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.     

CPAP adherence and partial upper airway obstruction during sleep

Nasal continuous positive airway pressure (CPAP) is the treatment of choice in severe obstructive sleep-disordered breathing (SDB). Partial obstruction is usually considered as mild SDB with poor CPAP adherence. In a retrospective study, we investigated the occurrence of partial obstruction in 233 age and BMI-matched male–female pairs and its impact on CPAP adherence after one year using static-charge-sensitive bed. Women had less SDB compared with men (21.8 vs 31.7% of time in bed (TIB), p < 0.001), less periodic breathing (5.8 vs 15.6%, p < 0.001) but tended to have more partial obstruction (10.5 vs 7.5%, p = 0.174). In women, partial obstruction accounted for 50.2% of breathing abnormalities, in men 37.2% (p < 0.001). CPAP adherence was 60.5% in women and 56.9% in men. When taking into account the proportion of partial obstruction (≤5 vs >5% of TIB) or periodic breathing, there were no differences in women’s CPAP adherence (p = 0.130 and p = 0.148, respectively). Men with periodic breathing over 5% of TIB tended to be more adherent to CPAP, (p = 0.052). The high occurrence of partial obstruction in both genders and particularly in women suggests that the apnea–hypopnea index underestimates the occurrence of SDB. There are no concerns of low adherence when treating symptomatic partial obstruction during sleep. Partial obstruction may not represent mild SDB but a different entity.     

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.     

Sleep-disordered breathing: a new risk factor of suspected fatty liver disease in overweight children and adolescents?

Introduction  The aim of this retrospective study was to investigate if sleep-disordered breathing (SDB) was an independent predictor of suspected fatty liver disease in a clinical sample of overweight children and adolescents. Materials and methods  Consecutive overweight and obese children attending a pediatric obesity clinic underwent polysomnography, fasting blood sample, and abdominal ultrasound. Results and discussion  The respiratory disturbance index, percentage of total sleep time with SO2 < 90%, and SaO2nadir were associated with higher alanine amino-transferases (ALT) independent of abdominal obesity. Multiple logistic regression selected waist circumference (odds ratio = 1.05; p = 0.05) and SaO2nadir (odds ratio = 0.87; p = 0.03) as predictors of suggestive fatty liver disease, defined as ALT > 40 U/L and/or hyperechoic liver on abdominal ultrasound. This study supports the association between the severity of SDB and suspected fatty liver disease in a clinical sample of overweight children and adolescents. We recommend more research on the influence of SDB on the development of fatty liver disease and on the effect of treating sleep apnea on liver function parameters.     

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.     

Evaluating obesity in fibromyalgia: neuroendocrine biomarkers, symptoms, and functions

The aim of this study was to investigate the associations between obesity and fibromyalgia syndrome (FMS). This study was conducted at the University of Utah Pain Management and Research Center, Salt Lake City, Utah. Thirty-eight FMS patients were included in this study. Neuroendocrine indices (catecholamines, cortisol, C-reactive protein [CRP], and interleukin-6), symptom measures (Fibromyalgia Impact Questionnaire), sleep indices (Actigraph), and physical functioning (treadmill testing) were measured. Body mass index (BMI) provided the primary indicator of obesity. Approximately 50% of the patients were obese and an additional 21% were overweight. Strong positive associations were found between BMI and levels of IL-6 (r = 0.52) and epinephrine (r = 0.54), and somewhat weaker associations with cortisol (r = 0.32) and CRP (r = 0.37). BMI was also related to maximal heart rate (r = 0.33) and inversely related to distance walked (r = −0.41). BMI was associated with disturbed sleep: total sleep time (r = −0.56) and sleep efficiency (r = −0.44). No associations between self-reported symptoms and BMI were found. This study provides preliminary evidence suggesting that obesity plays a role in FMS-related dysfunction.     

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.     

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.     

Sleep architecture in children and adolescents with cystic fibrosis and the association with severity of lung disease

Previous studies have shown that sleep complaints are common in adult patients with cystic fibrosis (CF). However, there is very little data on sleep in children and adolescents with CF and the association with severity of lung disease. A prospective study was conducted in CF children and age-matched controls. All patients completed sleep questionnaire and underwent an overnight polysomnographic study. Thirty-eight children and adolescents met the criteria for entry into the analysis, 24 children and adolescents with CF (S) and 14 controls (C). Sleep complaints were common in children and adolescents with CF; 43.5% reported sleep onset problem, 39.1% reported sleep maintenance problem, 30.4% were noted to snore at night, and 73.9% reported daytime sleepiness. Children and adolescents with CF had a significant decrease in sleep efficiency [SE; 75.2 ± 2.5% (S) vs 85.6 ± 1.7%(C); P < 0.01], prolonged rapid eye movement (REM) latency [150.5 ± 16.6 min (S) vs 85.6 ± 11.0 min (C); P < 0.05], and reduction in percentage of REM sleep [12.7 ± 1.5% (S) vs 18.3 ± 1.3% (C); P < 0.05]. The degree of sleep disruption as indicated by SE was correlated with forced expiratory volume in one second (FEV₁; r = 0.52, P < 0.05). However, there was no significant correlation between SE and minimum oxygen saturation [r = 0.30, P=not significant (NS)] or SE and maximal end-tidal pCO₂ (r = 0.11, P=NS). It is concluded that children and adolescents with CF have frequent sleep complaints and significant alteration in the sleep architecture. The magnitude of sleep disruption is associated with severity of lung disease, but is not directly correlated with the degree of nocturnal hypoxemia or hypoventilation. It is speculated that sleep disruption in children and adolescents with CF may have an impact on quality of life and clinical outcomes in this population.     

Tryptophan degradation and neopterin levels in treated rheumatoid arthritis patients

Increased kynurenine/tryptophan—reflects trytophan degradation—and neopterin levels have been regarded as a biochemical marker of cell-mediated immune response and inflammation. This study was designed to evaluate the usefulness of tryptophan degradation and neopterin levels in active rheumatoid arthritis patients under therapy. In this case–control study, kynurenine and tryptophan levels were determined by HPLC; neopterin and tumor necrosis factor-α levels were measured with ELISA in 32 active rheumatoid arthritis patients and 20 healthy controls. Although mean values of tryptophan, kynurenine, ratio of kynurenine to tryptophan, neopterin, and tumor necrosis factor-α levels did not show statistically significant differences between patient and control groups, neopterin levels correlated positively with kynurenine (r = 0.582, p < 0.02), kynurenine/tryptophan (r = 0.486, p < 0.05), erythrocyte sedimentation rate (r = 0.472, p < 0.05) and RF (r = 0.478, p < 0.05) in the rheumatoid arthritis group. CRP levels of the patient group correlated with kynurenine levels (r = 0.524, p < 0.03). Determination of tryptophan degradation and neopterin levels in chronic inflammatory disease may provide a better understanding of progression of the disease.     

Serum IL-6, TNFα, p55 srTNFα, p75 srTNFα, srIL-2α Levels and Disease Acitivity in Systemic Lupus Erythematosus

The aim of this study was to determine whether the levels of serum cytokines IL-6 and TNFα and of the soluble receptors p55 srTNFα, p75 srTNFα and srIL-2α are valuable markers of disease activity in patients with systemic lupus erythematosus (SLE) compared with the established parameters of anti-dsDNA, C3, C4 and CH₅₀. Forty patients with SLE, 19 ambulatory and 21 hospitalised, were included in this study. On the day of blood sampling a clinical examination was performed and SLEDAI and ECLAM disease activity scores were used to assess disease activity. Nineteen patients had inactive disease and 21 patients had active disease. Thirteen patients from the second group developed nephritis. In these patients the blood sampling and disease activity assessment were performed twice (at presentation and 6 months after treatment). Serum levels of cytokines and soluble receptors were measured by ELISA. Serum levels of cytokines and soluble receptors of patients with active disease were significantly higher than in patients with inactive disease (IL-6 p = 0.0004, TNFαp = 0.0015, srIL-2αp<0.0001, p55 srTNFαp<0.0001, p75 srTNFαp<0.0001). Serum soluble receptor levels of patients with inactive disease were higher than those of healthy controls (p55 srTNFαp<0.0001, p75 srTNFαp = 0.0002, srIL-2αp = 0.0012). No significant difference was found for TNFα and IL-6 (TNFαp = 0.015, IL-6 p = 0.019). Serum TNFα levels and especially srIL-2α, p55 srTNFα and p75 srTNFα levels correlated strongly with SLEDAI and ECLAM disease activity scores, anti-dsDNA, C3, C4 and CH₅₀ (p<0.0001). Serum soluble receptor (srIL-2α, p55 srTNFα, p75 srTNFα) levels were higher in patients with nephritis before treatment and decreased significantly 6 months after treatment (p = 0.005). The same trend was noticed with SLEDAI and ECLAM disease activity scores (p = 0.005) and anti-dsDNA (p = 0.008). In contrast, no significant differences were observed for C3 and C4 levels before and after treatment, which suggests that soluble receptors of cytokines are more sensitive markers of disease activity than C3 or C4 in predicting improvement. Serum levels of srIL-2α, p55 srTNFα and p75 srTNFα could provide useful information about disease activity in SLE patients, especially in cases where the other markers do not. Received: 3 March 1998 / Accepted: 13 July 1998     

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.     

Fetal growth is increased by maternal type 1 diabetes and HLA DR4-related gene interactions

Aims/hypothesis Intrauterine growth in non-diabetic pregnancies is reported to be influenced by type 1 diabetes susceptibility genes. In particular, the high-risk HLA DR4_DQB1*0302 haplotype is associated with increased birthweight. The aim of this study was to determine whether HLA DR4 was associated with increased birthweight in a maternal diabetes environment and whether effects persisted during early childhood. Subjects and methods Birthweight and gestational age were obtained in singleton births from mothers with type 1 diabetes (n = 1161) or whose fathers or siblings have type 1 diabetes (n = 872). Weight and height at ages 2 and 5 years were obtained from paediatric records. Data were adjusted for (gestational) age and sex and expressed as percentiles of German reference data. HLA DR typing was obtained for all children and 1090 children also had insulin gene (INS) variable number of tandem repeats (VNTR) typing. Results Maternal type 1 diabetes was associated with increased birthweight, gestational age and birthweight percentiles (all p < 0.0001). In children of mothers with type 1 diabetes, birthweight percentile was further related to maternal HbA_1c during pregnancy (r = 0.26; p < 0.0001) and was independently increased if children had HLA DR4 alleles (76th vs 64th percentile; p < 0.0001). HLA DR4 was not associated with birthweight in children of non-diabetic mothers. Birthweight was not associated with INS VNTR genotypes. High birthweight, but not HLA DR4 was associated with increased weight and BMI at ages 2 and 5 years (p < 0.0001). Conclusions/interpretation Our findings are consistent with the hypothesis that a diabetic intrauterine environment interacts with gene(s) marked by the type 1 diabetes susceptibility HLA DR4 alleles to increase fetal growth. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Iron status in Danes updated 1994. I: Prevalence of iron deficiency and iron overload in 1332 men aged 40–70 years. Influence of blood donation, alcohol intake, and iron supplementation

 Iron status, S-ferritin, and hemoglobin (Hb) were assessed in a population survey in 1994 (DAN-MONICA 10) comprising 1332 Caucasian Danish men equally distributed in age cohorts of 40, 50, 60 and 70 years. Blood donors (n=186) had lower S-ferritin, median 76 μg/l, than nondonors, median 169 μg/l (p<0.0001). S-ferritin in donors was inversely correlated with the number of phlebotomies (r _s=–0.57, p<0.0001). S-ferritin in nondonors (n=1146) was similar in men 40–60 years of age, median 176 μg/l, and subsequently decreased at 70 years of age to a median of 146 μg/l (p=0.01). In the entire series, the prevalence of small iron stores (S-ferritin 16–32 μg/l) was 2.7%, that of depleted iron stores (S-ferritin <16 μg/l) 0.45%, and that of iron deficiency anemia (S-ferritin <13 μg/l and Hb <129 g/l) 0.15%. Among nondonors, the prevalence of iron overload (S-ferritin >300 μg/l) was 20%. S-ferritin in nondonors correlated with body mass index (r _s=0.19, p=0.0001) and with alcohol intake (r _s=0.26, p=0.0001). In the entire series, 28% of the subjects took supplemental iron (median 14 mg ferrous iron daily). Iron supplements had no influence on iron status. Nondonors (n=170) treated with acetylsalicylic acid had lower S-ferritin, median 136 μg/l, than nontreated, median 169 μg/l (p<0.001) and those treated with H₂-receptor antagonists (n=30) had lower S-ferritin, median 142 μg/l, than nontreated, median 171 μg/l (p<0.04). Compared with the DAN-MONICA 1 iron status survey of Danish men in 1984, the prevalences of iron depletion and iron deficiency anemia are unchanged whereas the prevalence of iron overload has increased significantly. In Denmark, iron fortification of flour was abolished in 1987. This apparently had no negative effect on iron status in men. Received: November 19, 1998 / Accepted: April 25, 1999     

Modified Epworth Sleepiness Scale in Chinese children with obstructive sleep apnea: a retrospective study

Background and objective  The purpose of this study is to assess whether Chinese children with high apnea–hypopnea index (AHI) are sleepier by a modified Epworth Sleepiness Scale (ESS). Materials and methods  Records were retrospectively reviewed. We included children who were between 3 and 12 years old, admitted for overnight polysomnogram because of suspected obstructive sleep apnea syndrome (OSAS). A modified ESS was used to assess excessive daytime sleepiness (EDS) of the children. Results  One hundred ninety-two Chinese children were included. Children with high AHI, defined as AHI > 5.0, were sleepier than children with AHI less than or equal to 5. After adjustment by age, gender, and obesity, children with high AHI remained significantly sleepier. Modified ESS was significantly correlated with AHI (rho = 0.124, 95% CI = 0.004–0.281). Modified ESS score of >8 was the best cutoff point with the sensitivity and specificity of 0.29 and 0.91, respectively. The odds ratio of children with modified ESS > 10 having high AHI was 4.231 (95%CI = 1.248 to 14.338) and children with modified ESS > 8 had the highest odds ratio, 4.295(95%CI = 1.66 to 11.1), of having high AHI. Conclusion   Chinese children with high AHI appear to be sleepier than children with low AHI. Children with suspected OSAS and high modified ESS, i.e., ESS > 8, had significantly higher odds ratio of having high AHI. Increased sleepiness is a specific but not a sensitive symptom in snoring children with high AHI. Screening for EDS in snoring children may help us identify those with high AHI and prioritize the management of those children. All authors worked and the study was carried out in Kwong Wah Hospital in Hong Kong. There was no conflict of interest and no specific source of funding for the 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.     

Endothelial dysfunction and inflammatory reactions of elderly and middle-aged men with obstructive sleep apnea syndrome

Introduction  Obstructive sleep apnea syndrome (OSAS) is considered to be associated with cardiovascular complications, and atherosclerosis could mediate this relationship. Cardiovascular risk factors of OSAS still need to be elucidated in elderly patients, since studies about the association between OSAS and cardiovascular diseases have been done mainly in middle-aged adults. To investigate whether endothelial dysfunction, as an early marker of atherosclerosis, and inflammatory responses in OSAS were affected by age, we studied flow-mediated dilatation (FMD) and C-reactive protein (CRP) in elderly and middle-aged patients with OSAS. Materials and methods  This study enrolled 161 male subjects of 117 middle-aged (35–59 years old) and 44 elderly (≥60 years old) patients with OSAS. After they finished nocturnal polysomnography (NPSG), FMD was measured on the brachial artery and blood samples were obtained to determine serum CRP levels. Results and discussion  FMD was significantly lower in the elderly patients (p = 0.04), but no difference was observed between two age groups in body mass index (BMI), neck circumference, waist-to-hip ratio, apnea hypopnea index (AHI), serum CRP level, or NPSG findings related with nocturnal hypoxemia such as average O₂ saturation, percentage of time below 90% O₂ saturation, and oxygen desaturation index (ODI). From the results of stepwise multiple linear regression analysis, the lowest oxygen saturation was a significant determinant of FMD (β = 0.25, p < 0.01, adjusted R ² = 6%), and BMI (β = 0.22, p < 0.05) and waist-to-hip ratio (β = 0.21, p < 0.05) were significant variables to explain CRP (adjusted R ² = 11%, p < 0.01) in the middle aged patients. In the elderly patients, no variable was significant for predicting FMD, but AHI was significant determinant of CRP (β = 0.46, p < 0.01, adjusted R ² = 19%, p < 0.01). In predicting cardiovascular risks of OSAS, both hypoxia and obesity should be considered in the middle-aged group, whereas nocturnal respiratory disturbances are important in the elderly group.     

Associations between insulin resistance and TNF-α in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes

Aims/hypothesis Clear evidence exists that TNF-α inhibits insulin signalling and thereby glucose uptake in myocytes and adipocytes. However, conflicting results exist with regard to the role of TNF-α in type 2 diabetes. Methods We obtained blood and biopsy samples from skeletal muscle and subcutaneous adipose tissue in patients with type 2 diabetes (n = 96) and healthy controls matched for age, sex and BMI (n = 103). Results Patients with type 2 diabetes had higher plasma levels of fasting insulin (p < 0.0001) and glucose (p < 0.0001) compared with controls, but there was no difference between groups with regard to fat mass. Plasma levels of TNF-α (p = 0.0009) and soluble TNF receptor 2 (sTNFR2; p = 0.002) were elevated in diabetic patients. Insulin sensitivity was correlated with quartiles of plasma TNF-α after adjustment for age, sex, obesity, WHR, neutrophils, IL-6 and maximum O₂ uptake in the diabetes group (p < 0.05). The TNF mRNA content of adipose or muscle tissue did not differ between the groups, whereas muscle TNF-α protein content, evaluated by western blotting, was higher in type 2 diabetic patients. Immunohistochemistry revealed more TNF-α protein in type 2 than in type 1 muscle fibres. Conclusions/interpretation After adjustment for multiple confounders, plasma TNF-α is associated with insulin resistance. This supports the idea that TNF-α plays a significant role in the pathogenesis of chronic insulin resistance in humans. However, findings on the TNF-α protein levels in plasma and skeletal muscle indicate that measurement of TNF mRNA content in adipose or muscle tissue provides no information with regard to the degree of insulin resistance.     

Analysis of correlations between selected endothelial cell activation markers, disease activity, and nailfold capillaroscopy microvascular changes in systemic lupus erythematosus patients

The aim of the study was to evaluate the correlation between selected serum endothelial cell activation markers such as vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble thrombomodulin (sTM), soluble E-selectin (sE-selectin), disease activity, and microvascular changes determined by nailfold capillaroscopy in patients with systemic lupus erythematosus (SLE). Serum levels of VEGF, ET-1, sTM, and sE-selectin were determined by an enzyme-linked immunosorbent assay in 80 SLE patients. The disease activity was measured with Systemic Lupus Erythematosus Disease Activity Index score. Nailfold capillaroscopy was performed in all patients. Positive correlation was found between VEGF and both ET-1 (r = 0.294, p < 0.01) and sE-selectin (r = 0.274, p < 0.05) serum levels as well as between sTM and ET-1 (r = 0.273, p < 0.05) serum concentrations. We noticed also positive correlation between VEGF (r = 0.224, p < 0.05) and ET-1 (r = 0.471, p < 0.001) serum levels and disease activity, and also between VEGF serum concentration and grade of morphological changes observed by nailfold capillaroscopy (r = 0.458, p < 0.001). There was also positive correlation between capillaroscopic score and disease activity (r = 0.339, p < 0.01). Our data suggest that correlation between VEGF and both ET-1 and E-selectin serum levels as well as between sTM and ET-1 serum concentrations may reflect their participation in the pathogenesis of SLE. VEGF seems to reflect changes in microcirculation in the course of SLE, visualised by nailfold capillaroscopy. The relationship between changes in nailfold capillaroscopy, endothelial cell activation markers, and the clinical activity of SLE points to an important role of microvascular abnormalities in the clinical manifestation of the disease.