The sevoflurane-sparing effect of nitrous oxide: a clinical study

BACKGROUND: We studied the sevoflurane-sparing effect of nitrous oxide in a prospective randomised study. METHODS: Forty-two ASA I-II patients scheduled for elective knee arthroscopy under general anaesthesia were randomly assigned to a fresh gas flow consisting of oxygen in air or oxygen in nitrous oxide 1:2. All patients received a standardised anaesthesia consisting of induction with fentanyl and propofol and maintenance with sevoflurane adjusted according to clinical signs. The sevoflurane consumption was studied by means of weighing the vaporiser before and after every anaesthesia. RESULTS: The mean sevoflurane consumption was reduced from 0.62 to 0.25 g/min, a 60% reduction, by the use of oxygen in nitrous oxide 1:2 in the fresh gas flow. The emergence was faster for the patients receiving nitrous oxide. No major differences were observed during recovery. CONCLUSION: Nitrous oxide was found to be cost-effective for use during short ambulatory knee arthroscopy.     

MDA in plasma as a biomarker of exposure to pyrolysed MDI-based polyurethane: correlations with estimated cumulative dose and genotype for N-acetylation

The object of this study was to investigate whether exposure of pipe-layers to thermal degradation products of diphenylmethane diisocyanate (MDI) could be assessed by analysing 4,4-methylenedianiline (MDA) in hydrolysed plasma and urine, and whether the genotype for N-acetylation affected these biomarker levels. Blood and urine samples were drawn from 30-pipe-layers who had been welding polyurethane (PUR) insulated pipes during the preceding 3 months. MDA in hydrolysed plasma and urine was determined with a gas chromatography-mass spectrometry technique, and genotype for N-acetylation was analysed with a polymerase chain reaction technique. MDA in plasma was detected in 18 of the 30 pipe-layers. Their plasma concentrations of MDA varied from 0.05 to 8.48 g/1. There was a significant negative correlation between time since last welding of PUR-insulated pipes and P-MDA (r _s = 0.50, P = 0.005). There was also a significant positive correlation between the estimated number of welded PUR-insulated pipes during the preceding 3 months and P-MDA (r _s = 0.68, P = < 0.001). No significant association between genotype of N-acetylation and P-MDA was observed in a multiple regression analysis when adjustment was made for the estimated cumulative exposure to thermal degradation products of MDI. MDA in urine was detected in only four of the 30 pipe-layers. These four subjects had been welding PUR pipes on the same day as the sampling, or on the day before. The present results indicate the spot plasma samples analysed for MDA may give a rather good estimate of exposure to MDI during the preceding months. P-MDA, but not U-MDA, therefore seems to be a useful biomarker of long-term exposure to MDI. The individual N-acetylation capacity did not affect the plasma levels of MDA.     

MYC inhibition induces metabolic changes leading to accumulation of lipid droplets in tumor cells

The MYC genes are the most frequently activated oncogenes in human tumors and are hence attractive therapeutic targets. MYCN amplification leads to poor clinical outcome in childhood neuroblastoma, yet strategies to modulate the function of MYCN do not exist. Here we show that 10058-F4, a characterized c-MYC/Max inhibitor, also targets the MYCN/Max interaction, leading to cell cycle arrest, apoptosis, and neuronal differentiation in MYCN-amplified neuroblastoma cells and to increased survival of MYCN transgenic mice. We also report the discovery that inhibition of MYC is accompanied by accumulation of intracellular lipid droplets in tumor cells as a direct consequence of mitochondrial dysfunction. This study expands on the current knowledge of how MYC proteins control the metabolic reprogramming of cancer cells, especially highlighting lipid metabolism and the respiratory chain as important pathways involved in neuroblastoma pathogenesis. Together our data support direct MYC inhibition as a promising strategy for the treatment of MYC-driven tumors.     

Fracture of the Capitellum of the Humerus in Adults

In 2 cases of fracture of the capitellum of the humerus with avascular fragment the writer has made a cast of the capitellar fragment and manufactured a chrom-cobolt-molybdenum prosthesis, which has then been inserted in the joint. The result has been a painless, stable joint with a range of movement of 155°-35° and 150°-60° respectively. A third case is mentioned, which was treated with open reduction of the fracture where examination 20 months after the operation revealed a partial necrosis of the capitellar fragment; the functional result however was good.     

Hospital admissions among people 65+ related to multimorbidity, municipal and outpatient care

This study aimed at examine the number of planned and acute hospital admissions during 1 year among people 65+ and its relation to municipal care, outpatient care, multimorbidity, age and sex. Four thousand nine hundred and seven individuals having one or more admissions during 2001 were studied. Data were collected from two registers and comparisons were made between those having one, two and three or more hospital stays and between those with and without municipal care and services. Linear regression was used to examine factors predicting number of acute and planned admissions. Fifteen percent of the sample had three or more hospital stays (range 3-15) accounting for 35% of all admissions. This group had significantly more contacts in outpatient care with physician (median number of contacts (md)=15), compared to those with one (md: 8), or two admissions (md: 11). Main predictors for number of admissions were number of diagnosis groups and number of contacts with physician in outpatient care. Those who are frequently admitted to hospital constitute a small group that consume a great deal of inpatient care and also tend to have frequent contacts in outpatient care. Thus interventions focusing on frequent admissions are needed, and this requires collaboration between outpatient and hospital care.     

Human mesenchymal stromal cells modulate T‐cell responses through TNF‐α‐mediated activation of NF‐κB

Although mesenchymal stromal cells (MSCs) possess the capacity to modulate immune responses, little is known about the mechanisms that underpin these processes. In this study, we show that immunosupression is mediated by activation of nuclear factor kappa B (NF‐κB) in human MSCs. This pathway is activated by TNF‐α that is generated following TCR stimulation of T cells. Inhibition of NF‐κB through silencing of IκB kinase β or the TNF‐α receptor abolishes the immunosuppressive capacity of MSCs. Our data also indicate that MSC‐associated NF‐κB activation primarily leads to inhibition of T‐cell proliferation with little effect on expression of the activation markers CD69 and CD25. Thus, our data support the hypothesis that the TNF‐α/NF‐κB signalling pathway is required for the initial priming of immunosuppressive function in human MSCs. Interestingly, drugs that interfere with NF‐κB activation significantly antagonise the immunoregulatory effect of MSCs, which could have important implications for immunosuppression regimens in the clinic.