Comparison of treatment of severe high-density lipoprotein cholesterol deficiency in men with daily atorvastatin (20 mg) versus fenofibrate (200 mg) versus extended-release niacin (2 g)

To determine whether available lipid-modifying medication can increase high-density lipoprotein (HDL) cholesterol in well-defined genetic or familial HDL-deficiency states, we studied 19 men with HDL deficiency (HDL cholesterol <5th percentile for age and gender) 55 +/- 10 years of age. Concomitant risk factors included diabetes (n = 3) and hypertension (n = 7) and 8 patients had coronary artery disease. Molecular analysis revealed that 4 patients had a mutation in the ABCA1 gene. Patients were assigned to sequentially receive atorvastatin 20 mg/day, fenofibrate 200 mg/day, and extended-release niacin 2 g/day for 8 weeks, with a 4-week washout period between each treatment. Patients in whom a statin was required, according to current treatment guidelines, were kept on atorvastatin throughout the study. Baseline HDL cholesterol level was 0.63 +/- 0.12 mmol/L (24 +/- 5 mg/dl), triglycerides 2.01 +/- 0.98 mmol/L (180 +/- 86 mg/dl), and low-density lipoprotein (LDL) cholesterol 2.29 +/- 0.95 mmol/L (94 +/- 39 mg/dl). Mean percent changes in HDL cholesterol on atorvastatin, fenofibrate, and niacin were -6% (p = NS), +6% (p = NS), and +22% (p <0.05), respectively. Furthermore, niacin significantly increased the large alpha-1 apolipoprotein A-I-containing HDL subspecies (12 to 17 nm). In conclusion, niacin was the only effective drug to increase HDL cholesterol. The absolute increase in HDL cholesterol, approximately 0.10 mmol/L (3.9 mg/dl), is of uncertain clinical significance. Biomarkers of HDL-mediated cellular cholesterol efflux were not changed by niacin therapy. Atorvastatin or fenofibrate had little effect on HDL cholesterol; atorvastatin decreased the total cholesterol/HDL cholesterol ratio by 26%. Fenofibrate did not change HDL cholesterol levels and caused an increase in LDL cholesterol. Aggressive LDL cholesterol lowering may be the strategy of choice in such patients.     

Impact of amniotic fluid “sludge” on the risk of preterm delivery

Objective: To evaluate the impact of amniotic fluid “sludge” (AFS) on the risk of preterm delivery and to describe the effect of antibiotic treatment in that situation.

Methods: Case–control study including singleton pregnancies with or without AFS, between 15–32 weeks of gestation. Factors associated with preterm delivery before 32 weeks, 34 weeks and 37 weeks were evaluated with univariate and multivariate logistic regression. Since all women with AFS in this study were treated with antibiotics, a historical comparison was performed with similar patients with AFS found before 2007 and not treated with antibiotics.

Results: AFS was observed in 90/1220 patients (7.4%). AFS was associated with shorter cervical length, greater body mass index, cervical cerclage and preterm birth before 28 weeks. However, after adjustment, AFS did not remain associated with preterm delivery before 32 or 34 weeks. The historical comparison suggested that azithromycin could significantly reduce the risk of preterm delivery before 34 weeks (odds ratio: 0.2; 95% CI: 0.04–0.92).

Conclusions: AFS, treated with azithromycin, was associated with a higher risk of prematurity, but not independently after adjustment for cervical length and second trimester vaginal bleeding. Further studies need to evaluate the effect of antibiotics in pregnancies with AFS.     

Nanocomposite Foams of Polypropylene and Carbon Nanotubes: Preparation,Characterization, and Evaluation of their Performance as EMI Absorbers

Highly expanded nanocomposite foams of polypropylene and carbon nanotubes (PP/CNT) are formed using supercritical carbon dioxide (scCO₂) technology. The foaming parameters (temperature, pressure) are investigated to establish their influence on the morphology of the resulting foams and their impact on the electrical conductivity. As promising electromagnetic‐interference (EMI) absorbers, the EMI shielding performance of the foams is determined, and a preliminary relationship is established between foam morphology and the EMI shielding performance. The best candidates are highly expanded foams with a volume expansion of >25, containing 0.1 vol% CNTs; they are able to absorb more than 90% of the incident radiation between 25 and 40 GHz.

     

Mutations of the Imprinted CDKN1C Gene as a Cause of the Overgrowth Beckwith–Wiedemann Syndrome: Clinical Spectrum and Functional Characterization

Beckwith–Wiedemann syndrome (BWS) is an imprinting disorder associating macroglossia, abdominal wall defects, visceromegaly, and a high risk of childhood tumor. Molecular anomalies are mostly epigenetic; however, mutations of CDKN1C are implicated in 8% of cases, including both sporadic and familial forms. We aimed to describe the phenotype of BWS patients with CDKN1C mutations and develop a functional test for CDKN1C mutations. For each propositus, we sequenced the three exons and intron–exon boundaries of CDKN1C in patients presenting a BWS phenotype, including abdominal wall defects, without 11p15 methylation defects. We developed a functional test based on flow cytometry. We identified 37 mutations in 38 pedigrees (50 patients and seven fetuses). Analysis of parental samples when available showed that all mutations tested but one was inherited from the mother. The four missense mutations led to a less severe phenotype (lower frequency of exomphalos) than the other 33 mutations. The following four tumors occurred: one neuroblastoma, one ganglioneuroblastoma, one melanoma, and one acute lymphoid leukemia. Cases of BWS caused by CDKN1C mutations are not rare. CDKN1C sequencing should be performed for BWS patients presenting with abdominal wall defects or cleft palate without 11p15 methylation defects or body asymmetry, or in familial cases of BWS.     

Pupillary reflex dilation in response to incremental nociceptive stimuli in patients receiving intravenous ketamine

Pupillometry is a non-invasive monitoring technique, which allows dynamic pupillary diameter measurement by an infrared camera. Pupillary diameter increases in response to nociceptive stimuli. In patients anesthetized with propofol or volatile agents, the magnitude of this pupillary dilation is related to the intensity of the stimulus. Pupillary response to nociceptive stimuli has never been studied under ketamine anesthesia. Our objective was to describe pupillary reflex dilation after calibrated tetanic stimulations in patients receiving intravenous ketamine. After written consent, 24 patients of our pediatric burn care unit were included. They received an oral morphine premedication (0.3 mg kg^?1) 1 h before their scheduled daily dressing change. Just before the procedure, they received 1 mg kg^?1 of intravenous ketamine. Two minutes after this bolus, tetanic stimulations of incremental intensities were performed on the arm of each patient (5–10–20–30–40–60 mA, 60 s interval between stimulations). Pupillary diameter, heart rate and movements were recorded before and after each stimulation. Tetanic stimulations were associated with changes in pupillary diameter and heart rate. The magnitude of these changes was significantly influenced by the intensity of stimulation (ANOVA for repeated measures, p?<?0.001). Movement was associated with a 32% increase in diameter (ROC curves, AUC 0.758) with 65% sensitivity and 77% specificity. In children, pupillary reflex dilation to nociceptive stimuli persists under deep sedation obtained with 1 mg kg^?1 of intravenous ketamine combined with a 0.3 mg kg^?1 oral morphine premedication, and its magnitude depends on the intensity of the stimulation. Our results confirm that pupillometry could be a relevant way to monitor nociception in anaesthetised subjects, including those receiving ketamine. Trial registration clinicaltrials.gov, NCT 02648412