Reference values for airway resistance in newborns, infants and preschoolers from a Latin American population

Background and objective: Several studies have determined reference values for airway resistance measured by the interrupter technique (Rint) in paediatric populations, but only one has been done on Latin American children, and no studies have been performed on Mexican children. Moreover, these previous studies mostly included children aged 3 years and older; therefore, information regarding Rint reference values for newborns and infants is scarce. Methods: Rint measurements were performed on preschool children attending eight kindergartens (Group 1) and also on sedated newborns, infants and preschool children admitted to a tertiary‐level paediatric hospital due to non‐cardiopulmonary disorders (Group 2). Results: In both groups, Rint values were inversely associated with age, weight and height, but the strongest association was with height. The linear regression equation for Group 1 (n = 209, height 86–129 cm) was Rint = 2.153 ? 0.012 × height (cm) (standard deviation of residuals 0.181 kPa/L/s). The linear regression equation for Group 2 (n = 55, height 52–113 cm) was Rint = 4.575 ? 0.035 × height (cm) (standard deviation of residuals 0.567 kPa/L/s). Girls tended to have slightly higher Rint values than boys, a difference that diminished with increasing height. Conclusions: In this study, Rint reference values applicable to Mexican children were determined, and these values are probably also applicable to other paediatric populations with similar Spanish‐Amerindian ancestries. There was an inverse relationship between Rint and height, with relatively large between‐subject variability.     

Pulmonary function tests in preschool children with cystic fibrosis

Pulmonary function tests have rarely been assessed in preschool children with cystic fibrosis (CF). The objective of this multicenter study was to compare pulmonary function in 39 preschool children with CF (height, 90-130 cm; 16 homozygous Delta F508) and in 79 healthy control children. Functional residual capacity (helium dilution technique) and expiratory interrupter resistance (Rint(exp)) (interrupter technique) were measured. As compared with control children, children with CF had significantly higher Rint(exp), expressed as absolute values and as Z-scores (1.05 +/- 0.36 versus 0.80 +/- 0.20 kPa.L(-1). second, p < 0.0001; and 1.31 +/- 1.72 versus 0.19 +/- 0.97, p < 0.0001), and significantly lower specific expiratory interrupter conductance (1.29 +/- 0.34 versus 1.63 +/- 0.43 kPa(-1). second, p < 0.0001). The effect of the bronchodilator salbutamol on Rint(exp) was not significantly different between children with CF and control children. Rint(exp) Z-scores were significantly higher in children with CF who were exposed to passive smoke (n = 8) (p < 0.03). Children with CF and with a history of respiratory symptoms (n = 31) had significantly higher functional residual capacity Z-scores (p < 0.02) and lower specific expiratory interrupter conductance Z-scores (p < 0.04). Genotype did not influence the data. We conclude that Rint(exp) and functional residual capacity measurements may help to follow young children with CF who are unable to perform reproducible forced expiratory maneuvers.     

Airway challenge testing - accuracy of the interrupter technique

According to national and international recommendations the bronchial sensitivity should be determined based on the decrease of the FEV1 by 20 % (FEV1 - 20) or the increase of the airway resistance by means of body plethysmography by 100 % (Raw + 100). Measurement of airway resistance by interrupter technique (Rint) is a simple method and needs no active cooperation of the patient, but is not recommended in airway challenge testing. We investigated the role of the increase of Rint by 100 % (Rint + 100) compared to Raw + 100 and FEV1 - 20 during carbachol airway challenge testing by means of dosimetry. We examined 123 patients with following symptoms: 85 x coughing, 31 x coughing and dyspnea, 7 x medical opinion. Significant correlations between Rint and Raw were found before and after the challenge tests (Rint before/after 0,3 +/- 0,13/0,36 +/- 0,25 kPa*s/l; Raw before/after 0,24 +/- 0,09/0,50 +/- 0,41 kPa*s/l; r = 0,504/0,672; p < 0,001 [Pearson]). The median values of Rint and Raw were significantly different (p < 0,001 [Wilcoxon]). Moreover Rint systematically overestimated airway resistance in the normal range and underestimated the increase of airway resistance during challenge testing (r = 0,783; p < 0,001 [Pearson]). In 58 patients an increased airway responsiveness was found. In 21 oft these patients there was no increase of Rint above the initial value. Sensitivity/specificity/positive predictive value/negative predictive value in % to the detection of airway hyperresponsiveness were in Rint + 100 9/95/63/54, in FEV1 - 20 61/100/100/66 and in Raw + 100 98/100/100/98. In conclusion we found significant correlations between Rint and Raw, but the median values were systematically and significantly different. Rint + 100 had a low sensitivity to detect airway hyperresponsiveness and is not comparable with FEV1 - 20 or Raw + 100.     

Airway resistance and spirometry in children with perinatally acquired human immunodeficiency virus-type 1 infection

Airway resistance was measured by the interrupter technique in 54 children [aged 63.8 months (range: 9.1–131.6 months)], with perinatal human immunodeficiency virus-type 1 (HIV-1) infection and in a control group of 315 gender, height, and race-matched healthy children. In addition, 14 HIV-infected children, aged 75–131 months, had spirometry performed. Resistance was significantly higher in infected children than in controls (0.84 ± 0.3 vs 0.64 ± 0.08 kPa · l⁻¹ · s; t = 9.991; P < 0.0001). Resistance decreased with age in controls (r = −0.95; P < 0.001), but not in infected children (r = −0.22; P = 0.105). Resistance did not correlate with mothers' intravenous drug addiction, perinatal data, T-cell subset numbers, treatment, clinical course, or presence of respiratory complications. Resistance was higher (t = 3.103; P < 0.003) in p24 antigen-positive than in negative children. Thirty-nine children underwent a second evaluation 12.3 months (range 11.1–14 months) after the first. Resistance was higher (t = 3.960; P < 0.0001) at the second evaluation compared to the first. Eight of 14 children had abnormal spirometric measurements. We conclude that perinatal HIV-1 infection is associated with increased airway resistance and often abnormal spirometry. The degree of abnormalities in resistance depends on the duration of the infection rather than on HIV-1-related respiratory complications. Pediatr. Pulmonol. 1997; 24:406–414. © 1997 Wiley-Liss, Inc.     

Comparison of transient elastography,serum markers and clinical signs for the diagnosis of compensated cirrhosis

Background and Aims: Non‐invasive diagnosis of compensated cirrhosis is important. We therefore compared liver stiffness by transient elastography, APRI score, AST/ALT ratio, hyaluronic acid and clinical signs to determine which modality performed best at identifying compensated cirrhosis. Methods: Patients undergoing evaluation at a single center were recruited and had clinical, serological, endoscopy, radiological imaging, liver stiffness measurement and liver biopsy. Patients were stratified into cirrhotic and non‐cirrhotic. Results: In 404 patients (124 cirrhosis), transient elastography was diagnostically superior to the other modalities yielding an AUC 0.9 ± 0.04 compared with hyaluronic acid (AUC 0.81 ± 0.04: P < 0.05), clinical signs (AUC 0.74 ± 0.04: P < 0.05), APRI score (AUC 0.71 ± 0.03: P < 0.05) and AST/ALT ratio (AUC 0.66 ± 0.03: P < 0.05). The optimum cut‐off for transient elastography was 12 kPa giving a sensitivity of 89% and specificity of 87% for cirrhosis. In 238 hepatitis C patients (87 cirrhosis), transient elastography yielded an AUC 0.899 ± 0.02 for cirrhosis and in 166 non‐HCV patients (37 cirrhosis) the results were similar with an AUC 0.928 ± 0.03; with transient elastography being superior to HA, APRI, AST/ALT and clinical signs for all etiologies of cirrhosis (P < 0.05 for all). Importantly, transient elastography was statistically superior at identifying cirrhosis in 38 biopsy proven Childs Pugh A cirrhotics with no clinical, biochemical or radiological features of cirrhosis or portal hypertension (AUC 0.87 ± 0.04). Conclusion: Transient elastography accurately identified compensated cirrhosis; a liver stiffness of >12 kPa represents an important clinical measurement for the diagnosis of cirrhosis.     

Measurement of airway resistance using the interrupter technique in preschool children in the ambulatory setting.

This study describes the feasibility, repeatability, and interrater reliability of the measurement of airway resistance by the interrupter technique (Rint) in children 2-5 yrs of age, and examines whether reversibility to bronchodilator can be demonstrated in wheezy children. The mean of six Rint values was taken as a measurement. If subjects could complete one measurement and then a second 15 min after bronchodilator, baseline testing and reversibility testing were considered feasible. To measure repeatability, two measurements 30 s apart and measurements before and 15 min after placebo bronchodilator were compared. Measurements by two testers were compared for interrater reliability. Change in Rint in wheezy children was measured after bronchodilator. Fifty-six per cent of 2-3-yr-olds (n=79), 81% of 3-4-yr-olds (n=104) and 95% of 4-5-yr-olds (n=88) completed baseline testing, and 53%, 71% and 91% completed reversibility testing. Baseline measurements were 0.47-2.56 kPa x L(-1) x s. Repeatabilities (2 SD of the mean differences between measurements) at 30 s in the three age bands were 0.21, 0.17 and 0.15 kPa x L(-1) x s and 0.19 kPa x L(-1) x s after placebo. Using 0.21 kPa x L(-1) x s as the threshold for reversibility, reversibility was demonstrated in most wheezy children. Interrater reliability was 0.15 kPa x L(-1) x s. Preschool children can undertake measurements of airway resistance by the interrupter technique in ambulatory settings and reversibility to bronchodilator in wheezy children can be demonstrated. This technique promises to be a useful clinical and research tool.     

Short‐Term Effect of Atorvastatin on Endothelial Function in Healthy Offspring of Parents with Type 2 Diabetes Mellitus

Endothelial function is impaired in healthy subjects at risk of type 2 diabetes mellitus (DM). We investigated whether endothelial dysfunction can be normalized by statin therapy in this potentially predisposed population. Flow‐mediated dilation (FMD) was measured in 56 first‐degree relatives (FDRs) (normotensive, normal glucose tolerance) and 20 age‐, sex‐, and BMI‐matched controls with no family history of DM. Other measurements included insulin resistance index using the homeostasis model of insulin resistance (HOMA_IR), plasma lipids, and markers of inflammation. The FDRs were then randomized and treated with atorvastatin (80 mg) or placebo daily in a 4‐week double‐blind, placebo‐controlled trial. The FDRs had significantly impaired FMD (4.4 ± 8.1% vs. 13.0 ± 4.2%; P < 0.001), higher HOMA_IR (1.72 ± 1.45 vs. 1.25 ± 0.43; P= 0.002), and elevated levels of plasma markers of inflammation—highly sensitive C‐reactive protein (hsCRP) (2.6 ± 3.8 mg/L vs. 0.7 ± 1.0 mg/L; P= 0.06), interleukin (IL)‐6 (0.07 ± 0.13 ng/mL vs. 0.03 ± 0.01 ng/mL; P < 0.001), and soluble intercellular adhesion molecule (sICAM) (267.7 ± 30.7 ng/mL vs. 238.2 ± 20.4 ng/mL; P < 0.001). FMD improved in the atorvastatin‐treated subjects when compared with the placebo‐treated subjects (atorvastatin, from 3.7 ± 8.5% to 9.8 ± 7.3%; placebo, from 3.9 ± 5.6% to 4.7 ± 4.2%; P= 0.001). There were also reductions in the levels of IL‐6 (0.08 ± 0.02 ng/mL vs. 0.04 ± 0.01 ng/mL; P < 0.001) and hsCRP (3.0 ± 3.9 mg/L vs. 1.0 ± 1.3 mg/L; P= 0.006). Our study suggests that treatment with atorvastatin may improve endothelial function and decrease levels of inflammatory markers in FDRs of type 2 DM patients.     

"Normal" liver stiffness values differ between men and women: a prospective study for healthy living liver and kidney donors in a native Korean population

Background and Aim: Liver stiffness (LS) measurement can distinguish individuals with potential liver disease (LD) from the general population. However, if LS is sex‐sensitive, prevalence of LD may be incorrectly estimated when the same reference LS value is applied irrespective of sex. Here, we evaluated whether normal ranges of LS differ between healthy men and women. Methods: LS was measured in a cohort of healthy living liver and kidney donors, none of whom suffered from diabetes mellitus, hypertension, hepatitis B or C virus infection, heart or liver dysfunction, or metabolic syndrome. Patients with abnormal laboratory findings related to potential LD (platelet count < 150 × 10³/µL; aspartate aminotransferase > 40 IU/L; alanine aminotransferase [ALT] > 40 IU/L; albumin < 3.3 g/dL; total bilirubin > 1.2 mg/dL; gamma‐glutamyl transpeptidase > 54 IU/L; alkaline phosphatase > 115 IU/L) were excluded. Results: Among 242 patients analyzed, the mean age was 34.1 for men (n = 121) and 40.5 years for women (n = 121) (P < 0.001). Men had a higher mean LS value than women (5.2 ± 1.2 vs 4.8 ± 1.1 kPa/P < 0.001). Multivariate‐linear regression analysis identified sex as the only independent factor for LS values (β = 0.361/P = 0.021). Using the 5th–95th percentiles, we determined normal LS ranges of 3.7–7.0 kPa in men and 3.3–6.8 kPa in women. In subgroups with ALT < 30 IU/L (subgroup‐1, n = 216) and ALT < 20 IU/L (subgroup‐2, n = 163), men had significantly higher LS values than women (5.2 ± 1.3 vs 4.7 ± 1.1 kPa/P = 0.003 and 5.1 ± 1.2 vs 4.7 ± 1.1 kPa/P = 0.030, respectively), demonstrating an independent sex effect (β = 0.483/P = 0.003 and β = 0.389/P = 0.030, respectively). Conclusions: An independent sex effect on LS values was confirmed. Thus, sex‐specific references should be used for effective screening based on LS measurements.     

Glycaemic control in individuals with type 1 diabetes using an open source artificial pancreas system (OpenAPS)

Open source artificial pancreas systems (OpenAPS) have gained considerable interest in the diabetes community. We analyzed continuous glucose monitoring (CGM) records of 80 OpenAPS users with type 1 diabetes (T1D). A total of 19 495 days (53.4 years) of CGM records were available. Mean glucose was 7.6 ± 1.1 mmol/L, time in range 3.9–10 mmol/L was 77.5 ± 10.5%, <3.9 mmol/L was 4.3 ± 3.6%, <3.0 mmol/L was 1.3 ± 1.9%, >10 mmol/L was 18.2 ± 11.0% and > 13.9 mmol/L was 4.1 ± 4.0%, respectively. In 34 OpenAPS users, additional CGM records were obtained while using sensor-augmented pump therapy (SAP). After changing from SAP to OpenAPS, lower mean glucose (−0.6 ± 0.7; P < 0.0001), lower estimated HbA1c (−0.4 ± 0.5%; P < 0.0001), higher time in range 3.9–10 mmol/L (+9.3 ± 9.5%; P < 0.0001), less time < 3.0 mmol/L (−0.7 ± 2.2%; P = 0.0171), lower coefficient of variation (−2.4 ± 5.8; P = 0.0198) and lower mean of daily differences (−0.6 ± 0.9 mmol/L; P = 0.0005) was observed. Glycaemic control using OpenAPS was comparable with results of more rigorously developed and tested AP systems. However, OpenAPS was used by a highly selective, motivated and technology-adept cohort, despite not being approved for the treatment of individuals with T1D.     

Activity of Angiotensin‐Converting Enzyme After Treatment with L‐Arginine in Renovascular Hypertension

The renin‐angiotensin system plays a role in the pathophysiology of renovascular hypertension. In addition, some studies have demonstrated a beneficial effect of L‐arginine (L‐Arg), the precursor of nitric oxide (NO), in this model of hypertension. This study was designed to investigate the effects of L‐Arg on cardiovascular parameters and on the activity of the angiotensin‐converting enzyme (ACE), after 14 days of renovascular hypertension. The experiments were performed on conscious male Wistar rats. Two‐kidney, one‐clip renovascular hypertension (2K1C) was initiated in rats by clipping the left renal artery during 14 days, while control rats were sham‐operated. One group was submitted to a similar procedure and treated with L‐Arg (10 mg/ml; average intake of 300mg/day) from the 7th to the 14th day after surgery, whereas the respective control group received water instead. At the end of the treatment period, the mean arterial pressure (MAP) was measured in conscious animals. The rats were sacrificed and the ACE activity was assayed in heart and kidneys, using Hip‐His‐Leu as substrate. In a separate group, the heart was removed, the left ventricle (LV) was weighed and the LV/body weight ratios (LV/BW) were determined. We observed significant differences in MAP between the L‐Arg‐treated and untreated groups (129 ± 7 vs. 168 ± 6 mmHg; P < 0.01). The cardiac hypertrophy described for this model of hypertension was attenuated in the 2K1C‐L‐Arg‐treated group (14th day, wet LV/BW: 2K1C‐L‐Arg = 1.88 ± 0.1; 2K1C = 2.20 ± 0.1 mg/g; P < 0.05). L‐Arg administration caused an important decrease in cardiac ACE activity (2K1C‐L‐Arg: 118 ± 15; 2K1C: 266 ± 34 µmol/min/mg; P < 0.01). L‐Arg also decreased the ACE activity in the clipped kidney by 47% (P < 0.01), but not in the nonclipped kidney. These data suggest that increased NO formation and reduced angiotensin II formation are involved in the anthihypertensive effect of orally administered L‐arginine.     

Frequent red cell transfusions reduced vascular endothelial activation and thrombogenicity in children with sickle cell anemia and high stroke risk

Stroke is one of the most disabling complications of sickle cell anemia (SCA). The molecular mechanisms leading to stroke in SCA or by which packed red blood cell (PRBC) transfusion prevents strokes are not understood. We investigated the effects of PRBC transfusion on serum biomarkers in children with SCA who were at high‐risk for stroke. Serum samples from 80 subjects were analyzed, including baseline, study exit time point and 1 year after study exit. Forty of the 80 samples were from subjects randomized to standard care and 40 from transfusion arm. Samples were assayed for levels of BDNF, sVCAM‐1, sICAM‐1, MPO, Cathepsin‐D, PDGF‐AA, PDGF‐AB/BB, RANTES (CCL5), tPAI‐1, and NCAM‐1 using antibody immobilized bead assay. Significantly lower mean serum levels of sVCAM‐1 (2.2 × 10⁶ ± 0.8 × 10⁶ pg/mL vs. 3.1 × 10⁶ ± 0.9 × 10⁶ pg/mL, P < 0.0001), Cathepsin‐D (0.5 × 10⁶ ± 0.1 × 10⁶ pg/mL vs. 0.7 × 10⁶ ± 0.2 × 10⁶ pg/mL, P < 0.0001), PDGF‐AA (10556 ± 4033 pg/mL vs. 14173 ± 4631 pg/mL, P = 0.0008), RANTES (0.1 × 10⁶ ± 0.07 × 10⁶ pg/mL vs. 0.2 × 10⁶ ± 0.06 × 10⁶ pg/mL, P < 0.006), and NCAM‐1 (0.7 × 10⁶ ± 0.2 × 10⁶ pg/mL vs. 0.8 × 10⁶ ± 0.1 × 10⁶ pg/mL, P < 0.0006) were observed among participants who received PRBC transfusion, compared to those who received standard care. Twenty or more PRBC transfusion over 4 years was associated with lower serum levels of sVCAM‐1 (P < 0.001), PDGF‐AA (P = 0.025), and RANTES (P = 0.048). Low baseline level of BDNF (P = 0.025), sVCAM‐1 (P = 0.025), PDGF‐AA (P = 0.01), t‐PAI‐1 (P = 0.025) and sICAM‐1 (P = 0.022) was associated with higher probability of stroke free survival. Beyond improving hemoglobin levels, our results suggest that the protective effects of PRBC transfusion on reducing stroke in SCD may result from reduced thrombogenesis and vascular remodeling. Am. J. Hematol. 89:47–51, 2014. © 2013 Wiley Periodicals, Inc.     

Vascular and Autonomic Function in Preschool‐aged Children with Congenital Heart Disease

Objective. To compare indices of vascular health and heart rate variability in preschool‐aged children with repaired congenital heart disease (CHD) including tetralogy of Fallot (n = 6) and coarctation of the aorta (n = 6). Design. A cross‐sectional study design was used. All measures were noninvasive and collected over a single testing session under the supervision of a parent/guardian. Setting. Data collection took place in a quiet, temperature‐controlled room (23°± 1°C) with the participant in a supine position. Patients. Twelve (six females, six males) preschool‐aged children with repaired CHD (CHD: 4 ± 1 years) and 12 age‐ and gender‐matched healthy controls (CON: 5 ± 1 years) participated in the study. Outcome Measures. Supine, resting measures of heart rate variability (time, frequency, and nonlinear domains), whole‐body pulse wave velocity (ventricular depolarization to dorsalis pedis artery), brachial blood pressures, and carotid artery distensibility, lumen diameter, intima‐media thickness, and wall/lumen ratio were collected in both groups. Results. The groups were similar in age, height, and weight; however, CON had significantly higher body mass index values (CON: 16.9 ± 2.2, CHD: 15.1 ± 1.0, P < .05) and body mass index percentiles (CON: 69 ± 27%tile, CHD: 36 ± 24%tile, P < .01) compared to CHD. No group differences were found for resting brachial blood pressures, whole‐body pulse wave velocity, heart rate variability, and carotid artery distensibility, lumen diameter, and intima‐media thickness (P > .05). Carotid artery pulse pressures (CHD: 38 ± 6 mm Hg, CON: 31 ± 6 mm Hg, P < .05) and wall/lumen ratios (CHD: 0.091 ± 0.007, CON: 0.085 ± 0.006, P < .01) were significantly higher in the CHD group. Conclusions. These results may indicate that preschool‐aged children with repaired CHD display early signs of vascular remodeling, but not autonomic or vascular dysfunction. The effects of larger wall/lumen ratios on cardiovascular disease risk require further investigation.     

Splenectomy reduces fibrosis and preneoplastic lesions with increased triglycerides and essential fatty acids in rat liver cirrhosis induced by a choline‐deficient L‐amino acid‐defined diet

Aim: This study investigated whether splenectomy is of significance in non‐alcoholic steatohepatitis (NASH). Methods: Five‐week‐old Wistar rats were fed a choline‐deficient diet for 8 weeks to create a NASH model. A sham‐operation or splenectomy was then performed, and rats were killed 4 weeks later. Results: Liver fibrosis and liver preneoplastic lesions were significantly reduced in the splenectomy group compared to the sham‐operation group, and α‐smooth muscle actin (SMA) expression was significantly inhibited (liver fibrosis area: sham 8.63 ± 4.09%, splenectomy 5.45 ± 3.69%, P < 0.01; preneoplastic lesion size: sham 6.56 ± 3.68 ×10⁶ µm²/cm², splenectomy 4.63 ± 3.27 ×10⁶ µm²/cm², P < 0.05; the number of preneoplastic lesions: sham 8.33 ± 3.96/cm², splenectomy 5.17 ± 1.80/cm², P < 0.01; α‐smooth muscle actin‐positive area: sham 4.41 ± 2.48%, splenectomy 2.75 ± 1.66%, P < 0.01) On the other hand, liver triglycerides and essential fatty acids were significantly increased in the splenectomy group (liver triglycerides: sham 182 ± 35.0 mg/g, splenectomy 230 ± 35.0 mg/g, P < 0.05; liver linoleic acid: sham 17.2 ± 4.9 mg/g, splenectomy 23.3 ± 6.9 mg/g, P < 0.05; liver α‐linolenic acid: sham 118 ± 36.6 µg/g, splenectomy 162 ± 51.4 µg/g, P < 0.05). In addition, expressions of hepatic fatty acid metabolism‐related genes (e.g. acyl‐CoA oxidase, liver carnitine palmitoyl‐CoA transferase I, cytochrome P450 4A, long‐chain acyl‐CoA dehydrogenase and medium‐chain acyl‐CoA dehydrogenase) were significantly inhibited in the splenectomy group. Conclusion: These findings suggest that spleen plays an important regulatory role in the fibrosis, preneoplastic lesion and lipid metabolism of liver in a rat choline‐deficient L‐amino acid model.     

The inferior prognosis of adolescents with acute lymphoblastic leukaemia (ALL) is caused by a higher rate of treatment‐related mortality and not an increased relapse rate – a population‐based analysis of 25 years of the Austrian ALL‐BFM (Berlin‐Frankfurt‐Münster) Study Group

Adolescents aged 15–18 years with acute lymphoblastic leukaemia (ALL) have been historically reported to have a poorer prognosis than younger children. We retrospectively analysed the characteristics and outcome of 67 adolescents included in a population‐based series of 1125 non‐infant cases that were enrolled into four Austrian ALL‐BFM (Berlin‐Frankfurt‐Münster) multicentre trials at paediatric institutions within a 25‐year period. Five‐year event‐free survival (EFS) and overall survival (OS) were 66 ± 6% and 76 ± 5% respectively, and thus lower than in younger children (83 ± 1%, 91 ± 1%; P < 0·001). This was not due to an increased cumulative incidence of relapse (CIR) (5‐year CIR: 19 ± 5% vs. 13 ± 1%; P = 0·284), but due to an increased incidence of treatment‐related death [5‐year cumulative incidence of death (CID): 15 ± 4% vs. 3 ± 0%; P < 0·001] as a first event. Furthermore, while 44/67 (66%) non‐high‐risk adolescents had favourable 5‐year EFS and OS rates (76 ± 7%, 89 ± 5%), 18/67 (27%) high‐risk adolescents had an inferior outcome (5‐year EFS: 56 ± 12%, OS 61 ± 11%, P < 0·05). Among the latter patients the CID was significantly higher than in younger high‐risk children (22 ± 10% vs. 6 ± 2%; P = 0·020). Given that adolescent age is an independent risk factor for death as a first event, this specific age group may need particular vigilance when receiving intense BFM‐type chemotherapy, as relapse‐free survival is similar to younger children.     

Combined lamivudine and famciclovir therapy for patients with chronic hepatitis B

OBJECTIVE: No single antiviral drug is able to eradicate hepatitis B virus (HBV) infection. It has been shown in vitro that lamivudine and panciclovir (the active metabolite of famciclovir) act synergistically to inhibit HBV replication. To study the therapeutic efficacy of combined lamivudine and famciclovir therapy in patients with chronic hepatitis B. METHODS: Twenty‐one patients with chronic hepatitis B, who had been given lamivudine monotherapy for more than 6 months without improve­ment, had increased serum alanine aminotransferase (ALT) and HBV‐DNA levels, and were positive for hepatitis B surface antigen (HBsAg); 17 were positive for HBeAg. The diagnosis was verified by histology in 12 HBeAg‐positive cases. All patients were given combined therapy with lami­vudine (100 mg q.d.) and famciclovir (500 mg t.i.d.) orally for 4 months, and then with lamivudine alone for 5?10 months. RESULTS: Serum HBV‐DNA levels were initially 1 × 10^{8.19 ± 1.18} copies/mL, then decreased to 1 × 10^{5.25 ± 1.18} copies/mL at the end of the combined treatment and 1 × 10^{5.25 ± 1.82} copies/mL in the follow‐up period (P < 0.01). Serum ALT decreased from 225 ± 110 U/L before the trial to 79 ± 50 U/L at the end of the combined treatment and 81 ± 48 U/L in the follow‐up period (P < 0.01). In 17 HBeAg‐positive patients, eight (47.1%) had HBeAg/anti‐hepatitis B e antigen (HBeAg) seroconversion with a significant decrease of HBV‐DNA (<1 × 10⁴ copies/mL) and normal ALT (P < 0.01). Of four HBeAg‐negative patients, three had decreased levels of HBV‐DNA, to below 1 × 10⁴ copies/mL, which was associated with a significant decrease in ALT. Two patients had recurrent flare‐ups in the follow‐up period, but both HBV‐DNA and ALT were lower than the pretreatment levels. In 10 patients who underwent a second liver biopsy, improvements in inflammatory activity and fibrosis were seen in eight (80%) and four (40%) cases, respectively (P < 0.05). CONCLUSIONS: The combination treatment of lamivudine and famciclovir has synergistic or additive anti‐HBV effects, and may be an alternative therapy for patients with active chronic hepatitis B.     

Regional Citrate Anticoagulation for Intermittent Predilution Online Hemofiltration

There is no consensus on the optimal renal replacement treatment in intensive care units. Among intermittent dialysis methods, hemofiltration (HF) is preferred by some because of better hemodynamic stability and cytokine removal. We report our experience with regional citrate anticoagulation for intermittent predilution online HF. Forty‐one patients (age 69 ± 10 years, 73% male) with acute renal failure and an increased bleeding risk in intensive care units were included in this retrospective analysis. Citrate anticoagulation was performed with 4% citrate (starting at 400 mL/h) and 1 mol/L calcium chloride (starting at 7 mL/h). Calcium‐containing (1.25 mmol/L) infusate, prepared online, was used. Anticoagulation was assessed visually after HF in a subgroup of 36 procedures using a score of 5 (no clotting) to 1 (total occlusion). The duration of the 94 HF sessions performed was 4 h 50 min ± 47 min, and the infusate volume reached was 77 ± 9 L. During HF, ionized calcium increased (1.01 ± 0.14 to 1.13 ± 0.09 mmol/L, P < 0.001), and the increases in sodium (141 ± 5 to 143 ± 3 mmol/L, P < 0.001) and bicarbonate (23 ± 6 to 25 ± 4 mmol/L, P < 0.01) were significant, but small. There were two cases of metabolic alkalosis (pH > 7.5) not requiring any intervention. None of the circuits clotted. The mean anticoagulation assessment scores were 4.6 ± 0.6 at the arterial bubble trap, 4.2 ± 1.0 at the dialyzer, and 4.2 ± 0.9 at the venous bubble trap. To conclude, regional citrate anticoagulation for predilution online hemofiltration with calcium‐containing infusate provides a good anti‐thrombotic effect and has rare metabolic side effects.     

Risk Factors for Encapsulating Peritoneal Sclerosis in Long‐Term Peritoneal Dialysis: A Retrospective Observational Study

Encapsulating peritoneal sclerosis (EPS) is a serious complication that occurs in patients with long‐term peritoneal dialysis (PD). Investigation of risk factors that contribute to EPS in patients on long‐term PD therapy is needed. In a retrospective, observational study, data were collected for 107 patients treated with PD therapy for more than 5 years. Fifty cases of EPS were compared with 57 cases of non‐EPS. To evaluate the impact of PD‐associated peritonitis in EPS, univariate and multivariate logistic regression models were applied. Episodes of peritonitis, number of peritonitis episodes and the duration of peritonitis were included as explanatory variables in addition to previously reported risk factors. D/P Cr and serum β2MG levels in the EPS and non‐EPS groups were: 0.82 ± 0.10 and 0.67 ± 0.12 (P < 0.01), and 33.8 ± 8.54 and 29.2 ± 8.18 mg/L (P < 0.01), respectively. Episodes of peritonitis, number of peritonitis episodes and the duration of peritonitis was 68% and 42% (P < 0.01), 1.80 ± 2.19 and 0.75 ± 1.07 times (P < 0.01), and 18.1 ± 15.3 and 10.2 ± 4.90 days (P < 0.01), in the EPS and non‐EPS groups, respectively. Furthermore, multivariate logistic regression models demonstrated that both D/P Cr and the duration of peritonitis were independently associated with EPS (P < 0.01 and P < 0.05, respectively). In patients on long‐term PD therapy, D/P Cr and the duration of peritonitis are independently associated with EPS. Earlier treatment to promote an early recovery from PD‐associated peritonitis could be critical in preventing EPS.     

How should airways resistance be measured in young children: mask or mouthpiece?

The reproducibility and acceptability of airways resistance measurements using the interrupter technique (MicroRint) obtained using a mouthpiece were compared with those using a face mask. Fifty children aged 4-7 yrs performed four sets of six Rint measurements; two using a mouthpiece and two using a face mask with integral mouthpiece. Complete data were obtained from 45 (90%) children using the mouthpiece and 43 (86%) children using the mask. The two methods were equally repeatable with comparable intraclass correlation coefficients (ICC) and coefficients of variation. Mean Rint values obtained using the mouthpiece were significantly lower than those using the face mask ((mean+/-SD) mouthpiece=0.81+/-0.18 kPa x L(-1) x s, mask=0.88+/-0.24 kPa x L(-1) x s p=0.0002). Although the mean paired differences between the two methods were small (0.07 kPa x L(-1) x s), the ICC and limits of agreement confirmed that the two methods could not be used interchangeably. Sixty-seven per cent of children preferred the face mask but this was more time-consuming (p = 0.03). Children did not produce more repeatable results using their preferred method, nor did they improve with practice. Repeatable airway resistance measurements using the interrupter technique can be obtained from young children using either a mouthpiece or a face mask, but there are significant clinical and statistical differences between the results obtained.     

Adipokines in type 1 diabetes after successful pancreas transplantation: normal visfatin and retinol‐binding‐protein‐4, but increased total adiponectin fasting concentrations

Objective In type 1 diabetes mellitus (T1DM), the release of many hormones, not only from beta‐cells, but also from adipocytes (adipokines) may be altered. After successful pancreas–kidney‐transplantation (PKTx), T1DM patients can revert to a nondiabetic metabolism, but it is unclear whether alterations of adipokines are still present after PKTx. Design, patients and measurements Concentrations of adipokines [visfatin, retinol‐binding protein‐4 (RBP‐4), adiponectin, high molecular weight (HMW) adiponectin] were measured at fasting in 10 PKTx and in 19 T1DM. Nondiabetic healthy controls (CON, n = 9) and six nondiabetic patients after kidney transplantation (KTx) were examined as control groups. In PKTx, KTx and CON, indices of insulin sensitivity (OGIS) and beta cell function (adaptation index, AI) were calculated from 75 g oral glucose tolerance test (OGTT) data. Results Fasting serum visfatin (T1DM: 56 ± 4 μg/l, PKTx: 42 ± 6 μg/l, KTx: 39 ± 3 μg/l, CON: 40 ± 3 μg/l) and RBP‐4 (T1DM: 490 ± 26 μg/l, PKTx: 346 ± 39 μg/l, KTx: 401 ± 13 μg/l, CON: 359 ± 36 μg/l) was increased by 40% and 36%, respectively (each P < 0·03) in T1DM only. Levels were positively correlated with HbA1c in all subjects (visfatin: r = 0·43, P < 0·004; RBP‐4: r = 0·46, P < 0·03). Fasting plasma adiponectin was 80% higher in T1DM and in PKTx (T1DM: 18 ± 2 mg/l, PKTx: 18 ± 3 mg/l, KTx: 12 ± 3 mg/l, CON: 10 ± 1 mg/l; P < 0·04) and was positively correlated with diabetes duration (r = 0·37, P < 0·02). HMW/total adiponectin ratio was increased in T1DM (P < 0·02). PKTx displayed a normoglycaemic metabolism as insulin sensitive as CON, but AI was lower than in CON and KT (P < 0·01). Conclusions T1DM after successful PKTx show normal fasting visfatin and RBP‐4 levels and HMW‐adiponectin/adiponectin‐ratio, which are elevated in T1DM, whereas total adiponectin levels are similarly increased in T1DM and PKTx patients.     

Exercise Capacity Improves after Transcatheter Closure of the Fontan Fenestration in Children

Objectives. This study evaluated the aerobic capacity, exercise capacity, and arterial oxygen saturation (O₂Sat) in children before and after transcatheter Fontan fenestration closure. Design. Observational study comparing exercise parameters and hemodynamics before and after transcatheter fenestration closure in Fontan patients. Outcome Measures. Working capacity, exercise duration, oxygen consumption (VO₂), and arterial O₂Sat were evaluated during aerobic exercise. Results. Twenty patients (mean age 11.4 years) underwent standardized exercise testing before and after fenestration closure. Twelve patients underwent cycle ergometry testing (mean age 14.8 years) (group1), and eight younger patients (mean age 6.4 years) underwent Bruce treadmill testing (group 2). The same exercise protocol was used in each patient before and after fenestration closure (interval between tests: 118 ± 142 days). Immediately following fenestration closure at cardiac catheterization, cardiac index decreased (3.0 to 2.1 L/minute/m²) and Fontan pressure increased (11 ± 2 to 12 ± 2 mm Hg) with an increased arterial saturation (92 to 96%) (P < .001). The total group demonstrated no significant change in pre‐ and postclosure maximal heart rates (164 ± 21 and 169 ± 19 bpm). Rest and exercise O₂Sat increased (89 and 82 to 95 and 92%) (P < .0001). Exercise duration increased (7.7 ± 1.9 to 9.2 ± 2.4 minutes) (P < .0005). Maximal VO₂, indexed maximal VO₂, and total working capacity in kilopond‐meters (kpm) increased (1.2 ± 0.5, 27 ± 7 and 2466 ± 1012 to 1.3 ± 0.4 L/minute, 31 ± 9 mL/kg/minute and 2869 ± 1051 kpm, respectively) (P < .005). Conclusion. In children with a univentricular heart after Fontan palliation, transcatheter fenestration closure improves exercise arterial O₂Sat and aerobic capacity despite a restricted resting cardiac output documented by catheterization immediately after the closure procedure.