Metabolic dyslipidemia is characterized by high circulating triglyceride (TG) and low HDL cholesterol levels and is frequently accompanied by hepatic steatosis. Increased hepatic lipogenesis contributes to both of these problems. Because insulin fails to suppress gluconeogenesis but continues to stimulate lipogenesis in both obese and lipodystrophic insulin-resistant mice, it has been proposed that a selective postreceptor defect in hepatic insulin action is central to the pathogenesis of fatty liver and hypertriglyceridemia in these mice. Here we show that humans with generalized insulin resistance caused by either mutations in the insulin receptor gene or inhibitory antibodies specific for the insulin receptor uniformly exhibited low serum TG and normal HDL cholesterol levels. This was due at least in part to surprisingly low rates of de novo lipogenesis and was associated with low liver fat content and the production of TG-depleted VLDL cholesterol particles. In contrast, humans with a selective postreceptor defect in AKT2 manifest increased lipogenesis, elevated liver fat content, TG-enriched VLDL, hypertriglyceridemia, and low HDL cholesterol levels. People with lipodystrophy, a disorder characterized by particularly severe insulin resistance and dyslipidemia, demonstrated similar abnormalities. Collectively these data from humans with molecularly characterized forms of insulin resistance suggest that partial postreceptor hepatic insulin resistance is a key element in the development of metabolic dyslipidemia and hepatic steatosis.
Transient lactose intolerance has been identified as a possible causative factor in infant colic. A double-blind randomised placebo-controlled crossover study to investigate this has been undertaken in 53 babies with symptoms of colic. Pre-incubation of the feed with lactase resulted in breath hydrogen levels and total crying time which were both at least 45% lower than figures with placebo treatment, in 26% of the full trial group (95% confidence interval 12.9% to 44.4%), and in 38% of compliers (95% confidence interval 18.8% to 59.4%). The remainder did not respond to the same extent. These findings suggest that infant colic may have a multiple aetiology, and that in a significant number of cases the immediate cause is transient lactose intolerance, in which cases pretreatment of feeds with lactase can result in considerable symptomatic benefits.
The antipyretic analgesics, paracetamol, and non-steroidal anti-inflammatory agents NSAIDs are one of the most widely used classes of medications in children. The aim of this review is to determine if there are any clinically relevant differences in safety between ibuprofen and paracetamol that may recommend one agent over the other in the management of fever and discomfort in children older than 3 months of age.
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