Factors explaining the difference of total homocysteine between men and women in the European Investigation Into Cancer and Nutrition Potsdam study

Interestingly, plasma total homocysteine (tHcy) concentration is consistently higher in men than in women. This observation deserves further investigations because elevated tHcy concentrations have been shown to be independently associated with coronary, peripheral, and cerebral vascular diseases. It was the aim of the present study to define major determinants of plasma tHcy in a healthy middle-aged German population under particular consideration of the gender factor. The study population was obtained from an ongoing recruitment procedure for a cohort study and comprised 336 men and women, aged 40 to 65 years. Exclusion criteria were elevated creatinine levels in blood, history of skin or atherosclerotic diseases, current use of vitamins or other supplements, and heavy smoking. Plasma tHcy, folate, vitamin B12, vitamin B6, creatinine, testosterone and estradiol, protein, and hematocrit were measured. Fat-free mass was assessed by skinfold thickness. The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR), a key enzyme of folate and homocysteine metabolism, was determined by polymerase chain reaction (PCR) with restriction enzyme analysis. In this population, plasma tHcy ranged from 5 to 46 micromol/L. The frequency of the T allele of the MTHFR was 0.29, which is lower than in other populations. A total of 54.2% of this population was homozygote for the wild-type, 39.6% heterozygote, and 6.2% homozygote for the mutation. tHcy correlated negatively with folate and cobalamin concentration in blood and positively with creatinine. No correlation was seen with vitamin B6. From the gender-related variables, tHyc correlated significantly with fat-free mass and testosterone and inversely with estradiol. The difference between gender with regard to tHcy was mainly explained by differences in fat-free mass, but also by estradiol concentrations. The following contributions to the variation of tHcy were seen in a multivariate regression model: plasma cobalamin (11%), creatinine (11%), plasma folate (8%), fat-free mass (5%), estradiol (2%), MTHFR polymorphisms (2%), and plasma protein (1%). We concluded that tHcy in the general population has a variety of determinants ranging from nutrition, internal metabolic parameters to gender-related variables.     

Enlarged effects of adenosine in a septic patient with multiple myeloma and atrial flutter

We report the history of a 60-year-old patient with a multiple myeloma and Staphylococcus aureus associated sepsis to whom adenosine in a dose of 6 mg was administered, when a regular, narrow QRS complex tachycardia at a heart rate of 120 beats/minute started. Adenosine led to a complete AV-block and revealed atrial flutter. Atrial flutter waves persisted for about 15 seconds and were followed by atrial and ventricular asystole for about 20 seconds. Repeated nonsustained polymorphic ventricular tachycardias followed and after about 90 seconds sinus rhythm was restored.     

Klinisches Medikationsmanagement

best practice onkologie -     

A High-Order Discontinuous Galerkin Solver for Helically Symmetric Flows

We present a high-order discontinuous Galerkin (DG) scheme to solve thesystem of helically symmetric Navier-Stokes equations which are discussed in [28].In particular, we discretize the helically reduced Navier-Stokes equations emergingfrom a reduction of the independent variables such that the remaining variables are: $t$, $r$, $ξ$ with $ξ=az+bϕ$, where $r$, $ϕ$, $z$ are common cylindrical coordinates and $t$ thetime. Beside this, all three velocity components are kept non-zero. A new non-singularcoordinate $η$ is introduced which ensures that a mapping of helical solutions into thethree-dimensional space is well defined. Using that, periodicity conditions for thehelical frame as well as uniqueness conditions at the centerline axis $r=0$ are derived. Inthe sector near the axis of the computational domain a change of the polynomial basisis implemented such that all physical quantities are uniquely defined at the centerline.For the temporal integration, we present a semi-explicit scheme of third orderwhere the full spatial operator is split into a Stokes operator which is discretizedimplicitly and an operator for the nonlinear terms which is treated explicitly. Computations are conducted for a cylindrical shell, excluding the centerline axis, and forthe full cylindrical domain, where the centerline is included. In all cases we obtain theconvergence rates of order $mathcal{O}(h^{k+1})$ that are expected from DG theory.In addition to the first DG discretization of the system of helically invariant Navier-Stokes equations, the treatment of the central axis, the resulting reduction of the DGspace, and the simultaneous use of a semi-explicit time stepper are of particular novelty.     

Ewing sarcoma dissemination and response to T-cell therapy in mice assessed by whole-body magnetic resonance imaging

Background:

Novel treatment strategies in Ewing sarcoma include targeted cellular therapies. Preclinical in vivo models are needed that reflect their activity against systemic (micro)metastatic disease.

Methods:

Whole-body magnetic resonance imaging (WB-MRI) was used to monitor the engraftment and dissemination of human Ewing sarcoma xenografts in mice. In this model, we evaluated the therapeutic efficacy of T cells redirected against the Ewing sarcoma-associated antigen G_D2 by chimeric receptor engineering.

Results:

Of 18 mice receiving intravenous injections of VH-64 Ewing sarcoma cells, all developed disseminated tumour growth detectable by WB-MRI. All mice had lung tumours, and the majority had additional manifestations in the bone, soft tissues, and/or kidney. Sequential scans revealed in vivo growth of tumours. Diffusion-weighted whole-body imaging with background signal suppression effectively visualised Ewing sarcoma growth in extrapulmonary sites. Animals receiving G_D2-targeted T-cell therapy had lower numbers of pulmonary tumours than controls, and the median volume of soft tissue tumours at first detection was lower, with a tumour growth delay over time.

Conclusion:

Magnetic resonance imaging reliably visualises disseminated Ewing sarcoma growth in mice. G_D2-retargeted T cells can noticeably delay tumour growth and reduce pulmonary Ewing sarcoma manifestations in this aggressive disease model.     

Efficacy and safety of venlafaxine ER vs. amitriptyline ER in patients with major depression of moderate severity

INTRODUCTION: A double-blind, randomized phase-III study was conducted with the aim to compare the efficacy and safety of venlafaxine ER (extended release) with that of amitriptyline ER in moderately depressed outpatients. METHODS: Patients with major depression of moderate severity, HAM-D (Hamilton Depression scale, 21 items) score 20-26, were given a six-week double-blind treatment with venlafaxine ER and amitriptyline ER in a dosis of 75 mg each, which could be increased to 150 mg, if necessary. Efficacy was assessed using HAM-D and CGI (clinical global impression) scores. Safety analysis was carried out using the HAM-D item 3 to assess suicidality, the d2 test to evaluate attention and drug screening for benzodiazepines. Adverse events were recorded at each visit. RESULTS: 160 patients were randomized. There were 151 patients available for analysis in the intent-to-treat (ITT) population. The according-to-protocol (ATP) population consisted of 117 patients, with 60 patients in the venlafaxine ER group and 57 in the amitriptyline ER (extended release) group. The non-inferiority of venlafaxine ER compared to amitriptyline ER with reference to the primary efficacy parameter, the change of HAM-D total score, could be proven in both the ITT population and the ATP population. There were no significant differences between groups in the HAM-D response rates and the CGI scores of items 1 (severity) and 2 (improvement). Venlafaxine ER showed a more favorable safety profile than amitriptyline ER: adverse drug reactions were less frequent under venlafaxine ER than under amitriptyline ER. Most of the discontinuations in the amitriptyline ER group were due to dry mouth. The d2 test showed greater improvement of performance under venlafaxine ER. DISCUSSION: In this study with patients treated for major depression of moderate severity, the non-inferiority of venlafaxine ER compared to amitriptyline ER with respect to the chosen efficacy parameter could be demonstrated. Venlafaxine ER showed a more favorable safety profile than amitriptyline ER.     

Effect of glutamate carboxypeptidase II and reduced folate carrier polymorphisms on folate and total homocysteine concentrations in dialysis patients

This study was designed to examine the effect of two single nucleotide polymorphisms in the reduced folate carrier 1 (RFC1 80G>A) and the glutamate carboxypeptidase 2 (GCP2 1561C>T) gene on total homocysteine (tHcy) plasma level and folate status in 120 chronic dialysis patients. Red blood cell folate concentration was higher in patients with the GCP2 CT or TT genotype (ANOVA, P = 0.04). Among patient groups with different RFC1 genotypes, red blood cell folate level was not significantly different. A multivariate analysis confirmed that the GCP2 1561C>T genotype (P = 0.011) had a significant influence on the red blood cell folate concentration. Overall, serum folate, creatinine, and the GCP2 polymorphism explained nearly 50% of the variance of red blood cell folate. A linear multivariate regression analysis showed that red blood cell folate (P < 0.001), creatinine (P < 0.001), and the 5,10-methylenetetrahydrofolate reductase (MTHFR) 677T allele (P = 0.013) are independent predictors of tHcy plasma level explaining 49% of the variance of tHcy plasma concentration. GCP2 1561C>T and RFC1 80G>A showed no effect on tHcy and folate plasma level. In conclusion, GCP2 1561C>T, but not RFC1 80G>A, is a predictor of red blood cell folate level in chronic dialysis patients. Both polymorphisms have no major effect on tHcy plasma concentration in end-stage renal disease patients.