PET: brain tumor biochemistry

Most mechanisms of drugs which are used in brain tumor chemotherapy are well characterized: alkylation of DNA components (nitrosoureas), binding with tubulin protein resulting in metaphase arrest (vincristine), chromatid breaks and chromosome translocations (procarbazine), or inhibition of ribonucleotide reductase (hydroxyurea) [1]. These drugs exert their effects mainly during certain cell cycle phases of proliferating cells, particularly when DNA is synthesized. From this it can be assumed that the efficacy of these drugs depends on the fraction of proliferating cells. Thus it would be of great importance to estimate the proliferation rate of brain tumors which could guide chemotherapy in individual patients. Positron emission tomography (PET) measures quantitatively the in vivo tissue uptake of tracer substances. In tumors, the uptake appears to be altered in a characteristic way determined by biochemical properties of tumor tissue. Some aspects of brain tumor metabolism which are theoretically related to proliferation have been investigated with PET. In the following, the literature is reviewed with regard to: 1) tracer substances whose uptake has been thought to reflect tumor malignancy (11C-methionine, 18F-fluoro-deoxyglucose), and 2) tracers which theoretically could reflect mechanisms specifically related to DNA synthesis (11C-putrescine, ligands for peripheral benzodiazepine receptors).     

De novo epileptic confusional status in a patient with cobalamin deficiency

A 80-year-old man with cobalamin deficiency and no history of epilepsy developed a partial complex epileptic confusional status (ECS) unresponsive to acute i.v. diazepam. Brain CT scan and MRI investigation ruled out a focal cerebral lesion. Therapy with high doses (10,000 micrograms i.m. daily) of cobalamin alone was started, and the patient fully recovered in the following 72-hour. Control EEGs repeatedly performed days and weeks later showed progressive disappearance of the frontal interictal spiking, while the patient was on monotherapy with cobalamin (5,000 micrograms i.m. weekly). A month later the patient unfortunately discontinued replacement therapy and 13 weeks later he developed a fatal convulsive epileptic status. To our knowledge the association of ECS and cobalamin deficiency has not been previously reported.     

Initial experiences with the MR "magnitude contrast angiography of the lower extremities

45 patients with occlusive peripheral vascular disease were examined by MR angiography in a retrospective study. A FISP 3D sequence was used by acquiring a rephased and a dephased data set. The individual slices were post-processed by using a maximum-intensity-projection algorithm. The MRA results of the popliteal and tibioperoneal arteries were compared to conventional or digital angiography. In comparing these techniques MR angiography cannot be accepted for pre- and postoperative staging of patients with occlusive peripheral vascular disease. In future new MRA techniques may be useful in postoperative staging of patients with peripheral vascular stenosis.     

Phase I trial of inhaled natural interleukin 2 for treatment of pulmonary malignancy: toxicity, pharmacokinetics, and biological effects

Safety, local and systemic immunomodulation, and tumor response to treatment with aerosolized natural interleukin 2 (nIL-2) applied five times a day were studied in a Phase I trial in 16 patients with pulmonary malignancies refractory to conventional therapy. The toxicity of inhaled nIL-2 was different from that observed after systemic administration. Reversible airway irritation causing a nonproductive cough represented the dose-limiting toxicity. Mild to moderate reduction of the vital capacity and forced expiratory volume (FEV1) with minor effects on relative FEV1, peak expiratory flow, airway resistance, and PaO2 was experienced by individual patients. In 14 patients suffering from pulmonary metastases due to renal cell cancer, one durable complete response, one partial response, and one mixed response were observed. Inhalation of nIL-2 aerosol resulted in a dose-dependent expansion of pulmonary immunocompetent cells in bronchoalveolar lavage fluid. Posttreatment bronchoalveolar lavage showed an activated lymphocyte phenotype with increased HLA-DR expression. The only systemic biological effect detectable in peripheral blood was a marked increase of soluble interleukin 2 receptor serum levels. We conclude that treatment with aerosolized nIL-2 is an effective means for site-specific immunomodulation and deserves further investigation for the treatment of malignant and inflammatory lung disease.     

Synthesis and characterization of poly(ethylene aspartate)-metal complexes

Poly(ethylene aspartate) [PEA] was synthesized by the melt condensation of D,L-aspartic acid and ethylene glycol. PEA containing pendent amino and carbonyl groups in its repeating chain was used as the polymeric ligand for complexation with transition metal ions, viz. Co(II), Ni(II), Cu(II), Mn(II), Zn(II), Cd(II), Ca(II), Mg(II), Pb(II) and Hg(II). Complexation was found to be most effective in DMSO. The resulting polyester-metal complexes were solid coloured materials which have been characterized by IR spectroscopy, elemental analysis and magnetic susceptibility measurements. The thermal stability of the polyester-metal complexes was investigated by thermogravimetric analysis (TGA). On the basis of the physico-chemical studies, an oxygen and nitrogen coordinated structure for the polyester-metal complexes is proposed.     

A Markovian Extension of Valiant′s Learning Model

An "Occam algorithm" learning model maintains a tentative hypothesis consistent with past observations and, when a new observation is inconsistent with the current hypothesis, updates to the next-simplest hypothesis consistent with all observations. In previous work, observations were assumed to be stochastically independent. This paper initiates study of such models under weaker Markovian assumptions on the observations, In the special case where the sequence of hypotheses satisfies a monotonicity condition, it is shown that the number of mistakes in classifying the first t observations is O(√t log 1/π_i), where π_i is the stationary probability of the initial state, i, of the Markov chain.     

Neurocontrol for lateral vehicle guidance

A solution to autonomous lateral vehicle guidance using a neurocontroller that can learn from measured human-driving data without knowledge of the physical car parameters is discussed. Simulations and practical tests confirm that a small-size feedforward autonomous neural network (21 neurons) can learn to steer a vehicle at high speeds only from looking at human-driving examples. In this way, the network learns the total closed-loop behavior, including the nonlinear dynamics of the vehicle and the driver's individual driving style. The main result of practical investigations is that the neutral controller trained on human-driving examples exhibits an aperiodic behavior that does not vanish at higher speeds (tests performed up to 130 km/h) and produces fewer lateral deviations than the linear state controller     

Multidimensional augmented current equation including velocityovershoot

The augmented drift-diffusion current equation, which includes velocity overshoot effects through the space derivatives of the electric field, cannot be directly extended beyond one dimension. A new formalism is developed which considers the carrier heating and the distribution relaxation effects to obtain a multidimensional augmented drift diffusion current equation. The equivalent mobility containing the velocity overshoot correction is derived from the perturbation analysis on the carrier temperature using the energy balance equation. The issues related to the numerical implementation of this generalized model and the validity of the assumptions are also discussed     

The effect of core modelling on the self-force and self-energy of a dislocation

A verification example is solved using a core model recently introduced in a FEM approach to dislocation dynamics. The core model is compared to the more accepted cut-off procedures. It is demonstrated that these procedures give the correct self-force if the cut-off distance is selected properly. The cut-off procedures do however have some grave weaknesses. These limit their usefulness to a restricted number of problems.