Propofol infusion rate does not affect local pain on injection.

BACKGROUND: Local pain at the site of an i.v. injection of propofol is a well-known problem, particularly in infants. This randomised investigator-blinded crossover study was designed to assess the effect of the i.v. bolus infusion rate on propofol-induced pain at the site of injection. METHODS: Thirty unpremedicated patients scheduled for ear-nose-throat or plastic surgery at Malmö University Hospital, Sweden, were given two consecutive 2.0 ml injections of propofol 10 mg/ml (Diprivan, AstraZeneca, Sweden/UK), at different infusion rates (0.2 or 1.0 ml/s), immediately before induction of general anesthesia. Half of the patients (n=15) received the first bolus of propofol over 2 s and the second bolus over 10 s, and the other half (n=15) had their injections in reversed order. After each injection, the patient was asked by an investigator to indicate pain intensity on a visual analog scale (VAS) and to report the times of the appearance, maximum point and disappearance of pain. The injections were given approximately 2 min apart. The investigators scoring pain intensity, as indicated by the patients on a 10-point numerical rate scale, were blinded to the order in which the injections were given, as were the patients themselves. RESULTS: There were no statistically significant differences in the incidence (both 86%) of intensity (median; 25th; 75th percentiles, in VAS units: 3.1; 1.0; 5.3 and 3.3; 1.4; 5.0, respectively) or duration (66+/-31 and 73+/-26 s, respectively) of pain between the faster (1.0 ml/s) and slower (0.2 ml/s) bolus infusion rates of propofol studied. CONCLUSIONS: We conclude that the i.v. bolus infusion rate of propofol does not influence drug-induced local pain on injection, at least not within the infusion rate interval studied. Therefore, adjusting i.v. injection speed does not seem to be a clinically useful tool for reducing the intensity or duration of propofol-induced pain at the site of administration

CELSR2 is a candidate susceptibility gene in idiopathic scoliosis

A Swedish pedigree with an autosomal dominant inheritance of idiopathic scoliosis was initially studied by genetic linkage analysis, prioritising genomic regions for further analysis. This revealed a locus on chromosome 1 with a putative risk haplotype shared by all affected individuals. Two affected individuals were subsequently exome-sequenced, identifying a rare, non-synonymous variant in the CELSR2 gene. This variant is rs141489111, a c. G6859A change in exon 21 (NM_001408), leading to a predicted p. V2287I (NP_001399.1) change. This variant was found in all affected members of the pedigree, but showed reduced penetrance. Analysis of tagging variants in CELSR1-3 in a set of 1739 Swedish-Danish scoliosis cases and 1812 controls revealed significant association (p = 0.0001) to rs2281894, a common synonymous variant in CELSR2. This association was not replicated in case-control cohorts from Japan and the US. No association was found to variants in CELSR1 or CELSR3. Our findings suggest a rare variant in CELSR2 as causative for idiopathic scoliosis in a family with dominant segregation and further highlight common variation in CELSR2 in general susceptibility to idiopathic scoliosis in the Swedish-Danish population. Both variants are located in the highly conserved GAIN protein domain, which is necessary for the auto-proteolysis of CELSR2, suggesting its functional importance.Peer reviewe

Propofol infusion rate does not affect local pain on injection

BACKGROUND: Local pain at the site of an i.v. injection of propofol is a well-known problem, particularly in infants. This randomised investigator-blinded crossover study was designed to assess the effect of the i.v. bolus infusion rate on propofol-induced pain at the site of injection. METHODS: Thirty unpremedicated patients scheduled for ear-nose-throat or plastic surgery at Malmö University Hospital, Sweden, were given two consecutive 2.0 ml injections of propofol 10 mg/ml (Diprivan, AstraZeneca, Sweden/UK), at different infusion rates (0.2 or 1.0 ml/s), immediately before induction of general anesthesia. Half of the patients (n=15) received the first bolus of propofol over 2 s and the second bolus over 10 s, and the other half (n=15) had their injections in reversed order. After each injection, the patient was asked by an investigator to indicate pain intensity on a visual analog scale (VAS) and to report the times of the appearance, maximum point and disappearance of pain. The injections were given approximately 2 min apart. The investigators scoring pain intensity, as indicated by the patients on a 10-point numerical rate scale, were blinded to the order in which the injections were given, as were the patients themselves. RESULTS: There were no statistically significant differences in the incidence (both 86%) of intensity (median; 25th; 75th percentiles, in VAS units: 3.1; 1.0; 5.3 and 3.3; 1.4; 5.0, respectively) or duration (66+/-31 and 73+/-26 s, respectively) of pain between the faster (1.0 ml/s) and slower (0.2 ml/s) bolus infusion rates of propofol studied. CONCLUSIONS: We conclude that the i.v. bolus infusion rate of propofol does not influence drug-induced local pain on injection, at least not within the infusion rate interval studied. Therefore, adjusting i.v. injection speed does not seem to be a clinically useful tool for reducing the intensity or duration of propofol-induced pain at the site of administration

Genetics and pathogenesis of idiopathic scoliosis

Idiopathic scoliosis (IS), the most common spinal deformity, affects otherwise healthy children and adolescents during growth. The aetiology is still unknown, although genetic factors are believed to be important. The present review corroborates the understanding of IS as a complex disease with a polygenic background. Presumably IS can be due to a spectrum of genetic risk variants, ranging from very rare or even private to very common. The most promising candidate genes are highlighted.Peer reviewe

Inheritance and genetics in idiopathic scoliosis [Elektronisk resurs]

Idiopathic scoliosis is the most common spine deformity, affecting approximately 3% of children and adolescents. Its aetiology is still unknown. However, relatives of individuals with idiopathic scoliosis have a higher risk of developing scoliosis compared to the general population. The aim of this thesis was to improve our understanding of the hereditary and genetic background of idiopathic scoliosis. Self - reported data on scoliosis in twins (n=64,578) in the population - based Swedish Twin Registry were an alysed to estimate the relative importance of genetic effects on the phenotypic variance – that is, the heritability of scoliosis. Using structural equation model ing, we estimated that 38% of the phenotypic variance of scoliosis is due to additive genetic effects and 62% to unique environmental effects. In ScoliGeneS, an ongoing multi - centre study, we included individuals with idiopathic scoliosis and controls. The importance of a family history of scoliosis wa s investigated in 1,463 individuals with idiop athic scoliosis . Among those treated with a brace or surgery for scoliosis, 53% reported one or more relatives with scoliosis compared to 46% of the untreated, indicating a higher risk of treatment in the presence of a family history of scoliosis (odds rat io 1.32; 95% confidence interval 1.06 – 1.64). The prevalence of back problems was investigated in 1,069 adults with idiopathic scoliosis and in 1 58 controls. B ack problems were reported in 64% of the individuals with scoliosis compared to 29% of the control s (p<0.001, adjusted for sex, age and smoking). No differences betwee n untreated and treated individuals with idiopathic scoliosis regarding the prevalence of back problems in adulthood were seen. Four common single - nucleotide variants, previously shown to be associated with idiopathic scoliosis, were genotyped in 1,739 individuals with idiopathic scoliosis from the ScoliGeneS cohort and in 1,812 controls. In addition, the protein - coding regions of the genome – the exome – was sequenced in pooled samples (10x10) from 100 surgically treated patients in the ScoliGeneS cohort. We found a strong associ ation of idiopathic scoliosis with a common previously known variant downstream of the LBX1 gene (OR=1.5 3; p=7.0x 10 - 18 ). We identified twenty novel variants by exome sequencing after filtering and an initial genotyping validation. No significant association was f ound with idiopathic scoliosis in the large cohort of 1,739 cases and 1,812 controls. In summary, inherited factors are of importance in the development and progression of idiopathic scoliosis. A genetic variant downstream of the LBX1 gene is strongly associated with idiopathic scoliosis. We were unable to find genes of similar or stronger effect