Relationship between self-reported and performance-based tests in a hip and knee joint replacement population

Our objectives were: (1) to assess the relationship between self-reported measures (Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and Medical Outcomes Study Short Form-36 (SF-36)) and a performance-based timed-up-and-go (TUG) test in a hip and knee joint replacement population and (2) to determine the predictors of postoperative functional status as measured by the 12-week WOMAC and TUG scores. We surveyed 200 patients undergoing primary hip or knee replacement surgery for demographic data and outcome scores at baseline and 12-week follow-up. There was a weak correlation between preoperative TUG scores and preoperative SF-36 physical function scores (r = −0.28, p < 0.0001), SF-36 role-physical scores (r = −0.21, p = 0.0022) and WOMAC (r = 0.29, p < 0.0001) scores. The relationship was stronger between the postoperative TUG scores and WOMAC scores (r = 0.43, p < 0.0001), SF-36 physical function scores (r = −0.39, p < 0.0001) and SF-36 role-physical (r = −0.33, p < 0.0001) scores. Significant predictors for the TUG test at 12-week follow-up were age (p = 0.004) and preoperative TUG scores (p < 0.0001). Given low-to-moderate relationship between self-reported and performance-based tools, both tests are needed to assess the true level of patient disability.     

Plasma pancreatic polypeptide levels are associated with differences in body fat distribution in human subjects

Aims/hypothesis Pancreatic polypeptide (PP) is produced by the F-cells of the pancreas, and its plasma concentration has been used as a marker of parasympathetic activity. Recent work in rodents suggests that there is both sympathetic and parasympathetic innervation of white adipose tissue and that parasympathetic activity is anabolic resulting in lipid accumulation. We have examined whether in humans increased PP levels are associated with increased intra-abdominal fat (IAF), and thereby insulin resistance. Materials and methods We measured PP levels in 177 non-diabetic subjects (75 male/102 female; age 32–75 years) 3 min after an i.v. glucose bolus during a frequently sampled intravenous glucose tolerance test. IAF and s.c. fat (SCF) areas were measured by CT scan. The insulin sensitivity index (S _I) was quantified using Bergman’s minimal model. Results PP levels were higher in men than in women (96.2 ± 72.2 vs 76.1 ± 55.0 pg/ml, mean ± SD, p = 0.037), as was IAF area (124.7 ± 67.4 vs 83.0 ± 57.7 cm², p < 0.001). While PP levels were significantly associated with IAF (r = 0.16, p = 0.031), WHR (r = 0.30, p < 0.001) and age (r = 0.37, p < 0.01), they were not associated with SCF (r = 0.02, p = 0.829). The association between PP and IAF was not independent of age and/or sex. S _I was negatively associated with PP levels (r = −0.17, p = 0.026) and IAF area (r = −0.65, p < 0.001). The association between S _I and PP disappeared after adjusting for IAF area, indicating that S _I was not a major determinant of PP levels. Conclusions/interpretation In humans, age and sex may modulate the association between plasma PP level and IAF area, suggesting that they may be determinants of parasympathetic activity and thus IAF accumulation.     

The relation of serum vascular endothelial growth factor level with disease duration and activity in patients with rheumatoid arthritis

Vascular endothelial growth factor (VEGF) is known to be involved in the pathogenesis of rheumatoid arthritis (RA). In order to elucidate the association between VEGF levels and RA disease activity, VEGF concentrations were measured in RA patients at different phases and severity levels. Thirty-eight healthy subjects and 40 patients with RA were prospectively included in the study. Subjects were further categorized into four subgroups (high, moderate, low, or remission) using the disease activity score-28 (DAS28) scoring system. VEGF levels were significantly higher in patients than controls (p < 0.001). VEGF levels differed significantly in controls, early and late-phase RA patients (p = 0.002). A significant difference was found between controls and patients with high RA disease activity scores (p < 0.0001). VEGF levels were not correlated with age (r = −0.016; p = 0.921) or sex (r = 0.209; p = 0.921). VEGF values were correlated with erythrocyte sedimentation rate (r = 0.445; p = 0.004), but was not correlated with serum rheumatoid factor levels (r = −0.130; p = 0.424) in the patient group. In conclusion, higher VEGF levels are associated with late phase and high disease activity in RA, independent of age and sex.     

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.     

Association between ventilatory response to hypercapnia and obstructive sleep apnea–hypopnea index in asymptomatic subjects

The majority of awake ventilatory control studies have shown normal or decreased ventilatory response to hypercapnia (HCVR) in obstructive sleep apnea–hypopnea syndrome (OSAHS) patients. These findings are contrary to experimental studies suggesting increased loop gain and greater breathing instability in OSAHS patients. We have investigated the relationship between central chemoreflex sensitivity tested by HCVR and obstructive sleep apnea/hypopnea index (OSAHI) in asymptomatic subjects. Twenty normal volunteers (10 men and 10 women) from the general population without physical complaints including sleep-related symptoms were included. The subjects were studied for awake ventilatory responses to hypoxia (HVR) and hypercapnia. Overnight polysomnography (PSG) was performed in two consecutive nights with the first night used as acclimatization. The subjects have an average body mass index (BMI) of 27 ± 5 SD kg/m², ages of 35 ± 9 SD years and Epworth sleepiness scale of 2.1 ± 1.8 SD. A positive linear relationship was found between HCVR and logarithmically transformed OSAHI (r = 0.67, p = 0.001). BMI and age were not significantly correlated to HCVR or Log OSAHI. No relationship was found between HVR and Log OSAHI (r = 0.25, p = 0.29). Percentage oxygen saturation nadir during sleep was found to significantly correlate to both daytime HCVR (r = −0.60, p = 0.005) and Log OSAHI (r = −0.65, p = 0.002) and tended to correlate to HVR (r = −0.41, p = 0.07). Arousal index during sleep was not associated with either HCVR (p = 0.93) or HVR (p = 0.26). In conclusion, heightened central chemosensitivity was positively related to OSAHI in asymptomatic volunteers. We believe these findings are in keeping with the evolving theory of loop gain being a significant factor for respiratory control instability and obstructive apnea genesis. The mechanism can be applied to asymptomatic subjects with even minimal sleep-disordered breathing.     

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.     

Soluble receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin in ankylosing spondylitis: OPG is associated with poor physical mobility and reflects systemic inflammation

The objective of the study was to investigate the role of receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in ankylosing spondylitis (AS). Serum levels of soluble RANKL (sRANKL) and OPG were measured in 42 AS patients and 26 healthy controls. We evaluated the AS patient's disease activity, functional ability, global assessment, and physical mobility and tested markers of systemic inflammation, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels. Serum levels of sRANKL [mean (SD), 4.75 (1.88) vs. 3.70 (1.14) pmol/l, p = 0.015] and OPG [mean (SD), 5.18 (1.19) vs. 4.52 (0.85) pmol/l, p = 0.026] were significantly higher in the 42 AS patients than the 26 healthy controls. Interestingly, serum OPG levels correlated significantly with ESR (r = 0.417, p = 0.007), CRP (r = 0.524, p < 0.001), tragus-to-wall distance (r = 0.556, p < 0.001), fingertip-to-floor distance (r = 0.423, p = 0.007), and occiput-to-wall distance (r = 0.465, p = 0.002) and correlated inversely with modified Schober index (r = −0.525, p = 0.001), cervical rotation (r = −0.403, p = 0.022), lateral lumbar flexion (r = −0.587, p < 0.001), and chest expansion (r = −0.553, p < 0.001). Moreover, in the AS patients with higher (≥4.925 pmol/l, n = 21) serum OPG levels, there were significant increases in the tragus-to-wall distance (p = 0.007), fingertip-to-floor distance (p = 0.023), and CRP levels (p = 0.014) and decreased in the modified Schober index (p = 0.012), lateral lumbar flexion (p = 0.019), and chest expansion (p = 0.005). Serum levels of sRANKL and OPG are increased in the AS patients and may participate in the disease process of AS. Production of OPG has association with poor physical mobility and may reflect systemic inflammation in AS.     

Reliability and validity studies of the Turkish version of the Epworth Sleepiness Scale

The Epworth Sleepiness Scale (ESS) is a self-administered eight-item questionnaire that is widely used in English speaking countries for assessment of daytime sleepiness in adults. The aim of this study was to investigate the reliability and validity of the ESS in the Turkish language. The Turkish version of the ESS (ESStr) was applied to 194 healthy controls and 150 consecutive subjects attending the sleep centre with symptoms of sleep-disordered breathing. Test–retest reliability of the ESStr was tested in a separate group of 30 subjects. The ESStr scores of 60 subjects with mild to severe obstructive sleep apnoea (OSA) were compared with the ESStr scores of 60 healthy controls matched for age, gender, and body mass index (BMI). Concurrent validity with the Functional Outcomes of Sleep Questionnaire (FOSQtr) was also assessed in 12 subjects. The questionnaire had a high level of internal consistency as measured by Cronbach’s alpha (≥0.86). The test–retest intraclass correlation coefficient was r  = 0.81 (95% confidence interval: 0.64–0.90) (p < 0.001) and Spearman’s correlation coefficient was r = 0.80 (p = 0.01). The control group had lower ESStr scores than subjects with sleep-disordered breathing (3.6 ± 3 vs 12.6 ± 6, respectively; p < 0.001). Subjects with mild sleep-disordered breathing also had lower scores of the ESStr than those with moderate and severe sleep-disordered breathing (10 ± 6.2 vs 14 ± 5. and 10 ± 6.2 vs 16 ± 5.4, respectively; both p < 0.05), but there were no significant differences between moderate and severe subjects with sleep apnoea. There were significant correlations between the ESStr and total FOSQtr and its subscales (r  = −0.22 to r = −0.92; all p  = 0.05). Factor analysis of item scores showed that the ESStr had only one factor. The ESStr is a reliable and valid measure of daytime sleepiness. These features and the simplicity of the ESStr make it a valuable measure for clinical management and research.     

The Neuropad test: a visual indicator test for human diabetic neuropathy

Aims/hypothesis The commercially available Neuropad test was developed as a simple visual indicator test to evaluate diabetic neuropathy. It uses a colour change to define the integrity of skin sympathetic cholinergic innervation. We compared the results of Neuropad assessment in the foot with established measures of somatic and autonomic neuropathy. Methods Fifty-seven diabetic patients underwent Neuropad assessment, quantitative sensory and autonomic function testing, and evaluation of intra-epidermal nerve fibre density in foot skin biopsies. Results Neuropad responses correlated with the neuropathy disability score (r _s = 0.450, p < 0.001), neuropathic symptom score (r _s = 0.288, p = 0.03), cold detection threshold (r _s = 0.394, p = 0.003), heat-as-pain perception threshold visual analogue score 0.5 (r _s = 0.279, p = 0.043) and deep-breathing heart rate variability (r _s = −0.525, p < 0.001). Intra-epidermal nerve fibre density (fibres/mm) compared with age- and sex-matched control subjects (11.06 ± 0.82) was non-significantly reduced (7.37 ± 0.93) in diabetic patients with a normal Neuropad response and significantly reduced in patients with a patchy (5.01 ± 0.93) or absent (5.02 ± 0.77) response (p = 0.02). The sensitivity of an abnormal Neuropad response in detecting clinical neuropathy (neuropathy disability score ≥5) was 85% (negative predictive value 71%) and the specificity was 45% (positive predictive value 69%). Conclusions/interpretation The Neuropad test may be a simple indicator for screening patients with diabetic neuropathy.     

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.     

Relationship between glyco-oxidation, antioxidant status and microalbuminuria in type 2 diabetic patients

Aims/hypothesis  This study examined the relationship, if any, between glucose-induced oxidative stress, antioxidant status and microalbuminuria in patients with type 2 diabetes. Methods  The study involved 99 consecutive type 2 diabetic patients (57 men, 42 women). Patients with persistent microalbuminuria were identified and the following variables evaluated: fasting plasma glucose, HbA_1c, malonyldialdehyde (MDA), pentosidine, AGE, the total radical-trapping antioxidant parameter (TRAP), vitamin E, creatinine, estimated GFR and lipid profile. Results  Patients were divided into two groups, i.e. 37 individuals without microalbuminuria (AER <20 μg/min) and 62 with microalbuminuria (AER ≥20 μg/min). The following variables were significantly higher in patients with microalbuminuria than in those without microalbuminuria (mean ± SD): fasting plasma glucose 9.41 ± 2.88 vs 8.19 ± 1.93 mmol/l, p < 0.05; HbA_1c 7.97 ± 1.51 vs 7.39 ± 1.03%, p < 0.05; MDA 1.18 ± 0.35 vs 1.02 ± 0.29 μmol/l, p < 0.05; pentosidine 98.5 ± 24.6 vs 82.9 ± 20.9 pmol/ml, p < 0.005; and AGE 13.2 ± 4.8 vs 10.6 ± 3.8 μg/mg protein, p < 0.01. However, vitamin E and TRAP did not differ between the two groups. Serum creatinine values and estimated GFR were similar in the two groups. Only in patients with microalbuminuria were significant linear correlations seen between AER and both oxidation (HbA_1c r = 0.33, p < 0.01; MDA r = 0.59, p < 0.001; pentosidine r = 0.48, p < 0.001; and AGE r = 0.44, p < 0.001) and antioxidation variables (vitamin E r = −0.55, p < 0.001; TRAP r = −0.49, p < 0.001). Considering all variables together, multiple regression revealed a correlation between microalbuminuria and vitamin E, TRAP, HbA_1c and MDA, but not pentosidine or AGE. Conclusions/interpretation  Our data suggest that microalbuminuria in type 2 diabetic patients might be promoted by an insufficient counter-regulation of the antioxidant system in the event of increased glyco-oxidation/glycation.     

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.     

High prevalence of low plasma thiamine concentration in diabetes linked to a marker of vascular disease

Aims/hypothesis To assess thiamine status by analysis of plasma, erythrocytes and urine in type 1 and type 2 diabetic patients and links to markers of vascular dysfunction. Methods Diabetic patients (26 type 1 and 48 type 2) with and without microalbuminuria and 20 normal healthy control volunteers were recruited. Erythrocyte activity of transketolase, the concentrations of thiamine and related phosphorylated metabolites in plasma, erythrocytes and urine, and markers of metabolic control and vascular dysfunction were determined. Results Plasma thiamine concentration was decreased 76% in type 1 diabetic patients and 75% in type 2 diabetic patients: normal volunteers 64.1 (95% CI 58.5–69.7) nmol/l, type 1 diabetes 15.3 (95% CI 11.5–19.1) nmol/l, p < 0.001, and type 2 diabetes 16.3 (95% CI 13.0–9.6) nmol/l, p < 0.001. Renal clearance of thiamine was increased 24-fold in type 1 diabetic patients and 16-fold in type 2 diabetic patients. Plasma thiamine concentration correlated negatively with renal clearance of thiamine (r = −0.531, p < 0.001) and fractional excretion of thiamine (r = −0.616, p < 0.001). Erythrocyte transketolase activity correlated negatively with urinary albumin excretion (r = −0.232, p < 0.05). Thiamine transporter protein contents of erythrocyte membranes of type 1 and type 2 diabetic patients were increased. Plasma thiamine concentration and urinary excretion of thiamine correlated negatively with soluble vascular adhesion molecule-1 (r = −0.246, p < 0.05, and −0.311, p < 0.01, respectively). Conclusions/interpretation Low plasma thiamine concentration is prevalent in patients with type 1 and type 2 diabetes, associated with increased thiamine clearance. The conventional assessment of thiamine status was masked by increased thiamine transporter content of erythrocytes.     

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.     

Developmental changes of oxalate excretion in enterally fed preterm infants

Summary  To further substantiate gestational age-related changes in oxalate excretion, we studied urinary oxalate excretion in 66 preterm infants born at 23.4–34.7 weeks of gestation. Spot urine of 66 preterm infants was analysed by ion chromatography as soon as they were completely orally fed with enriched breast milk and/or special preterm milk formula (days 7 to 57 of postnatal life). Infants with evidence of renal, gastrointestinal, muscular or metabolic disease were not included. Newborns on parenteral nutrition were excluded. Oxalate/creatinine ratios (Ox/Cr) decreased with gestational age (three age groups: group 1, 23 0/7–28 0/7; group 2, 28 1/7–32 0/7; and group 3, 32 1/7–35 0/7 weeks of gestation). The mean Ox/Cr was highest in group 1 (398.2 mmol/mol ± 116.8; n = 21). Differences between groups 1 + 3 were statistically significant; p = 0.001; those between groups 1 + 2 and between groups 2 + 3 were not. Ox/Cr correlated inversely with gestational and maturational age (r = −0.41, p = 0.001; r = −0.33, p = 0.007) and positively with postnatal age (r = 0.32, p = 0.008). It correlated inversely with birth weight as well as actual weight at sample collection (r = −0.46 and −0.44, p < 0.001). Ox/Cr was significantly linked to energy and carbohydrate intake (r = 0.3 and 0.4, p = 0.03 and 0.001). These results were independent of sex. In the present study we show that urinary oxalate excretion in preterm infants depends on gestational age. Competing interests: None declared The authors B. Bohnhorst and A. M. Das contributed equally.     

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.     

Accelerated atrophy of lower leg and foot muscles—a follow-up study of long-term diabetic polyneuropathy using magnetic resonance imaging (MRI)

Aims/hypothesis  The aim of the study was to determine the loss of muscle volume in the lower leg and foot in long-term diabetic patients in relation to the presence of neuropathy. Methods  We re-examined 26 type 1 diabetic patients who had participated in magnetic resonance imaging (MRI) studies on muscle volume in the lower leg and foot 9 to 12 years earlier. Re-examination involved MRI, isokinetic dynamometry, clinical examination, electrophysiological studies and quantitative sensory examinations. Results  Annual loss of muscle volume of ankle dorsal and plantar flexors was 4.5 (5.5–3.9)% (median [range]) and 5.0 (7.0–4.2)% in neuropathic patients, 1.9 (3.2–1.0)% and 1.8 (2.6–1.3)% in non-neuropathic patients, and 1.7 (2.8–0.8)% and 1.8 (2.4–0.8)% in controls, respectively (p < 0.01). Annual change of volume and strength correlated for ankle dorsal flexors (r _s = 0.73, p < 0.01) and for ankle plantar flexors (r _s = 0.63, p < 0.05) in diabetic patients. In addition, annual change of muscle volume for dorsal and plantar flexors was related to the combined score of all measures of neuropathy (r _s = −0.68, p < 0.02 and r _s = −0.73, p < 0.01, respectively). Foot muscle volume declined annually by 3.0 (3.4–1.0)% in neuropathic patients and by 1.1 (4.0–0.2)% in non-neuropathic patients, both values being significantly different from controls (0.2 [−2.5 to 2.4]%). Loss of foot muscle volume was related to severity of neuropathy assessed at clinical evaluation (r _s = −0.6, p < 0.05). Conclusions/interpretation  Muscular atrophy in long-term diabetic neuropathy occurs early in the feet, progresses steadily in the lower legs, relates to severity of neuropathy and leads to weakness at the ankle. An erratum to this article can be found at     

Circulating nitric oxide (NO), asymmetric dimethylarginine (ADMA), homocysteine,and oxidative status in obstructive sleep apnea–hypopnea syndrome (OSAHS)

Obstructive sleep apnea–hypopnea syndrome (OSAHS) with episodic hypoxia–reoxygenation is associated with increased cardiovascular morbidity and mortality. Therefore, increased homocysteine, asymmetric dimethylarginine (ADMA), oxidative status, and decreased nitric oxide levels have been implicated as possible mechanisms for development of cardiovascular diseases. We aimed to investigate changes in the levels of these substances in patients with OSAHS in comparison with nonapneic controls. Thirty-four OSAHS patients and 15 healthy controls were included in this study. In the blood samples, oxidative status and nitric oxide levels were measured with spectrophotometric methods. Plasma ADMA and homocysteine levels were determined by using high-performance liquid chromatography with fluorescence detection. Nitric oxide levels were significantly low in OSAHS patients (p < 0.05) and correlated with mean SaO₂ (r = 0.513, p < 0.002) and lowest SaO₂ (r = 0.363, p < 0.03). Oxidative status, ADMA, and homocysteine levels were higher in OSAHS patients, but difference did not reach statistical significance. After dividing patients into moderate (AHI = 5–29) and severe (AHI ≥ 30) OSAHS groups, significantly increased homocysteine levels were observed in the severe OSAHS group (p < 0.05). Nitric oxide levels negatively correlated with oxidative status in total OSAHS patients (r = −0.415, p < 0.02) and also in severe OSAHS group (r = −0.641, p < 0.007). Hyperhomocysteinemia and diminished NO production may be causal factors in endothelial dysfunction seen in OSAHS and may explain the association between OSAHS and cardiovascular diseases. These modifiable factors should be monitored in patients suspected of having OSAHS.     

Quantitative ultrasound is better correlated with bone mineral density and biochemical bone markers in elderly women

The association between quantitative ultrasound (QUS) and bone turnover in postmenopausal women of different ages is an area of continuous investigation. The aim of this study was to investigate the relationship of ultrasound parameters [broadband ultrasound attenuation (BUA) and speed of sound (SOS)] to bone mineral density (BMD) and biochemical markers of bone turnover in three age groups of postmenopausal women. One hundred and twenty-three postmenopausal Caucasian women were divided into three groups according to their age: group A, range 44–54 years, mean age (±SD) 48.3 ± 2.3; group B, range 55–65 years, mean age 59.4 ± 2.1; and group C, range 66–77 years, mean age 68.2 ± 3.1. Ultrasound parameters were measured by the DTU-one imaging ultrasonometer in the calcaneus. BMD was assessed by dual-energy X-ray absorptiometry (DEXA) at the lumbar spine, femoral neck, and trochanter. Bone turnover was assessed by serum bone-specific alkaline phosphatase (BAP), urinary excretion of free deoxypyridinoline, N-telopeptides (NTX), and C-telopeptide breakdown products of type I collagen (CTX). QUS and BMD were significantly correlated in all sites, except hip BMD in group A. The most significant correlation was observed between BUA and femoral neck BMD in group C (r = 0.626, p < 0.01). BUA correlated significantly with BAP, NTX, and CTX (r = −0.434, −0.511, −0.478, respectively; p < 0.01), and SOS with BAP and NTX (r = −0.351 and −0.356, respectively; p < 0.05) only in group C. In groups A and B, ultrasound parameters did not correlate significantly to biochemical markers. Ultrasound parameters were better correlated to hip BMD and to biochemical markers of bone turnover in elderly postmenopausal women. These ultrasound measurements could be used as a screening test for bone status, either in nonambulatory third aged women or in those living in rural areas where attending medical centers with DEXA equipment and biochemical laboratories is difficult.     

Circulating soluble adhesion molecules in patients with systemic sclerosis: correlation between circulating soluble vascular cell adhesion molecule-1 (sVCAM-1) and impaired left ventricular diastolic function

The objective of this paper is to investigate the relation between circulating soluble adhesion molecules and cardiac involvement, as assessed by echocardiography in patients with systemic sclerosis (SSc). Nineteen patients with SSc were submitted for assessment of serum levels of circulating soluble intercellular adhesion molecules (sICAM-1), and soluble vascular cell adhesion molecules-1 (sVCAM-1), and echocardiography. Abnormal left ventricular filling patterns (↓E/A ratio) were detected in ten patients (52.6%) with significant negative correlation with sVCAM-1 (r=−0.484, P < 0.05). It was also significantly correlated with age (r=−0.791, P < 0.01), age of onset (r=−0.468, P < 0.05), degree of dyspnea (r=−0.687, P < 0.01), and erythrocyte sedimentation rate (ESR) (r=−0.489, P < 0.05). Our findings suggest an important role for sVCAM-1 as a marker of disease severity and impaired left ventricular filling pattern in SSc. Received: 30 December 1999 / Accepted: 13 July 2000