Longitudinal development of obesity in the post-Fontan population.

BACKGROUND/OBJECTIVES: An elevated body mass index (BMI) in childhood is a significant risk factor for cardiovascular disease, and it may pose an additional risk to children and adults with palliated univentricular congenital heart disease. However, little is known about longitudinal development of obesity in this population. The objective of this study is to determine the prevalence of overweight (OW) and obese (OB) habitus at the time of Fontan palliative surgery, to track changes in BMI after surgery, and ultimately to determine whether factors such as gender, ethnicity, preoperative heart defect and ventricular dominance are associated with later development of OW or OB. SUBJECTS/METHODS: A retrospective chart review of 84 patients undergoing Fontan palliation was performed. Demographic data including gender, ethnicity, preoperative heart defect and ventricular dominance were recorded. Height, weight and BMI were obtained at the time of Fontan and on a yearly basis post surgery. RESULTS: At the time of Fontan palliation, 10.7% of patients were OB or OW. During the five years following palliation, the percentage of OB or OW patients trended upward, from 20.3% the year following surgery to 30% at 5 years post Fontan. Repeated measures generalized estimating equation showed a significant association between Hispanic ethnicity and increased BMI Z-scores for the 5 years after Fontan palliation (P<0.001); there was no association between BMI Z-scores and patient sex, lesion or ventricular dominance. CONCLUSIONS: During the first 5 years after Fontan palliation, there is a trend toward increasing percentages of OB and OW patients. In addition, there is a significant association between Hispanic ethnicity and being OW or OB before and after surgery. Further study is needed to determine whether OW/OB status is associated with worse health outcomes in this patient population.

Beta-adrenergic receptor polymorphisms and cardiac graft function in potential organ donors.

Prior studies have demonstrated associations between beta-adrenergic receptor (ßAR) polymorphisms and left ventricular dysfunction-an important cause of allograft nonutilization for transplantation. We hypothesized that ßAR polymorphisms predispose donor hearts to LV dysfunction after brain death. A total of 1043 organ donors managed from 2001-2006 were initially studied. The following ßAR single nucleotide polymorphisms were genotyped: ß1AR 1165C/G (Arg389Gly), ß1AR 145A/G (Ser49Gly), ß2AR 46G/A (Gly16Arg) and ß2AR 79C/G (Gln27Glu). In multivariable regression analyses, the ß2AR46 SNP was significantly associated with LV systolic dysfunction, with each minor allele additively decreasing the odds for LV ejection fraction <50%. The ß1AR1165 and ß2AR46 SNPs were associated with higher dopamine requirement during the donor management period: donors with the GG and AA genotypes had ORs of 2.64 (95% CI 1.52-4.57) and 2.70 (1.07-2.74) respectively for requiring >10 µg/kg/min of dopamine compared to those with the CC and GG genotypes. However, no significant associations were found between ßAR SNPs and cardiac dysfunction in 364 donors managed from 2007-2008, perhaps due to changes in donor management, lack of power in this validation cohort, or the absence of a true association. ßAR polymorphisms may be associated with cardiac dysfunction after brain death, but these relationships require further study in independent donor cohorts.

The 4G/4G genotype of the PAI-1 (serpine-1) 4G/5G polymorphism is associated with decreased lung allograft utilization.

Widespread thrombi are found among donor lungs rejected for transplantation. The 4G/5G polymorphism in the plasminogen activator inhibitor (PAI-1) gene impacts transcription and the 4G allele is associated with increased PAI-1 levels. We hypothesized that the 4G/4G genotype would be associated with decreased lung graft utilization, potentially because of worse oxygenation in the donor. We genotyped donors managed by the California Transplant Donor Network from 2001 to 2008 for the 4G/5G polymorphism in the PAI-1 gene. Non-Hispanic donors from 2001 to 2005 defined the discovery cohort (n = 519), whereas donors from 2006 to 2008 defined the validation cohort (n = 369). We found, that the odds of successful lung utilization among Non-Hispanic white donors were lower among donors with the 4G/4G genotype compared to those without this genotype in both the discovery (OR = 0.55, 95% CI = 0.3-0.9, p = 0.02) and validation (OR = 0.5, 95% CI = 0.3-0.9, p = 0.03) cohorts. This relationship was independent of age, gender, cause of death, drug use and history of smoking. Donors with the 4G/4G genotype also had a lower PaO2/FiO2 ratio (p = 0.03) and fewer donors with the 4G/4G genotype achieved the threshold PaO2/FiO2 ratio ≥ 300 (p = 0.05). These findings suggest a role for impaired fibrinolysis resulting in worse gas exchange and decreased donor utilization.

Incidence and spectrum of congenital heart disease in Oman.

We analysed the incidence and spectrum of congenital heart disease (CHD) in the Sultanate of Oman from 1994 to 1996. CHD was detected in 992 of 139,707 live births (incidence 7.1/1000 live births). The common CHDs were ventricular septal defect (24.9%), atrial septal defect (14.4%) and patent ductus arteriosus (10.3%). The frequency of atrioventricular septal defects (5.9%) was higher than reported from other countries. Age at diagnosis was under 1 month in 38% and 1-12 months in 40%. Cyanotic CHD was found in 21.7% of the whole group and 35% of neonates. Although this was a hospital-based study, we believe we included almost all the infants and children with CHD in the country. The incidence and pattern of CHD in Oman were similar to those reported from developed countries in Europe and America, except for a higher frequency of atrioventricular septal defects. The high prevalence of consanguinity in the country did not affect the overall incidence of CHD.

Management of hypercholesterolemia in childhood and adolescence.

There is strong evidence that the onset of atherosclerosis occurs in childhood. Identifying and treating children and adolescents at risk for hypercholesterolemia should lead to a decrease in adult atherosclerotic disease. Based on current information, and the National Cholesterol Education Program (NCEP) guidelines, screening in children and adolescents should be limited to those individuals with specific cardiac risk factors or those from families with a strong history of atherosclerotic disease. Treatment of identified patients should be initiated with dietary control. Subsequent use of cholesterol-lowering medication is best limited to those patients who fail at least 6 months of dietary control measures. Drug therapy includes the use of bile acid sequestrants, nicotinic acid and, more recently, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. There has been limited experience with HMG CoA reductase inhibitors in children and adolescents. However, preliminary data suggests that they are both more effective and have less side effects than either bile acid sequestrants or niacin. Long-term cohort studies will be needed to determine whether screening and treating children and adolescents with hypercholesterolemia is truly of long-term benefit and, if so, which treatment strategies will be preferred.

Isolated hypoplasia of right ventricle with atrial septal defect: a rare form of cyanotic heart disease.

Isolated hypoplasia of right ventricle is a rare kind of congenital heart disease that can present with cyanosis in childhood. We evaluated the clinical profile, diagnosis and management strategy of isolated hypoplasia of right ventricle in children. During 1993-1997, six children were diagnosed to have isolated right ventricular hypoplasia in our institution. Two patients were referred because of cyanosis, while cardiac murmur was the reason for referral in the remaining four. Besides clinical evaluation, all these patients had chest radiography, electrocardiography and echo-doppler studies. At echocardiography the valve diameters were measured and the degree of hypoplasia was quantified as standard deviation units. Cardiac catheter studies and angiography, and surgical intervention were carried out where indicated. Both operated and unoperated patients were followed up for 3-5 years. Cyanosis (severe--2, mild--4) and a soft ejection systolic murmur at the left sternal border were present in all patients. The second sound was normal. On two-dimensional echocardiography, all had hypoplasia of right ventricular (trabecular portion) and bi-directional shunt across atrial septal defect. Cardiac catheterisation was performed in four patients, which confirmed the echo findings and revealed normal right heart pressures. These four patients underwent surgical procedures. Simple closure of atrial septal defect was sufficient in two patients. Two others required bi-directional cavopulmonary anastomoses, and atrial septal defect closure was tolerated only by one of these two patients. Complete correction is not always feasible and adequacy of right ventricle to receive the entire venous return should be accurately assessed prior to, as well as during surgery.

Effects of milk somatic cell count on cottage cheese yield and quality.

Eight Holstein cows in midlactation were selected for low milk somatic cell count (SCC) and the absence of the pathogens that cause mastitis. Milk collection and cottage cheese manufacture from low SCC milk were replicated on each of 4 d (control period). Each cow was infused with 1000 cfu of Streptococcus agalactiae. One week after infusion, milk from the same eight cows was collected and commingled. On each of 4 d, cottage cheese was made from milk with high SCC (treatment period). A mass-balance protocol, accounting for protein and total solids, was used to determine recoveries in whey, wash water, and uncreamed curd. Actual yields, yields adjusted for composition, and theoretical yields of uncreamed curd were calculated. Mean milk SCC for the periods with the low SCC (control) and the high SCC (treatment) were 83 x 10(3) and 872 x 10(3) cells/ml, respectively. The recovery of protein in the uncreamed curd was higher during the low SCC period than during the high SCC period (75.85% vs. 74.35%). High SCC and the associated higher proteolytic activity caused higher protein loss in the whey and wash water and more curd fines. The percentage of total solids recovery in uncreamed curd was higher for high SCC milk because the lactose content of the high SCC milk was 0.27% lower than that of the low SCC milk. The moisture content of the curd was higher for the high SCC milk (82.75% vs. 83.81%). Proteolysis during refrigerated storage was faster in cottage cheese made from high SCC milk. The yield efficiency of uncreamed curd, adjusted for composition based on 81% moisture, was 4.34% lower for the cottage cheese curd made from high SCC milk.

Cheddar cheese: influence of milking frequency and stage of lactation on composition and yield.

Cheddar cheese was made from milk collected from two groups of cows milked either two or three times daily during early, mid, and late lactation. Milk from cows in late lactation had lower casein as a percentage of true protein and a higher acid degree value than did milk from cows in early lactation. Milk from cows milked three times daily had lower concentrations of milk fat and casein and higher acid degree values than did milk from cows milked twice daily, and thus this milk would be expected to result in decreased cheese yield. Cheese composition was not affected by milking frequency. Stage of lactation effects on cheese composition were confined to differences in salt content and a trend for higher moisture in cheese made from milk of cows in late lactation. Stage of lactation influenced the pH and degradation of alpha s-casein in cheese during aging. Fat and protein losses in whey at draining were higher for milk from cows in late lactation than from milk from cows in early lactation. The typical differences in fatty acid composition of milk from cows in early lactation that cause lower melting point may have caused higher fat loss in press whey. Fat loss in whey at draining was higher in cheese made from milk from cows milked three times daily than in cheese made from milk from cows milked twice daily, but the protein loss was not influenced. The ADV of milk was positively correlated to the fat loss in whey. Lower recoveries of fat and protein in cheese from milk of cows in late lactation were observed and may cause small but economically important decreases in cheese yield. Low SCC of milk from cows in late lactation may have minimized the changes in cheese composition and yield from stage of lactation.