Pediatric Single‐Lumen Cannula Venovenous Extracorporeal Membrane Oxygenation: A French Center Experience

Single‐lumen cannula venovenous (VV) extracorporeal membrane oxygenation (ECMO) is a special extracorporeal life support (ECLS) technique used for neonatal and pediatric refractory hypoxemia. This is an alternative flow rate ECLS that consists of successive clamping on the drainage and the injection lines. Currently, the Armand‐Trousseau's pediatric intensive care unit remains the only pediatric ECMO center proposing this partial assistance. This article details a technical note and a retrospective analysis of our experience in refractory hypoxemia. The retrospective study, from 2007 to 2011, included all pediatric and neonatal patients treated by single‐lumen cannula VV ECMO. The study was focused on pre‐ECMO patient characteristics and complications during ECMO course. During the last 5 years, 67 pediatric patients were assisted by this single‐lumen cannula VV ECMO. Sixty‐one patients (91%) were newborns. Thirty‐nine patients presented with meconium aspiration syndrome (58%), which was the most frequent etiology. Before cannulation, mean oxygenation index (OI) was 32 ± 11, alveolar‐arterial oxygen difference was 604 ± 47 mm Hg, and partial pressure arterial oxygen/fraction inspired oxygen ratio was 59.2 ± 35.8. Forty‐eight patients (72%) presented pulmonary hypertension, and 66 patients were treated by nitric oxide (98%). Fifty patients (75%) were treated by vasopressors or inotropic drugs. Average duration of ECMO was 13.2 ± 7.8 days. There were forty‐six survivors (69%). The worst prognosis was for respiratory syncytial virus pneumonia. Complications like acute renal injury and hematologic and transfusion acts were not so different than those observed in classical ECMO techniques. Nevertheless, 19 patients presented a stroke (28% of the overall population), but this high rate did not seem to be due to the ECLS technique used. Single‐lumen cannula VV ECMO is a partial and efficient ECMO support. Our experience shows that this technique is as efficient and less invasive than two cannulas ECMO. The single‐lumen cannula VV ECMO is a simple and safe ECLS support used for neonatal or pediatric refractory hypoxemia. Because this is a partial assistance, it is a promising ECLS support.     

Acute hyperinsulinism modulates plasma apolipoprotein B-48 triglyceride-rich lipoproteins in healthy subjects during the postprandial period

The role of postprandial insulin in the regulation of postprandial lipid metabolism is still poorly understood. The roles of hyperinsulinemia and insulin resistance in the alteration of postprandial lipid metabolism are not clear either. To improve knowledge in this area, we submitted healthy men to acute hyperinsulinemia in two different ways. In the first study, we compared in 10 men the effects of four isolipidic test meals that induce different degrees of hyperinsulinemia on postprandial lipid metabolism. Three different carbohydrate sources were compared according to their glycemic indexes (GIs; 35, 75, and 100 for white kidney bean, spaghetti, and white bread test meals, respectively); the fourth test meal did not contain any carbohydrates. Postprandial plasma insulin levels were proportional to the GIs (maximal plasma insulin concentrations: 113 +/- 16 to 266 +/- 36 pmol/l). We found a strong positive correlation during the 6-h postprandial period between apolipoprotein (apo) B-48 plasma concentration and insulin plasma concentration (r2 = 0.70; P = 0.0001). In a second study, 5 of the 10 subjects again ingested the carbohydrate-free meal, but during a 3-h hyperinsulinemic- (550 +/- 145 pmol/l plasma insulin) euglycemic (5.5 +/- 0.8 mmol/l plasma glucose) clamp. A biphasic response was observed with markedly reduced levels of plasma apoB-48 during insulin infusion, followed by a late accumulation of plasma apoB-48 and triglycerides. Overall, the data obtained showed that portal and peripheral hyperinsulinism delays and exacerbates postprandial accumulation of intestinally derived chylomicrons in plasma and thus is involved in the regulation of apoB-48-triglyceride-rich lipoprotein metabolism, in the absence of insulin-resistance syndrome.     

Determination of apolipoprotein B-48 in plasma by a competitive ELISA

BACKGROUND: Apolipoprotein B-48 (apoB-48) is produced by the small intestine, as part of chylomicrons, and appears to be a suitable marker for clinical studies of postprandial lipoproteins and related cardiovascular risk. Our aim was to develop, for routine analysis, an assay to quantify apoB-48 in plasma samples. METHODS: A microtiter plate was coated with a C-terminal apoB-48-specific heptapeptide. Plasma samples were incubated with appropriate detergent to allow competition between immobilized antigen and plasma apoB-48. Appropriate calibration curves were obtained in the ELISA, using calibrated lymph and chylomicrons. RESULTS: Treatment of plasma samples with the mild detergent Triton X-100 allowed an efficient competition between immobilized antigen and plasma apoB-48. No cross-reactivity was found with apoB-100, as checked by ELISA and Western blot analysis. Intra- and interassay CVs were 5.4% and 5. 5%, respectively. In healthy subjects, apoB-48 concentrations markedly increased in the postprandial state, in parallel with triglycerides. CONCLUSIONS: This new ELISA allows determination of the concentration of apoB-48 in normolipidemic plasma.     

Distinct molecular portraits of human failing hearts identified by dedicated cDNA microarrays

Aims: This study aimed to investigate whether a molecular profiling approach should be pursued for the classification of heart failure patients. Methods and results: Applying a subtraction strategy we created a cDNA library consisting of cardiac- and heart failure-relevant clones that were used to construct dedicated cDNA microarrays. We measured relative expression levels of the corresponding genes in left ventricle tissue from 17 patients (15 failing hearts and 2 nonfailing hearts). Significance analysis of microarrays was used to select 159 genes that distinguished between all patients. Two-way hierarchical clustering of the 17 patients and the 159 selected genes led to the identification of three major subgroups of patients, each with a specific molecular portrait. The two nonfailing hearts clustered closely together. Interestingly, our classification of patients based on their molecular portraits did not correspond to an identified etiological classification. Remarkably, patients with the highest medical urgency status (United Network for Organ Sharing, Status 1A) clustered together. Conclusion: With this pilot feasibility study we demonstrated a novel classification of end-stage heart failure patients, which encourages further development of this approach in prospective studies on heart failure patients at earlier stages of the disease.     

Randomized,double‐blind,multicenter evaluation of pramipexole extended release once daily in early Parkinson's disease

The objective of this study was to evaluate the efficacy and safety of pramipexole extended release (ER) administered once daily in early Parkinson's disease (PD). Pramipexole immediate release (IR) administered three times daily (TID) is an efficacious and generally well‐tolerated treatment for PD. A pramipexole ER formulation is now available. We performed a randomized, double‐blind, placebo and active comparator–controlled trial in subjects with early PD. The primary efficacy and safety evaluation of pramipexole ER compared with placebo took place at week 18. Two hundred fifty‐nine subjects were randomized 2:2:1 to treatment with pramipexole ER once daily, pramipexole IR TID, or placebo. Levodopa rescue was required by 7 subjects in the placebo group (14%), 3 subjects in the pramipexole ER group (2.9%, P = 0.0160), and 1 subject in the pramipexole IR group (1.0%, P = 0.0017). Adjusted mean [standard error (SE)] change in Unified Parkinson Disease Rating Scale (UPDRS) II [activities of daily living (ADL)] + III (motor) scores from baseline to week 18, including post‐levodopa rescue evaluations, was ?5.1 (1.3) in the placebo group, ?8.1 (1.1) in the pramipexole ER group (P = 0.0282), and ?8.4 (1.1) in the pramipexole IR group (P = 0.0153). Adjusted mean (SE) change in UPDRS ADL + motor scores, censoring post‐levodopa rescue data, was ?2.7 (1.3) in the placebo group, ?7.4 (1.1) in the pramipexole ER group (P = 0.0010), and ?7.5 (1.1) in the pramipexole IR group (P = 0.0006). Adverse events more common with pramipexole ER than placebo included somnolence, nausea, constipation, and fatigue. Pramipexole ER administered once daily was demonstrated to be efficacious compared with placebo and provided similar efficacy and tolerability as pramipexole IR administered TID. © 2010 Movement Disorder Society     

Time course proteomic profiling of cellular responses to immunological challenge in the sea urchin, Heliocidaris erythrogramma

Genome sequences and high diversity cDNA arrays have provided a detailed molecular understanding of immune responses in a number of invertebrates, including sea urchins. However, complementary analyses have not been undertaken at the level of proteins. Here, we use shotgun proteomics to describe changes in the abundance of proteins from coelomocytes of sea urchins after immunological challenge and wounding. The relative abundance of 345 reproducibly identified proteins were measured 6, 24 and 48 h after injection. Significant changes in the relative abundance of 188 proteins were detected. These included pathogen-binding proteins, such as the complement component C3 and scavenger receptor cysteine rich proteins, as well as proteins responsible for cytoskeletal remodeling, endocytosis and intracellular signaling. An initial systemic reaction to wounding was followed by a more specific response to immunological challenge involving proteins such as apolipophorin, dual oxidase, fibrocystin L, aminopeptidase N and α-2-macroglobulin.     

Does the edge effect impact on the measure of spatial accessibility to healthcare providers?

Background

Spatial accessibility indices are increasingly applied when investigating inequalities in health. Although most studies are making mentions of potential errors caused by the edge effect, many acknowledge having neglected to consider this concern by establishing spatial analyses within a finite region, settling for hypothesizing that accessibility to facilities will be under-reported. Our study seeks to assess the effect of edge on the accuracy of defining healthcare provider access by comparing healthcare provider accessibility accounting or not for the edge effect, in a real-world application.

Methods

This study was carried out in the department of Nord, France. The statistical unit we use is the French census block known as ‘IRIS’ (Ilot Regroupé pour l’Information Statistique), defined by the National Institute of Statistics and Economic Studies. The geographical accessibility indicator used is the “Index of Spatial Accessibility” (ISA), based on the E2SFCA algorithm. We calculated ISA for the pregnant women population by selecting three types of healthcare providers: general practitioners, gynecologists and midwives. We compared ISA variation when accounting or not edge effect in urban and rural zones. The GIS method was then employed to determine global and local autocorrelation. Lastly, we compared the relationship between socioeconomic distress index and ISA, when accounting or not for the edge effect, to fully evaluate its impact.

Results

The results revealed that on average ISA when offer and demand beyond the boundary were included is slightly below ISA when not accounting for the edge effect, and we found that the IRIS value was more likely to deteriorate than improve. Moreover, edge effect impact can vary widely by health provider type. There is greater variability within the rural IRIS group than within the urban IRIS group. We found a positive correlation between socioeconomic distress variables and composite ISA. Spatial analysis results (such as Moran’s spatial autocorrelation index and local indicators of spatial autocorrelation) are not really impacted.

Conclusion

Our research has revealed minor accessibility variation when edge effect has been considered in a French context. No general statement can be set up because intensity of impact varies according to healthcare provider type, territorial organization and methodology used to measure the accessibility to healthcare. Additional researches are required in order to distinguish what findings are specific to a territory and others common to different countries. It constitute a promising direction to determine more precisely healthcare shortage areas and then to fight against social health inequalities.