone is safe in optimizing levodopa in long-term treatment of idiopathic Parkinson's disease. Monitoring of liver or other safety parameters during entacapone treatment is not required.

Aged↗
PubMed2001

Use of doxycycline to decrease the growth rate of abdominal aortic aneurysms: a randomized, double-blind, placebo-controlled pilot study.

OBJECTIVE: Eradication of Chlamydia pneumoniae infection and inhibition of elastolytic matrix metalloproteinases with doxycycline have been suggested to reduce the growth rates of small abdominal aortic aneurysms (AAA). We designed a study to investigate the efficacy of doxycycline in reducing the expansion of small AAAs. SUBJECTS AND METHODS: This was a prospective, double-blind, randomized, placebo-controlled study that was set in a university referral hospital. The study group consisted of 32 of 34 initially eligible patients who had an AAA diameter perpendicular to the aortic axis of 30 mm or more in size or a ratio of infrarenal to suprarenal aortic diameter of 1.2 or more and a diameter less than 55 mm. Patients were randomly assigned to receive either doxycycline (150 mg daily) or placebo during a 3-month period and underwent ultrasound surveillance during an 18-month period. Outcome measures included aneurysm expansion rates, the number of patients who had AAA rupture or repair, C pneumoniae antibody titers, and serum concentrations of C-reactive protein. RESULTS: The aneurysm expansion rate in the doxycycline group was significantly lower than that in the placebo group during the 6- to 12-month (P = .01) and the 12- to 18-month periods (P =.01). Five patients (41%) in the placebo group and 1 patient (7%) in the doxycycline group had an overall expansion of the aneurysm of 5 mm or more during the 18-month follow-up. Among the placebo group patients, a higher expansion rate was observed in those with enhanced C pneumoniae immunoglobulin G antibody titers (> 128) than in those with lower titers (P = .03). Doxycycline treatment had no clear effect on antibody titers. However, at 6-month follow-up, C-reactive protein levels in the doxycycline group were significantly lower than the baseline levels (P = .01). CONCLUSIONS: The results of this small pilot study suggest that doxycycline may favorably alter the outcome of patients with small AAA. However, because of the small size of this randomized study and of the potentially confounding effect of pretreatment risk factors, doxycycline-based treatment cannot be justified only on the ground of the current results. Because of the high prevalence of this disorder and its clinical, social, and economic relevance, a multicenter study should be performed to further investigate whether there is any place for medical treatment of small AAAs.

Aged↗