Founder effects could explain 83% of the Swedish JLNS mutation spectrum and probably contribute to the high JLNS prevalence found in preadolescent Swedish children. Due to the severe cardiac phenotype in JLNS, the importance of stringent β-blocker therapy and compliance, and consideration of ICD implantation in the case of therapy failure is stressed.

Background-Early diagnosis and risk stratification is of clinical importance in the long QT syndrome (LQTS), however, little genotype-specific data are available regarding fetal LQTS. We investigate third trimester fetal heart rate, routinely recorded within public maternal health care, as a possible marker for LQT1 genotype and phenotype. Methods and Results-This retrospective study includes 184 fetuses from 2 LQT1 founder populations segregating p.Y111C and p.R518X (74 noncarriers and 110 KCNQ1 mutation carriers, whereof 13 double mutation carriers). Pedigree-based measured genotype analysis revealed significant associations between fetal heart rate, genotype, and phenotype; mean third trimester prelabor fetal heart rates obtained from obstetric records (gestational week 29-41) were lower per added mutation (no mutation, 143±5 beats per minute; single mutation, 134±8 beats per minute; double mutations, 111±6 beats per minute; P<0.0001), and lower in symptomatic versus asymptomatic mutation carriers (122±10 versus 137±9 beats per minute; P<0.0001). Strong correlations between fetal heart rate and neonatal heart rate (r=0.700; P<0.001), and postnatal QTc (r=−0.762; P<0.001) were found. In a multivariable model, fetal genotype explained the majority of variance in fetal heart rate (−10 beats per minute per added mutation; P<1.0×10). Arrhythmia symptoms and intrauterine β-blocker exposure each predicted −7 beats per minute, P<0.0001. Conclusions-In this study including 184 fetuses from 2 LQT1 founder populations, third trimester fetal heart rate discriminated between fetal genotypes and correlated with severity of postnatal cardiac phenotype. This finding strengthens the role of fetal heart rate in the early detection and risk stratification of LQTS, particularly for fetuses with double mutations, at high risk of early life-threatening arrhythmias. (Circ Arrhythm Electrophysiol. 2015;8:806-814.

The study showed that the PV expansion by a colloid was greater when given at a slow than at a fast infusion rate, an effect more pronounced for albumin. This difference was not seen for NaCl. The PV-expanding effect was poor for NaCl and better for albumin than for the other colloids.

Xenon is a more potent anesthetic than nitrous oxide, and give more profound analgesia. This investigation was performed to assess the potential of xenon for becoming an anesthetic inspite of its high manufacturing cost. Seven ASA I-II patients undergoing cholecystectomy (n = 4), hernia repair (n = 2), or mammoplasty (n = 1) were studied. Denitrogenation by 15-20 min of oxygen breathing under propofol anesthesia was followed by fentanyl-supplemented xenon anesthesia administered via an automatic minimal flow system which held the oxygen concentration at 30%. Xenon anesthesia lasted 76-228 min and 8-14 l of xenon (ATPD) was used, of which 5.6-8.1 l was expended during the first 15 min. Anesthesia appeared to be satisfactory, and the patients woke up rapidly after xenon was discontinued. The automatic system made minimal flow xenon anesthesia easy to administer, but nitrogen accumulation is still a problem. Assuming a xenon price of 10 US$ per litre, the average cost for xenon was about 65 US$ for the first 15 min and then about 25 US$ for each subsequent hour of anesthesia.

This is an author produced version of a paper published in Intensive care medicine. This paper has been peerreviewed but does not include the final publisher proofcorrections or journal pagination.Citation for the published paper: Dubniks M, Persson J, Grände PO. "Effect of blood pressure on plasma volume loss in the rat under increased permeability" Intensive care medicine, 2007, Vol: 33, Issue: 12, pp. 2192 http://dx.doi.org/10.1007/s00134-007-0756-2Access to the published version may require journal subscription. Published with permission from: Springer Verlag Design: Prospective randomised laboratory study.Subject: Forty-five adult male Sprague-Dawley rats.Interventions: Permeability was increased via an anaphylactic reaction by injection of 0.5 ml dextran 70. One hour later, volume expansion with 15 ml/kg of 5% albumin was given for 15 min.Plasma volume was measured just before and 2.5 hours after the albumin infusion ( 125 I-albumin tracer technique). The study included a control group, a noradrenalin group and a metoprolol/clonidine group (n=10 in each group). The vasoactive treatment started after albumin infusion and continued throughout the experiment. Plasma volume was also measured in a separate group without albumin infusion, to evaluate the effect of noradrenalin-induced increase in blood pressure under hypovolemia (n=9). CVP was measured to estimate the venous pressure effect of noradrenalin (n=6). Results:The remaining increase in plasma volume 2.5 h after infusion of 15 ml/kg of albumin was 11.8 ± 3.6 ml/kg in the control group compared with 0.5 ± 6.3 ml/kg in the noradrenalin group (p < 0.001) and with 12.5 ± 4.9 ml/kg in the metoprolol/clonidine group (ns). The reduction in plasma volume by noradrenalin infusion was much smaller in the group not given albumin, or 3.5 ± 3.0 ml/kg. Conclusion:Noradrenalin infusion increases the loss of plasma volume during a state of increased permeability which, according to the 2-pore theory of transvascular fluid exchange, may be explained by increased hydrostatic capillary pressure. The loss was less pronounced in hypovolemia.3

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BackgroundThe R518X/KCNQ1 mutation is a common cause of autosomal recessive (Jervell and Lange Nielsen Syndrome- JLNS) and autosomal dominant long QT syndrome (LQTS) worldwide. In Sweden p.R518X accounts for the majority of JLNS cases and is the second most common cause of LQTS. Here we investigate the clinical phenotype and origin of Swedish carriers of the p.R518X mutation.MethodsThe study included 19 Swedish p.R518X index families, ascertained by molecular genetics methods (101 mutation-carriers, whereof 15 JLNS cases and 86 LQTS cases). In all families analyses included assessment of clinical data (symptoms, medications and manually measured electrocardiograms), genealogy (census records), haplotype (microsatellite markers) as well as assessment of mutation age and associated prevalence (ESTIAGE and DMLE computer software).ResultsClinical phenotype ranged from expectedly severe in JLNS to surprisingly benign in LQTS (QTc 576 ± 61 ms vs. 462 ± 34 ms, cumulative incidence of (aborted) cardiac arrest 47% vs. 1%, annual non-medicated incidence rate (aborted) cardiac arrest 4% vs. 0.04%).A common northern origin was found for 1701/1929 ancestors born 1650-1950. Historical geographical clustering in the coastal area of the Pite River valley was shown. A shared haplotype spanning the KCNQ1 gene was seen in 17/19 families. Mutation age was estimated to 28 generations (95% CI 19;41). A high prevalence of Swedish p.R518X heterozygotes was suggested (~1:2000-4000).ConclusionsR518X/KCNQ1 occurs as a common founder mutation in Sweden and is associated with an unexpectedly benign phenotype in heterozygous carriers.

Albumin 5% was a more effective plasma volume expander than gelatin and HES. Saline, with a four times larger volume, and erythrocytes in about 1/3 of the volume had a similar volume-expanding effect to gelatin and HES.