Adverse events associated with pediatric complementary and alternative medicine in the Netherlands:a national surveillance study

Pediatric use of complementary and alternative medicine (CAM) in the Netherlands is highly prevalent. The risks of pediatric CAM use are, however, largely unknown. Therefore, a 3-year survey was carried out at the Dutch Pediatric Surveillance Unit. Pediatricians were asked to register cases of adverse events associated with pediatric CAM usage. In 3 years, 32 unique adverse events were registered. Twenty-two of these adverse events were indirect and not related to the specific CAM therapy but due to delaying, changing, or stopping of regular treatment, a deficient or very restrictive diet or an incorrect diagnosis by a CAM therapist. These events were associated with many different CAM therapies. Nine events were deemed direct adverse events like bodily harm or toxicity and one-third of them occurred in infants. Only supplements, manual therapies, and (Chinese) herbs were involved in these nine events. In one case, there was a risk of a serious adverse event but harm had not yet occurred. Conclusion: Relatively few cases of adverse events associated with pediatric CAM usage were found, mostly due to delaying or stopping conventional treatment. Nevertheless, parents, pediatricians and CAM providers should be vigilant for both direct and indirect adverse events in children using CAM, especially in infants

Glycogen storage disease type I : clinical, biochemical and genetic aspects, and implications for treatment and follow-up (management of glycogen storage disease type I)

In conclusion, the ESGSD I and its related studies have added to a better understanding of the clinical course, treatment, outcome and pathophysiology of GSD I and its complications. This increased insight has offered the possibility to develop extended recommendations for long-term treatment and follow-up. However, about some hallmarks and the practical interpretation of dietary treatment controversy still exists. Furthermore, a lot of questions about the pathophysiology and management of the (long-term) complications are not solved yet. Continuation of the ESGSD I as the ISGSD I offers the possibility to tackle these questions. In 2008, we hope to present some of the answers along with improved consensus guidelines for the management of GSD I, and we will come up, for certainty, with new unsolved questions.

Renal Function in Glycogen Storage Disease Type I, Natural Course, and Renopreservative Effects of ACE Inhibition

Background and objectives: Renal failure is a major complication in glycogen storage disease type I (GSD I). We studied the natural course of renal function in GSD I patients. We studied differences between patients in optimal and nonoptimal metabolic control and possible renoprotective effects of angiotensin converting enzyme inhibition

Inhibition of mitochondrial fatty acid oxidation in vivo only slightly suppresses gluconeogenesis but enhances clearance of glucose in mice

Mitochondrial fatty acid oxidation (mFAO) is considered to be essential for driving gluconeogenesis (GNG) during fasting. However, quantitative in vivo data on de novo synthesis of glucose-6-phosphate upon acute inhibition of mFAO are lacking. We assessed hepatic glucose metabolism in vivo after acute inhibition of mFAO by 30 mg kg(-1) 2-tetradecylglycidic acid (TDGA) in hypoketotic hypoglycemic male C57BL/6J mice by the infusion of [U-C-13]glucose, [2-C-13]glycerol, [1-H-2] galactose, and paracetamol for 6 hours, which was followed by mass isotopomer distribution analysis in blood glucose and urinary paracetamol-glucuronide. During TDGA treatment, endogenous glucose production was unaffected (127 +/- 10 versus 118 +/- 7 mu mol kg(-1) minute(-1), control versus TDGA, not significant), but the metabolic clearance rate of glucose was significantly enhanced (15.9 +/- 0.9 versus 26.3 +/- 1.1 mL kg(-1) minute(-1), control versus TDGA, P <0.05). In comparison with control mice, de novo synthesis of glucose-6-phosphate (G6P) was slightly decreased in TDGA-treated mice (108 +/- 19 versus 85 +/- 6 mu mol kg(-1) minute(-1), control versus TDGA, P <0.05). Recycling of glucose was decreased upon TDGA treatment (26 +/- 14 versus 12 4 mu mol kg(-1) minute(-1), control versus TDGA, P <0.05). Hepatic messenger RNA (mRNA) levels of genes encoding enzymes involved in de novo G6P synthesis were unaltered, whereas glucose-6-phosphate hydrolase mRNA expressions were increased in TDGA-treated mice. Glucokinase and pyruvate kinase mRNA levels were significantly decreased, whereas pyruvate dehydrogenase kinase isozyme 4 expression was increased 30-fold; this suggested decreased glycolytic activity. Conclusion: Acute pharmacological inhibition of mFAO using TDGA had no effect on endogenous glucose production and only a marginal effect on de novo G6P synthesis. Hence, fully active mFAO is not essential for maintenance of hepatic GNG in vivo in fasted mice

Apoptotic neutrophils in the circulation of patients with glycogen storage disease type 1b (GSD1b)

Glycogen storage disease type 1b (GSD1b) is a rare autosomal recessive disorder characterized by hypoglycemia, hepatomegaly, and growth retardation, and associated-for unknown reasons-with neutropenia and neutrophil dysfunction. In 5 GSD1b patients in whom nicotinamide adenine dinucleotide phosphate-oxidase activity and chemotaxis were defective, we found that the majority of circulating granulocytes bound Annexin-V. The neutrophils showed signs of apoptosis with increased caspase activity, condensed nuclei, and perinuclear clustering of mitochondria to which the proapoptotic Bcl-2 member Bax had translocated already. Granulocyte colony-stimulating factor (G-CSF) addition to in vitro cultures did not rescue the GSD1b neutrophils from apoptosis as occurs with G-CSF-treated control neutrophils. Moreover, the 2 GSD1b patients on G-CSF treatment did not show significantly lower levels of apoptotic neutrophils in the bloodstream. Current understanding of neutrophil apoptosis and the accompanying functional demise suggests that GSD1b granulocytes are dysfunctional because they are apoptotic. (C) 2003 by The American Society of Hematolog