Electron beam therapy with coil-generated magnetic fields

This paper presents an initial study on the issues involved in the practical implementation of the use of transverse magnetic fields in electron beam therapy. By using such magnetic fields the dose delivered to the tumor region can increase significantly relative to that deposited to the healthy tissue. Initially we calculated the magnetic fields produced by the Helmholtz coil and modified Helmholtz coil configurations. These configurations, which can readily be used to generate high intensity magnetic fields, approximate the idealized magnetic fields studied in our previous publications. It was therefore of interest to perform a detailed study of the fields produced by these configurations. Electron beam dose distributions for 15 MeV electrons were calculated using the ACCEPTM code for a 3T transverse magnetic field produced by the modified Helmholtz configuration. The dose distribution was compared to those obtained with no magnetic field. The results were similar to those obtained in our previous work, where an idealized step function magnetic field was used and a 3T field was shown to be the optimal field strength. A simpler configuration was also studied in which a single external coil was used to generate the field. Electron dose distributions are also presented for a given geometry and given magnetic field strength using this configuration. The results indicate that this method is more difficult to apply to radiotherapy due to its lack of symmetry and its irregularity. For the various configurations dealt with here, a major problem is the need to shield the magnetic field in the beam propagation volume, a topic that must be studied in detail.     

Clinical presentation and anatomic position of L3-L4 disc herniation: a prospective and comparative study

OBJECTIVE: A prospective, controlled cohort study was conducted to assess the anatomic transverse location and clinical presentation of L3-L4 disc herniation compared with lower lumbar levels. METHODS: This study prospectively identified 37 patients diagnosed with L3-L4 disc herniation (study group) and 52 patients diagnosed with L4-L5 and L5-S1 herniation (control group). The following clinical data were collected: age, femoral stretch test, motor strength, sensation, and deep tendon reflexes. The anatomic transverse location of the disc fragments was assessed by computed tomography or magnetic resonance imaging and was classified as either central, posterolateral, foraminal, or far lateral. RESULTS: The patients in the study group were older than the patients in the control group, and neurologic deficit was more common. The transverse location was foraminal and extraforaminal in 59% of the study group compared with 27% of the control group. These differences were statistically significant. CONCLUSIONS: The incidence of foraminal and far lateral disc herniation is significantly higher at the L3-L4 level compared with lower lumbar levels. When examining an older patient complaining of thigh pain, special attention should be given to the quadriceps strength, patellar reflex, and femoral stretch test. The L3-L4 foraminal and extraforaminal area should be assessed carefully.     

Fatal exertional heat stroke: a case series

BACKGROUND: Exertional heat stroke (EHS) is one of the most serious conditions that occur when excess heat, generated by muscular exercise, exceeds the body's heat-dissipation rate. The consequent elevated body core temperature causes damage to the body's tissues, resulting in a characteristic multiorgan syndrome, which is occasionally fatal. METHODS: We analyzed the fatal EHS cases that occurred in the Israeli Defence Forces during the last decade according to Minard's paradigm for evaluation of EHS predisposing factors, aiming to characterize the common features and unique circumstances leading to fatality. RESULTS: Accumulation of predisposing factors, particularly those concerning training regulations, coupled with inappropriate treatment at site, were found to be strong predictors of a grave prognosis. Analysis of the pathologic findings of the fatal EHS cases on autopsy revealed a possible association between the duration and length of exercise prior to EHS occurrence and the extent of pathologic findings. CONCLUSIONS: Strict adherence to existing training regulations may prevent further heat stroke fatalities.     

Rasagiline alone and in combination with riluzole prolongs survival in an ALS mouse model

Abstract. Rasagiline is an antiapoptotic compound with neuroprotective potential. We examined its neuroprotective effect alone and in combination with the putative glutamate release blocker riluzole in the G93A model of familial amyotrophic lateral sclerosis (fALS). Endpoints of experimental treatment were survival and motor activity. The drug had a significant dose-dependent therapeutic effect on both preclinical and clinical motor function and survival of the animals. We also found that the combination of rasagiline with riluzole is safe and increases survival by about 20 % in a dosedependent manner. Therefore, we conclude that the combination of rasagiline and riluzole is a promising clinical combination for the improvement of current neuroprotective treatment strategies of ALS.     

The "brainy side" of human embryonic stem cells

The recent isolation of human embryonic stem (ES) cells is evoking great hopes for their future utilization in cell-replacement therapies and human development research. The hallmarks of ES cells, pluripotency and self-renewal capacity, suggest an infinite source for tissues of virtually all desired types. Specifically, human ES cells may potentially be the basis for effective treatments of a wide range of human neurodegenerative disorders. To enable the translation of this novel biomedical field into the clinic, mechanisms that control the differentiation of human embryonic stem cells into fully functional neuronal cells should be analyzed and controlled.     

The calculation of transport properties in quantum liquids using the maximum entropy numerical analytic continuation method: application to liquid para-hydrogen

We present a method based on augmenting an exact relation between a frequency-dependent diffusion constant and the imaginary time velocity autocorrelation function, combined with the maximum entropy numerical analytic continuation approach to study transport properties in quantum liquids. The method is applied to the case of liquid para-hydrogen at two thermodynamic state points: a liquid near the triple point and a high-temperature liquid. Good agreement for the self-diffusion constant and for the real-time velocity autocorrelation function is obtained in comparison to experimental measurements and other theoretical predictions. Improvement of the methodology and future applications are discussed.     

Parametric description of cardiac vagal control

Heart rate variability (HRV) indices that reflect the magnitude of respiratory sinus arrhythmia (RSA) are commonly applied as non-invasive measures of cardiac vagal control. Recently, however, serious doubts have been raised about the accuracy and validity of such assessments. To evaluate these methods, we derived a theoretical model for the dependence of mean heart rate and RSA on gradual vagal blockade by atropine, and compared its predictions to actual experimental results. The experiment involved the injection of nine consecutive intravenous bolus doses of atropine to eight young healthy male subjects. Seven-minute recordings of ECG and respiration were made for each atropine dose. The heart rate (HR) signal was derived from the ECG recording, and mean heart rate and the power of the high frequency peak of HRV (which measures the magnitude of RSA) were computed. The experimental data were fitted to the model's equations, and optimal values were obtained for the model's parameters. A tight agreement is observed between the theoretical fitted curves and the experimental data. The parameters that were computed from fitting the experimental data to the mean heart rate equation display a surprisingly small variance among the different subjects. The parameters that were computed from fitting the experimental data to the RSA equation, and the resulting shape of these fitted curves, explain many of the conflicting results previously published, and provide a new quantitative insight to cardiac vagal activity.     

Progression of mouse mammary tumors: MCP-1-TNFalpha cross-regulatory pathway and clonal expression of promalignancy and antimalignancy factors

The progression of breast cancer is affected by multiple cellular and microenvironmental components. The monocyte chemoattractant MCP-1, IL-6 and matrix metalloproteinases (MMP) were suggested to promote, each on its own, breast cancer progression. We recently demonstrated that the high-tumorigenicity phenotype of the DA3 and CSML murine mammary adenocarcinoma cells is correlated with a high expression of MCP-1, IL-6 and MMP. This raised the possibility that common intrinsic tumor-derived factors regulate the concordant expression of these 3 components. The aim of the present study was to gain insight into the mode by which the secretion of MCP-1, IL-6 and MMP from murine mammary adenocarcinoma cells is regulated. This was investigated in cellular clones established from a highly malignant variant of the DA3 tumor (DA3-high). We also determined the secretion of the antimalignancy chemokine IP-10 from these cells. The results indicate that the secretion levels of IL-6, MMP and IP-10 varied between the clones. In contrast, all the clones secreted uniformly high levels of MCP-1, suggesting that MCP-1 constitutes an important feature of the malignancy phenotype of mammary carcinoma. In most of the clones, elevated levels of 1 of the 3 promalignancy factors did not correlate with a high expression of the other 2 factors and vice versa. These findings indicate that the 3 promalignancy factors are not coregulated by a common intrinsic tumor-derived factor. Rather, these results suggest that the individual capacities of the different clones to secrete these factors are summed up in the high-malignancy DA3 parental tumor population, which secretes relatively high levels of MCP-1, IL-6 and MMP as compared to DA3 cells expressing a low-malignancy phenotype. In contrast to the lack of coordinated intrinsic regulation of MCP-1, IL-6 and MMP, it was found that recombinant TNFalpha, a product of tumor-associated macrophages contributing to breast cancer progression, upregulated the secretion of MCP-1, IL-6 and MMP from all the clones. These results suggest a key role for this microenvironmental, monocyte-derived cytokine in the coordinated regulation of these 3 molecules. Furthermore, additional results demonstrated that monocytic cell-derived TNFalpha upregulated MCP-1 secretion from the tumor cells and that MCP-1 in turn promoted the secretion of TNFalpha from monocytic cells. This may result in a positive feedback loop, whereby the tumor cells and the monocytic cells at tumor site promote each other's ability to express and secrete promalignancy factors. We next attempted to assess the contribution of the promalignancy factors MCP-1, IL-6 and MMP and of the antimalignancy factor IP-10 to mammary adenocarcinoma progression. To this end, a preliminary formula was developed in which the net balance between secretion levels of the promalignancy factors and that of the antimalignancy IP-10 chemokine from different clones was related to their in vivo tumorigenicity profile. This formula suggests that a balance between the secretion levels of these factors plays an important role in determining the malignancy phenotype of mammary carcinomas. In all, our findings demonstrate that the mammary tumor cell population is composed of a heterogeneous assortment of clones whose individual characteristics are averaged in the whole population. The malignancy potential of such tumors is thus determined, inter alia, by a combinatorial effect of several promalignancy and antimalignancy factors secreted from each of the clones comprising these tumors. Our results also suggest that the expression of such factors is determined by several nonmutually exclusive regulatory mechanisms.