High frequency of lipoprotein risk levels for cardiovascular disease in Takayasu arteritis

The objective of this study is to characterize the lipoprotein risk levels in Takayasu arteritis (TA) patients and its possible association with disease activity and glucocorticoid use. Twenty-five female TA patients were consecutively included and compared with 30 age-, gender-, and body mass index-matched healthy controls. Demographic features and the lipid profile were determined and cardiovascular risk levels were evaluated according to NCEP/ATPIII. Total cholesterol (TC), LDL-c, HDL-c, and triglycerides were determined after a 12-h overnight fast. Exclusion criteria were conditions that interfere in the lipid profile. The disease duration was 6.6 ± 7.4 years; 30% had clinical activity and 80% had laboratory activity. Regarding NCEP/ATPIII risk levels, TA patients presented higher frequency of lipid risk compared to controls: high TC (48% vs. 20%, p = 0.04), low HDL-c (20% vs. 0%, p = 0.015), and high triglycerides (36% vs. 10%, p = 0.026). No difference was observed related to LDL-c risk levels between both groups (40% vs. 20%, p = 0.14). Remarkably, 60% of the patients had at least one lipid risk factor for cardiovascular disease. No difference in the lipids was observed between patients with and without clinical activity; however, those with laboratory activity showed lower levels of HDL-c (1.37 ± 0.42 vs. 2.00 ± 0.63 mmol/L, p = 0.012) than patients without this activity. A negative correlation was found between HDL-c and CRP levels (r = −0.42, p = 0.04). Lipids were similar in patients under glucocorticoid compared to those without this therapy. This is the first study to identify that TA, an inflammatory disease, has a proatherogenic lipid profile which is associated to laboratory disease activity.     

Risk factors for cardiovascular disease and endothelin-1 levels in Takayasu arteritis patients

The objective of this study was to evaluate traditional risk factors for cardiovascular disease (CVD) and endothelin-1 (ET-1) levels in Takayasu arteritis (TA) patients. Twenty-two TA patients and 37 controls were evaluated. TA patients had a higher prevalence of hypertension (63.6% vs. 21.6%, p = 0.001) and higher levels of triglycerides (129.5 mg/dL ± 70.8 vs. 88.4 mg/dL ± 60.8, p = 0.017) than controls. Mean number of CVD risk factors was 1.64 ± 1.22 in TA patients and 1.03 ± 1.44 among controls, p = 0.030. More TA patients presented at least one CVD risk factor when compared to controls (77.2% vs. 51.3%, p = 0.048). ET-1 levels were higher in patients than in controls (1.49 pg/mL ± 0.45 vs. 1.27 pg/mL ± 0.32, p = 0.034), however no significant difference was found between patients with active and inactive disease. In this study, TA patients presented a higher prevalence of hypertension, higher levels of triglycerides, and ET-1 than controls.     

Mizoribine attenuates renal injury and macrophage infiltration in patients with severe lupus nephritis

The purine synthesis inhibitor mizoribine (MZR) has been successfully used without serious adverse effects in the treatment of several renal diseases including lupus nephritis. Besides its immunosuppressive effects, MZR has recently been reported to ameliorate tubulointerstitial fibrosis in rats via suppression of macrophage infiltration. However, there has been little information regarding the beneficial effects of MZR from the histologic standpoint in human lupus nephritis. Pre- and posttreatment renal biopsy specimens obtained from nine patients with diffuse proliferative lupus nephritis (DPLN) were divided into two groups (group A, five patients who received immunosuppressive treatment with MZR and group B, four patients who received immunosuppressive treatment without MZR) and histologically evaluated. Grading was done according to the 2003 classification system for lupus nephritis developed by the International Society of Nephrology/Renal Pathology Society, which considers the activity and chronicity indices, an immunohistologic study to assess intraglomerular and interstitial infiltration by macrophages, and the expression of osteopontin. Although in all the patients the posttreatment renal biopsy showed improvement of histologic grading and activity indices, group A patients showed a significant decrease of the chronicity indices and of intraglomerular infiltration by macrophages when compared to group B patients (2.6 ± 0.5 vs 4.0 ± 1.4 and 0.5 ± 0.2 vs 2.4 ± 1.9 cells per glomerulus, respectively; p < 0.05). Although this was a preliminary study in a small number of subjects, these histological observations may further confirm the beneficial effects of MZR for selected patients with DPLN.     

Long-term Follow-up of Patients Undergoing Postconditioning During ST-Elevation Myocardial Infarction

Reperfusion injury may offset the optimal salvage of myocardium achieved during primary coronary angioplasty. Thus, coronary reperfusion must be combined with cardioprotective adjunctive therapies in order to optimize myocardial salvage and minimize infarct size. Forty-three patients with their first ST-elevation myocardial infarction were randomized to myocardial postconditioning or standard of care at the time of primary coronary angioplasty. Postconditioning was performed immediately upon crossing the lesion with the guide wire and consisted of four cycles of 30 s occlusion followed by 30 s of reperfusion. End-points included infarct size, myocardial perfusion grade (MPG), left-ventricular ejection fraction (LVEF), and long-term clinical events (death and heart failure). Despite similar ischemic times (≅4.5 h) (p = 0.9) a reduction in infarct size was observed among patients treated with the postconditioning protocol. Peak creatine phosphokinase (CPK), as well as its myocardial band (MB) fraction, was significantly lower in the postconditioning group when compared with the control group (CPK—control, 2,444 ± 1,928 IU/L vs. PC, 2,182 ± 1,717 IU/L; CPK-MB—control, 242 ± 40 IU/L vs. PC, 195 ± 33 IU/L; p = 0.64 and p < 0.01, respectively). EF in the postconditioning group was improved when compared with the control group (control, 43% ± 15 vs. PC, 52% ± 9; p = 0.05). After a mean follow-up of 3.4 years, a 6-point absolute difference in LVEF was still evident in the postconditioning group (p = 0.18). MPG was better among patients treated with the postconditioning protocol compared with control (2.5 ± 0.5 vs. 2.1 ± 0.6; p = 0.02). Due to the small sample size no significant differences in clinical events were detected (p value for death = 0.9; p value for heart failure = 0.2). A simple postconditioning protocol applied at the onset of mechanical reperfusion, resulted in reduction of infarct size, better epicardial and myocardial flow, and improvement in left ventricular function. The beneficial effects of postconditioning on cardiac function persist beyond 3 years.     

Diabetic polyneuropathy is associated with respiratory muscle impairment in type 2 diabetes

Aims/hypothesis Diabetes has a major negative effect on intensive care unit outcome. This has been partly attributed to impaired respiratory neuromuscular function. However, data on respiratory neuromuscular involvement in diabetes are lacking. This study therefore aimed to assess respiratory neuromuscular function related to diabetic polyneuropathy in patients with type 2 diabetes. Methods Respiratory neuromuscular function was assessed by the use of volitional tests and twitch mouth (TwPmo) and twitch transdiaphragmatic (TwPdi) pressures during non-volitional bilateral anterior magnetic phrenic nerve stimulation in 21 male type 2 diabetic patients without pulmonary disease and in 23 healthy, well-matched controls (forced expiratory volume in 1 s 103 ± 11 vs 103 ± 12% predicted; p = 0.9). Results Both volitionally assessed maximal inspiratory and expiratory mouth pressures, and sniff nasal and transdiaphragmatic pressures were comparable between diabetic patients and controls (p > 0.1 for all). TwPmo was reduced in diabetic patients compared with controls (1.3 ± 0.5 vs 1.0 ± 0.4 kPa; p = 0.04), while TwPdi was comparable (1.7 ± 0.5 vs 1.6 ± 0.7 kPa; p = 0.6). Following subgroup analysis, patients with no or mild polyneuropathy (n = 10) as assessed by neurological disability scoring had normal respiratory neuromuscular function, whereas patients with moderate or severe polyneuropathy (n = 11) presented with markedly impaired respiratory neuromuscular function as indicated by TwPmo (1.3 ± 0.4 vs 0.8 ± 0.3 kPa; p = 0.01) and TwPdi (1.9 ± 0.6 vs 1.1 ± 0.4 kPa; p < 0.01). Conclusions/interpretation With regard to volitional tests, diabetes does not affect respiratory neuromuscular function. In contrast, the application of non-volitional phrenic nerve stimulation provides strong evidence that diabetic polyneuropathy, as simply assessed by neurological disability scoring, is associated with substantially impaired respiratory neuromuscular function in type 2 diabetic patients.     

An orientation session improves objective sleep quality and mask acceptance during positive airway pressure titration

The aim of this study was to determine whether an orientation session led by a polysomnography (PSG) technician during the night of positive airway pressure (PAP) titration can improve objective sleep quality and acceptance of nasal mask in patients referred to a sleep laboratory. Consecutive patients (n = 1,481), referred for PAP titration during PSG, were retrospectively evaluated. Patients were distributed in two groups: the control group, patients referred for PAP titration (n = 699) who did not undertake an orientation session led by a PSG technician, and the oriented group, patients referred to PAP titration (n = 782) who followed the orientation session. Demographic data were similar (p > 0.05) between groups (control vs oriented) for: male/female proportion (76:24 vs 75:25%), age (mean ± SD; 53 ± 12 vs 52 ± 12 years), Epworth Sleepiness Scale score (12 ± 6 vs 12 ± 6), and body mass index (31 ± 6 vs 31 ± 6 kg/m²). PSG data were different (p < 0.05) between the groups for: total sleep time (312 ± 81 vs 326 ± 85 min), sleep efficiency (74 ± 17 vs 77 ± 14%), sleep latency (22 ± 24 vs 18 ± 29 min), S1 (8 ± 8 vs 6 ± 5%), S3  4 (19 ± 11 vs 21 ± 13%), rapid eye movement sleep (17 ± 9 vs 18 ± 9%), and wake after sleep onset (106 ± 68 vs 93 ± 58 min). After the orientation session, the number of patients who did not accept nasal mask during PSG recording was higher in the control group than the oriented group (80 vs 44; p = 0.001). An orientation session led by a PSG technician can improve objective sleep quality and nasal mask acceptance during the night of PAP titration. Such an addition to PAP titration could be an efficient intervention to improve PAP compliance.     

Poor potential of proliferation and differentiation in bone marrow mesenchymal stem cells derived from children with severe aplastic anemia

The pathogenesis of severe aplastic anemia (SAA) has not been completely understood, and insufficiency of the hematopoietic microenvironment can be an important factor. Here, we compared the basic properties of mesenchymal stem cells (MSCs), a major component of bone marrow microenvironment, from five SAA children with those of MSCs from five controls. Although MSCs from SAA children and controls were similar in morphology and immunophenotypic profile, SAA MSCs had slower expansion rate and smaller cumulative population doubling (1.83 ± 1.21 vs 3.36 ± 0.87; p = 0.046), indicating lower proliferative capacity. After osteogenic induction, SAA MSCs showed lower alkaline phosphatase activity (optical density, 1.46 ± 0.04 vs 2.27 ± 0.32; p = 0.013), less intense von Kossa staining, and lower gene expression of core binding factor α1 (0.0015 ± 0.0005 vs 0.0056 ± 0.0017; p = 0.013). Following adipogenic induction, SAA MSCs showed less intense Oil red O staining (optical density, 0.86 ± 0.22 vs 1.73 ± 0.42; p = 0.013) and lower lipoprotein lipase expression (0.0105 ± 0.0074 vs 0.0527 ± 0.0254; p = 0.013). These findings provided evidence that defects in bone marrow MSCs of SAA children do exist.     

Risk factors of vertebral fractures in women with systemic lupus erythematosus

The aim of the current study was to analyze the role of traditional and systemic lupus erythematosus (SLE)-related risk factors in the development of vertebral fractures. A cross-sectional study was performed in women with SLE attending a single center. A vertebral fracture was defined as a reduction of at least 20% of vertebral body height. Two hundred ten patients were studied, with median age of 43 years and median disease duration of 72 months. Osteopenia was present in 50.3% of patients and osteoporosis in 17.4%. At least one vertebral fracture was detected in 26.1%. Patients with vertebral fractures had a higher mean age (50 ± 14 vs. 41 ± 13.2 years, p = 0.001), disease damage (57.1% vs. 34.4%, p = 0.001), lower bone mineral density (BMD) at the total hip (0.902 ± 0.160 vs. 982 ± 0.137 g/cm², p = 0.002), and postmenopausal status (61.9% vs. 45.3%, p = 0.048). Stepwise logistic regression analysis revealed that only age (p = 0.001) and low BMD at the total hip (p = 0.007) remained as significant factors for the presence of vertebral fracture. The high prevalence of vertebral fractures in the relatively young population implies that more attention must be paid to detect and treat vertebral fractures.     

Serum and synovial fluid levels of interleukin-17 in correlation with disease activity in patients with RA

The aim of this study was to evaluate serum and synovial levels of IL-17A by ELISA in rheumatoid arthritis (RA) and find out the correlations between IL-17A levels and various clinical, laboratory parameters and RA disease activity and severity indices. Group I consists of 30 adult active RA patients fulfilling the ARA 1987 revised criteria, with knee effusion and receiving basic therapy, and with a mean age of 41.47 ± 11.49 years and mean disease duration of 9.5 ± 4.16 years. Group II consisted of 13 healthy volunteers, age- and sex-matched, with a mean age of 39.08 ± 14.19 years. RA patients showed significantly higher mean serum IL-17A levels than controls (11.25 ± 9.67 vs. 0.6 ± 1.4 pg/mL, respectively, p = 0.0002). Synovial IL-17A levels showed a significant positive correlation with serum IL-17A levels (r = 0.5 and p = 0.005). RA patients with negative rheumatoid factor (RF) had non-significantly higher mean serum IL-17A levels (12 ± 9.86 pg/mL) compared to those with positive RF (10.82 ± 9.81 pg/mL); however, the mean synovial IL-17A levels were nearly the same. Significant positive correlations were found between both serum and synovial IL-17A levels and DAS-28 scores (r = 0.556, 0.392 and p = 0.001, 0.032, respectively). RA patients with class III functional status showed significantly higher mean serum IL-17A levels (17.53 ± 13.43 pg/mL) than classes I and II (8.97 ± 6.97 pg/mL, p = 0.009). These led us to conclude that the elevated serum and synovial IL-17A levels in RA patients parallel the degree of disease activity and severity. This may highlight the usefulness of IL-17 (especially serum level) as a possible marker for more aggressive joint involvement and damage.     

Intravenous lidocaine for fibromyalgia syndrome: an open trial

Fibromyalgia is a disorder characterized by chronic widespread pain. In this study, we investigated the effect of intravenous infusions of lidocaine in pain and quality of life of patients with fibromyalgia. Twenty-three consecutive patients were included in the study, which consisted on five sequential intravenous 2% lidocaine infusions with rising dosages (2–5 mg/kg, days 1–5). Fibromyalgia Impact Questionnaire (FIQ), Health Assessment Questionnaire, and a visual analog scale (VAS) for pain were applied before the first lidocaine infusion, immediately after the fifth infusion and 30 days after the fifth infusion. A significant improvement was observed in the FIQ scores after the fifth infusion (73.52 ± 16.56 vs 63.29 ± 21.21, p = 0.02), which was maintained after 30 days (73.52 ± 16.56 vs 63.85 ± 24.59, p = 0.04). Similar results were seen concerning the VAS: 8.19 ± 1.76 vs 6.84 ± 2.44, p = 0.01 and 8.19 ± 1.76 vs 7.17 ± 2.35, p = 0.05, respectively. Intravenous lidocaine infusions are safe and effective in the management of fibromyalgia.     

Impaired short-term blood pressure regulation and autonomic dysbalance in children with type 1 diabetes mellitus

Aims Because reduction in baroreceptor sensitivity (BRS) has been associated with hypertension in the normal population and with increased cardiovascular morbidity and mortality in patients with diabetes mellitus, we measured BRS in a patient cohort of children with type 1 diabetes mellitus. Methods Two hundred and eight children (150 patients with type 1 diabetes mellitus, mean age 13.9 ± 2.8 years, 70 boys, mean HbA_1c 7.8 ± 1.4%; and 58 healthy controls, mean age 14.1 ± 3.1 years, 32 boys) were studied. BRS and heart rate variability (HRV) were analysed from a short-time ECG and BP recording using the sequence method (BRS) and the frequency domain method (HRV). Results There were 111 of 150 patients (74%) and 5 of 58 controls (8.6%) that showed impaired BRS. Mean BRS differed significantly between patients and controls (18.4 ± 7.2 vs 25.8 ± 8.2 ms/mm, p < 0.001). BRS correlated inversely with systolic BP (r = −0.23, p = 0.009) and was related to diabetes duration (r = −0.194, p = 0.027). Analysis of HRV showed greater sympathetic and less parasympathetic influence in patients than in controls (low frequency/high frequency ratio 1.3 ± 0.8 vs 0.9 ± 0.6, p < 0.05); the low frequency/high frequency ratio was inversely correlated with BRS (r = −0.28, p = 0.001). Conclusions/interpretation Diabetic children show reduced BRS. In our patient group, the single risk factor for this finding was found to be the disease duration. The degree of BRS impairment was related to the degree of autonomic dysbalance. R. Dalla Pozza and S. Bechtold contributed equally to this study.     

Idiopathic deep venous thrombosis and arterial endothelial dysfunction in the elderly

Arterial and venous thrombosis have always been regarded as different pathologies and epidemiological studies have examined the association between venous thrombosis and indicators of atherosclerosis and/or arterial thromboembolic events. We measured the flow-mediated dilation (FMD), a well-known marker of arterial endothelial dysfunction, in young–middle-aged and old-aged patients with and without unprovoked deep venous thrombosis (DVT). The aim of this study was to investigate whether DVT was a significant predictor for impaired FMD, considering all the patients and young–middle-aged (age < 65 years) and old-aged (age ≥ 65 years) patients separately. FMD was measured in the brachial artery on a population of 120 subjects with the same atherosclerosis risk factors, 68 male and 52 female, 70 young–middle-aged subjects (mean age ± SD 49.5 ± 10.5 years) and 50 old-aged subjects (76.2 ± 7.7 years). Patients with DVT showed a significant decrease of FMD compared to patients without DVT (6.8 ± 5.5% vs. 10.9 ± 3.5%, p < 0.001). Moreover, old-aged patients showed a significant decrease of FMD compared to the young–middle-aged subjects (7.4 ± 4.1% vs. 9.8 ± 5.3%, p = 0.005). In the whole study population, DVT was strongly associated with FMD (risk factors adjusted β = −4.14, p < 0.001). A significant interaction between age and the presence of DVT on predicting FMD was found (p = 0.003) suggesting a differential behavior of DVT as predictor of FMD. In young–middle-aged group, multivariate model confirmed that DVT was the most significant predictor of continuous FMD (β = −6.06, p < 0.001). On the contrary, DVT was no more a predictor of FMD in the old age group (β = −0.73, p=0.556). Furthermore, old-aged patients without DVT showed a statistically significant decrease of FMD compared to the young–middle-aged subjects without DVT (8.2±2.1% vs. 12.6±2.7%, p<0.001) and old-aged patients with DVT showed a not statistically significant decrease of the FMD compared to the young–middle-aged patients with DVT (6.7±5.3% vs. 6.8±5.7%, p = 0.932). In conclusion, young–middle-aged patients with spontaneous DVT show an impaired FMD, whereas this impairment in old-aged subjects is evident independently from the presence or absence of DVT. Aging per se may be associated with physiologic abnormalities in the systemic arteries and with endothelial dysfunction.     

Does exercise affect the antioxidant system in patients with ankylosing spondylitis?

We aimed to investigate the effect of regular supervised exercise program on functinal status, disease activity, and total antioxidant status (TAS) level in patients with ankylosing spondylitis (AS). Thirty-two patients (mean age: 44 years) with AS were included in the study and divided into two groups. Group 1, the exercise group (n = 16), attended a supervised exercise program that consisted of aerobic, strengthening, and stretching exercises for 1 h a day, five times a week for 3 weeks. Group 2, the control group, received a home exercise program (n:16). Bath AS Activity Index (BASDAI) and Bath AS Functional Index (BASFI) were calculated and serum TAS levels were measured for each patient at 0 and 3 weeks. There was no significant difference in patients' baseline characteristics (age, disease duration, BASFI, and BASDAI scores) between exercise and control groups. In the exercise group, there were significant improvements between pre-exercise and post-exercise assessments in BASFI (2.8 ± 1,8; 1.7 ± 1,40, p = 0.004) and BASDAI scores (2.1 ± 1.7; 1.2 ± 1.3, p = 0.01). Mean TAS levels were significantly decreased after supervised exercise program (1.48 ± 0.16 mmol/L; 1.36 ± 0.20 mmol/L, p = 0.03). In the control group, BASFI score (2.4 ± 1.7; 2.9 ± 2.1, p = 0.19), BASDAI score (2.6 ± 2.2; 3.1 ± 2.6, p = 0.33), and mean TAS levels (1.38 ± 0.23 mmol/L; 1.39 ± 0.20 mmol/L, p = 0.66) did not differ significantly between 0 and 3 weeks. Short-term, supervised exercise program improved functional status and decreased disease activity. However, the mechanism of this beneficial clinical effect does not seem to be through antioxidant activity.     

Serum from children with polyarticular juvenile idiopathic arthritis (pJIA) inhibits differentiation, mineralization and may increase apoptosis of human osteoblasts “in vitro”

We examined the effects of polyarticular juvenile idiopathic arthritis (pJIA) serum on proliferation, differentiation, mineralization, and apoptosis of human osteoblast cells (hOb) in culture. The hOb were cultured with 10% serum from active pJIA and healthy controls (CT) and were tested for DNA synthesis, alkaline phosphatase (AP) activity, osteocalcin (OC) secretion, calcium levels, caspase 3 activity, and DNA fragmentation. None of the patients had used glucocorticoids for at least 1 month before the study, or any other drug that can affect bone mineral metabolism. Human inflammatory cytokine levels (IL-6, IL-8, IL-10, IL-1β, TNF-α, and IL-12p70) were measured in pJIA and CT sera. Low levels of AP activity was observed in pJIA cultures compared with CT cultures (67.16 ± 53.35 vs 100.11 ± 50.64 μmol p-nitrophenol/h⁻¹ mg⁻¹ protein, P = 0.008). There was also a significant decrease in OC secretion (9.23 ± 5.63 vs 12.82 ± 7.02 ng/mg protein, P = 0.012) and calcium levels (0.475 ± 0.197 vs 0.717 ± 0.366 mmol/l, P = 0.05) in pJIA hOb cultures. No difference was observed in cell proliferation (323.56 ± 108.23 vs 328.91 ± 88.03 dpm/mg protein, P = 0.788). Osteoblasts cultured with JIA sera showed lower levels of DNA and increased fragmentation than osteoblasts cultured with CT sera. pJIA sera showed higher IL-6 values than CT (21.44 ± 9.31 vs 3.58 ± 2.38 pg/ml, P < 0.001), but no difference was observed related to IL-8, IL-10, IL-1β, TNF-α, and IL-12p70 between pJIA and controls. This study suggests that serum from children with pJIA inhibits differentiation, mineralization and may increase apoptosis of hOb cultures, and inflammatory cytokines such as IL-6 might be a mechanism in this find. These results may represent an alternative therapeutic target for prevention and treatment of bone loss in JIA.     

Mycophenolate mofetil in systemic sclerosis-associated interstitial lung disease

This study aimed to assess the effect of mofetil mycophenolate (MMF), an inhibitor of lymphocyte proliferation, on lung function and skin in patients with systemic sclerosis (SSc)-associated interstitial lung disease (SSc-ILD). In this retrospective study, we reviewed the medical files of 10 patients with SSc-ILD (eight females, 10 patients with diffuse SSc; mean age, 59.7 ± 12.7 years; disease duration, 7.7 ± 4.7 years). Patients were treated with MMF (2 g/day) for 12 months. Lung function tests and the modified Rodnan total skin score (mRTSS) were assessed at baseline and at 12 months. Results were analyzed by paired Student’s t test. There was a significant increase in forced vital capacity and a nonsignificant increase in carbon monoxide diffusing capacity at 12 months in patients on MMF (p = 0.04 and 0.66, respectively). There was no effect on mRTSS. MMF stabilizes lung function of SSc-ILD after 12 months of treatment.     

Integrated backscatter analysis of carotid intima–media complex in patients with systemic lupus erythematosus

A number of studies based on conventional ultrasound scanning (CUS) gave contrasting results about the occurrence of early atherosclerosis in patients with systemic lupus erythematosus (SLE), while no study on early arterial sclerosis in the same patients are available. Recently, information on early arterial sclerosis can be provided by the integrated backscatter (IBS) analysis which reflects the collagen and calcium content within the vascular wall. In order to evaluate if atherosis and/or sclerosis of carotid arteries are early features of SLE, we performed carotid CUS and IBS analysis in 16 SLE patients (15 females; aged 37 ± 10 years), free from clinically evident cardiovascular diseases and cardiovascular risk factors, with the only exception of five patients who had arterial hypertension. The same investigations were performed in 16 sex- and age-matched healthy control subjects. No statistically significant difference was observed either in carotid corrected IBS values or in carotid intima–media thickness (IMT) values between SLE patients and control subjects (−17.9 ± 2.5 dB vs −19.0 ± 1.7 dB, p = 0.14; 0.66 ± 0.08 mm vs 0.62 ± 0.13 mm, p = 0.35, respectively). The little sub-group of hypertensive SLE patients exhibited a significantly higher carotid corrected IBS mean value compared to control subjects (−16.4 ± 3.1 dB vs −19.0 ± 1.7 dB, p = 0.026), while it did not significantly differ in carotid IMT value from control group (0.67 ± 0.09 mm vs 0.62 ± 0.13 mm, respectively; p = 0.86). These findings show that neither atherosis nor sclerosis of carotid arteries are early features of SLE patients free from cardiovascular risk factors. Further studies are needed to clearly demonstrate that early carotid sclerosis affects hypertensive SLE patients.     

Effect of music on anxiety and pain during joint lavage for knee osteoarthritis

Joint lavage for knee osteoarthritis is an invasive procedure that can be stressful and painful. We aimed to assess the impact of music therapy on perioperative anxiety, pain and tolerability of the procedure in patients undergoing joint lavage performed with two needles. We randomized all patients diagnosed with knee osteoarthritis and undergoing joint lavage in our department from November 2009 to October 2010 to an experimental group listening to recorded music or a control group receiving no music intervention. Perioperative anxiety and pain related to the procedure were self-reported on a visual analogic scale (0–100 mm visual analog scale [VAS]), and heart rate and blood pressure were measured during the procedure. Tolerability was assessed on a four-grade scale directly after the procedure. We included 62 patients (31 in each group). Mean age was 68.8 ± 12.6 years (72% females). As compared with the control group, the music group had lower levels of perioperative anxiety (40.3 ± 31.1 vs. 58.2 ± 26.3 mm; p = 0.046) and pain related to the procedure (26.6 ± 16.2 vs. 51.2 ± 23.7 mm; p = 0.0005). Moreover, heart rate was lower in the music group (69.5 ± 11.4 vs. 77.2 ± 13.2; p = 0.043) but not diastolic or systolic blood pressure. Tolerability was higher in the music group (p = 0.002). Music is a simple and effective tool to alleviate pain and anxiety in patients undergoing joint lavage for knee osteoarthritis.     

Effect of type 2 diabetes mellitus on exercise intolerance and the physiological responses to exercise in peripheral arterial disease

Aims/hypothesis There are conflicting data about the effect of type 2 diabetes mellitus on exercise tolerance in peripheral arterial disease. To elucidate this problem, we compared the tolerance and physiological responses to treadmill and cycle exercise in 31 patients with peripheral arterial disease and intermittent claudication. Materials and methods One group of these patients had type 2 diabetes (n = 12) and its members were matched for sex and age with a group of patients who did not have diabetes (n = 12). Since BMI and body weight were greater in the diabetic group (28.4 ± 3.7 vs 25.2 ± 2.4 kg/m²; 84.0 ± 14.6 vs 73.8 ± 8.0 kg), we also studied a third, ‘heavy’ group of non-diabetic patients with claudication of similar age (n = 7; BMI = 30.9 ± 5.3 kg/m²; body weight = 85.2 ± 8.2 kg). Results Compared with the ‘light’ non-diabetic group, maximum treadmill times were shorter for the diabetic and heavy non-diabetic groups (1,448 vs 845 and 915 s; ANOVA p = 0.01); maximum cycle time also tended to be shorter (ANOVA, p = 0.08) in the diabetic and heavy non-diabetic groups (median = 1,231 vs 730 and 797 s). The majority of physiological responses assessed were not different between the groups, although the time constant of oxygen uptake during submaximal treadmill and cycle exercise was significantly larger (ANOVA p < 0.05) for the diabetic group. Conclusions/interpretation These data demonstrate that exercise tolerance is lower in diabetic than non-diabetic patients with claudication, but that this difference is due to obesity rather than diabetes itself.     

Effect of short-term ACE inhibitor treatment on peripheral insulin sensitivity in obese insulin-resistant subjects

Aims/hypothesis This study was designed to investigate the effect of short-term ACE inhibitor treatment on insulin sensitivity and to examine possible underlying metabolic and haemodynamic effects in obese insulin-resistant subjects.Methods A randomised, double-blind placebo-controlled trial was performed in 18 obese insulin-resistant men (age, 53 ± 2 years; BMI, 32.6 ± 0.8 kg/m²; homeostasis model assessment of insulin resistance, 5.6 ± 0.5; systolic blood pressure [SBP], 140.8 ± 3.2; diastolic blood pressure [DBP], 88.8 ± 1.6 mmHg), who were free of any medication. The aim was to examine the effects of 2 weeks of ACE inhibitor treatment (ramipril, 5 mg/day) on insulin sensitivity, forearm blood flow, substrate fluxes across the forearm, whole-body substrate oxidation and intramuscular triacylglycerol (IMTG) content.Results Ramipril treatment decreased ACE activity compared with placebo (−22.0 ± 1.7 vs 0.2 ± 1.1 U/l, respectively, p < 0.001), resulting in a significantly reduced blood pressure (SBP, −10.8 ± 2.1 vs −2.7 ± 2.0 mmHg, respectively, p = 0.01; DBP, −10.1 ± 1.3 vs −4.2 ± 2.1 mmHg, respectively, p = 0.03). Ramipril treatment had no effect on whole-body insulin-mediated glucose disposal (before: 17.9 ± 2.0, after: 19.1 ± 2.4 μmol kg body weight⁻¹ min⁻¹, p = 0.44), insulin-mediated glucose uptake across the forearm (before: 1.82 ± 0.39, after: 1.92 ± 0.29 μmol 100 ml forearm tissue⁻¹ min⁻¹, p = 0.81) and IMTG content (before: 45.4 ± 18.8, after: 48.8 ± 27.5 μmol/mg dry muscle, p = 0.92). Furthermore, the increase in carbohydrate oxidation (p < 0.001) and forearm blood flow (p < 0.01), and the decrease in fat oxidation (p < 0.001) during insulin stimulation were not significantly different between treatments.Conclusions/interpretation Short-term ramipril treatment adequately reduced ACE activity and blood pressure, but had no significant effects on insulin sensitivity, forearm blood flow, substrate fluxes across the forearm, whole-body substrate oxidation and IMTG content in obese insulin-resistant subjects.     

Increased osteoclastic activity in acute Charcot’s osteoarthopathy: the role of receptor activator of nuclear factor-kappaB ligand

Aims/hypothesis Our aims were to compare osteoclastic activity between patients with acute Charcot’s osteoarthropathy and diabetic and healthy controls, and to determine the effect of the receptor activator of nuclear factor-kappaB ligand (RANKL) and its decoy receptor osteoprotegerin (OPG). Methods Peripheral blood monocytes isolated from nine diabetic Charcot patients, eight diabetic control and eight healthy control participants were cultured in the presence of macrophage-colony stimulating factor (M-CSF) alone, M-CSF and RANKL, and also M-CSF and RANKL with excess concentrations of OPG. Osteoclast formation was assessed by expression of tartrate-resistant acid phosphatase on glass coverslips and resorption on dentine slices. Results In cultures with M-CSF, there was a significant increase in osteoclast formation in Charcot patients compared with healthy and diabetic control participants (p = 0.008). A significant increase in bone resorption was also seen in the former, compared with healthy and diabetic control participants (p < 0.0001). The addition of RANKL to the cultures with M-CSF led to marked increase in osteoclastic resorption in Charcot (from 0.264 ± 0.06% to 41.6 ± 8.1%, p < 0.0001) and diabetic control (0.000 ± 0.00% to 14.2 ± 16.5%, p < 0.0001) patients, and also in healthy control participants (0.004 ± 0.01% to 10.5 ± 1.9%, p < 0.0001). Although the addition of OPG to cultures with M-CSF and RANKL led to a marked reduction of resorption in Charcot patients (41.6 ± 8.1% to 5.9 ± 2.4%, p = 0.001), this suppression was not as complete as in diabetic control patients (14.2 ± 16.5% to 0.45 ± 0.31%, p = 0.001) and in healthy control participants (from 10.5 ± 1.9% to 0.00 ± 0.00%, p < 0.0001). Conclusions/interpretation These results indicate that RANKL-mediated osteoclastic resorption occurs in acute Charcot’s osteoarthropathy. However, the incomplete inhibition of RANKL after addition of OPG also suggests the existence of a RANKL-independent pathway.