Differentiation of tumour and inflammation: characterisation of [methyl-3H]methionine (MET) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) uptake in human tumour and inflammatory cells

Purpose

Previous studies suggest that radiolabelled amino acids could be superior to FDG in differentiating tumour and inflammation. Therefore the aim of this study was to investigate the uptake of FET and MET in human tumour and inflammatory cells and to investigate their uptake kinetics.

Methods

For uptake studies, cells were incubated with 370 kBq FET or 3.7 kBq MET for 15 min. Kinetic studies were performed at variable concentrations of FET and MET. Competitive inhibition studies were done with BCH, MeAIB and L-serine.

Results

All inflammatory cells incorporated more MET than the tumour cells. The uptake of FET, in contrast, was significantly lower in all inflammatory cells than in the tumour cells. In tumour cells the uptake of MET was about five times the uptake of FET. The competitive inhibitors reduced uptake of both tracers to 20–40% in tumour cells and to 70% in inflammatory cells. Kinetic studies showed that MET and FET transport was saturable in all cells except macrophages and followed a Michaelis-Menten kinetic. Highest capacity (V _max) and affinity (K _m) for the uptake of MET was observed in granulocytes. Capacity and affinity for FET uptake were highest in the DHL-4 cells.

Conclusion

In contrast to MET, FET accumulated to a significantly greater extent in tumour cells than in inflammatory cells. The marked differences between tumour and inflammatory cells concerning FET and MET uptake suggest that FET and MET are substrates of different subtypes of the L system.     

Diabetes, leukoencephalopathy and rage

Longstanding diabetes mellitus damages kidney, retina, peripheral nerve and blood vessels, but brain is not usually considered a primary target. We describe direct involvement of the brain, particularly white matter, in long-term (9 months) experimental diabetes of mice, not previously modeled, correlating magnetic resonance (MR) imaging with quantitative histological assessment. Leukoencephalopathy and cerebral atrophy, resembling that encountered in diabetic humans, developed in diabetic mice and was accompanied by time-related development of cognitive changes in behavioural testing. Increased RAGE (receptor for advanced glycation end products) expression, a mediator of widespread diabetic complications, increased dramatically at sites of white matter damage in regions of myelination. RAGE expression was also elevated within neurons, astrocytes and microglia in grey matter and within oligodendrocytes in white matter. RAGE null diabetic mice had significantly less neurodegenerative changes when compared to wild-type diabetic mice. Our findings identify a robust and novel model of cerebral, particularly white matter, involvement with diabetes associated with abnormal RAGE signaling.     

Cerebrospinal fluid insulin-like growth factors IGF-1 and IGF-2 in infantile autism

There has been little exploration of major biologic regulators of cerebral development in autism. We measured insulin-like growth factors (IGF) -1 and -2 from cerebrospinal fluid (CSF) by radio immunoassay in 25 children with autism (median age 5y 5mo; range 1y 11mo-15y 10mo; 20 males, 5 females), and in 16 age-matched comparison children without disability (median age 7y 4mo; range 1y 1mo-15y 2mo; eight males, eight females). IGF-1 and -2 concentrations were further correlated with age of patients and head size. CSF IGF-1 concentration was significantly lower in patients with autism than in the comparison group. The CSF concentrations of children with autism under 5 years of age were significantly lower than their age-matched comparisons. The head circumferences correlated with CSF IGF-1 in children with autism but no such correlation was found in the comparison group. There was no difference between the two groups in CSF IGF-2 concentrations. No patients with autism had macrocephaly. We conclude that low concentrations of CSF IGF-1 at an early age might be linked with the pathogenesis in autism because IGF-1 is important for the survival of Purkinje cells of the cerebellum. The head growth might be explained by the actions of IGF-1 and -2 reflected in CSF concentrations.     

Pavlovian conditioning of nausea and vomiting

Cancer patients undergoing cytotoxic drug treatment often experience side-effects, the most distressing being nausea and vomiting. Despite antiemetic drugs, 25-30% of the chemotherapy patients report these side-effects when being re-exposed to the stimuli that usually signal the chemotherapy session and its drug infusion. These symptoms are called anticipatory nausea and anticipatory vomiting. The present paper summarizes the evidence that anticipatory vomiting is acquired by Pavlovian conditioning, and, consequently, may be alleviated by conditioning techniques. To explore the mechanisms that induce and alleviate conditioned nausea and vomiting further, a conditioned nausea model was established in healthy humans using body rotation as the nausea-inducing treatment. The validity of this motion sickness model to examine conditioning mechanisms in the acquisition and alleviation of conditioned nausea was demonstrated. Cortisol and tumor-necrosis factor-alpha were elevated as endocrine and immunological correlates of nausea. Data in the rotation-induced motion sickness model indicated that gender is an important moderator variable to be considered in further studies. The paper concludes with a review of applications of the demonstrated conditioning principles as interventions to ameliorate distressing anticipatory nausea or anticipatory vomiting in cancer patients undergoing chemotherapy.     

Neurogenic stunned myocardium after embolization in two children with vein of Galen aneurysmal malformation

Introduction

This study reports the first cases of neurogenic stunned myocardium in two children with vein of Galen aneurysmal malformation after interventional treatment.

Patients

Two newborns with vein of Galen aneurysmal malformation and high output cardiac failure developed a severe reversible left ventricular dysfunction shortly after embolization, concurrently with acute hydrocephalus.

Results

There was a resolution of the cardiac symptoms of left ventricular dysfunction within a few days under treatment with milrinone and dobutamine.

Conclusions

Reversible left ventricular dysfunction is observed in adult patients mainly after subarachnoid hemorrhage and is called neurogenic stunned myocardium (NSM). Other forms of brain injuries have also been identified accounting for this condition in adults. In pediatric population especially with specific cerebral diseases, NSM may be underdiagnosed.     

Evaluation of 100 brain examinations using a 3 Tesla MR-compatible incubator—safety, handling, and image quality

Introduction

Several studies have revealed the importance of brain imaging in term and preterm infants. The aim of this retrospective study was to review safety, handling, and image quality of MR brain imaging using a new 3 Tesla MR-compatible incubator.

Methods

Between 02/2011 and 05/2012 100 brain MRIs (84 infants, mean gestational age 32.2?±?4.7 weeks, mean postmenstrual age at imaging 40.6?±?3.4 weeks) were performed using a 3 Tesla MR-compatible incubator with dedicated, compatible head coil. Seventeen examinations (13 infants, mean gestational age 35.1?±?5.4 weeks, mean postmenstrual age at imaging 47.8?±?7.4 weeks) with a standard head coil served as a control. Image analysis was performed by a neuroradiologist and a pediatric radiologist in consensus.

Results

All but two patients with known apnea were transferred to the MR unit and scanned without problems. Handling was easier and faster with the incubator; relevant motion artifacts (5.9 vs. 10.8 %) and the need for repetitive sedation (43.0 vs. 86.7 %) were reduced. Considering only images not impaired by motion artifacts, image quality (4.8?±?0.4 vs. 4.3?±?0.8, p?=?0.047) and spatial resolution (4.7?±?0.4 vs. 4.2?±?0.6, p?=?0.011) of T2-weighted images were scored significantly higher in patients imaged with the incubator. SNR increased significantly (171.6?±?54.5 vs. 80.5?±?19.8, p?<?0.001) with the use of the incubator.

Conclusion

Infants can benefit from the use of a 3 Tesla MR-compatible incubator because of its safety, easier, and faster handling (compared to standard imaging) and possibility to obtain high-quality MR images even in unstable patients.     

NEWS FROM THE INTERNATIONAL COUNCIL ON WOMEN'S HEALTH ISSUES

The purpose of this study was to test the psychometric properties of a vertical version of horizontally oriented three Appraisal of Violent Situation scales that elicit women's subjective appraisals of severity, dangerousness, and controllability of violence. Construct validity of the vertical scale eliciting 64 abused women's perceptions of severity of violence experienced was supported by a low to modest correlation between that scale and the Severity of Violence Against Women Scale. Concurrent validity between the horizontal and vertical versions of the scales was demonstrated with a subsample of 26 abused women completing both. Results provide preliminary support for the revised scales.