Evaluation of an individually tailored smoking-cessation intervention for patients with rheumatoid arthritis in an outpatient clinic.

OBJECTIVE: The aim of this study was to evaluate an individually tailored smoking-cessation intervention delivered in rheumatology care and compare the characteristics of patients who quit smoking with those who did not. METHOD: This was an open single-group prospective intervention study over 24 months, with assessments at baseline and at 6, 12, 18, and 24 months. Current smokers with rheumatoid arthritis (RA) were invited to a smoking-cessation programme including behavioural change support, with or without pharmacotherapy. Data on disease activity, medical treatment, and patient-reported outcomes were retrieved from the Swedish Rheumatology Quality Register. The primary outcome was the proportion of patients at month 24 who reported having quit smoking with self-reported 7 day smoking abstinence. RESULTS: In total, 99 patients participated in the study. Median age was 58 years (interquartile range 50-64); 69% were female and 88% rheumatoid factor and/or anti-cyclic citrullinated peptide positive. At 24 months, 21% of the patients had quit smoking. At 6, 12, and 18 months, 12%, 12%, and 14% of patients, respectively, had quit smoking. For patients still smoking at 24 months, the median number of cigarettes per day was significantly reduced from 12 to 6 (p ≤ 0.001). Among patients who had quit smoking at 24 months, a smaller proportion reported anxiety at baseline compared to those still smoking (28% vs 58%, p = 0.02). CONCLUSION: A smoking-cessation intervention including behavioural change support with or without pharmacotherapy can be helpful for a substantial number of RA patients. Anxiety is associated with lower smoking-cessation success rates.

Application of 1H NMR spectroscopy to the metabolic phenotyping of rodent brain extracts: A metabonomic study of gut microbial influence on host brain metabolism.

1H NMR Spectroscopy has been applied to determine the neurochemical profiles of brain extracts from the frontal cortex and hippocampal regions of germ free and normal mice and rats. The results revealed a number of differences between germ free (GF) and conventional (CV) rats or specific pathogen-free (SPF) mice with microbiome-associated metabolic variation found to be both species- and region-dependent. In the mouse, the GF frontal cortex contained lower amounts of creatine, N-acetyl-aspartate (NAA), glycerophosphocholine and lactate, but greater amounts of choline compared to that of specific pathogen free (SPF) mice. In the hippocampus, the GF mice had greater creatine, NAA, lactate and taurine content compared to those of the SPF animals, but lower relative quantities of succinate and an unidentified lipid-related component. The GF rat frontal cortex contained higher relative quantities of lactate, creatine and NAA compared to the CV animals whilst the GF hippocampus was characterized by higher taurine and phosphocholine concentrations and lower quantities of NAA, N-acetylaspartylglutamate and choline compared to the CV animals. Of note is that, in both rat and mouse brain extracts, concentrations of hippocampal taurine were found to be greater in the absence of an established microbiome. The results provide further evidence that brain biochemistry can be influenced by gut microbial status, specifically metabolites involved in energy metabolism demonstrating biochemical dialogue between the microbiome and brain.

A comparison of patients' and physicians' assessments of disease activity using the Swedish version of the Systemic Lupus Activity Questionnaire.

OBJECTIVES: We compared patients' assessments of systemic lupus erythematosus (SLE) disease activity by a Swedish version of the Systemic Lupus Activity Questionnaire (SLAQ) with physicians' assessments by the Systemic Lupus Activity Measure (SLAM) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). We also explored the performance of the SLAQ in patients with short (< 1 year) versus long (≥ 1 year) disease duration. METHOD: Patients filled out the SLAQ before physicians' assessments. Correlations between SLAQ total, subscales (Symptom score, Flares, Patients global) and SLAM and SLEDAI-2K, as well as between the corresponding items in SLAQ and SLAM, were evaluated using Spearman's ρ. Comparisons between patients with different disease durations were performed with Mann-Whitney U or chi-squared tests. RESULTS: We included 203 patients (79% women), with a median age of 45 years [interquartile range (IQR) 33-57 years] and disease duration of 5 years (IQR 0-14 years). Correlations between physicians' SLAM without laboratory items (SLAM-nolab) and patients' assessments were: SLAQ total, ρ = 0.685, Symptom score, ρ = 0.651, Flares, ρ = 0.547, and Patients global, ρ = 0.600. Of the symptom items, fatigue (ρ = 0.640), seizures (ρ = 0.635), and headache (ρ = 0.604) correlated most closely. Neurology/stroke syndrome, skin, and lymphadenopathy correlated less well (ρ < 0.24). Patients' and physicians' assessments were notably more discordant for patients with short disease durations. CONCLUSION: We confirm that the SLAQ can be used to monitor disease activity. However, the discrepancy between patients' and physicians' assessments was greater for patients with short versus long disease duration. We encourage further use of the SLAQ, but would like to develop a shorter version which would be valuable in modern, partly web-based, clinical care.

Physical therapists' assessments, analyses and use of behavior change techniques in initial consultations on musculoskeletal pain: direct observations in primary health care.

BACKGROUND: Behavioral medicine (BM) treatment is recommended to be implemented for pain management in physical therapy. Its implementation requires physical therapists (PTs), who are skilled at performing functional behavioral analyses based on physical, psychological and behavioral assessments. The purpose of the current study was to explore and describe PTs' assessments, analyses and their use of behavioral change techniques (BCTs) in initial consultations with patients who seek primary health care due to musculoskeletal pain. METHODS: A descriptive and explorative research design was applied, using data from video recordings of 12 primary health care PTs. A deductive analysis was performed, based on a specific protocol with definitions of PTs' assessment of physical and psychological prognostic factors (red and yellow flags, respectively), analysis of the clinical problem, and use of BCTs. An additional inductive analysis was performed to identify and describe the variation in the PTs' clinical practice. RESULTS: Red and yellow flags were assessed in a majority of the cases. Analyses were mainly based on biomedical assessments and none of the PTs performed functional behavioral analyses. All of the PTs used BCTs, mainly instruction and information, to facilitate physical activity and improved posture. The four most clinically relevant cases were selected to illustrate the variation in the PTs' clinical practice. The results are based on 12 experienced primary health care PTs in Sweden, limiting the generalizability to similar populations and settings. CONCLUSION: Red and yellow flags were assessed by PTs in the current study, but their interpretation and integration of the findings in analyses and treatment were incomplete, indicating a need of further strategies to implement behavioral medicine in Swedish primary health care physical therapy.

Determination of the minimal clinically important difference for seven measures of fatigue in Swedish patients with systemic lupus erythematosus.

OBJECTIVE: To estimate the minimal clinically important difference (MCID) in seven self-administered measures assessing fatigue in Swedish patients with systemic lupus erythematosus (SLE). METHOD: The participants (n = 51, women 98%, age 52.8 ± 12.1 years, disease duration 18.7 ± 13.6 years) met in groups of six to nine persons. After completing seven fatigue questionnaires [the Fatigue Severity Scale (FSS); the Multidimensional Assessment of Fatigue (MAF) scale; the 20-item Multidimensional Fatigue Inventory (MFI); the Chalder Fatigue Scale (CFS); the Short Form-36 Vitality subscale (VT); the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) scale; and the Numeric Rating Scale (NRS)], each respondent had a minimum of five face-to-face discussions, followed by an individual comparative assessment of their own level of fatigue (seven-grade scale). This method resulted in 260 contrasting assessments; MCIDs were first calculated using the paired differences and then established by a regression approach. Patients were asked to comment on their experience with the questionnaires and whether they captured their fatigue adequately. RESULTS: The paired approach (using 'little more fatigue' as an anchor for MCID during the face-to-face comparative assessments) provided estimates of 4.6-17.0; the regression approach provided estimates of 4.3-10.8. Estimates using the regression approach were consistently lower than those using the paired model. The MCID estimates were least favourable and fewer respondents supported the use of the NRS compared to the other self-reported questionnaires. CONCLUSIONS: All seven instruments detect MCIDs for fatigue in Swedish patients with SLE. However, the single-question measure was not supported by the MCID estimates or by comments from the respondents.

Lifestyle habits and fatigue among people with systemic lupus erythematosus and matched population controls.

OBJECTIVE: The objective of this paper is to identify clusters of fatigue in patients with systemic lupus erythematosus (SLE) and matched controls, and to analyze these clusters with respect to lifestyle habits, health-related quality of life (HRQoL), anxiety and depression. METHODS: Patients with SLE (n = 305) and age- and gender-matched population controls (n = 311) were included. Three measurements of fatigue (Fatigue Severity Scale (FSS), Vitality (VT, from SF-36) and Multidimensional Assessment of Fatigue scale (MAF) and hierarchic cluster analysis were used to define clusters with different degrees of fatigue. Lifestyle habits were investigated through questionnaires. HRQoL was assessed with the SF-36 and anxiety/depression with the Hospital Anxiety and Depression Scale. RESULTS: Three clusters, denominated "High," "Intermediate" and "Low" fatigue clusters, were identified. The "High" contained 80% patients, and 20% controls (median; VT 25, FSS 5.8, MAF 37.4). These had the most symptoms of depression (51%) and anxiety (34%), lowest HRQoL (p < 0.001) and they exercised least frequently. The "Intermediate" (48% patients and 52% controls) (median; VT 55, FSS 4.1, MAF 23.5) had similarities with the "Low" regarding sleep/rest whereas social status and smoking were closer to the "High." The"Low" contained 22% patients and 78% controls (median; VT 80, FSS 2.3, MAF 10.9). They had the highest perceived HRQoL (p < 0.001), least symptoms of anxiety (10%), no depression, smoked least (13%) and reported the highest percentage (24%) of exercising ≥ 3 times/week. CONCLUSION: Fatigue is common, but not a general feature of SLE. It is associated with depression, anxiety, low HRQoL and less physical exercise. Patients with SLE and population controls with a healthy lifestyle reported lower levels of fatigue. Whether lifestyle changes can reduce fatigue, which is a major problem for a majority of SLE patients, needs to be further explored.

Constitutive TLR4 signalling in intestinal epithelium reduces tumor load by increasing apoptosis in APC(Min/+) mice.

The microbial pattern-recognizing Toll-like receptors (TLRs) are major signal transducers known to shape and influence the postnatal maturation of host intestinal epithelium. Perturbations in this intricate host-microbe cross-talk have been reported to be associated with uncontrolled epithelial cell growth and thus potential cancer development by mechanisms which are largely unknown. We therefore generated transgenic mice carrying a constitutively active TLR4 (CD4-TLR4) linked to an intestinal epithelial cell-specific promoter. Ex vivo analysis of transgenic crypt-villus organoid cultures revealed an increased proliferative capacity and a lowered cyclooxygenase 2 (Cox-2) expression in these organoids compared with wild-type control cultures. Introducing the CD4-TLR4 transgene into APC(Min/+) mice (CD4-TLR4-APC(Min/+)), a model of colorectal carcinoma, resulted in a dramatic drop in tumor load as compared with control APC(Min/+) mice. Intestinal tumors from CD4-TLR4-APC(Min/+) mice displayed reduced Cox-2 protein, elevated interferon ß expression and increased caspase-3 activity, which correlated with increased apoptosis in vivo. Thus, our data reveal that host microbiota-mediated signal transduction via TLR4 in intestinal epithelial cells is far more complex than what is previously reported.

Health-related quality of life, fatigue and mood in patients with SLE and high levels of pain compared to controls and patients with low levels of pain.

Objective The objective of this paper is to investigate health-related quality of life (HRQoL), fatigue, anxiety and depression in patients with systemic lupus erythematosus (SLE) and higher levels of pain and to compare them to patients with lower levels of pain and controls. Method Patients were dichotomized into two groups based on SLE-related pain score on the visual analog scale (VAS): low-pain group (76%, n=64, VAS 0-39 mm) and high-pain group (24%, n=20, VAS 40-100 mm). Sex- and age-matched controls were randomly selected from the general population. Participants were asked to complete questionnaires regarding self-reported pain, HRQoL, fatigue, anxiety and depression. Medical assessments also were recorded. Result Fatigue score in the high-pain group (median, 36.5; interquartile range (IQR), 32.5-39.7) was significantly higher (p<0.001) compared to the low-pain group (median, 23; IQR, 14.6-34.1), as well as scores for anxiety (median, 9; IQR, 6.5-11.5) and depression (median, 7.5; IQR, 5.5-9) (p<0.001). The high-pain group had significantly lower scores compared to the low-pain group in all dimensions in the SF-36 (p ≤ 0.001-0.007). No statistical differences were detected between the low-pain group and controls in any measurement except for the dimensions physical function, general health, vitality and social function in SF-36. Conclusion Patients with SLE scoring higher degrees of pain were burdened with more fatigue, anxiety and depression and lower levels of HRQoL compared to patients with lower levels of pain who did not differ significantly from the general population in most dimensions. These results elucidate the importance of identifying patients with higher degrees of pain who are probably in need of more extensive multidimensional interventions to decrease symptom burden.

Lipocalin 2 performs contrasting, location-dependent roles in APCmin tumor initiation and progression.

Evidence that lipocalin 2 (LCN2) is oncogenic has grown in recent years and comes from both animal models and expression analysis from a variety of human cancers. In the intestine, LCN2 is overexpressed in colitis patients and its overexpression is a negative prognostic indicator in colorectal cancer. Functionally, LCN2 has a number of different activities that may contribute to its oncogenic potential, including increasing matrix metalloproteinase activity, control of iron availability and stimulating inflammation. In this report, we examined APCmin intestinal tumorigenesis in an LCN2-deficient background. We found that the loss of LCN2 increased tumor multiplicity specifically in the duodenum, suggesting a potential tumor-suppressive activity. Concurrently, however, LCN2 increased the average small intestinal tumor size particularly in the distal small intestine. We found that this increase was correlated to tumor iron(II) content, suggesting that an iron-scavenging role is important for LCN2 oncogenic activity in the intestine.

An exploration of patient-reported symptoms in systemic lupus erythematosus and the relationship to health-related quality of life.

OBJECTIVE: The aim of this study was to explore the most distressing symptoms of systemic lupus erythematosus (SLE) and determine how these relate to health-related quality of life (HRQoL), anxiety/depression, patient demographics, and disease characteristics (duration, activity, organ damage). METHODS: In a cross-sectional study, patients with SLE (n = 324, age 18-84 years) gave written responses regarding which SLE-related symptoms they experienced as most difficult. Their responses were categorized. Within each category, patients reporting a specific symptom were compared with non-reporters and analysed for patient demographics, disease duration, and results from the following questionnaires: the Medical Outcomes Study 36-item Short Form Health Survey (SF-36), the Hospital Anxiety and Depression Scale (HADS), the Systemic Lupus Activity Measure (SLAM), the SLE Disease Activity Index (SLEDAI), and the Systemic Lupus International Collaboration Clinics/American College of Rheumatology (SLICC/ACR) damage index. RESULTS: Twenty-three symptom categories were identified. Fatigue (51%), pain (50%), and musculoskeletal distress (46%) were most frequently reported. Compared with non-reporters, only patients reporting fatigue showed a statistically significant impact on both mental and physical components of HRQoL. Patients with no present symptoms (10%) had higher HRQoL (p < 0.001) and lower levels of depression (p < 0.001), anxiety (p < 0.01), and disease activity (SLAM) (p < 0.001). CONCLUSION: Fatigue, pain, or musculoskeletal distress dominated the reported symptoms in approximately half of the patients. Only patients reporting fatigue scored lower on both mental and physical aspects of HRQoL. Our results emphasize the need for further support and interventions to ease the symptom load and improve HRQoL in patients with SLE. Our findings further indicate that this need is particularly urgent for patients with symptoms of pain or fatigue.

Digital in-line holography on amplitude and phase objects prepared with electron beam lithography.

We report on the fabrication and characterization of amplitude and phase samples consisting of well defined Au or Al features formed on ultrathin silicon nitride membranes. The samples were manufactured using electron beam lithography, metallization and a lift-off technique, which allow precise lateral control and thickness of the metal features. The fabricated specimens were evaluated by conventional microscopy, atomic force microscopy and with the digital in-line holography set-up at the Lund Laser Centre. The latter uses high-order harmonic generation as a light source, and is capable of recovering both the shape and phase shifting properties of the samples. We report on the details of the sample production and on the imaging tests with the holography set-up.

Physical activity in patients with systemic lupus erythematosus and matched controls.

BACKGROUND: As physical activity reduces cardiovascular disease (CVD) in the general population, studies concerning the frequency of physical activity in patients with systemic lupus erythematosus (SLE) are needed. Earlier studies indicate that patients with SLE are physically inactive but there are few studies that compare physical activity in SLE to that in the general population. The aim of this study was to examine different aspects of physical activity in patients with SLE and population controls and to investigate how they relate to disease activity and organ damage. METHODS: Two hundred and seventy-two patients with SLE and 272 population controls, individually matched for age, gender, and living region, were investigated clinically. For patients, the investigation included assessment of disease activity using the SLE Disease Activity Index (SLEDAI) and organ damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC) Damage Index. All participants filled out an extensive questionnaire concerning physical activity, exercise capacity, and sedentary behaviour. RESULTS: The mean age of the patients was 47 (SD 15) years. Patients reported lower (p < 0.001) capacity for walking, jogging, and running and more limiting factors for these activities than controls (p < 0.001). Patients exercised less often than controls (p < 0.01) and patients with SLICC ≥ 2 points reported less physical activity on 'low to moderate' intensity compared to their controls (p < 0.05). Sedentary behaviour was reported by 18% of the patients and 26% of the controls (ns). CONCLUSION: Patients with SLE reported lower exercise capacity and less frequent exercise than controls. Additionally, patients with more organ damage reported less physical activity, and these, together with patients who have a sedentary behaviour, should be the focus of intervention programmes to support increased physical activity and exercise in SLE.

Paediatric drug use with focus on off-label prescriptions in Swedish outpatient care--a nationwide study.

AIM: To determine drug prescription and proportion of off-label dispensing in the Swedish paediatric outpatient population. METHODS: All dispensed outpatient prescriptions to children aged 0 < 18 years as well as the proportion of off-label drug use during 2007 were analysed using data from the Swedish Prescribed Drug Register. RESULTS: In total, 2.19 million drug prescriptions of 898 different drug substances were dispensed to paediatric patients, and of those substances, 64% had been dispensed off-label at least once. The overall off-label rate of all prescriptions was 13.5%, among which topical drugs as well as sex hormones were the most commonly prescribed off-label drugs. More than half of all children in Sweden had received at least one prescribed drug in 2007. CONCLUSIONS: There is a high prescribing of medicines to children in outpatient care in Sweden with a considerable amount of off-label prescriptions. Topically administered drugs, sex hormones, antidepressants, hypnotics, cardiovascular drugs and nonsteroidal anti-inflammatory drugs were commonly prescribed off-label.

Vaccination against nicotine alters the distribution of nicotine delivered via cigarette smoke inhalation to rats.

Preclinical models of nicotine vaccine pharmacology have relied on i.v. or s.c. administration of nicotine. Models using cigarette smoke inhalation might more accurately simulate nicotine exposure in smokers. Nicotine vaccine effects were examined in rats using two cigarette smoke exposure models: a 10 min nose-only exposure (NSE) producing serum nicotine levels equivalent to the nicotine boost from 1 cigarette in a smoker, and a 2h whole-body exposure (WBE) producing serum nicotine levels similar to those associated with regular mid-day smoking. Vaccination prior to 10min smoke NSE reduced nicotine distribution to brain by 90%, comparable to its effect on nicotine administered i.v. Vaccination prior to 2 h smoke WBE reduced nicotine distribution to brain by 35%. The nicotine concentration in broncheoalveolar lavage (BAL) fluid obtained after 2 h WBE was increased by 230% in vaccinated rats but was also increased in rats passively immunized with a nicotine-specific monoclonal antibody, and so was likely due to transfer of antibody from serum rather than local production at the pulmonary mucosa. Nicotine-specific IgA was not detectable in BAL fluid, but titers in serum were appreciable at 21-25% of the IgG titer and could contribute to vaccine efficacy. Both vaccination and passive immunization are effective in reducing nicotine distribution to brain in rats when nicotine is delivered via inhaled cigarette smoke. These data validate results previously obtained in rodents for nicotine vaccines using i.v. or s.c. nicotine dosing and provide a quantitative method for studying aspects of nicotine exposure which are unique to cigarette smoke inhalation.

Expression profile of nuclear receptors upon Epstein -- Barr virus induced B cell transformation.

BACKGROUND: Infection of human B cells with Epstein - Barr virus (EBV) induces metabolic activation, morphological transformation, cell proliferation and eventual immortalization. AIM: To identify the nuclear receptors, which are the cellular interaction partners of EBNAs, that will help to elucidate the mechanism of B cell transformation. METHODS: We have compared the nuclear receptor profile in the naïve and EBV-transformed B-lymphocytes, using TaqMan LDA microfluidic card technology. RESULTS: Out of 48 nuclear receptor, 17 showed differential expression at the mRNA level. The expression of 5 genes was elevated in EBV-transformed cells, whereas 12 genes were downregulated in lymphoblastoid cells (LCLs). 7 genes were studied at the protein level; 2 genes were up regulated (Nr2F2 and RARA) and 4 genes were down regulated (ERB, NUR77, PPARG, and VDR) in LCLs. CONCLUSION: The nuclear receptor profiling on EBV infected B cells showed alterations of nuclear receptors expression at both mRNA and protein levels compared with non infected peripheral blood cells. Further analysis on a possible role of each nuclear receptor in EBV induced cell transformation should be performed.

High-speed structured planar laser illumination for contrast improvement of two-phase flow images.

A high-speed method to remove blurring effects caused by multiple scattering in planar laser images of two-phase flows is demonstrated. The technique is based on structured illumination and is for the first time to our knowledge applied on a dynamic medium. As structured illumination requires three successive images to be recorded and to freeze the flow motion in time, a high-speed laser and imaging system is employed. We show that by using a time delay of 55 micros between the images a single-shot representation of a dilute flow of water droplets can be achieved. By having an additional inner stream with known structure and composition, the efficiency of the method is quantitatively evaluated, showing an increase from 58% to 93% in image contrast. Such an improvement allows more accurate analysis and interpretation of scattering two-phase flow images.

The importance of IgE antibody levels in anti-IgE treatment.

BACKGROUND: Dosages of anti-immunoglobulin (Ig)E in treatment of allergic asthma is based on total IgE body pool assuming that IgE antibodies responsible for the disease are evenly distributed among patients. This assumption was evaluated. METHODS: Median and quartile concentrations of IgE and IgE antibodies to cat and mite in 6461 sera submitted to an allergy laboratory during 2003-2005 were calculated and expressed in groups of different IgE levels. RESULTS: Of 3872 (60%) samples from adults with a serum IgE level of 30-700 kU/l, 22.2% had IgE antibodies (>or=0.35 kU(A)/l) to mite, 36.0% to cat and 8.1% to both. The relative concentration of IgE antibody of IgE decreased with increasing IgE, indicating a more specific response in patients with slightly elevated serum IgE. At a hypothetical serum IgE level of 10 kU/l, the threshold recommended for anti-IgE treatment, 25% of the originally mite- and/or cat-positive population in the <75 kU/l IgE group still would have detectable IgE antibodies. CONCLUSIONS: Sera from patients sensitized to mite and cat with moderate serum IgE levels have a high proportion of IgE antibodies; in the 30-74 kU/l group, as much as 10% of the IgE could be specific to one allergen. An increase of the anti-IgE dosage given to such patients should be considered, especially because IgE antibodies with different, relevant specificities have an additive effect in triggering inflammatory cells.

Recent advances in combinatorial chemistry applied to development of anti-HIV drugs.

A compilation of combinatorial chemistry techniques applied to anti-HIV drug development is presented in this review. This synthetic strategy together with high throughput screening assays has allowed the discovery and optimization of novel lead anti-HIV compounds.

Genotype-phenotype relationships in an investigation of the role of proteases in abdominal aortic aneurysm expansion.

BACKGROUND: The aim of the study was to investigate the effect of functional polymorphisms in promoters of matrix metalloproteinase (MMP) 2, MMP-3, MMP-9, MMP-12 and plasminogen activator inhibitor (PAI) 1 genes on the growth rate of small abdominal aortic aneurysms (AAA). METHODS: Some 455 individuals with a small AAA (4.0-5.5 cm) were monitored for aneurysm growth by ultrasonography (mean follow-up 2.6 years). They also provided a DNA sample for analysis of the -1306 C > T, -1171 5A > 6A, -1562 C > T, -82 A > G and -675 4G > 5G alleles of MMP-2, MMP-3, MMP-9, MMP-12 and PAI-1, respectively. Mean linear AAA growth rates were calculated by flexible modelling; the sample size was sufficient to detect variants that influenced the growth rate by 25 per cent. RESULTS: For MMP-2, MMP-9 and MMP-12 genotypes, growth rates were similar to the mean linear growth rate of 3.08 mm per year. For MMP-3, growth rates were 3.05 (for 5A5A), 3.19 (for 5A6A) and 2.90 (for 6A6A) mm per year. For PAI-1, patients with 4G4G, 4G5G and 5G5G genotypes had growth rates of 3.18, 2.92 and 3.47 mm per year, respectively, for aneurysms with a baseline diameter of 45.1, 44.6 and 46.2 mm. The increased growth rate for patients with PAI-1 5G5G genotype was not statistically significant (P = 0.061), although these patients had the lowest plasma PAI-1 concentrations (P = 0.018). CONCLUSION: There was no evidence that any specific MMP polymorphism had a clinically significant effect on AAA expansion. The plasminogen system may have a small but clinically significant role in AAA development. Much larger studies would be needed to evaluate genes of smaller effect.