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.     

N-terminal pro-B-type natriuretic peptide and functional capacity in patients with obstructive sleep apnea

The obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular abnormalities including left ventricular hypertrophy, left ventricular diastolic dysfunction, and endothelial dysfunction. The present study evaluated whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) and peak oxygen consumption (peak VO₂), both integral markers of cardiovascular function, are related to OSAS severity. In addition, we tested whether NT-proBNP levels depend on body composition in OSAS patients, similar to what has been reported in patients without OSAS. Eighty-nine patients with untreated OSAS underwent NT-proBNP measurement, dual X-ray absorptiometry, and cardiopulmonary exercise testing. In a representative subgroup (n = 32), transthoracic echocardiography was performed. The severity of OSAS was classified based on apnea–hypopnea index (AHI) values as mild (AHI 5–15 h⁻¹), moderate (AHI 15–30 h⁻¹), and severe (AHI >30 h⁻¹). OSAS was mild in 19 (21%), moderate in 21 (24%), and severe in 49 (55%) patients. NT-proBNP levels did not differ among patients with mild [30 (10–57)], moderate [37 (14–55)], and severe [24 (13–49) pg/ml; p = 0.8] OSAS and were not related to body mass index (r = 0.07; p = 0.5), percent lean body mass (r = −0.17; p = 0.1), and percent fat mass (r = 0.18; p = 0.1). Percent predicted peak VO₂ was on average normal and did not differ among patients with mild (115 ± 26), moderate (112 ± 23), and severe OSAS (106 ± 29%; p = 0.4). Body weight-indexed peak VO₂ did not differ among patients with mild (31.9 ± 10.3), moderate (32.1 ± 7.9), and severe OSAS (30.0 ± 9.9 ml kg⁻¹ min⁻¹; p = 0.6) either. Lower NT-proBNP (β = −0.2; p = 0.02) was independently but weakly associated with higher body weight-indexed peak VO₂. In the echocardiography subgroup, NT-proBNP was not significantly related to left ventricular mass index (r = 0.26; p = 0.2). In conclusion, NT-proBNP and peak VO₂ are not related to OSAS severity, and NT-proBNP poorly reflects left ventricular hypertrophy in OSAS. The lack of a relationship between NT-proBNP and OSAS severity is not due to a significant influence of body composition on NT-proBNP. There is an association between higher NT-proBNP and lower peak VO₂, indicating that NT-proBNP is a marker of cardiorespiratory fitness in patients with OSAS. However, the association is too weak to be clinically useful.     

Comprehension of complex instructions deteriorates with age and vascular morbidity

Verbal comprehension is critical to the success of medical counseling. Here, we tested how age and vascular risk factors affect the ability to understand complex instructions. Verbal comprehension, cognitive functions, and vascular risk factors were assessed in 39 mid- and 38 late-life community-dwelling individuals (48 to 59 years and >59 years of age, respectively). To test for verbal comprehension, we used a modified version of the Token Test (TT). In midlife individuals, education (β = 0.572, p < 0.05) was the only predictor for extended-TT performance. In late-life individuals, age (β = −1.015, p < 0.001) and body mass index (β = −0.651, p = 0.003) were significantly correlated with extended-TT performance and explained 50% of the variance in extended-TT performance (adjusted R ² = 0.503). This relation is only partly explained by conventional neuropsychological measures as the ones used in our test battery. These results indicate that aging and overweight impair comprehension of complex instructions. Therefore, medical counseling appropriate for midlife individuals may be less successful in elderly people and particularly in those with metabolic disturbances.     

Anti-agalactosyl IgG antibody in ankylosing spondylitis and psoriatic arthritis

Anti-agalactosyl IgG antibody (anti-Gal(0) IgG) has been regarded as a useful serological marker for rheumatoid arthritis (RA). It is unknown whether it is also elevated in serum and implicated in the pathogenesis of joint inflammation in seronegative spondyloarthropathy (SpA) such as ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Sera were collected from 43 patients with AS or PsA with axial joint involvement, 22 patients with RA, and 25 healthy normal individuals for the detection of anti-Gal(0) IgG with a cup-type lectin enzyme immunoassay (Eitest CA^.RF). The disease activity of the AS/PsA was evaluated by Bath Ankylosing Spondylitis Disease Activity Score (BASDAI), the serum C-reactive protein (CRP) and IgA were measured by nephelometry, and erythrocyte sedimentation rate (ESR) was measured by Westergren’s method. The median titers of anti-Gal(0) IgG were significantly elevated in patients with RA (167.85, 15.73∼797.58 AU/mL) and AS/PsA (186.15, 34.71∼651.19 AU/mL), compared to those of the normal controls (13.04, 12.00∼202.43 AU/mL). The titers of the anti-Gal(0) IgG in patients with AS/PsA were correlated to the BASDAI scores (r ² = 0.422, SEE = 1.443, p < 0.001) and serum CRP (r ² = 0.345, SEE = 2.434, p < 0.001) but not to IgA (r ² = 0.0259, SEE = 126.30, p < 0.001) or ESR (r ² = 0.171, SEE = 31.053, p = 0.0059). Collectively, the anti-Gal(0) IgG is elevated and vaguely correlated with the disease activity of AS/PsA although its titers in these patients were erratic. The result of the present investigation has suggested that anti-Gal(0) IgG may be more ubiquitously present in inflammatory arthritides including RA or SpA.     

A comparative study of arterial stiffness, flow-mediated vasodilation of the brachial artery, and the thickness of the carotid artery intima–media in patients with systemic autoimmune diseases

Patients with autoimmune diseases may have increased vascular risk leading to higher mortality rates. Novel imaging techniques are necessary for the early assessment and management of these patients. In this study, we compared augmentation index (AIx) and pulse wave velocity (PWV), indicators of arterial stiffness, to brachial arterial flow-mediated vasodilation (FMD) and common carotid artery intima–media thickness (ccIMT), standard indicators of endothelial dysfunction and atherosclerosis, respectively. We wished to assess the vascular status of autoimmune patients by using a novel, cheap, and reproducible technique, the arteriograph. Altogether, 101 patients with systemic autoimmune diseases including primary antiphospholipid syndrome, systemic sclerosis, rheumatoid arthritis, and polymyositis, all having various types of vasculopathies, as well as 36 healthy individuals were investigated. Arterial stiffness was assessed by a TensioClinic arteriograph, a recently validated technique. Brachial arterial FMD and ccIMT were determined using high-resolution ultrasonography. Autoimmune patients exerted impaired FMD (3.7 ± 3.8%), increased ccIMT (0.7 ± 0.2 mm), AIx (1.2 ± 32.2%), and PWV (9.7 ± 2.4 m/s) in comparison to control subjects (FMD = 8.4 ± 4.0%; ccIMT = 0.6 ± 0.1 mm; Aix = −41.1 ± 22.5%; PWV = 8.0 ± 1.5 m/s; p < 0.05). We found a significant negative correlation of FMD with AIx (R = −0.64; p < 0.0001) and PWV (R = −0.37; p = 0.00014). There were significant positive correlations between ccIMT and AIx (R = 0.34; p = 0.0009), ccIMT and PWV (R = 0.44; p < 0.0001), as well as AIx and PWV (R = 0.47; p < 0.0001). AIx, PWV, and ccIMT positively correlated and FMD negatively correlated with the age of the autoimmune patients. Arterial stiffness indicated by increased AIx and PWV may be strongly associated with endothelial dysfunction and overt atherosclerosis in patients with autoimmune diseases. Assessment of arterial stiffness, FMD, and ccIMT are reproducible and reliable noninvasive techniques for the complex assessment of vascular abnormalities in patients at high risk.     

Soluble receptor activator of NFkappa B-ligand and osteoprotegerin in rheumatoid arthritis - relationship with bone mineral density,disease activity and bone turnover

The aim of our study was to investigate determinants of bone mineral density (BMD) measured by dual X-ray absorptiometry at the lumbar spine (BMD-LS) and at the femoral neck (BMD-FN) in patients with rheumatoid arthritis (RA) with special respect to bone resorbing proinflammatory cytokines and their physiological antagonists. In 142 RA patients the following parameters were measured in parallel with BMD: serum levels of soluble receptor activator of nuclear factor kappa-B-ligand (sRANKL), osteoprotegerin (OPG), interleukin (IL)-6, soluble glycoprotein 130 (sgp130), 25-hydroxyvitamin D3 (25OHD₃), 1,25-dihydroxyvitamin D3 (1,25[OH]₂D₃), intact parathyroid hormone, osteocalcin, ionized calcium, renal excretion of pyridinolin and deoxypyridinolin, C-reactive protein, and erythrocyte sedimentation rate (ESR). No significant differences of sRANKL, OPG, IL-6, and spg130 were found between patients with osteoporosis (47.9% of patients), osteopenia (36.6%), and normal BMD (15.5%). However, total sRANKL was significantly higher in postmenopausal women with osteoporosis at FN than in those without (p < 0.05) and showed a negative correlation with BMD-LS in patients older than 60 years (p = 0.01). BMD-LS and BMD-FN (p < 0.001) and total sRANKL (p < 0.01) were negatively related with the age of the patients. Only IL-6 (positive correlation, p < 0.001) and 1,25(OH)₂D₃ (negative correlation, p < 0.001) but not sRANKL, OPG, and sgp130 were related to disease activity. Using multiple linear regression analysis, menopause was identified as the crucial negative determinant of BMD-LS (R ² = 0.94, p = 0.001), whereas cumulative glucocorticoid dose (β = −0.80, p = 0.001) and ESR (β = −0.44, p = 0.016) were the negative determinants of BMD-FN (R ² = 0.86, p = 0.001). The results indicate that influences of age and gender must be considered in investigations on the relationship between BMD and sRANKL in RA and that high serum levels of sRANKL seems to be associated with osteoporosis only in subgroups of RA patients.     

Prognostic value of morphological classifications and clinical variables in elderly and young patients with multiple myeloma

 The prognostic value of morphological classifications and clinical variables was compared between 31 elderly (≥65 years) and 43 young (<65 years) patients with myeloma. Prognostic factors were divided into three groups: factors useful in elderly patients, e.g., calcium, albumin; factors useful in young patients, e.g., platelet, creatinine, light-chain type; and factors useful in both patients, e.g., clinical stage, hemoglobin, LDH, CRP, bone marrow plasma cell and plasmablast percentages, light- and electron-microscopic classifications. The 5-year survival rates of elderly patients with calcium <12 and ≥12 mg/dl were 66.2 and <11.1%, respectively (p<0.01). Those of the young patients were 64.1 and 33.3%, respectively. The 5-year survival rates of elderly patients with platelets ≥200×10⁹/l and <100×10⁹/l were 59.7 and 50.0%, respectively. Those of the young patients were 68.9 and 33.3%, respectively (p<0.05). The 5-year survival rates of elderly patients with few and numerous electron-microscopic abnormalities were 90 and 0%, respectively (p<0.01), those of young patients were 92.9 and <14.3%, respectively (p<0.01). These findings suggest that individual clinical variables may differ in prognostic importance in elderly and young patients. Received: March 11, 1998 · Accepted: September 14, 1998     

Haemoglobin levels are associated with bone mineral density in the elderly: a population-based study

Hypoxemia has been associated with low bone mineral density (BMD) in animal and human models. We assessed the association of haemoglobin levels with ultrasound-derived (UD) T score, Z score and the stiffness index in all 358 subjects aged 75+ living in Tuscania (Italy). Also, we searched for the haemoglobin cutoff levels that might best identify participants with osteoporosis. In the multivariable linear regression analysis, haemoglobin levels were associated among participants with the UD T score [β = 0.13; 95% confidence interval (CI) = 0.01–0.25; p = 0.030], Z score (β = 0.11; 95% CI = 0.01–0.22; p = 0.045) and stiffness index (β = 1.87; 95% CI = 0.51–3.21; p = 0.007) after adjusting for potential confounders. Haemoglobin levels <140 g/L in men and <130 g/L in women best predicted osteoporosis in linear discriminant analysis. Haemoglobin is independently associated with all UD-BMD parameters. Haemoglobin levels <140 g/L in men and 130 g/L in women might be adopted in clinical practice to identify older subjects in whom screening for osteoporosis might yield higher effectiveness.     

Common variants in the TCF7L2 gene help to differentiate autoimmune from non-autoimmune diabetes in young (15–34 years) but not in middle-aged (40–59 years) diabetic patients

Aims/hypothesis  Type 1 diabetes in children is characterised by autoimmune destruction of pancreatic beta cells and the presence of certain risk genotypes. In adults the same situation is often referred to as latent autoimmune diabetes in adults (LADA). We tested whether genetic markers associated with type 1 or type 2 diabetes could help to discriminate between autoimmune and non-autoimmune diabetes in young (15–34 years) and middle-aged (40–59 years) diabetic patients. Methods  In 1,642 young and 1,619 middle-aged patients we determined: (1) HLA-DQB1 genotypes; (2) PTPN22 and INS variable-number tandem repeat (VNTR) polymorphisms; (3) two single nucleotide polymorphisms (rs7903146 and rs10885406) in the TCF7L2 gene; (4) glutamic acid decarboxylase (GAD) and IA-2-protein tyrosine phosphatase-like protein (IA-2) antibodies; and (5) fasting plasma C-peptide. Results  Frequency of risk genotypes HLA-DQB1 (60% vs 25%, p  = 9.4×10⁻³⁴; 45% vs 18%, p  = 1.4 × 10⁻¹⁶), PTPN22 CT/TT (34% vs 26%, p  = 0.0023; 31% vs 23%, p  = 0.034), INS VNTR class I/I (69% vs 53%, p  = 1.3 × 10⁻⁸; 69% vs 51%, p  = 8.5 × 10⁻⁵) and INS VNTR class IIIA/IIIA (75% vs 63%, p  =  4.3 × 10⁻⁶; 73% vs 60%, p  = 0.008) was increased in young and middle-aged GAD antibodies (GADA)-positive compared with GADA-negative patients. The type 2 diabetes-associated genotypes of TCF7L2 CT/TT of rs7903146 were significantly more common in young GADA-negative than in GADA-positive patients (53% vs 43%; p  = 0.0004). No such difference was seen in middle-aged patients, in whom the frequency of the CT/TT genotypes of TCF7L2 was similarly increased in GADA-negative and GADA-positive groups (55% vs 56%). Conclusions/interpretation  Common variants in the TCF7L2 gene help to differentiate young but not middle-aged GADA-positive and GADA-negative diabetic patients, suggesting that young GADA-negative patients have type 2 diabetes and that middle-aged GADA-positive patients are different from their young GADA-positive counterparts and share genetic features with type 2 diabetes. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users. G. Sundkvist died in September 2006.     

Circulating endothelial progenitor cells, endothelial function, carotid intima–media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria

Aims/hypothesis  Type 1 diabetes is associated with premature arterial disease. Bone-marrow derived, circulating endothelial progenitor cells (EPCs) are believed to contribute to endothelial repair. The hypothesis tested was that circulating EPCs are reduced in young people with type 1 diabetes without vascular injury and that this is associated with impaired endothelial function and increased carotid intima–media thickness (CIMT). Methods  We compared 74 people with type 1 diabetes with 80 healthy controls. CD34, CD133, vascular endothelial (VE) growth factor receptor-2 (VEGFR-2) and VE-cadherin antibodies were used to quantify EPCs and progenitor cell subtypes using flow-cytometry. Ultrasound assessment of endothelial function by brachial artery flow-mediated dilatation (FMD) and CIMT was made. Circulating endothelial markers, inflammatory markers and plasma plasminogen activator inhibitor-1 (PAI-1) levels were measured. Results  CD34+VE-cadherin+, CD133+VE-cadherin+ and CD133+VEGFR-2+ EPC counts were significantly lower in people with diabetes (46–69%; p = 0.004–0.043). In people with type 1 diabetes, FMD was reduced by 45% (p < 0.001) and CIMT increased by 25% (p < 0.001), these being correlated (r = −0.25, p = 0.033). There was a significant relationship between FMD and CD34+VE-cadherin+ (r = 0.39, p = 0.001), CD133+VEGFR-2+ (r = 0.25, p = 0.037) and CD34+ (r = 0.34, p = 0.003) counts. Circulating high-sensitivity C-reactive protein, PAI-1, interleukin-6 and E-selectin were significantly higher in the diabetes group (p < 0.001 to p = 0.049), the last two of these correlating with FMD (r = −0.27, p = 0.028 and r = −0.24, p = 0.048, respectively). Conclusions/interpretation  These findings suggest that abnormalities of endothelial function in addition to pro-inflammatory and pro-thrombotic states are already common in people with type 1 diabetes before development of clinically evident arterial damage. Low EPC counts confirm risk of macrovascular complications and may account for impaired endothelial function and predict future cardiovascular events. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Ambulatory pulse pressure, decreased nocturnal blood pressure reduction and progression of nephropathy in type 2 diabetic patients

Aims/hypothesis  We followed type 2 diabetic patients over a long period to evaluate the predictive value of ambulatory pulse pressure (PP) and decreased nocturnal BP reduction (non-dipping) for nephropathy progression. Methods  Type 2 diabetic patients (n = 112) were followed for an average of 9.5 (range 0.5–14.5) years. At baseline, all patients underwent 24 h ambulatory BP measurement. Urinary albumin excretion rate was evaluated by three urinary albumin:creatinine ratio measurements at baseline and follow-up. Results  At baseline, patients who subsequently progressed to a more advanced nephropathy stage (n = 35) had reduced diastolic night/day BP variation and higher 24 h systolic BP and PP values; they also had more advanced nephropathy and were more likely to smoke than those with no progression of nephropathy (n = 77). In a Cox regression analysis, independent predictors of nephropathy progression were 24 h PP (p < 0.01), diastolic night:day BP ratio (p = 0.02) and smoking (p = 0.02). The adjusted hazards ratio (95% CI) for each mmHg increment in 24 h PP was 1.04 (1.01–1.07), whereas the adjusted hazards ratio (95% CI) for each 1% increase in diastolic night:day BP ratio was 1.06 (1.01–1.11). Only one of 33 patients (3.0%) with both a diastolic night:day BP ratio and a 24 h PP below the median progressed, whereas 17 of 32 patients (53.1%) with both a diastolic night:day BP ratio and a 24 h PP equal to or above the median progressed to a more advanced nephropathy stage (p < 0.001). Conclusions/interpretation  Ambulatory PP, impaired nocturnal BP decline and smoking are strong, independent predictors of nephropathy progression in type 2 diabetic patients.     

Circulating CD133<Superscript>+</Superscript>VEGFR2<Superscript>+</Superscript> and CD34<Superscript>+</Superscript>VEGFR2<Superscript>+</Superscript> cells and arterial function in patients with beta-thalassaemia major

Arterial dysfunction has been documented in patients with beta-thalassaemia major. This study aimed to determine the quantity and proliferative capacity of circulating CD133⁺VEGFR2⁺ and CD34⁺VEGFR2⁺ cells in patients with beta-thalassaemia major and those after haematopoietic stem cell transplantation (HSCT), and their relationships with arterial function. Brachial arterial flow-mediated dilation (FMD), carotid arterial stiffness, the quantity of these circulating cells and their number of colony-forming units (CFUs) were determined in 17 transfusion-dependent thalassaemia patients, 14 patients after HSCT and 11 controls. Compared with controls, both patient groups had significantly lower FMD and greater arterial stiffness. Despite having increased CD133⁺VEGFR2⁺ and CD34⁺VEGFR2⁺ cells, transfusion-dependent patients had significantly reduced CFUs compared with controls (p = 0.002). There was a trend of increasing CFUs across the three groups with decreasing iron load (p = 0.011). The CFUs correlated with brachial FMD (p = 0.029) and arterial stiffness (p = 0.02), but not with serum ferritin level. Multiple linear regression showed that CFU was a significant determinant of FMD (p = 0.043) and arterial stiffness (p = 0.02) after adjustment of age, sex, body mass index, blood pressure and serum ferritin level. In conclusion, arterial dysfunction found in patients with beta-thalassaemia major before and after HSCT may be related to impaired proliferation of CD133⁺VEGFR2⁺ and CD34⁺VEGFR2⁺ cells.     

Hypoxemia and obesity modulate plasma C-reactive protein and interleukin-6 levels in sleep-disordered breathing

C-reactive protein (CRP) and interleukin-6 (IL-6) are pro-inflammatory proteins and important risk factors for atherosclerosis. Plasma CRP levels in snoring children may or may not be elevated. Since obesity is prevalent among snoring children and is associated with elevated CRP levels, we aimed to investigate the relative contributions of sleep-disordered breathing (SDB) and obesity to the inflammatory processes in snoring children in this prospective study. Two hundred forty-four children (mean age 8.9 ± 3.4 years) underwent polysomnographic evaluation. CRP was measured the following morning, and plasma IL-6 levels from 111 randomly selected children were also examined. Plasma CRP and IL-6 levels were elevated in children with SDB. Log plasma CRP levels were higher in the moderate-severe SDB group (apnea/hypopnea index, AHI ≥ 5) compared to the mild SDB group (AHI ≥ 1 and <5; p < 0.0001) or the control group (AHI < 1; p = 0.0001). Log plasma CRP levels correlated with AHI, arousal index, relative BMI, and SpO₂ nadir (r = 0.30, p < 0.0001; r = 0.21, p = 0.002; r = 0.39, p < 0.0001, r = −0.36, p < 0.0001, respectively). Log plasma CRP levels were lower in children with SpO₂ nadir ≥90 (p < 0.0001). Sub-analysis of the 116 non-obese children in the cohort revealed similar findings. Log plasma IL-6 levels were increased in children with moderate–severe SDB compared to controls (p = 0.03) and correlated with AHI (r = 0.28, p = 0.003) and SpO₂ nadir (r = −0.24, p = 0.02). Children with SDB display significant severity-dependent increases in plasma CRP and IL-6 levels independent of obesity.     

Social Support,Health Service Use and Mental Health Among Caregivers of the Elderly in Rural China

This cross-sectional study was designed to investigate the status of social support, health service use and mental health among caregivers for the elderly in a Chinese rural community. With randomized stratified sampling method, 199 caregivers providing long-term care for the elderly recruited from a Chinese rural community responded to the survey and were administered the questionnaire, measuring the caregiving outcome for the elderly. The social support was assessed with the social support scale (SSS) and social network scale (SNS). Health service utilization was assessed with the questionnaire on health service use (HSU). Depression was evaluated with the Center for Epidemiological Studies—Depression Scale (CES-D). Most caregivers are elder’s spouse (39.7%), son (26.1%) and daughter-in-law (18.1%). Three common health service used by the caregivers are visiting physician (68.0%), help from relatives or friends (43.9%) and seeking help of herbal doctors or traditional healers (34.0%). Between caregivers for healthy and non-healthy elders, there was significant difference of depression scale score (t = 3.195, p < 0.01), not of SSS and SNS scale scores (p > 0.05). The score of depression scale are associated with caregivers’ age (β = 0.260) and income (β = −0.231), care-recipients’ gender (β = 0.187) and age (β = 0.800), caring time (β = 0.138) and the total SNS score (β = −0.194) (all p < 0.05). The findings suggest, in Chinese rural area, family provides main source for caregiving to the elderly, with spouse and sons playing central roles. Most often elderly caregivers utilize medical resources. Depression during the process of caregiving is associated with caregivers and care-recipients’ background characteristics, with potential mediator effect of social support. It is implied that social support may be important when providing mental health service to the elderly caregivers in Chinese rural areas.     

Th-17 associated cytokines in patients with reactive arthritis/undifferentiated spondyloarthropathy

We and others have previously shown that IL-17 is elevated in the synovial fluid of patients with reactive arthritis (ReA)/undifferentiated spondyloarthropathy (uSpA) having acute synovitis. Major source for IL-17 is Th17 cells, which differentiate from Th0 cells under the influence of TGF-β and IL-6, IL1-β and are maintained by IL-21 and 23. There is a paucity of data on these cytokines in ReA/uSpA. Thus, we measured the levels of Th-17 differentiating and maintaining cytokines in synovial fluid of patients with ReA and uSpA. Fifty patients with ReA/uSpA (ReA 24, uSpA 26), 19 patients with rheumatoid arthritis (RA) and 11 patients with osteoarthritis (OA) were included in the study. Synovial fluid (SF) were collected from knee joint and stored at −80°C until analysis. Cytokines were assayed using ELISA in SF specimens. The median IL-17A levels were significantly elevated in ReA (48.3 pg/ml) and uSpA (32.5 pg/ml) as compared to non-inflammatory OA controls (<7.8 pg/ml; p < 0.0001), while comparable to RA (57.9 pg/ml). Further, IL-6 median values were higher in ReA (25.2 ng/ml) and uSpA (13.6 ng/ml) as compared to OA (0.76 ng/ml; p < 0.0001), and comparable to RA (15.8 ng/ml). The median levels of IL-1β, IL-21 levels were elevated in ReA, uSpA and RA as compared to OA but were not statistically significant. TGF-β levels in ReA and uSpA were similar to OA but lower than in RA (4340 pg/ml; p < 0.05). IL-23 was not detectable in any synovial fluid sample. However, levels of these cytokines did not correlate with disease activity parameters. Significant positive correlation was observed between IL-17 and IL-1β (r = 0.38, p < 0.005), IL-17 and IL-6 (r = 0.659, p < 0.0001), and IL-1β and IL-6 (r = 0.391, p < 0.0001) in ReA and uSpA group. Inflammatory synovitis in ReA/uSpA is mediated by pro-inflammatory cytokines like IL-17, IL-6, IL-1β, and IL-21. However, IL-23 was not detectable in SF. Good correlation between IL-17, IL-6, and IL 1β suggest that either they are co-regulated or they regulate each other.     

Clinical significance of metabolic tumor volume by PET/CT in stages II and III of diffuse large B cell lymphoma without extranodal site involvement

The objective of this study was to investigate whether metabolic tumor volume (MTV) by positron emission tomography (PET) can be a potential prognostic tool when compared with Ann Arbor stage, in stages II and III nodal diffuse large B cell lymphoma (DLBCL). We evaluated 169 patients with nodal stages II and III DLBCL who underwent measurements with PET prior to rituximab combined with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP). Cutoff point of MTV was measured using the receiver operating characteristic (ROC) curve. During a median period of 36 months, stage II was 59.2% and III was 40.8%. Using the ROC curve, the MTV of 220 cm³ was the cutoff value. The low MTV group (<220 cm³) had longer progression-free survival (PFS) and overall survival (OS), compared with the high MTV group (≥220 cm³) (p < 0.001, p < 0.001). Stage II patients had longer survival than those in stage III (PFS, p = 0.011; OS, p = 0.001). The high MTV group had lower PFS and OS patterns, regardless of stage, compared with the low MTV group (p < 0.001, p < 0.001). Multivariate analysis revealed an association of the high MTV group with lower PFS and OS (PFS, hazard ratio (HR) = 5.300, p < 0.001; OS, HR = 7.009, p < 0.001), but not stage III (PFS, p = 0.187; OS, p = 0.054). Assessment of MTV by PET had more potential predictive power than Ann Arbor stage in the patients that received R-CHOP.     

Visceral adiposity and leptin are independently associated with C-reactive protein in Korean type 2 diabetic patients

The inflammatory marker, C-reactive protein (CRP) is associated with long-term cardiovascular events. The aim of the study was to investigate the factors contributing to serum CRP, assess the relationship between CRP level and the parameters of visceral obesity, and examine the association between leptin and CRP level in type 2 diabetic patients. 150 patients with type 2 diabetes were enrolled. These patients were recently diagnosed (≤3 years) with type 2 diabetes and were drug naive or taking sulfonylureas only. BMI, WC, and serum concentration of CRP, glycosylated hemoglobin (HbA1c), glucose, lipids, plasminogen activator-1 (PAI-1) and leptin were measured. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). We measured the carotid intima-media thickness (IMT). Fat mass assessed by dual-energy X-ray absorptionmetry and abdominal fat distribution was determined by CT scan. Serum concentration of CRP was significantly correlated with BMI (γ = 0.257, P < 0.01), WC (γ = 0.293, P < 0.01), fat mass (γ = 0.213, P < 0.01), total adipose tissue (γ = 0.263, P < 0.01), visceral adipose tissue (γ = 0.296, P < 0.01), insulin (γ = 0.189, P = 0.047), PAI-1 (γ = 0.206, P < 0.01), leptin (γ = 0.322, P < 0.01), mean IMT (γ = 0.132, P = 0.042), and HOMA-IR (γ = 0.172, P = 0.045). After adjustment for age and gender, multiple regression analysis showed that serum CRP was significantly associated with leptin (β = 0.326, P = 0.01) and visceral adipose tissue (β = 0.265, P = 0.035). In conclusion, serum CRP level is significantly associated with obesity, especially the visceral adipose tissue, and serum leptin is another important independent factor associated with CRP in Korean type 2 diabetic patients.     

Masked nocturnal hypertension—a novel marker of risk in type 2 diabetes

Aims/hypothesis  This study was designed to evaluate the prevalence of masked nocturnal hypertension (MNHT) and its impact on arterial stiffness and central blood pressure in patients with type 2 diabetes. Methods  Middle-aged patients (n = 414) with type 2 diabetes underwent clinic and ambulatory BP measurements and applanation tonometry. Results  MNHT (clinic BP < 130/80 mmHg and night-time BP ≥ 120/70 mmHg) was found in 7.2% of patients (n = 30). Compared with patients with both clinical and nocturnal normotension (n = 70), patients with MNHT had higher aortic pulse wave velocity (PWV) (10.2 ± 1.8 m/s vs 9.4 ± 1.7 m/s; p = 0.03) and higher central BP (117.6 ± 13.9/74.0 ± 9.1 mmHg vs 110.4 ± 16.4/69.7 ± 9.6 mmHg, p = 0.04). In patients with clinical normotension, night-time systolic BP correlated significantly with PWV. Conclusions/interpretation  Thirty per cent of patients with clinical normotension had nocturnal hypertension. This was accompanied by increased arterial stiffness and higher central BP. We conclude that in clinically normotensive patients with type 2 diabetes, ambulatory BP measurement may help clinicians to identify patients with increased cardiovascular risk.     

Comparison of Changes in Early Inflammatory Markers Between Sirolimus- and Paclitaxel-Eluting Stent Implantation

Background  Systemic inflammation after coronary intervention identifies patients at increased risk of subsequent cardiac events. Cardiac events, especially in-stent restenosis, are less frequent after use of sirolimus-eluting stent (SES) compared with paclitaxel-eluting stent (PES). However, the underlying mechanism for this disparity is not well investigated. We hypothesize that an attenuated inflammatory response after SES implantation may be a contributor. Purpose  In the present study, we sought to determine the early inflammatory response after SES implantation in patients with single-vessel disease compared with PES implantation, and evaluate the relationship between inflammatory response and late clinical outcomes in a randomized design. Methods  Thirty-two patients with stable angina were randomly enrolled into the two groups, SES or PSE group (n = 16 respectively). Peripheral blood samples were taken before PCI, 24 and 72 h after stenting. The plasma concentrations of C-reactive protein (CRP) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). The clinical and angiographic follow-up was performed at 8 months after stenting. Results  The data showed that there was no significant difference in clinical and angiographic baseline characteristics between the two groups. The plasma CRP and IL-6 levels at 24 h after stenting were significant higher in both groups compared with baseline (p < 0.01 respectively). Likewise, the CRP levels at 72 h after stenting were also significant higher compared with baseline in both groups (p < 0.01 respectively). However, the plasma levels of IL-6 at 24 h and CRP at 72 h after stenting were higher in PES group compared with SES group (p < 0.05). At 8 months follow-up, the rates of major adverse cardiac events, target lesion revascularization, in-stent and in-segment restenosis were similar in both groups. However, the late loss in both in-stent and in-segment was significantly higher in the PES group than in SES group (p < 0.001 respectively). Conclusions  Our findings suggest that a drug-eluting stent implantation could trigger a systemic inflammatory response as previously demonstrated. However, SES implantation results in a lower inflammatory response compared with PES implantation, which seems to be associated with greater late of in-stent and in-segment loss at 8-month follow-up with PES.     

Abnormal surface markers expression on bone marrow CD34<Superscript>+</Superscript> cells and correlation with disease activity in patients with systemic lupus erythematosus

Defects of hematopoietic stem cells (HSCs) have been suggested to contribute to the development of systemic lupus erythematosus (SLE). The aim of this study was to investigate the phenotypic characteristics of bone marrow (BM) CD34⁺ cells in patients with SLE and its relationship with SLE disease activity. Ten SLE patients and 10 healthy subjects were recruited and their BM CD34⁺ cells were analyzed by flow cytometric analysis with CD45/SSC gating for the expression of CD90, CD95, CD117, CD123, CD164, CD166, FAS-L, and HLA-DR. The percentage of BM CD34⁺ cells was significantly decreased in active SLE patients (1.48 ± 0.41%, n = 7) compared to the healthy controls (2.31 ± 0.75%, n = 10, p < 0.01), but no significant difference was found between the inactive patients (2.04 ± 0.44%, n = 3) and the controls. The expression of CD95, CD123, and CD166 on BM CD34⁺ cells were significantly increased in SLE patients (48.31 ± 10.59%, 44.9 ± 21.5%, 30.9 ± 19.54%, respectively, n = 10) when compared with the control subjects (24.33 ± 11.1%, 19.5 ± 4.4%, 10.7 ± 5.5%, respectively, n = 10, p < 0.05). The increased CD123 expression was negatively correlated with the number of peripheral white blood cells (r = −0.700, p < 0.05, n = 10). The percentage of CD166 expression was found significantly correlated with the index of SLE disease activity (r = 0.472, p < 0.05, n = 10) and 24 h proteinuria (r = 0.558, p < 0.05, n = 10), but negatively correlated with serum C3 level (r = −0.712, p < 0.01, n = 10). Our study found that the surface marker expression of CD95, CD123, and CD166 on BM CD34⁺ cells were significantly increased in patients. This supports the hypothesis that there are abnormalities of the HSC in SLE. Since CD166 and CD123 correlated with the overall lupus activity, their role as a biomarker of inflammatory disease activity also requires further study.