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An increase in free radical activity has been observed in patients suffering from a variety of illnesses and has been correlated with disease severity. Free radical production is increased by the administration of total parenteral nutrition (TPN) and may be linked to its adverse effects. Some of the complications of TPN can be ameliorated by partial enteral feeding. The aim of this study was to investigate free radical activity during critical illness and during the administration of parenteral nutrition.Three groups of surgical infants were studied: (1) control infants (n = 8) before minor surgery, (2) stable infants on the ward recovering from a major operation (n = 24), (3) critically ill infants in the neonatal intensive care unit (NICU, n = 28). Fourteen patients in the ward and 17 patients in NICU were receiving parenteral nutrition. Of the 31 patients on TPN, 9 were also receiving minimal enteral feeding (3% to 24% of total calorie intake). Plasma malondialdehyde (MDA), an index of free radical activity, was measured in all 60 infants. The Paediatric Risk of Mortality (PRISM) score was obtained on NICU patients. The cytokines tumor necrosis factor (TNF-alpha) and interleukin 6 (IL-6) were measured in 25 patients.Plasma MDA was significantly higher in (1) the stable patients on the ward compared with control patients (P.001) and (2) patients in NICU compared with stable patients in the ward (P.001). Parenteral nutrition was associated with higher levels of plasma MDA both in stable patients in the ward and critically ill infants in NICU. There was no correlation between the PRISM score and MDA. In patients not receiving TPN there is a correlation between MDA and TNF-alpha (r = 0.54, P = .02) and between MDA and IL-6 (r = 0.74, P = .001). The level of free radical activity in patients on TPN is not changed by partial enteral feeding.Critical illness causes a rise in free radical production. Parenteral nutrition causes a significant elevation in free radical activity in both stable infants in the ward and critically ill infants in NICU. The addition of minimal enteral feeding to parenteral nutrition does not reduce free radical activity. We hypothesize that the parenteral nutrition solution directly initiates free radical production.

The aim of this study was to identify mutations in the lipoprotein lipase (LPL) gene in 20 unrelated patients with familial lipoprotein deficiency (FLLD) and to investigate the genotype/phenotype relationship. The previously reported G188E mutation (Monsalve et al., J Clin Invest 86:728-734, 1990) was screened for and found to be present in seven individuals (12/40 alleles). In addition, three patients were heterozygous for the 2.0 kb insertion (Langlois et al., Proc Nalt Acad Sci US 86:948-952, 1989). Two approaches were taken for new mutation detection; single-strand conformation polymorphism and sequencing to identify micro-mutations in the proximal promoter and exons 1-9 of the LPL gene and Southern blotting to identify gross mutations. Ten different point mutations were found (W86G, A158T, H183Q, G188E, S193R, P207L, L252X, N291S, M301T, L303P). Additionally, a two nucleotide deletion in exon 6 (delta1006-1007), a six nucleotide deletion in exon 8 (delta1441-1447), and a silent substitution in the wobble position of codon E118 were identified. In vitro mutagenesis and expression in COS-B cells suggested that the A158T and S193R substitutions virtually abolished enzyme activity. In analysing the genotype/phenotype relationship, there was no strong association between age at diagnosis, severity of symptoms, lipid levels, and the nature/position of the mutation. Triglyceride levels, however, were higher in compound heterozygotes compared to true homozygotes, possibly reflecting increased instability of heterodimers. Overall, 29 of 40 (72.5%) mutant alleles were identified. Failure to identify the mutation in 11 alleles might reflect the inadequacy of the method or the possibility that mutations lie within regions of the gene not screened in the study because of lack of availability of sequence.

The methods proposed by Nilsson-Ehle and Ekman [8] for the specific estimation of lipoprotein lipase and hepatic lipase activities in post-heparin plasma were investigated. The procedure for hepatic lipase was found to be specific, but the lipoprotein lipase assay required modification to abolish hepatic lipase interference. The modified procedures were fully validated and found to be relatively simple, rapid and specific and were used to investigate children with primary and secondary hyperlipidaemic states.

CONTRIBUTORS IN THE NETWORK OF TEACHERS IN PHARMACOTHERAPY (NOTIP) (ALPHABETIZED BY COUNTRY): Atanasova, Ivanka (Sofia University St. Kliment Ohridski, Sofia, Bulgaria); Ganeva, Maria (Trakia University, Stara Zagora, Bulgaria); Gatchev, Emil (Medical University of Sofia, Sofia, Bulgaria); Kostadinova, II (Medical University Plovdiv, Plovdiv, Bulgaria); Mimica Matanovic, S (University of Osijek, Osijek, Croatia); Vitezic, D (University of Rijeka Medical School, Rijeka, Croatia); Wozniak, Greta (University of Cyprus, Nicosia, Cyprus); Kmonickova, E (Charles University, Pilsen, Czech Republic); Urbanek, Karel (Palacky University, Olomouc, Czech Republic); Damkier, P (University of Southern Denmark, Odense, Denmark); Huupponen, RK (University of Turku, Turku, Finland); Auffret, Marine (Hospices civils de Lyon, Lyon, France); Bejan-Angoulvant, T (Université de Tours, Tours, France); Chouchana, Laurent (Hospital Cochin, Paris, France); Cracowski, Jean-Luc (University Grenoble Alpes, La Tronche, France); Drici, MD (University of Nice Côte d'Azur, Nice, France); Faillie, JL (CHU Montpellier, Montpellier, France); Geniaux, Hélène (CHU de Limoges, Limoges, France); Molimard, M (Université de Bordeaux, Bordeaux, France); Orlikowski, D (Versailles Saint-Quentin-en-Yvelines University, Versailles, France); Palin, Karine (University of Bordeaux, Bordeaux, France); Pers, Y-M (CHU Montpellier, Montpellier, France); Picard, Nicolas (CHU de Limoges, Limoges, France); Simon, N (Aix-Marseille University, Marseille, France); Toussirot, E (CHU de Besancon, Besancon, France); Boger, RH (University Medical Center Hamburg-Eppendorf, Hamburg, Germany); Cascorbi, I (University of Kiel, Kiel, Germany); Mueller, SC (University Medicine Rostock, Rostock, Germany); Regenthal, R (University of Leipzig, Leipzig, Germany); Schwab, M (Eberhard Karl University of Tübingen, Tübingen, Germany); Schwaninger, MS (University of Luebeck, Luebeck, Germany); Thuermann, PA (University Witten/Herdecke, Witten, Germany); Wojnowski, L (University Medical Center Mainz, Mainz, Germany); Kouvelas, D (Aristotle University of Thessaloniki, Thessaloniki, Greece); Riba, P (Semmelweis University, Budapest, Hungary); Kerins, David M (University College, Cork, Ireland); Williams, David J (Royal College of Surgeons in Ireland, Dublin, Ireland); Cosentino, M (University of Insubria, Varese, Italy); De Ponti, Fabrizio (University of Bologna, Bologna, Italy); Filippelli, Amelia (University of Salerno, Baronissi, Italy); Leone, R (University of Verona, Verona, Italy); Locatelli, Vittorio (University of Milano - Bicocca, Monza, Italy); Jansone, Baiba (University of Latvia, Riga, Latvia); Gulbinovic, Romaldas (Vilnius University, Vilnius, Lithuania); Mifsud, Janet (University of Malta, Msida, Malta); Braszko, Jan J (Medical University of Bialystok, Bialystok, Poland); kocic, I (Medical University of Gdansk, Gdansk, Poland); Breitenfeld, Luiza (Beira Interior University, Covilh~a, Portugal); Castelo-Branco, M (University of Beira Interior, Covilh~a, Portugal); Conea, Simona (“Vasile Goldis” Western University of Arad, Arad, Romania); Magyar, Ioan (University of Oradea, Oradea, Romania); Bevc, S (University of Maribor, Maribor, Slovenia); Krzan, Mojca (University of Ljubljana, Ljubljana, Slovenia); Bernal, ML (University of Zaragoza, Zaragoza, Spain); Capellà, D (University of Girona, Girona, Spain); Carcas, A (Universidad Autónoma de Madrid, University of Maribor, Spain); De Abajo, FJ (University of Alcalá, Alcalá de Henares, Spain); Lopez-Rico, M (University of Salamanca, Salamanca, Spain); Lucena, MI (University of Malaga, Malaga, Spain); Pontes, C (Universitat Autonoma de Barcelona, Sabadell, Spain); Sanz, EJ (Universidad de La Laguna, La Laguna, Spain); Böttiger, Y (Linköping University, Linköping, Sweden); Le Grevès, Madeleine (Uppsala University, Uppsala, Sweden); de Waard-Siebinga, I (University Medical Center Groningen, Groningen, The Netherlands); Janssen, Ben JA (Maastricht University, Maastricht, The Netherlands); Knol, Wilma (University Medical Center Utrecht, Utrecht, The Netherlands); Pandit, Rahul (University Medical Center Utrecht, Utrecht, The Netherlands); van Rosse, F (Erasmus Medical Center, Rotterdam, The Netherlands); Dent, G (Keele University, Keele, United Kingdom); Ferro, Albert (King's College London, London, United Kingdom); Hitchings, AW (St George's, University of London, London, United Kingdom); Kapil, V (Queen Mary University London, London, United Kingdom); Linton, KD (University of Sheffield, Sheffield, United Kingdom); Loke, YK (University of East Anglia, Norwich, United Kingdom); Okorie, Michael (Brighton and Sussex Medical School, Brighton, United Kingdom); Plumb, Richard David (Queen's University Belfast, Belfast, United Kingdom); Pontefract, Sarah (University of Birmingham, Birmingham, United Kingdom); Ranmuthu, S (Queen Mary University London, London, United Kingdom); Sampson, AP (University of Southampton, Southampton, United Kingdom); Thanacoody, HKR (Newcastle University, Newcastle upon Tyne, United Kingdom); Whitfield, Jonathan P (University of Aberdeen, Aberdeen, United Kingdom); Wilson, Kurt (University of Manchester, Manchester, United Kingdom) Improvement and harmonization of European clinical pharmacology and therapeutics (CPT) education is urgently required. Because digital educational resources can be easily shared, adapted to local situations and re‐used widely across a variety of educational systems, they may be ideally suited for this purpose Methods With a cross‐sectional survey among principal CPT teachers in 279 out of 304 European medical schools, an overview and classification of digital resources was compiled. Results Teachers from 95 (34%) medical schools in 26 of 28 EU countries responded, 66 (70%) of whom used digital educational resources in their CPT curriculum. A total of 89 of such resources were described in detail, including e‐learning (24%), simulators to teach pharmacokinetics and/or pharmacodynamics (10%), virtual patients (8%), and serious games (5%). Together, these resources covered 235 knowledge‐based learning objectives, 88 skills, and 13 attitudes. Only one third (27) of the resources were in‐part or totally free and only two were licensed open educational resources (free to use, distribute and adapt). A narrative overview of the largest, free and most novel resources is given. Conclusion Digital educational resources, ranging from e‐learning to virtual patients and games, are widely used for CPT education in EU medical schools. Learning objectives are based largely on knowledge rather than skills or attitudes. This may be improved by including more real‐life clinical case scenarios. Moreover, the majority of resources are neither free nor open. Therefore, with a view to harmonizing international CPT education, more needs to be learned about why CPT teachers are not currently sharing their educational materials.