Mathematical Modeling of Human Glioma Growth Based on Brain Topological Structures: Study of Two Clinical Cases

Gliomas are the most common primary brain tumors and yet almost incurable due mainly to their great invasion capability. This represents a challenge to present clinical oncology. Here, we introduce a mathematical model aiming to improve tumor spreading capability definition. The model consists in a time dependent reaction-diffusion equation in a three-dimensional spatial domain that distinguishes between different brain topological structures. The model uses a series of digitized images from brain slices covering the whole human brain. The Talairach atlas included in the model describes brain structures at different levels. Also, the inclusion of the Brodmann areas allows prediction of the brain functions affected during tumor evolution and the estimation of correlated symptoms. The model is solved numerically using patient-specific parametrization and finite differences. Simulations consider an initial state with cellular proliferation alone (benign tumor), and an advanced state when infiltration starts (malign tumor). Survival time is estimated on the basis of tumor size and location. The model is used to predict tumor evolution in two clinical cases. In the first case, predictions show that real infiltrative areas are underestimated by current diagnostic imaging. In the second case, tumor spreading predictions were shown to be more accurate than those derived from previous models in the literature. Our results suggest that the inclusion of differential migration in glioma growth models constitutes another step towards a better prediction of tumor infiltration at the moment of surgical or radiosurgical target definition. Also, the addition of physiological/psychological considerations to classical anatomical models will provide a better and integral understanding of the patient disease at the moment of deciding therapeutic options, taking into account not only survival but also life quality

Homeostatic regulation of the endoneurial microenvironment during development, aging and in response to trauma, disease and toxic insult

The endoneurial microenvironment, delimited by the endothelium of endoneurial vessels and a multi-layered ensheathing perineurium, is a specialized milieu intérieur within which axons, associated Schwann cells and other resident cells of peripheral nerves function. The endothelium and perineurium restricts as well as regulates exchange of material between the endoneurial microenvironment and the surrounding extracellular space and thus is more appropriately described as a blood–nerve interface (BNI) rather than a blood–nerve barrier (BNB). Input to and output from the endoneurial microenvironment occurs via blood–nerve exchange and convective endoneurial fluid flow driven by a proximo-distal hydrostatic pressure gradient. The independent regulation of the endothelial and perineurial components of the BNI during development, aging and in response to trauma is consistent with homeostatic regulation of the endoneurial microenvironment. Pathophysiological alterations of the endoneurium in experimental allergic neuritis (EAN), and diabetic and lead neuropathy are considered to be perturbations of endoneurial homeostasis. The interactions of Schwann cells, axons, macrophages, and mast cells via cell–cell and cell–matrix signaling regulate the permeability of this interface. A greater knowledge of the dynamic nature of tight junctions and the factors that induce and/or modulate these key elements of the BNI will increase our understanding of peripheral nerve disorders as well as stimulate the development of therapeutic strategies to treat these disorders

Oral health-related quality of life and dental status in an outpatient psychiatric population: A multivariate approach

Research related to oral health in people with mental health problems may deepen our understanding of the quality of life of such individuals. This study aimed to investigate the relationship between oral status, health perceptions and life satisfaction, and their impacts on oral health-related quality of life (OHQoL). Data were collected from 113 patients in outpatient psychiatric care using a structured interview and an oral examination. Six multivariate models (one comprising the total population, three separate diagnostic groups, and two sex groups) investigated the variance in OHQoL. In the total population, the number of teeth, subjective life satisfaction, perception of physical health, sex, and relying on chance accounted for 40% of the variance. In the group consisting of patients diagnosed with schizophrenia 41% of the variance was explained by the variables 'number of teeth' and 'perception of physical health'. In the group diagnosed with mood disorders, the variable 'number of teeth' accounted for 58% of the variance. The variance in the remaining group of diagnoses was explained, up to 38%, by life satisfaction and reliance on chance. The sex models revealed significant differences: men considered the responsibility of caring for their oral health as a health matter, while women saw oral health as a more subjective issue. The perception of OHQoL was found to be dependent on the particular psychiatric diagnosis and sex. Such findings can be of use in the development of rehabilitation, as well as preventive strategies that could be individually tailored to maintain OHQoL and oral health

Analysis of the interleukin-1 and interleukin-6 polymorphisms in patients with chronic periodontitis. A pilot study

The aim of this study was to analyse whether the interleukin-1 (IL-1) and IL-6 gene polymorphisms were associated with the susceptibility of chronic periodontitis. Genomic DNA was obtained from 20 patients with chronic periodontitis and 31 periodontally healthy subjects. All subjects were of North European heritage. The test subjects were kept in a maintenance program after periodontal treatment but yet showing signs of recurrent disease. Genotyping of the IL-1 alpha[+4845C>T], IL-1 beta [-3954C>T] and IL-6 [-174G>C] polymorphisms was carried out using an allelic discrimination Assay-by-Design method on ABI PRISM 7900 Sequence Detection System. All genotypes were analyzed using the GeneMapper 2.0 software. A similar distribution of Single Nucleotide Polymorphism (SNP) was seen in both groups. Analysis by logistic regression including gender, IL-1 alpha [+4845C>T], IL-1 beta [-3954C>T], IL-6 [-174G>C] genotypes, the composite IL-1 genotype, the combination of the composite IL-1 genotype and the IL-6 -174G>C genotype and adjusting for smoking did not result in any statistically significant difference. SNPs in IL-1 alpha[+4845C>T], IL-1 beta [-3954C>T] and IL-6 [-174G>C] do not seem to increase the susceptibility to chronic periodontitis in this group of subjects

Pharmacokinetics of Levetiracetam during Pregnancy, Delivery, in the Neonatal Period, and Lactation

Purpose: To study pharmacokinetics of levetiracetam (LEV) during pregnancy, delivery, lactation, and in the neonatal period. Methods: Fourteen women with epilepsy receiving LEV treatment during pregnancy and lactation contributed with 15 pregnancies to this prospective study in which LEV concentrations in plasma and breast milk were determined. Trough maternal plasma samples were collected each trimester, and at baseline after delivery. Blood samples were obtained at delivery from mothers, from the umbilical cord, and from newborns during 2 days after delivery. LEV concentration was also determined in breast milk and in plasma collected from 11 of the mothers and their suckling infants after birth. Results: The umbilical cord/maternal plasma concentration ratios ranged from 0.56-2.0 (mean 1.15, n = 13). LEV plasma concentrations in the neonates declined with an estimated half-life of 18 h (n = 13). The mean milk/maternal plasma concentration ratio was 1.05 (range, 0.78-1.55, n = 11). The infant dose of LEV was estimated to 2.4 mg/kg/day, equivalent to 7.9% of the weight-normalized maternal dose. Plasma concentrations in breastfed were approximately 13% of the mother's plasma levels. Maternal plasma concentrations during third trimester were only 40% of baseline concentrations outside pregnancy (p < 0.001, n = 7) Conclusions: Our observations suggest considerable transplacental transport of LEV and fairly slow elimination in the neonate. Plasma concentrations of LEV in nursed infants are low despite an extensive transfer of LEV into breast milk. Pregnancy appears to enhance the elimination of LEV resulting in marked decline in plasma concentration, which suggests that therapeutic monitoring may be of value

Pharmacokinetics of levetiracetam during pregnancy, delivery, in the neonatal period, and lactation

Purpose: To study pharmacokinetics of levetiracetam (LEV) during pregnancy, delivery, lactation, and in the neonatal period. Methods: Fourteen women with epilepsy receiving LEV treatment during pregnancy and lactation contributed with 15 pregnancies to this prospective study in which LEV concentrations in plasma and breast milk were determined. Trough maternal plasma samples were collected each trimester, and at baseline after delivery. Blood samples were obtained at delivery from mothers, from the umbilical cord, and from newborns during 2 days after delivery. LEV concentration was also determined in breast milk and in plasma collected from 11 of the mothers and their suckling infants after birth. Results: The umbilical cord/maternal plasma concentration ratios ranged from 0.56-2.0 (mean 1.15, n = 13). LEV plasma concentrations in the neonates declined with an estimated half-life of 18 h (n = 13). The mean milk/maternal plasma concentration ratio was 1.05 (range, 0.78-1.55, n = 11). The infant dose of LEV was estimated to 2.4 mg/kg/day, equivalent to 7.9% of the weight-normalized maternal dose. Plasma concentrations in breastfed were approximately 13% of the mother's plasma levels. Maternal plasma concentrations during third trimester were only 40% of baseline concentrations outside pregnancy (p < 0.001, n = 7) Conclusions: Our observations suggest considerable transplacental transport of LEV and fairly slow elimination in the neonate. Plasma concentrations of LEV in nursed infants are low despite an extensive transfer of LEV into breast milk. Pregnancy appears to enhance the elimination of LEV resulting in marked decline in plasma concentration, which suggests that therapeutic monitoring may be of value