Neurokirurgisen potilaan nestehoito leikkauksen aikana

The major aims with fluid therapy for neurosurgical procedures are to minimize the risk for inadequate cerebral perfusion pressure and to maintain good neurosurgical conditions. Excessive fluid restriction to minimize cerebral oedema may lead to haemodynamic instability. Patient positioning, especially sitting and prone positions, may also promote haemodynamic changes due to diminished venous return to the heart. The effect of fluid therapy on coagulation must be considered, because normal coagulation capacity is of particular importance in neurosurgery to prevent bleeding complications. The haemodynamic profile and complications of the sitting position were analysed retrospectively in 72 neurosurgical patients. Stroke volume (SV)-directed administration of fluids (hydroxyethyl starch 130/0.4 (HES) or Ringer's acetate (RAC)) during neurosurgery in the sitting and the prone position were studied in 60 adult patients; the effects of a totally balanced fluid concept, and mannitol on blood coagulation in vitro was examined in 22 healthy volunteers. The sitting position is associated with hypotension and a risk for venous air embolism (VAE). The crystalloid vs. colloid volume ratio intraoperatively was 1.5. The formation and maximum strength of the fibrin clot were decreased after an aver-age dose of 440 mL of HES in one study, but in the other study an average dose of 460 mL of HES did not impair the coagu-lation profile. No difference appeared in blood loss between the groups. The combination of balanced colloid and crystalloid had similar coagulation effects in vitro as did their respective combinations of unbalanced solutions. Mannitol alone and in combination with HES delayed the initiation of coagulation and fibrin formation and reduced the maximum clot fimness in vitro. The sitting position induces hypotension and carries a risk for VAE. SV-directed administration of either crystalloid or colloid in the sitting and prone position stabilizes the haemodynamic parameters. Most of the patients undergoing neurosurgery in either position can be managed with an acceptable volume of RAC. The haemodynamic response of goal-directed HES administration was more favourable with regard to cardiac index, and a bolus of HES (< 500mL) may be administered when instant restoration of the intravascular volume with minimal fluid loading is indicated. The effect of fluid therapy with HES on coagulation measured in the studies with thromboelastometry varied, but he intraoperative blood loss in these patients was very low. No advantage with the totally balanced fluid therapy for coagulation emerged. Mannitol alone or in combination with HES in vitro impairs clot propagation and clot strength.Perioperativ vätskebehandling av neurokirurgiska patienter Vätsketerapi ges vid nästan alla kirurgiska ingrepp för att upprätthålla vätskebalansen. Den främsta målsättningen med vätsketerapi för neurokirurgiska patienter är att minimera risken för otillräckligt blodflöde till hjärnan och samtidigt upprätthålla goda operationsförhållanden för neurokirurgen. För att minimera hjärnsvullnad ges inte mera vätska än nödvändigt, men för knapp vätsketillförsel kan leda till försämrad blodcirkulation. Placeringen av patienten under operationen, speciellt i sittande eller magläge, kan också påverka blodcirkulationen på grund av ansamling av blod i venerna och minskat tillbakaflöde till hjärtat. Effekten av vätsketerapi på blodets koagulation måste beaktas, emedan normal koagulation är av speciell vikt inom neurokirurgin för att undvika blödningskomplikationer. Påverkan på blodcirkulationen samt eventuella komplikationer hos 72 neurokirurgiska patienter opererade i sittande läge utvärderades i efterhand. Målstyrd vätsketerapi med krystalloid (Ringer's acetat) eller kolloid vätska (hydroxyetylstärkelse 130/0.4) undersöktes hos 60 vuxna, elektiva neurokirurgiska patienter opererade i sittande eller magläge. Effekten på blodets koagulering i provrörsmiljö av balanserade vätskor och mannitol, som används inom neurokirurgin för att sänka hjärntrycket, undersöktes hos 22 friska frivilliga. Sittande läge under operationen innebär en risk för sänkt blodtryck samt venös luftemboli. Målstyrd vätsketerapi med antingen krystalloid eller kolloid vätska stabiliserar blodcirkulationen i sittande och magläge. De flesta neurokirurgiska patienter som opereras i endera ställningen kan skötas med enbart krystalloid i moderata volymer. Målstyrd vätsketerapi med kolloid gav ett bättre gensvar med tanke på hjärtats pumpfunktion, och en vätskebolus (< 500ml) med kolloid kan ges när omedelbar återupprättande av blodvolymen med minimal vätskebelastning är indicerad. Effekten av vätsketerapi med kolloid på koagulationen varierade i de olika studierna, men blodförlusten i samband med operation hos dessa patienter var låg. Med tanke på blodets koagulationskapacitet finns det inga fördelar med fullständigt balanserad vätskebehandling. Mannitol ensam och i kombination med kolloid vätska försämrar blodets koagulation. Målstyrd vätsketerapi har tidiagre undersökts främst med kolloida vätskor. Enligt resultaten av denna avhandling kan målstyrd vätskebehandling med krystalloid vätska användas för neurokirurgiska patienter och därmed undviks de möjliga biverkningarna med kolloider

Prone Versus Sitting Position in Neurosurgery-Differences in Patients' Hemodynamic Management

OBJECTIVE: Neurosurgery in general anesthesia exposes patients to hemodynamic alterations in both the prone and the sitting position. We aimed to evaluate the hemodynamic profile during stroke volume-directed fluid administration in patients undergoing neurosurgery either in the sitting or the prone position. METHODS: In 2 separate prospective trials, 30 patients in prone and 28 patients in sitting position were randomly assigned to receive either Ringer acetate (RAC) or hydroxyethyl starch (HES; 130 kDa/0.4) for optimization of stroke volume. After combining data from these 2 trials, 2-way analysis of variance was performed to compare patients' hemodynamic profile between the 2 positions and to evaluate differences between RAC and HES consumption. RESULTS: To achieve comparable hemodynamics during surgery, a higher mean cumulative dose of RAC than HES was needed (679 mL +/- 390 vs. 455 mL +/- 253; P <0.05). When fluid consumption was adjusted with weight, statistical difference was lost. Fluid administration did not differ between the prone and sitting position. Mean arterial pressure was lower and cardiac index and stroke volume index were higher over time in patients in the sitting position. CONCLUSIONS: The sitting position does not require excess fluid treatment compared with the prone position. HES is slightly more effective than RAC in achieving comparable hemodynamics, but the difference might be explained by patient weight. With goal-directed fluid administration and moderate use of vasoactive drugs, it is possible to achieve stable hemodynamics in both positions.Peer reviewe

Venous air embolisms and sitting position in Helsinki pineal region surgery

Peer reviewe

Praying Sitting Position for Pineal Region Surgery : An Efficient Variant of a Classic Position in Neurosurgery

BACKGROUND: The sitting position has lost favor among neurosurgeons partly owing to assumptions of increased complications, such as venous air embolisms and hemodynamic disturbances. Moreover, the surgeon must assume a tiring posture. We describe our protocol for the "praying position" for pineal region surgery; this variant may reduce some of the risks of the sitting position, while providing a more ergonomic surgical position. METHODS: A retrospective review of 56 pineal lesions operated on using the praying position between January 2008 and October 2015 was performed. The praying position is a steeper sitting position with the upper torso and the head bent forward and downward. The patient's head is tilted about 30 degrees making the tentorium almost horizontal, thus providing a good viewing angle. G-suit trousers or elastic bandages around the lower extremities are always used. RESULTS: Complete lesion removal was achieved in 52 cases; subtotal removal was achieved in 4. Venous air embolism associated with persistent hemodynamic changes was nonexistent in this series. When venous air embolism was suspected, an immediate reaction based on good teamwork was imperative. No cervical spine cord injury or peripheral nerve damage was reported. The microsurgical time was CONCLUSIONS: A protocolized praying position that includes proper teamwork management may provide a simple, fast, and safe approach for proper placement of the patient for pineal region surgery.Peer reviewe

Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldSystemic lupus erythematosus (SLE) is a complex systemic autoimmune disease caused by both genetic and environmental factors. Genome scans in families with SLE point to multiple potential chromosomal regions that harbor SLE susceptibility genes, and association studies in different populations have suggested several susceptibility alleles for SLE. Increased production of type I interferon (IFN) and expression of IFN-inducible genes is commonly observed in SLE and may be pivotal in the molecular pathogenesis of the disease. We analyzed 44 single-nucleotide polymorphisms (SNPs) in 13 genes from the type I IFN pathway in 679 Swedish, Finnish, and Icelandic patients with SLE, in 798 unaffected family members, and in 438 unrelated control individuals for joint linkage and association with SLE. In two of the genes--the tyrosine kinase 2 (TYK2) and IFN regulatory factor 5 (IRF5) genes--we identified SNPs that displayed strong signals in joint analysis of linkage and association (unadjusted P<10(-7)) with SLE. TYK2 binds to the type I IFN receptor complex and IRF5 is a regulator of type I IFN gene expression. Thus, our results support a disease mechanism in SLE that involves key components of the type I IFN system

Allelic imbalance in gene expression as a guide to cis-acting regulatory single nucleotide polymorphisms in cancer cells

Using the relative expression levels of two SNP alleles of a gene in the same sample is an effective approach for identifying cis-acting regulatory SNPs (rSNPs). In the current study, we established a process for systematic screening for cis-acting rSNPs using experimental detection of AI as an initial approach. We selected 160 expressed candidate genes that are involved in cancer and anticancer drug resistance for analysis of AI in a panel of cell lines that represent different types of cancers and have been well characterized for their response patterns against anticancer drugs. Of these genes, 60 contained heterozygous SNPs in their coding regions, and 41 of the genes displayed imbalanced expression of the two cSNP alleles. Genes that displayed AI were subjected to bioinformatics-assisted identification of rSNPs that alter the strength of transcription factor binding. rSNPs in 15 genes were subjected to electrophoretic mobility shift assay, and in eight of these genes (APC, BCL2, CCND2, MLH1, PARP1, SLIT2, YES1, XRCC1) we identified differential protein binding from a nuclear extract between the SNP alleles. The screening process allowed us to zoom in from 160 candidate genes to eight genes that may contain functional rSNPs in their promoter regions

The association between genetic variants in hMLH1 and hMSH2 and the development of sporadic colorectal cancer in the Danish population

<p>Abstract</p> <p>Background</p> <p>Mutations in the mismatch repair genes <it>hMLH1 </it>and <it>hMSH2 </it>predispose to hereditary non-polyposis colorectal cancer (HNPCC). Genetic screening of more than 350 Danish patients with colorectal cancer (CRC) has led to the identification of several new genetic variants (e.g. missense, silent and non-coding) in <it>hMLH1 </it>and <it>hMSH2</it>. The aim of the present study was to investigate the frequency of these variants in <it>hMLH1 </it>and <it>hMSH2 </it>in Danish patients with sporadic colorectal cancer and in the healthy background population. The purpose was to reveal if any of the common variants lead to increased susceptibility to colorectal cancer.</p> <p>Methods</p> <p>Associations between genetic variants in <it>hMLH1 </it>and <it>hMSH2 </it>and sporadic colorectal cancer were evaluated using a case-cohort design. The genotyping was performed on DNA isolated from blood from the 380 cases with sporadic colorectal cancer and a sub-cohort of 770 individuals. The DNA samples were analyzed using Single Base Extension (SBE) Tag-arrays. A Bonferroni corrected Fisher exact test was used to test for association between the genotypes of each variant and colorectal cancer. Linkage disequilibrium (LD) was investigated using HaploView (v3.31).</p> <p>Results</p> <p>Heterozygous and homozygous changes were detected in 13 of 35 analyzed variants. Two variants showed a borderline association with colorectal cancer, whereas the remaining variants demonstrated no association. Furthermore, the genomic regions covering <it>hMLH1 </it>and <it>hMSH2 </it>displayed high linkage disequilibrium in the Danish population. Twenty-two variants were neither detected in the cases with sporadic colorectal cancer nor in the sub-cohort. Some of these rare variants have been classified either as pathogenic mutations or as neutral variants in other populations and some are unclassified Danish variants.</p> <p>Conclusion</p> <p>None of the variants in <it>hMLH1 </it>and <it>hMSH2 </it>analyzed in the present study were highly associated with colorectal cancer in the Danish population. High linkage disequilibrium in the genomic regions covering <it>hMLH1 </it>and <it>hMSH2</it>, indicate that common genetic variants in the two genes in general are not involved in the development of sporadic colorectal cancer. Nevertheless, some of the rare unclassified variants in <it>hMLH1 </it>and <it>hMSH2 </it>might be involved in the development of colorectal cancer in the families where they were originally identified.</p

Y-Chromosomal SNPs in Finno–Ugric-Speaking Populations Analyzed by Minisequencing on Microarrays

An increasing number of single nucleotide polymorphisms (SNPs) on the Y chromosome are being identified. To utilize the full potential of the SNP markers in population genetic studies, new genotyping methods with high throughput are required. We describe a microarray system based on the minisequencing single nucleotide primer extension principle for multiplex genotyping of Y-chromosomal SNP markers. The system was applied for screening a panel of 25 Y-chromosomal SNPs in a unique collection of samples representing five Finno–Ugric populations. The specific minisequencing reaction provides 5-fold to infinite discrimination between the Y-chromosomal genotypes, and the microarray format of the system allows parallel and simultaneous analysis of large numbers of SNPs and samples. In addition to the SNP markers, five Y-chromosomal microsatellite loci were typed. Altogether 10,000 genotypes were generated to assess the genetic diversity in these population samples. Six of the 25 SNP markers (M9, Tat, SRY10831, M17, M12, 92R7) were polymorphic in the analyzed populations, yielding six distinct SNP haplotypes. The microsatellite data were used to study the genetic structure of two major SNP haplotypes in the Finns and the Saami in more detail. We found that the most common haplotypes are shared between the Finns and the Saami, and that the SNP haplotypes show regional differences within the Finns and the Saami, which supports the hypothesis of two separate settlement waves to Finland