Importance Evidence that longer-term and exclusive breastfeeding reduces child obesity risk is based on observational studies that are prone to confounding.Objective To investigate effects of an intervention to promote increased duration and exclusivity of breastfeeding on child adiposity and circulating insulin-like growth factor (IGF)-I, which regulates growth.Design, Setting, and Participants Cluster-randomized controlled trial in 31 Belarusian maternity hospitals and their affiliated clinics, randomized into 1 of 2 groups: breastfeeding promotion intervention (n=16) or usual practices (n=15). Participants were 17 046 breastfeeding mother-infant pairs enrolled in 1996 and 1997, of whom 13 879 (81.4%) were followed up between January 2008 and December 2010 at a median age of 11.5 years.Intervention Breastfeeding promotion intervention modeled on the WHO/ UNICEF Baby-Friendly Hospital Initiative (World Health Organization/United Nations Children's Fund).Main Outcome Measures Body mass index (BMI), fat and fat-free mass indices (FMI and FFMI), percent body fat, waist circumference, triceps and subscapular skinfold thicknesses, overweight and obesity, and whole-blood IGF-I. Primary analysis was based on modified intention-to-treat (without imputation), accounting for clustering within hospitals and clinics. ResultsThe experimental intervention substantially increased breastfeeding duration and exclusivity when compared with the control (43% vs 6% exclusively breastfed at 3 months and 7.9% vs 0.6% at 6 months). Cluster-adjusted mean differences in outcomes at 11.5 years of age between experimental vs control groups were: 0.19 (95% CI, Ϫ0.09 to 0.46) for BMI; 0.12 (Ϫ0.03 to 0.28) for FMI; 0.04 (Ϫ0.11 to 0.18) for FFMI; 0.47% (Ϫ0.11% to 1.05%) for percent body fat; 0.30 cm (Ϫ1.41 to 2.01) for waist circumference; Ϫ0.07 mm (Ϫ1.71 to 1.57) for triceps and Ϫ0.02 mm (Ϫ0.79 to 0.75) for subscapular skinfold thicknesses; and Ϫ0.02 standard deviations (Ϫ0.12 to 0.08) for IGF-I. The cluster-adjusted odds ratio for overweight/obesity (BMI Ն85th vs Ͻ85th percentile) was 1.18 (95% CI, 1.01 to 1.39) and for obesity (BMI Ն95th vs Ͻ85th percentile) was 1.17 (95% CI, 0.97 to 1.41). Conclusions and RelevanceAmong healthy term infants in Belarus, an intervention that succeeded in improving the duration and exclusivity of breastfeeding did not prevent overweight or obesity, nor did it affect IGF-I levels at age 11.5 years. Breastfeeding has many advantages but population strategies to increase the duration and exclusivity of breastfeeding are unlikely to curb the obesity epidemic.

Background The duration and exclusivity of breastfeeding in infancy have been inversely associated with future cardiometabolic risk. We investigated the effects of an experimental intervention to promote increased duration of exclusive breastfeeding on cardiometabolic risk factors in childhood. Methods and results We followed-up children in the Promotion of Breastfeeding Intervention Trial, a cluster-randomized trial of a breastfeeding promotion intervention based on the World Health Organization/United Nations Children’s Fund Baby-Friendly Hospital Initiative. 17,046 breastfeeding mother-infant pairs were enrolled in 1996/7 from 31 Belarussian maternity hospitals and affiliated polyclinics (16 intervention vs 15 control sites); 13,879 (81.4%) children were followed-up at 11.5 years, with 13,616 (79.9%) fasted and without diabetes. The outcomes were blood pressure; fasting insulin, adiponectin, glucose and apolipoprotein A1; and presence of metabolic syndrome. Analysis was by intention to treat, accounting for clustering within hospitals/clinics. The intervention substantially increased breastfeeding duration and exclusivity compared with the control arm (43% vs. 6% and 7.9% vs. 0.6% exclusively breastfed at 3 and 6 months, respectively). Cluster-adjusted mean differences at 11.5 years between experimental vs control groups were: 1.0mmHg (95% CI: −1.1, 3.1) for systolic and 0.8mmHg (−0.6, 2.3) for diastolic blood pressure; −0.1mmol/l (−0.2, 0.1) for glucose; 8% (−3%, 34%) for insulin; −0.33μ/ml (−1.5, 0.9) for adiponectin; and 0.0g/l (−0.1, 0.1) for ApoA1. The cluster-adjusted odds ratio for metabolic syndrome, comparing experimental vs control groups, was 1.21 (0.85, 1.72). Conclusions An intervention to improve breastfeeding duration and exclusivity among healthy term infants did not influence cardiometabolic risk factors in childhood. Clinical Trial Registration Information Current Controlled Trials: ISRCTN37687716 (http://www.controlled-trials.com/ISRCTN37687716); Clinicaltrials.gov. Identifier: NCT01561612.

SUMMARY. Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) were measured in 198 patients with renal dysfunction [132 men: median (range) age 66.1 (8.2-90.3) years]. cTnT was measured by two methods: ELISA and Enzymun (Boehringer Mannheim UK, Lewes, UK), both with a detection limit of 0.05 pg/L in 179 and 78 patients, respectively. cTnI was measured in 80 patients by the OPUS plus and OPUS Magnum systems (Dade-Behring, Milton Keynes, UK) with a detection limit of 0.5 pg/L.Patients were classified as having chronic renal impairment (CRI), chronic renal failure (CRF), acute renal failure including those with multiple organ failure on renal replacement therapy (ARF), and patients with chronic renal failure treated with haemodialysis (HD). Cardiac troponins were detectable in the serum of patients with renal dysfunction. cTnT was detectable in 113/179 (63.1%) and 33/78 (42.3%) by the ELISA and Enzymun methods respectively. cTnI was detectable in 17/80 (21.3%). cTnT (ELISA and Enzymun methods) and cTnI were detectable with increased frequency in the CRF, H D and ARF patient groups compared with the CRI group. Cardiac troponin concentrations did not correlate with serum creatine kinase (CK) activity, CK-MB, or urea or creatinine levels. Serial cardiac troponin measurements may be required to confirm or exclude a diagnosis of acute coronary syndromes in patients with renal dysfunction. Additional key phrases: haemodialysis; multiple organ failureThere is a high prevalence of cardiovascular complications in patients receiving renal replacement therapy.' The precise genesis of these are unknown, but hypertension, problems in fluid and electrolyte balance, metabolic abnormalities, including hyperlipidaemia and a direct toxic cardiomyopathy all contribute.2 We have measured cardiac troponin T (cTnT) and cardiac troponin I (cTnI) in the serum of patients with renal dysfunction to see if cardiac troponins were detectable and if they correlated with any other clinical or biochemical findings. METHODSPatients were classified as having chronic renal impairment (CRI, creatinine 120-200 pmol/L, Correspondence: Dr. P 0 Collinson.

Alginate-encapsulated HepG2 cells cultured in microgravity have the potential to serve as the cellular component of a bioartificial liver. This study investigates their performance in normal and liver failure (LF) human plasma over 6-8 h in a fluidized bed bioreactor. After 8 days of microgravity culture, beads containing 1.5 x 10(9) cells were perfused for up to 8 h at 48 mL/min with 300 mL of plasma. After exposure to 90% LF plasma, vital dye staining showed maintained cell viability, while a 7% increase in lactate dehydrogenase activity indicated minimal cell damage. Glucose consumption, lactate production, and a 4.3-fold linear increase in alpha-fetoprotein levels were observed. Detoxificatory function was demonstrated by quantification of bilirubin conjugation, urea synthesis, and Cyp450 1A activity. These data show that in LF plasma, alginate-encapsulated HepG2 cells can maintain viability, and metabolic, synthetic, and detoxificatory activities, indicating that the system can be scaled-up to form the biological component of a bioartificial liver.

SUMMARY An investigation of serum immunoreactive trypsin concentration and pancreatic isoamylase activity in patients with diabetes mellitus has shown that exocrine pancreatic deficit is maximal in insulin dependent diabetics, intermediate in those controlled with sulphonylureas, and absent in patients controlled with biguanides or diet or both. A significant correlation between the serum concentrations of both these pancreatic enzymes and C peptide was found. Serum pancreatic enzyme concentrations were not related to glycosylated haemoglobin concentrations, the dosage of insulin, or the age of onset of diabetes. The concentration of immunoreactive trypsin was found to be low in most of the insulin dependent diabetics in whom this enzyme was measured at the time of the clinical onset of diabetes. Thus exocrine pancreatic deficit in diabetes closely parallels the endocrine ,8 cell deficit and occurs concurrently with, or antedates, the clinical presentation of type I diabetes. It is therefore possible that in type I diabetes similar mechanisms are entailed in the pathogenesis of impaired endocrine and exocrine pancreatic function.Exocrine pancreatic function is impaired in insulin dependent diabetics. This conclusion is supported by direct measurement of pancreatic enzyme concentrations in duodenal aspirates' and by the finding of low serum concentrations of immunoreactive trypsin and pancreatic isoamylase activity45 in such patients. Measurement of these pancreatic enzymes in the serum also showed diminished exocrine pancreatic reserve in diabetics treated with sulphonylureas but not in those controlled by biguanides or diet.24 These results suggested correlation of exocrine and endocrine pancreatic reserve.The present study confirms such a correlation and also assesses the pancreatic exocrine deficit in relation to the clinical onset of insulin dependent diabetes. The effect of duration, age of onset, and quality of control of diabetes on exocrine pancreatic function was also studied.

SummaryPhenylketonuria (PKU) is an autosomal recessive inborn error of metabolism (OMIM 261600). Treatment with a lowphenylalanine diet following early ascertainment by newborn screening prevents impaired cognitive development, the major disease phenotype in PKU. The overall birth prevalence of PKU in European, Chinese and Korean populations is ∼ 1/10,000. Since the human PAH locus contains PKU-causing alleles and polymorphic core haplotypes that describe and corroborate an out-of-Africa range expansion in modern human populations, it is of interest to know the prevalence of PKU in different ethnic groups with diverse geographical origin. We estimated PKU prevalence in South East England, where a sizeable proportion of the population are of Sub-Saharan African or South Asian ancestry. Over the period 1994 to 2004 167 children were diagnosed with PKU. Using birth registration and census data to derive denominators, PKU birth prevalence per 10,000 live births (95% Bayesian credible intervals) was estimated to be 1.14 (0.96-1.33) among white, 0.11 (0.02-0.37) among black, and 0.29 (0.10-0.63) among Asian ethnic groups. This suggests that PKU is up to an order of magnitude less prevalent in populations with Sub-Saharan African and South Asian ancestry that have migrated to the UK.

Objectives This paper reports early screening results from the newborn sickle cell disease screening programme recently implemented in England. Setting England. Screening is offered at 5-8 days of age as part of the existing bloodspot test and offered to all babies irrespective of ethnicity. Methods The laboratory methods recommended are high performance liquid chromatography (HPLC) and iso-electric focusing (IEF). 15 Two methods of analysis must be applied to all screen positive results. The conditions screened for are:- Sickle cell anaemia (Hb SS), Hb SC disease, Hb S/β-thalassaemia, Hb S/DPunjab, Hb S/OArab, Hb S/HPFH. Carriers identified for the common haemoglobin variants are reported to parents and follow-up counselling is offered. A bespoke laboratory quality assurance programme has been established which has defined standards of satifactory performance. Results Provisional figures from the first seven months of screening (up to March 2004) 108,255 infants were screened gave a screen positive rate of 1:900 for these high prevalence areas and a carrier rate of 2.7%. Figures for 2004-2005 show about 250 significant screen positive results for sickle cell disorders and about 6,500 carriers were identified. The birth prevalence for screen positive results from 2004-05 is 1:1500. We estimate that when there is countrywide data, the national birth prevalence will be about 1:2000-1:2,500. Conclusion The results from the national newborn sickle cell screening programme in England - show that the sickle cell disorders are as common as cystic fibrosis (CF) in England, although the distribution of cases is concentrated in London and other urban areas. The findings and approach to implementation adopted in England may be of interest to other Western European countries with increasing rates of sickle cell disease who are considering such programmes and also to other developed countries.

AimsTo assess the role of brain natriuretic peptide (BNP) in both the acute and chronic settings in children with left ventricular (LV) failure. Methods and resultsWe undertook a retrospective review of all BNP levels taken over a 2-year period in our institution. Minimum followup was 90 days. Ninety-two BNP samples from 48 patients were reviewed. Twenty patients (42%) reached the combined endpoint of death, transplantation, or listing for transplantation. Median age was 3 years and 3 months. Mean BNP levels in NYHA or Ross classes I-IV were 29, 239, 744, and 1593 pg/mL, respectively, with significant differences between mean logBNP in classes I-III (P , 0.001). LogBNP levels correlated with fractional shortening (P , 0.001), LVEDd z-score (P , 0.001), and tissue Doppler velocities (P , 0.02). From serial data there was a strong correlation between change in BNP and change in clinical status (F 9.5, P , 0.001). Receiver-operator curve (ROC) demonstrated that BNP . 290 pg/mL predicts poor outcome with sensitivity of 0.80, specificity of 0.87, and likelihood ratio of 6.4 in paediatric patients with chronic LV dysfunction. A separate ROC from acute presentations did not demonstrate superiority of BNP over other assessments. ConclusionBNP levels in paediatric heart failure (HF) patients show a strong correlation to both impaired heart function on echocardiogram and clinical status. Serial BNP levels follow the clinical course. In chronic HF, a BNP level of .290 pg/mL is predictive of an adverse outcome.--