Stearidonic and γ-linolenic acids in echium oil improves glucose disposal in insulin resistant monkeys.

Echium oil (EO) contains stearidonic acid (18:4), a n-3 polyunsaturated fatty acids (PUFAs), and gamma-linolenic acids (18:3), a n-6 PUFA that can be converted to long chain (LC)-PUFAs. We aimed to compare a safflower oil (SO)-enriched diet to EO- and fish oil (FO)-enriched diets on circulating and tissue PUFAs levels and glycemic, inflammatory, and cardiovascular health biomarkers in insulin resistant African green monkeys. In a Latin-square cross-over study, eight monkeys consumed matched diets for 6 weeks with 3-week washout periods. Monkeys consuming FO had significantly higher levels of n-3 LC-PUFAs and EO supplementation resulted in higher levels of circulating n-3 LC-PUFAs and a significant increase in dihomo-gamma linolenic acid (DGLA) in red blood cells and muscle. Glucose disposal was improved after EO consumption. These data suggest that PUFAs in EO supplementation have the capacity to alter circulating, RBC and muscle LC-PUFA levels and improve glucose tolerance in insulin-resistant monkeys.

Cycled enteral antibiotics reduce sepsis rates in paediatric patients on long-term parenteral nutrition for intestinal failure.

BACKGROUND: Long-term parenteral nutrition has transformed the prognosis for children suffering from intestinal failure. However, parenteral nutrition itself is associated with considerable morbidity and mortality including that caused by sepsis. AIM: To examine a strategy of cycled enteral antibiotics in reducing the incidence of sepsis in paediatric intestinal failure patients. METHODS: Retrospective analysis of the incidence of sepsis rates of patients on long-term parenteral nutrition, at a tertiary paediatric hospital. Patients were separated into those who received cycled enteral antibiotics and a control group. Sepsis rates before and during cycled enteral antibiotics were compared with comparable timeframes between the cycled enteral antibiotics and control groups. Central venous catheter removal rates were also compared. RESULTS: Fifteen patients (eight cycled enteral antibiotics, & seven controls) received 9512 parenteral nutrition days, with a total of 132 sepsis episodes. All eight patients of the treatment group demonstrated a decrease in the frequency of episodes of sepsis following the introduction of cycled enteral antibiotics. The cycled enteral antibiotics group had a significant reduction in infection rate during the treatment period (from 2.14 to 1.06 per 100 parenteral nutrition days, P = 0.014: median effect size -1.04 CI 95%-1.93, -0.22), whereas the controls had no significant change (1.91 - 2.36 per 100 parenteral nutrition days P = 0.402: median effect size 0.92 CI 95%-1.96, 4.17). The central venous catheter survival rates increased in the cycled enteral antibiotics group from 0.44 central venous catheter removals per 100 parenteral nutrition days to 0.27 central venous catheter removals per 100 parenteral nutrition days, although this was not statistically significant. CONCLUSIONS: Cycled enteral antibiotics significantly reduced the rate of sepsis in a small group of paediatric intestinal failure patients. Larger well-designed prospective studies are warranted to further explore this finding.

High incidence of cardiomyopathy in beta-thalassaemia patients receiving regular transfusion and iron chelation: reversal by intensified chelation.

Cardiac scintigraphy has been performed in 60 beta-thalassaemia major patients aged 8-35 years who received regular blood transfusions and subcutaneous desferrioxamine (DFX) chelation. Fifty-seven showed no clinical, radiological or electrocardiographic evidence of heart disease and 3 had clinically apparent cardiac failure. Twenty-two patients (37%) showed severe cardiac functional impairment defined by a resting left ventricular ejection fraction (LVEF) less than 45% and/or a drop of greater than 12% on stress, while 19 were normal and 19 had a mild abnormality. There was no significant correlation between abnormality of LVEF and age, serum ferritin, number of units transfused, dose and duration of subcutaneous DFX therapy, liver disease or sexual maturation. Non-compliant patients (defined as the use of subcutaneous DFX less than 4 times weekly) generally showed worse cardiac function. Repeat study on 17 patients after 6-28 months of better compliance with subcutaneous or intravenous DFX (using an indwelling catheter) showed a significant overall improvement in LVEF associated with a significant drop in serum ferritin. We conclude that cardiac scintigraphy uncovers a high incidence of cardiac functional abnormality in asymptomatic, well-transfused thalassaemia patients, particularly those poorly compliant with chelation. Those with poor LVEF results should be offered intensive chelation therapy to improve cardiac function.

Transfusional iron overload: the relationship between tissue iron concentration and hepatic fibrosis in thalassaemia.

The interrelationships between liver iron concentration, the duration of iron-loading, and hepatic fibrosis, assessed morphometrically, have been studied in 32 specimens of liver obtained from 19 heavily transfused patients with thalassaemia major whose age ranged from 4 to 19 yr. Similar observations were made in a matched group of thalassaemic patients treated with long-term chelation therapy. The degree of liver damage ranged from very slight increase in fibrous tissue to severe fibrosis and cirrhosis. The severity of the fibrosis was closely correlated both with liver iron concentration and with age. While the relationship between fibrosis and age was linear, both the severity and the rate of fibrosis were exponentially related to liver iron concentration, damage accelerating as liver iron concentration exceeded 3 per cent, dry weight. By producing a modest but significant reduction in liver iron concentration chelation therapy resulted in a disproportionate but predictable retardation in the progression of the fibrosis. The factors affecting the distribution of iron between parenchymal and reticuloendothelial cells were also examined. In general stainable iron was uniformly distributed between parenchymal and reticuloendothelial cells from the early stages of iron-loading. Parenchymal siderosis was relatively heavier in splenectomised patients and in patients with liver iron concentrations above 3 per cent, dry weight than in non-splenectomised patients or patients with liver iron levels of less than 3 per cent, dry weight, but this did not affect the severity of the fibrosis. The relevance of these findings to the traditional concepts of the pathology of transfusional siderosis is discussed.

Serum ferritin in children with thalassaemia regularly transfused.

A controlled trial of continuous chelation therapy in regularly transfused children with homozygous beta-thalassaemia has been in progress at the Hospital for Sick Children since April 1966. In the sixth and seventh years of the trial the effect of this treatment on iron overload has been assessed by estimating serum ferritin levels and liver iron concentrations in both chelator-treated and control groups. When compared with non-chelated controls, results of both these estimations were invariably lower in the chelated group. However, all the results in both groups were very high, and fell within the ranges observed in untreated idiopathic haemochromatosis. A close correlation was found between serum ferritin levels and liver iron concentrations in these children, indicating that serum ferritin is a valuable alternative to liver iron concentration in the assessment of visceral iron overload, even when massive tissue siderosis is present.

Long-term chelation therapy in thalassaemia major: effect on liver iron concentration, liver histology, and clinical progress.

A prospective trial of continuous chelation therapy in children with homozygous thalassaemia on a high transfusion regimen was started in April 1966. The effect of treatment on iron concentration in the liver and on hepatic histology was examined in 49 biopsy specimens obtained from nine chelator-treated patients and nine control patients between April 1966 and April 1973.Chelation therapy was associated with a significant reduction in liver iron concentration, and by the end of the trial the values for the two groups showed no overlap. A similar difference was seen in the amount of hepatic fibrosis, which showed little or no change in the chelator-treated patients but was progressive in the controls.No major clinical differences were seen, probably because both groups included several older children who were heavily loaded with iron at the start of the trial. Among the younger patients, however, puberty was delayed in four of five controls but in only one of four chelator-treated children. Prepubertal growth rate was significantly greater in the chelator-treated patients than in the controls.