Symptoms of obstructive sleep apnea in a Caribbean sample

Obstructive sleep apnea (OSA) is a prevalent sleep disorder that disproportionately affects blacks. While clinical and epidemiologic data indicate intraethnic differences in several medical diseases, little is known about whether OSA symptoms differ within the black ethnic group. We estimated the rate of OSA symptoms in a community-based sample of Caribbean-born black men and women. We also ascertained which sociodemographic and/or medical factors were associated with OSA risk. A total of 554 patients (mean age = 48.17 ± 16.75 years) participated in the study; 55% were women. Data were collected in four primary-care clinics in Brooklyn, NY. A health educator explained the purpose of the study to interested patients and assisted consenting participants in completing questionnaires, which required 15 min to complete. Participants reporting habitual snoring, excessive daytime sleepiness, and sleep fragmentation were considered at high OSA risk. The rate of OSA symptoms was: snoring (45%), excessive daytime sleepiness (33%), and difficulty maintaining sleep (34%). Many reported falling asleep while watching television (47%) or while driving (14%). Based on logistic regression analysis, a history of heart disease was the most important predictor of the likelihood of expressing OSA symptoms, with a corresponding multivariate-adjusted odds ratio of 11 (95% confidence interval = 3.03–40.63). Findings suggest the need to investigate whether Caribbean-born blacks are at greater risk for developing OSA than African Americans and whites. Caribbean-born blacks with a history of heart disease should be a prime target for interventions that promote adequate screening and timely OSA diagnosis.     

Mandibular advancement splint titration in obstructive sleep apnoea

Introduction  Mandibular advancement splints (MAS) allowing self-adjustment may be better tolerated, but the optimum titration protocol needs systematic study. Aim  The aims of the study are to assess the effectiveness of a titratable MAS device in consecutive patients with body mass index (BMI) < 35 kg/m² and obstructive sleep apnoea [OSA, apnoea–hypopnoea index (AHI) 10–40/h] and compare two methods of adjustment [self-adjustment or adjustment after polysomnographic (PSG) feedback]. Materials and methods  Twenty-eight patients (24 M, mean age 49 years, mean BMI 27.6 kg/m²) with symptomatic (Epworth Sleepiness score > 8/24, snoring, choking or poor sleep quality) OSA (mean AHI 25.7/h, range 10–46/h) had a MAS set at 70% maximal protrusion and were randomised to subjective self-adjustment for 6 weeks (n = 16) or objective adjustment (n = 12; fixed position for 3 weeks, then PSG based feedback at 3 weeks with self-adjustment instructions). Primary outcome variable (AHI) and OSA symptoms were compared by t tests and chi-squared tests at baseline and after 6 weeks. Resolution of apnoea was defined as AHI < 5/h; improvement was defined as AHI decreased by >50% but still >5/h. Results  The groups had similar baseline demographics, OSA severity and occlusal type. MAS therapy improved or resolved OSA in 20 out of 28 (71%) and was reportedly used nightly by 91% of the objective group and 63% of the subjective group (p = 0.04). MAS were used all night by 75% of the objective group and 69% of the subjective group (p > 0.05). MAS adjustment following PSG feedback did not lower AHI further from 3 weeks (baseline 26.5 ± 12.0/h, 3 weeks 15.3 ± 13.5/h p = 0.01, 6 weeks 11.7 ± 10.0/h, p = 0.11). The overall improvement was similar to that achieved with subjective adjustment (baseline AHI 25.4 ± 7.4/h, 6 weeks 14.3 ± 10.7/h, p = 0.0002). Symptomatic benefit was reported by both groups. Conclusion  In selected patients, titratable MAS improved or resolved OSA in the majority of patients and was well tolerated. PSG-based feedback at 3 weeks allowed objective confirmation of efficacy and increased device use but did not result in greater improvement in AHI or symptoms. Neither titration method was significantly superior for us to provide firm endorsement. However, we recommend a follow-up sleep study to confirm MAS efficacy.     

Cardiologist’s knowledge and attitudes about obstructive sleep apnea: a survey study

Obstructive sleep apnea (OSA) is associated with cardiovascular diseases, yet available data suggests cardiologists underreport OSA. This study assessed whether cardiologists’ knowledge and attitudes about OSA contribute to this finding. A previously validated questionnaire, the “Obstructive Sleep Apnea Knowledge and Attitudes Questionnaire” (OSAKA), was modified by the addition of 20 knowledge items and one attitude question to include a total of 38 knowledge items and six attitude questions. The questionnaire was mailed to a random sampling of 420 cardiologists in the USA. Ninety-two cardiologists (22%) returned completed questionnaires. Mean age was 48 ± 10 years, 74% were male, and 52% were general cardiologists. Mean score on the original OSAKA portion of the questionnaire (76%) was similar to previously reported scores of primary care physicians (PCPs), while the total knowledge score was 77%. Scores did not differ by gender (p = 0.7) or subspecialty (p = 0.3), and there were no correlations between knowledge and age or years in practice. While 80% stated that identifying patients at risk for OSA was very or extremely important, only 68% felt confident identifying these patients, and only 18% felt confident managing OSA patients. There was no difference in mean total attitude score when analyzed by age, gender, years of practice, and subspecialty. Total knowledge scores correlated with attitude scores (r = 0.29, p = 0.004). Cardiologists’ knowledge about OSA is comparable to that of PCPs. Cardiologists may lack confidence identifying and managing patients with OSA, factors that may contribute to their low rate of reporting OSA. The institution at which the work was done: MetroHealth Medical Center at Case Western Reserve University.     

Hemostatic implications of endothelial cell apoptosis in obstructive sleep apnea

Patients with obstructive sleep apnea (OSA) are at increased risk of atherothrombosis independent of the Framingham risk factors. Studies on hemostasis factors in OSA are scarce and inconsistent. We sought to understand the variation in atherothrombotic propensity as a function of apoptotic circulating endothelial cells (CECs) in OSA by investigating the relationship between CEC apoptosis and plasma levels of hemostatic factors tissue factor (TF) and von Willebrand Factor (vWF) in apneic subjects. Apoptotic CECs were detected by flow cytometry in 35 male subjects free of cardiovascular diseases (AHI range 8–43) and 12 healthy male controls (AHI range 2–5) before and after 8 weeks of nasal continuous positive airway pressure (nCPAP). Quantitative determination of TF and vWF was performed using an enzyme-linked immunosorbent assay (ELISA) kit. The mean levels of TF (66.78 ± 41.59 pg/ml) and vWF (189.70 ± 69.24 IU/dl) were significantly higher in OSA patients compared with those in healthy subjects (42.83 ± 14.18 pg/ml; and 124.48 ± 31.43 IU/dl). Apoptotic CECs were elevated in patients with OSA and correlated strongly with TF and vWF levels (p = 0.02 and p < 0.001; respectively). There were no correlations between TF, vWF and apnea hypopnea index, or arousal index. Only the percentage of time spent <90% oxygen saturation was inversely associated with TF (r = 0.38; p = 0.02). Following nCPAP therapy, there was significant decrease in TF levels that correlated with decrease in apoptotic CECs. In patients with OSA, increased prothrombotic factors are strongly determined by apoptotic CECs. Treatment with nCPAP may alleviate the coagulation propensity.     

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.     

Gender differences in Saudi patients with obstructive sleep apnea

Obstructive sleep apnea (OSA) remains under-recognized in women possibly due to differences in clinical presentation, difference in tolerance to symptoms, and rate of usage and referral to sleep services. No reports have addressed OSA in women in the Middle Eastern (Arab) population. Therefore, we conducted this study to assess the differences in demographics, clinical presentation, and polysomnographic (PSG) findings between Saudi women and men diagnosed to have (OSA). The study group comprised 191 consecutive Saudi women and 193 consecutive men who were referred to the Sleep Disorders Centre and were found by in-laboratory PSG to have OSA. Demographic and clinical data were obtained by personal interviews. Women were significantly older than men (53.9 and 43.0 years, respectively; p < 0.001). Similarly, their body mass index was significantly higher than men (p < 0.001). Insomnia was more common among women (39.8%) compared to men (25.9%; p = 0.005). Other sleep symptoms including witnessed apnea, and excessive daytime sleepiness did not show any statistical difference between the two groups. Women were more likely than men to be diagnosed with hypothyroidism, diabetes, hypertension, cardiac disease, and asthma. Apnea–hypopnea index (AHI) was statistically higher in men compared to women; however, most of apnea/hypopnea events in women occurred during rapid eye movement sleep, and the mean duration of hypopnea and apnea was significantly lower in women (p = 0.004). Sleep efficiency was lower in women (71.5% vs. 77.7%) in men (p < 0.001). The desaturation index was higher in men (p = 0.01), but no difference was found in lowest SaO₂ or time with SaO₂ less than 90%. The present study showed important clinical and PSG differences between Saudi women and men with OSA. Clinicians need to be aware of these differences when assessing women for the possibility of OSA as they may be symptomatic at a lower AHI and have significant comorbid conditions that can be adversely affected if their OSA was not timely managed.     

Effects of obstructive sleep apnea treatment on left atrial volume and left atrial volume index

Obstructive sleep apnea (OSA) and increased left atrial volume (LAV) both independently increase cardiovascular mortality. We hypothesized that treatment of OSA with continuous positive airway pressure (CPAP) may decrease LAV. We retrospectively identified 47 OSA patients receiving CPAP who had echocardiograms done before and after polysomnography. Compliance was defined as CPAP use at-least five nights weekly and 5 h per night. The compliant group (n = 23) had a significant decrease in diastolic blood pressure (DBP; 4.4 ± 8.9 mmHg, p < 0.05) and mean arterial pressure (MAP; 4.7 ± 10.3 mmHg, p < 0.05), while no significant changes were observed in the noncompliant group (n = 24). LAV data were available in 13 compliant and 20 noncompliant patients. LAV decreased nonsignificantly (3.54 ± 16.6 mL, n = 13, p = 0.65) in CPAP-compliant patients, while it increased (15.47 ± 22.3 mL, n = 20, p < 0.006) in noncompliant patients. Similar changes were seen in the LAV index. Untreated OSA was associated with an increase in LAV and LAV index without significant changes in blood pressure. Treatment of OSA was associated with a decrease in DBP and MAP with a nonsignificant decrease in LAV. Treatment of OSA may prevent adverse left atrial remodeling. There are no conflicts of interest or financial disclosures for any of the authors.     

Randomised trial of compliance with flexible (C-Flex) and standard continuous positive airway pressure for severe obstructive sleep apnea

Introduction  Obstructive sleep apnea (OSA) is often treated with continuous positive airway pressure (CPAP) but the effectiveness of treatment is probably limited by poor compliance. CPAP manufacturers are thus attempting to devise more comfortable PAP devices in an effort to improve compliance. An example of such a novel device is Flexible expiratory-modulated PAP (C-Flex mode Respironics REMstar Pro, Murraysville, PA, USA). Materials and methods  We aimed to compare compliance between C-Flex and standard CPAP in patients with severe OSA in a randomised controlled trial. Nineteen patients with severe OSA (mean ± SD Apnea Hypopnea Index = 78 ± 33/h, Epworth 14 ± 4, PAP 8–17 cm H₂O, BMI = 39 ± 10 kg/m²) and aged 20–63 years were randomly assigned to 4 weeks of either C-Flex (setting II, n = 9) or CPAP (n = 10). Results  Patients treated with C-Flex exhibited a trend toward higher compliance with their PAP devices compared to patients treated with standard CPAP (4.7 ± 2.9 vs. 3.0 ± 2.1 h/night, p = 0.15, effect size = 0.68). Paradoxically, improvements in subjective sleepiness (Epworth Sleepiness Scale) were greater in those who received CPAP than C-Flex (8.1 + 4.9 vs. 2.1 + 4.0 points, p = 0.014, effect size = 1.46). Improvements in objective wakefulness (Modified Maintenance of Wakefulness Test) and simple reaction times (Psychomotor Vigilance Task) were not significantly different between treatments. This randomised trial provides some evidence that C-Flex might increase initial treatment compliance, compared to CPAP, in patients with severe OSA. However, this trend toward greater compliance was not associated with better short-term treatment outcomes for patients. These findings need to be confirmed in a larger, longer-term trial. Stipend from Massey University (to NSM). None of the authors have had any financial relationships with Respironics Inc., who are the manufacturers of the device tested. Respironics International Inc., through their New Zealand suppliers Care Medical, provided six C-Flex machines for the purposes of this trial.     

Nocturnal change of circulating intercellular adhesion molecule 1 levels in children with snoring

Hypoxia promotes adherence of leukocytes to endothelial cells by inducing expression of adhesion molecules like intercellular adhesion molecule 1 (ICAM-1). Increased serum levels of circulating ICAM-1 (cICAM-1) have been reported in adults with sleep apnea and associated hypoxemia. This investigation assessed the hypothesis that the overnight change of cICAM-1 levels in children with snoring is correlated with the severity of obstructive sleep-disordered breathing. Evening and morning serum levels of cICAM-1 were measured in children with snoring referred for polysomnography. Twenty-five children with an apnea–hypopnea index greater than or equal to 5 episodes/h (5.5 ± 1.8 years), 30 subjects with an index less than 5 and greater than 1 (6.3 ± 2 years), and 19 children with an index less than or equal to 1 (7.1 ± 3 years) were recruited. Overnight change in cICAM-1 (log-transformed ratio of morning-to-evening levels) was similar in subjects with an apnea–hypopnea index greater than or equal to 5 episodes/h compared to those with an index less than 5 and greater than 1 or to children with an index less than or equal to 1 (−0.001 ± 0.08 vs −0.03 ± 0.09 vs −0.06 ± 0.1; p > 0.05). When multiple regression analysis was applied, apnea–hypopnea index, respiratory arousal index, and oxygen saturation of hemoglobin nadir were not significant predictors of overnight change in cICAM-1 levels. Thus, in children with snoring, overnight change in cICAM-1 levels is not related to severity of obstructive 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.     

Etanercept can induce resolution of renal deterioration in patients with amyloid A amyloidosis secondary to rheumatoid arthritis

The benefit of biological therapies in rheumatoid arthritis (RA) treatment is well known, but their role in amyloid A (AA) amyloidosis secondary to RA is unclear. The aim of this study was to clarify the clinical benefit of etanercept in RA patients with AA amyloidosis. We treated 14 RA patients who had serum amyloid A protein (SAA) 1.3 allele, with biopsy-confirmed AA amyloidosis with etanercept and investigated the efficacy of etanercept treatment, focusing on renal function retrospectively. The AA amyloidosis improved and stabilized after 89.1 ± 27.2 weeks. Proteinuria decreased from 2.24 ± 0.81 to 0.57 ± 0.41 g/day (P < 0.01) and SAA fell from 250 ± 129 to 26 ± 15μg/ml (P < 0.01), respectively. Diarrhea secondary to gastrointestinal AA amyloidosis was less. Overall, the serum creatinine levels did not benefit with treatment, but in those with a creatinine values <2.0 mg/dl the creatinine level continued to fall (P = 0.021). Serum albumin increased following 96 weeks of etanercept treatment (P = 0.003). Etanercept treatment led to clinical improvement in proteinuria and serum albumin levels accompanied by a fall in SAA levels.     

Automated detection of sleep disordered breathing using a nasal pressure monitoring device

To assess the accuracy of a single channel portable monitoring device (RUSleeping™ RTS, Respironics, Murrysville, PA) that measures nasal pressure (a surrogate for airflow) to detect sleep disordered breathing (SDB). Twenty-five adult patients referred to a community sleep laboratory with suspected obstructive sleep apnea (OSA) participated in this investigation. The portable monitoring device was used in the sleep laboratory to acquire data concurrently with a standard multi-channel polysomnogram (PSG) to assess SDB. Respiratory events were scored manually on the PSG using standard criteria for clinical research to quantify an apnea–hypopnea index (AHI) based on events during sleep. The portable monitoring device automatically calculated an unedited respiratory event index (REI) based on recording time. These data were then compared using the Pearson product–moment correlation coefficient, Bland–Altman analysis, receiver operating characteristic (ROC) curves, and likelihood ratios. All 25 subjects completed the study. Mean age of subjects was 42.4 ± 12.9 years and mean body mass index was 31.0 ± 7.4 kg m⁻². There was good agreement between the REI and the AHI (R = 0.77, p < 0.001, mean difference 2.6 events per hour [2 SD: 39.8] using a Bland–Altman plot). The area under the ROC curve for detecting SDB (PSG AHI greater than or equal to five events per hour) with the REI was 0.94 (95% CI 0.84–1.0). For an REI >11.9 events per hour, the sensitivity was 0.89 (95% CI 0.65–0.99) and the specificity was 0.86 (95% CI 0.42–1.0) with a likelihood ratio of 6.2 for a positive test (LR+) and 0.13 for a negative test (LR−). Similar results were observed for detecting moderate–severe SDB (PSG AHI ≥ 15 events h⁻¹) using REI >15.2 events h⁻¹. In a population of subjects with suspected OSA, this portable monitoring device can automatically quantify an REI that compares well to the AHI scored manually on a concurrent PSG. Such a device may prove useful to assess SDB in high risk populations with self-administered testing in ambulatory settings such as the home. This study was performed at the Sleep Center of Greater Pittsburgh Sleep Laboratory.     

Is the clinical presentation different between men and women admitting to the sleep laboratory?

Objectives  Sleep and sleep disorders are different in several important ways between men and women. We aimed to investigate gender differences in initial symptoms and associating medical diseases of patients admitting to our sleep clinic. Methods  Ninety-one patients, 20 women (22%) and 71 men (78%), admitting consecutively to the sleep clinic were studied. A detailed sleep and medical history of the patients was recorded. All patients were questioned for Epworth Sleepiness Scale (ESS) and underwent an entire night of diagnostic polysomnography. Apnea–hypopnea index (AHI) was identified as the total number of apnea and hypopnea per hour of sleep. Hypopnea was defined as a decrease of airflow by at least 50% and desaturations were defined as ≥4% decrease in oxygen saturation. Results  The mean values for age, body mass index, blood pressures and ESS score did not significantly differ between men and women, but AHI (events/h) was significantly higher in men (29.1 ± 22.7) than women (17.9 ± 17.7, p < 0.05). Snoring was the most common symptom in both men (95%) and women (90%). Among the main presenting complaints, only morning headache (12 of women 60%, 31 of men 43%, p = 0.04) and dry mouth on awakening (ten of women 50%, 57 of men 80%, p = 0.02) showed a significant difference between the two genders, while among the medical diseases only hypothyroidism (four of women 20% and three of men 4%, p = 0.03) and depression (nine of women 45% and 16 of men 22%, p = 0.02) were seen as statistically higher in women than in men. Conclusions  Primary care physicians should be aware of obstructive sleep apnea (OSA) in women and the importance of referring women for sleep studies when they complain of symptoms associated with OSA, even if other non-specific symptoms such as morning headaches are reported. Also, hypothyroidism and depression are accompanied with sleep disorders especially in women.     

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.     

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.     

Adiposity in relation to age as predictor of severity of sleep apnea in children with snoring

Correlation between obesity and obstructive sleep apnea has been documented in both adults and children. This investigation evaluated importance of body mass index (BMI) in relation to age as predictor of severity of obstructive sleep-disordered breathing (SDB). Children with habitual snoring referred for polysomnography were recruited. BMI Z score (≥1.036 vs <1.036, i.e. at risk for overweight or overweight vs normal) was assessed as predictor of severity of SDB (apnea-hypopnea index [AHI] >five vs ≤five episodes per hour) at different ages (≤6 vs >6 years). Two hundered eighty-four participants were recruited: 75 young children (4.6 ± 1 years) with high BMI (1.9 ± 0.7); 95 young subjects (4.5 ± 1.1 years) with low BMI (−0.2 ± 1.3); 55 older children (9.2 ± 1.8 years) with high BMI (1.8 ± 0.5); and 59 older participants (9.7 ± 2.2 years) with low BMI (−0.2 ± 1.1). Odds ratios for AHI >5 in young/high BMI children, young/low BMI subjects, and older/high BMI subjects relative to older/low BMI participants were: 6.5 (95% confidence interval 2.1–19.9), 7.3 (2.4–22) and 2 (0.6–7.3), respectively. Large tonsil size was associated with young age (odds ratio 1.97; 1.2–3.3). Among children with habitual snoring, adiposity does not predict severity of obstructive SDB in early childhood probably due to the prominent role of adenotonsillar hypertrophy. However, it may have a more important contribution to severity of SDB in older children. Presented at the European Respiratory Society Meeting, Munich, September 4, 2006.     

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

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

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

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

Repeated Low-dose of Erythropoietin is Associated with Improved Left Ventricular Function in Rat Acute Myocardial Infarction Model

Objective To evaluate the potential protective affects of Epo on left ventricular (LV) function and remodeling after acute myocardial infarction (MI). Methods Epo was injected into the peritoneum of male Wistar rats (250 g) during 6 weeks post induction of MI. Rats were divided into five groups: MI treated with single high dose (MT1, 5,000 U/kg, n = 10), single high dose (5,000 U/kg) and repeated high doses (MTHi, 1,000 U/kg twice a week; n = 8), or single high dose (5,000 U/kg) and repeated low doses (MTLo, 750 U/kg once a week, n = 10), MI non-treated (MNT, n = 10), sham (S, n = 5). Echocardiography was performed 3.6 ± 1.5 days and 43.7 ± 2.3 days post MI. Collagen deposition and infarct size were measured on histological sections using computerized image analysis. Apoptosis was assessed by ApopTag staining. Results Baseline fractional shortening (FS) was similar between groups. Six weeks after MI the FS of MTLo (26.9%) was significantly higher compared to MNT (17.8%), MT1 (19.5%) and MTH (22.3%) (p = 0.01). However, remodeling indices (end diastolic and end systolic areas, LV circumference) did not improve in the Epo groups, and even worsened in the MTHi group. There was significantly less collagen staining in non-infarct areas in MT1 and MTHi groups compared to MNT and MTLo (0.38 ± 0.3%, 0.49 ± 0.34%, vs 0.89 ± 0.41%, 0.95 ± 0.33%, respectively, p < 0.001). The number of ApopTag positive nucleus was significantly higher in the MNT group compared to the MT1, MTHi, MTLo groups (14.4 ± 8, 7.6 ± 4, 5.8 ± 7, 4.8 ± 5, respectively, p = 0.01 for trend). Conclusion Repeated low doses of Epo after MI improved LV function, but the role of Epo on remodeling is not clear. It did not reduce left ventricular indices, but reduces fibrosis and apoptosis. High Epo doses reduced LV function and aggravated remodeling.