Abnormal lipid concentrations in cystic fibrosis

BACKGROUND: Concentrations of cholesterol and triacylglycerol are commonly believed to be low in persons with cystic fibrosis and thus not of concern. OBJECTIVE: The goal was to determine whether concentrations of cholesterol and triacylglycerol are related to glucose tolerance or nutritional status in patients with cystic fibrosis. DESIGN: Fasting lipid profiles were measured in 192 patients ( +/- SD age: 21 +/- 11 y) in conjunction with an oral-glucose-tolerance test. RESULTS: Cystic fibrosis patients in all age groups had higher triacylglycerol (1.51 +/- 0.95 mmol/L) and lower cholesterol (3.57 +/- 0.96 mmol/L) concentrations than US population means. Thirty patients (16%) had hypertriglyceridemia (3.22 +/- 1.22 mmol/L), and 8 patients (4%) had elevated cholesterol (6.05 +/- 1.32 mmol/L). In most cases, hypertriglyceridemia was isolated; only 3 subjects had elevation of both cholesterol and triacylglycerol. Lipid concentrations were not related to body mass index, weight, glucose tolerance, the areas under the curve for glucose or insulin, or glycated hemoglobin. Lipid concentrations also did not correlate with cystic fibrosis genotype, use of systemic steroids, blood pressure, liver enzymes, C-reactive protein, or pulmonary function. CONCLUSIONS: Isolated hypertriglyceridemia appears to be common in cystic fibrosis, whereas cholesterol concentrations are generally low. Hypertriglyceridemia may be related to chronic low-grade inflammation or to a dietary macronutrient imbalance with excessive simple carbohydrate absorption relative to fat absorption. Whether it is associated with a risk of cardiovascular disease in this population is uncertain, but the clinical significance of triacylglycerol elevation may become important as survival improves.     

Health technology assessment for medical devices in Europe. What must be considered

OBJECTIVE: To inform about the specifics of medical devices and the resulting consequences for health technology assessment (HTA) and to present the European industry position on this topic. METHODS: The paper is based on an intensive debate within Eucomed, the European trade association in the field of medical devices, informed by an HTA Experts Group, comprising experts from within and outside the medical device industry. RESULTS: Based on the specifics of medical devices, there are a number of methodologic considerations that require a tailored HTA, differing from the approach taken for, for example, pharmaceutical products. These differences have an impact on the selection of the technology, the timing of the assessment, the study design, and the patient population. CONCLUSION: The European medical device industry can commit to an HTA that takes into consideration the specifics of medical technologies, which is appropriate and fair, and which is done under full participation of industry. Under these circumstances HTA can be a useful tool to support rational decision making in health care.     

Neuroleptic malignant syndrome in a patient with succinic semialdehyde dehydrogenase deficiency

A patient suffering from a rare enzyme deficiency developed a malignant neuroleptic syndrome after having been treated with one single dose of haloperidol. We investigated the patient's serum for all frequent polymorphisms in cytochrome P450 2D6, assuming him to be a poor neuroleptic metabolizer. We will also discuss other potential mechanisms inducing this disturbance and its differential diagnoses.     

Leukemic predisposition of pSca-1/Cb2 transgenic mice

OBJECTIVE: The gene encoding the peripheral cannabinoid receptor Cb2 is located in the common virus integration site Evi11 and is associated with hematopoietic malignancies in mice. To determine the effect of Cb2 overexpression on hematopoietic development in vivo, Cb2 transgenic mice were generated. MATERIALS AND METHODS: A Cb2 expression vector was constructed containing a Cb2 cDNA fragment cloned into the 14kb Sca-1 (Ly-6E.1) gene. Two transgenic lines in which Cb2 expression is controlled by the Sca-1 promoter were generated, and the effect on hematopoietic development was studied. Expression of Cb2 mRNA or protein was studied by RNase protection analysis and ligand binding assays, respectively. Leukemic predisposition was investigated by injecting newborn transgenic as well as control animals with Cas-Br-M murine leukemia virus (Cas-Br-M MuLV). RESULTS: Although increased expression of the Cb2 gene was observed in hematopoietic tissues, follow-up of more than 1 year did not reveal any hematologic defect. Interestingly, infection of newborn pSca-1/Cb2 transgenic mice with Cas-Br-M MuLV revealed that significantly more transgenic mice developed leukemia than virus-treated control littermates. Because these studies provide evidence for the cooperative potential of Cb2 in leukemia progression, we wished to identify genes that may collaborate with Cb2 in leukemic transformation. Our study suggests that Evi1, another common target for proviral integration in mouse leukemias, may be overexpressed in virus-induced leukemias in pSca-1/Cb2 transgenic mice. CONCLUSIONS: The data indicate that hematopoietic precursor cells that express high levels of Cb2 possess increased susceptibility for leukemia development and that Cb2 and Evi1 might collaborate in leukemogenesis.     

Using the net benefit regression framework to construct cost-effectiveness acceptability curves: an example using data from a trial of external loop recorders versus Holter monitoring for ambulatory monitoring of "community acquired" syncope

Background  

Cost-effectiveness acceptability curves (CEACs) describe the probability that a new treatment or intervention is cost-effective. The net benefit regression framework (NBRF) allows cost-effectiveness analysis to be done in a simple regression framework. The objective of the paper is to illustrate how net benefit regression can be used to construct a CEAC.     

Feeding intolerance in very-low-birthweight infants: What is it and what can we do about it?

The increased survival of very-low-birth-weight infants has resulted in the need to better understand the immaturities that challenge optimal nutrition for these infants and how to surmount them. This is critical if we are to prevent short and long term morbidity associated with poor nutrition. Here we describe several of these immaturities including those related to digestion and absorption, suck-swallow incoordination, delayed gastric emptying, and intestinal motility and how they lead to the common problem of feeding intolerance. Scientifically based strategies for introducing, stopping and continuing enteral feedings in association with parenteral nutrition are presented.     

Carbon Dioxide and Gadopentetate Dimeglumine Venography to Guide Percutaneous Vertebroplasty

Percutaneous vertebroplasty with polymethylmethacrylate (PMMA) is an effective procedure for relieving pain due to vertebral body compression fractures. The technique employs iodinated contrast venography to exclude needle placement directly within the basivertebral complex. We present two cases in which carbon dioxide (CO₂) and gadopentetate dimeglumine venography was used to guide percutaneous vertebroplasty in patients with a contraindication to iodinated contrast.