Delayed neuroexcitatory symptoms after an uneventful anaesthesia are uncommon, although described in many reports. We want to report on two cases. The first patient developed muscle hypertonicity, jerky movements and unconsciousness after an uneventful anaesthesia with propofol, and later the same thing happened after anaesthesia with thiopentone. The second patient developed similar symptoms after an uneventful anaesthesia with propofol, but she never recovered completely after this and is now severely disabled. A search of the literature and the Swedish adverse drug reactions register revealed many similar cases. In both our patients the causal relationship between propofol and the neuroexcitatory symptoms remains uncertain, but we want to alert readers about this possible adverse reaction.

The perioperative risks can be considerable and are mainly related to the respiratory system, from respiratory failure to difficult/impossible intubation.

Angioedema in the mouth or upper airways is a feared adverse reaction to angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, which is used for hypertension, heart failure and diabetes complications. This candidate gene and genome-wide association study aimed to identify genetic variants predisposing to angioedema induced by these drugs. The discovery cohort consisted of 173 cases and 4890 controls recruited in Sweden. In the candidate gene analysis, ETV6, BDKRB2, MME, and PRKCQ were nominally associated with angioedema (p < 0.05), but did not pass Bonferroni correction for multiple testing (p < 2.89 × 10 −5). In the genome-wide analysis, intronic variants in the calcium-activated potassium channel subunit alpha-1 (KCNMA1) gene on chromosome 10 were significantly associated with angioedema (p < 5 × 10 −8). Whilst the top KCNMA1 hit was not significant in the replication cohort (413 cases and 599 ACEi-exposed controls from the US and Northern Europe), a meta-analysis of the replication and discovery cohorts (in total 586 cases and 1944 ACEi-exposed controls) revealed that each variant allele increased the odds of experiencing angioedema 1.62 times (95% confidence interval 1.05-2.50, p = 0.030). Associated KCNMA1 variants are not known to be functional, but are in linkage disequilibrium with variants in transcription factor binding sites active in relevant tissues. In summary, our data suggest that common variation in KCNMA1 is associated with risk of angioedema induced by ACEi or ARB treatment. Future whole exome or genome sequencing studies will show whether rare variants in KCNMA1 or other genes contribute to the risk of ACEi-and ARBinduced angioedema.

Malignant hyperthermia (MH), a potentially lethal disorder of skeletal muscle calcium homeostasis, manifests only on exposure to certain anaesthetic drugs. The mode of inheritance appears to be autosomal dominant with both locus and allelic heterogeneity having been reported. Association analysis of eight MH candidate loci in UK families has indicated that several genes influence susceptibility in individual families, rather than MH simply being a major gene defect. In support of this hypothesis, we present data on a replica analysis of an independent sample of European MH families.

Background: A diagnosis of malignant hyperthermia susceptibility (MHS) by in vitro contraction testing can often only be performed at specialized laboratories far away from where the patients live. Therefore, we have designed a protocol for genetic screening of the RYR1---cDNA and for functional testing of newly identified ryanodine receptor 1 (RYR1) gene variants in B lymphocytes isolated from peripheral blood samples drawn at the local primary care centres. Methods: B lymphocytes were isolated for the extraction of RYR1---mRNA and genomic DNA and for establishment of lymphoblastoid B cell lines in five patients carrying yet unclassified mutations in the RYR1. The B lymphoblastoid cell lines were used to study resting cytoplasmic calcium concentration, the peak calcium transient induced by the sarco(endo)plasmic reticulum CaATPase inhibitor thapsigargin and the dose dependent calcium release induced by the ryanodine receptor agonist 4---chloro---m---cresol. Results: It was possible to extract mRNA for cDNA synthesis and to create B lymphocyte clones from all samples. All B lymphoblastoid cell lines carrying RYR1 candidate mutations showed significantly elevated resting cytoplasmic calcium levels as well as a shift to lower concentrations of 4---chloro---m---cresol inducing calcium release compared to controls. Conclusions: Peripheral blood samples are stable regarding RNA and DNA extraction and establishment of lymphoblastoid B cell lines after transportation at ambient temperature over large distances by ordinary mail. Functional tests on B cells harbouring the newly identified amino acid substitutions indicate that they alter