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.     

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.     

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.     

Electroporation enhances transfection efficiency in murine cutaneous wounds

Transfection of wounds with DNA-encoding growth factors has the potential to improve healing, but current means of nonviral gene delivery are inefficient. Repeated high doses of DNA, necessary to achieve reliable gene expression, are detrimental to healing. We assessed the ability of in vivo electroporation to enhance gene expression. Full-thickness cutaneous excisional wounds were created on the dorsum of female mice. A luciferase- encoding plasmid driven by a CMV promoter was injected at the wound border. Following plasmid administration, electroporative pulses were applied to injection sites. Pulse parameters were varied over a range of voltage, duration, and number. Animals were euthanized at intervals after transfection and the luciferase activity measured. Application of electric pulses consistently increased luciferase expression. The electroporative effect was most marked at a plasmid dose of 50 micro g, where an approximate tenfold increase was seen. Six 100- micro s-duration pulses of 1750 V/cm were found to be the most effective in increasing luciferase activity. High numbers of pulses tended to be less effective than smaller numbers. This optimal electroporation regimen had no detrimental effect on wound healing. We conclude that electroporation increases the efficiency of transgene expression and may have a role in gene therapy to enhance wound healing.     

Multiple sclerosis: Oligoclonal IgG, ξ-λ light chain distribution and measles antibodies in brain extracts

The presence of measles antibodies in white and grey brain material and in 8 demyelination plaques from 6 patients affected with multiple sclerosis was investigated with the hemagglutination inhibition (HI) and complement fixation (CF) techniques.White and grey matter of 5 controls were run in parallel. No measles antibodies could be detected, except for one plaque, where the answer could be considered as doubtful. The immunoglobulin G (IgG) content and the ξ/λ light chain ratios of all the samples were evaluated. No unique monoclonal immunoglobulin population could be detected, but ξ or λ predominant oligoclonal populations appeared in controls as well as in MS IgG.