High level of extracellular potassium and its correlates after severe head injury: relationship to high intracranial pressure

OBJECT: Disturbed ionic and neurotransmitter homeostasis are now recognized as probably the most important mechanisms contributing to the development of secondary brain swelling after traumatic brain injury (TBI). Evidence obtained in animal models indicates that posttraumatic neuronal excitation by excitatory amino acids leads to an increase in extracellular potassium, probably due to ion channel activation. The purpose of this study was therefore to measure dialysate potassium in severely head injured patients and to correlate these results with measurements of intracranial pressure (ICP), patient outcome, and levels of dialysate glutamate and lactate, and cerebral blood flow (CBF) to determine the role of ischemia in this posttraumatic ion dysfunction. METHODS: Eighty-five patients with severe TBI (Glasgow Coma Scale Score < 8) were treated according to an intensive ICP management-focused protocol. All patients underwent intracerebral microdialyis. Dialysate potassium levels were analyzed using flame photometry, and dialysate glutamate and dialysate lactate levels were measured using high-performance liquid chromatography and an enzyme-linked amperometric method in 72 and 84 patients, respectively. Cerebral blood flow studies (stable xenon computerized tomography scanning) were performed in 59 patients. In approximately 20% of the patients, dialysate potassium values were increased (dialysate potassium > 1.8 mM) for 3 hours or more. A mean amount of dialysate potassium greater than 2 mM throughout the entire monitoring period was associated with ICP above 30 mm Hg and fatal outcome, as were progressively rising levels of dialysate potassium. The presence of dialysate potassium correlated positively with dialysate glutamate (p < 0.0001) and lactate (p < 0.0001) levels. Dialysate potassium was significantly inversely correlated with reduced CBF (p = 0.019). CONCLUSIONS: Dialysate potassium was increased after TBI in 20% of measurements. High levels of dialysate potassium were associated with increased ICP and poor outcome. The simultaneous increase in dialysate potassium, together with dialysate glutamate and lactate, supports the concept that glutamate induces ionic flux and consequently increases ICP, which the authors speculate may be due to astrocytic swelling. Reduced CBF was also significantly correlated with increased levels of dialysate potassium. This may be due to either cell swelling or altered vasoreactivity in cerebral blood vessels caused by higher levels of potassium after trauma. Additional studies in which potassium-sensitive microelectrodes are used are needed to validate these ionic events more clearly.

High extracellular potassium and its correlates after severe head injury: relationship to high intracranial pressure

Disturbed ionic and neurotransmitter homeostasis are now recognized to be probably the most important mechanisms contributing to the development of secondary brain swelling after traumatic brian injury (TBI). Evidence obtained from animal models indicates that posttraumatic neuronal excitation via excitatory amino acids leads to an increase in extracellular potassium, probably due to ion channel activation. The purpose of this study was therefore to measure dialysate potassium in severely head injured patients and to correlate these results with intracranial pressure (ICP), outcome, and also with the levels of dialysate glutamate, lactate, and cerebral blood flow (CBF) so as to determine the role of ischemia in this posttraumatic ionic dysfunction. Eighty-five patients with severe TBI (Glasgow Coma Scale score < 8) were treated according to an intensive ICP management-focused protocol. All patients underwent intracerebral microdialyis. Dialysate potassium levels were analyzed by flame photometry, as were dialysate glutamate and dialysate lactate levels, which were measured using high-performance liquid chromatography and an enzyme-linked amperometric method in 72 and 84 patients respectively. Cerebral blood flow studies (stable Xenon--computerized tomography scanning) were performed in 59 patients. In approximately 20% of the patients, potassium values were increased (dialysate potassium > 1.8 mmol). Mean dialysate potassium (> 2 mmol) was associated with ICP above 30 mm Hg and fatal outcome. Dialysate potassium correlated positively with dialysate glutamate (p < 0.0001) and lactate levels (p < 0.0001). Dialysate potassium was significantly inversely correlated with reduced CBF (p = 0.019). Dialysate potassium was increased after TBI in 20% of measurements. High levels of dialysate potassium were associated with increased ICP and poor outcome. The simultaneous increase of potassium, together with dialysate glutamate and lactate, supports the hypothesis that glutamate induces ionic flux and consequently increases ICP due to astrocytic swelling. Reduced CBF was also significantly correlated with increased levels of dialysate potassium. This may be due to either cell swelling or altered potassium reactivity in cerebral blood vessels after trauma.

Highly Substituted Isoxazoles: The Baylis-Hillman reaction of substituted 4-isoxazolecarbaldehydes and attempted cyclization to isoxazole-annulated derivatives

In an attempt to understand the effect of position of the formyl group on the efficiency of Baylis-Hillman reaction within isoxazolecarboxaldehydes, the reactions of substituted 4-isoxazolecarboxaldehydes to obtain highly substituted isoxazoles are described. Attempts to obtain isoxazole-annealed derivatives from these Baylis-Hillman adducts involving SNR’-SNAr substitu-tion strategy are also described.

Precise Near-to-Head Acoustics with Binaural Synthesis

For enhanced immersion into a virtual scene more than just the visual sense should be addressed by a Virtual Reality system. Additional auditory stimulation appears to have much potential, as it realizes a multisensory system. This is especially useful when the user does not have to wear any additional hardware, e.g., headphones. Creating a virtual sound scene with spatially distributed sources requires a technique for adding spatial cues to audio signals and an appropriate reproduction. In this paper we present a real-time audio rendering system that combines dynamic crosstalk cancellation and multi-track binaural synthesis for virtual acoustical imaging. This provides the possibility of simulating spatially distributed sources and, in addition to that, near-to-head sources for a freely moving listener in room-mounted virtual environments without using any headphones. A special focus will be put on near-to-head acoustics, and requirements in respect of the head-related transfer function databases are discussed.

Measurement and meaning of head movements in everyday face-to-face communicative interaction

Methodological approaches in which data on nonverbal behavior are collected usually involve interpretive methods in which raters must identify a set of defined categories of behavior. However, present knowledge about the qualitative aspects of head movement behavior calls for recording detailed transcriptions of behavior. These records are a prerequisite for investigating the function and meaning of head movement patterns. A method for directly collecting data on head movement behavior is introduced. Using small ultrasonic transducers, which are attached to various parts of an index person's body (head and shoulders), a microcomputer defines receiver-transducers distances. Three-dimensional positions are calculated by triangulation. These data are used for further calculations concerning the angular orientation of the head and the direction, size, and speed of head movements (in rotational, lateral, and sagittal dimensions).

Recurrence due to neoplastic seeding in head and neck cancer: report of two cases and review of the literature

AIMS AND BACKGROUND Tumor progression due to seeding of tumor cells after definitive treatment for squamous cell carcinomas of the head and neck is an uncommon condition that can considerably worsen the outcome of patients with head and neck cancer. METHODS AND STUDY DESIGN We report two cases of recurrence due to neoplastic seeding from oropharyngeal and oral cancer, respectively. We performed a literature review with MEDLINE as the main search engine. RESULTS Seeding was found to occur most often in tracheotomy scars and gastrostomy sites. The oral cavity, hypopharynx and oropharynx were the primary sites in most cases, and advanced tumor stage seemed to be a risk factor for seeding. Treatment options include salvage surgery, which requires thorough resections, radiotherapy when possible, and palliative management. The prognosis of such events is poor. CONCLUSION Although neoplastic seeding is a well-known phenomenon in cancer surgery, many questions remain unanswered, especially regarding preventive measures and management strategies.

Saddlepoint approximations to sensitivities of tail probabilities of random sums and comparisons with Monte Carlo estimators

This article proposes computing sensitivities of upper tail probabilities of random sums by the saddlepoint approximation. The considered sensitivity is the derivative of the upper tail probability with respect to the parameter of the summation index distribution. Random sums with Poisson or Geometric distributed summation indices and Gamma or Weibull distributed summands are considered. The score method with importance sampling is considered as an alternative approximation. Numerical studies show that the saddlepoint approximation and the method of score with importance sampling are very accurate. But the saddlepoint approximation is substantially faster than the score method with importance sampling. Thus, the suggested saddlepoint approximation can be conveniently used in various scientific problems.

Identification of gunshots to the head by detection of RNA in backspatter primarily expressed in brain tissue

Traces of backspatter recovered from the inside of the barrel of a gun that was used to deliver suicidal or homicidal contact shots may be a source of valuable forensic evidence and first systematic investigations of the persistence of victim DNA from inside firearms have been presented. The aim of the present study was to include victim RNA in such analyses to determine the origin of tissues in addition and parallel to standard DNA profiling for forensic identification purposes. In a first step, suitable mRNA (C1orf61) and micro-RNAs (miR-124a and miR-124*) that are primarily expressed in brain tissue were selected from potential candidates and confirmed using quantitative PCR (qPCR). Secondly, a co-extraction procedure for RNA and DNA was established and brain differentiability of the selected RNAs was demonstrated via qPCR using samples from experimental shots at ballistic models. In a third step, this procedure was successfully applied to analyse samples from real casework comprising eight cases of suicidal contact shots. In this pilot study, we are first to report the possibility of co-extracting mRNA, miRNA and DNA from ballistic trace samples collected from the inside of firearms and we demonstrate that RNA and DNA based analyses can be performed in parallel to produce informative and highly complementary evidence.

Outcomes in Advanced Head and Neck Cancer Treated with Up-front Neck Dissection prior to (Chemo)Radiotherapy.

OBJECTIVE Our aim was to compare outcomes with and without up-front neck dissection prior to (chemo)radiotherapy in head and neck squamous cell carcinoma. STUDY DESIGN Case series with chart review. SETTING Tertiary referral center. SUBJECTS AND METHODS Outcomes of oropharyngeal, laryngeal, and hypopharyngeal squamous cell carcinoma cases with neck lymph node metastases treated from January 2001 to March 2012 were analyzed. Due to imbalances in baseline characteristics between groups treated with (n = 129) and without (n = 95) up-front neck dissection, propensity score matching was performed. RESULTS Median follow-up was 48 months (range, 12-148). With up-front neck dissection, the hazard ratio for the primary end point, disease-free survival, was 0.63 (95% confidence interval: 0.37-1.06, P = .08). Up-front neck dissection reduced acute grade ≥3 toxicity significantly when xerostomia was excluded (odds ratio: 0.40, 95% confidence interval: 0.20-0.82, P = .012). CONCLUSION Our results indicate less acute treatment toxicity without any significant difference in terms of oncologic outcome with up-front neck dissection prior to (chemo)radiotherapy as compared with (chemo)radiotherapy alone. Well-designed randomized trials are required to verify this result and further investigate the impact of this strategy on late toxicity and oncologic outcome.

Contribution of transmembrane and cytoplasmic domains to membrane protein association

Membrane proteins are critical to every aspect of cell physiology, with their association mediating important biological functions. The transmembrane and cytoplasmic domains are known to be important for their association. In order to characterize their role in detail, we have applied different biophysical techniques in detergent micelles to two model systems. The first study involves FcRγ, a single transmembrane domain protein existing as a disulfide linked homodimer. We investigated the role of a conserved transmembrane polar residue and the cytoplasmic tail in FcRγ homo-interactions. Our results by various biophysical techniques including SDS-PAGE, circular dichroism and sedimentation equilibrium in detergent micelles indicate importance of both the transmembrane polar residue and cytoplasmic tail in maintaining proper conformation for FcRγ homo-interactions. A contrasting second study was on L-selectin, another single transmembrane domain protein with a large extracellular domain and a short cytoplasmic tail. Previous cross-linking experiments indicate its possible dimerization. However, the purified fragment of L-selectin and corresponding mutants did not dimerize when analyzed by TOXCAT assay, sedimentation equilibrium and fluorescence resonance energy transfer. It was likely that the presence of juxtamembrane positively charged residues led to decreased migrational rates in SDS PAGE. In conclusion, complementary biophysical techniques should be used with care when studying membrane protein association in detergent micelles. As an extension to our study on L-selectin, we also investigated its interaction with Calmodulin (CaM) in detergent micelles. CaM was found to interact with different detergents. We applied fluorescence and NMR spectroscopy to characterize the interaction of both the apo and Ca 2+ bound form of CaM, with commonly used detergents, below and above their respective critical micelle concentrations. The interaction of apo-CaM with detergents was found to vary with the nature of the detergent head group, whereas Ca2+-CaM interacted with individual detergent molecules irrespective of the nature of their head group. NMR titration experiments of CaM with detergents indicated involvement of specific residues from the N-lobe, linker and C-lobe of CaM. ^

Validity and reliability of using MVP 4 Function Walk4Life digital pedometers to assess physical activity levels among preschool-aged Head Start children

The Surgeon General recommends preschoolers 3-5 years old accumulate 60 minutes of moderate-to-vigorous physical activity (MVPA) per day. However, there is limited data measuring physical activity (PA) and MVPA amongst this population. The purpose of this cross-sectional study is to determine the validity, reliability, and feasibility of using MVP 4 Function Walk4Life digital pedometers (MVP-4) in measuring MVPA among preschoolers using the newly modified direct observational technique, System for Observing Fitness Instruction Time-Preschool Version (SOFIT-P) as the gold standard. An ethnically diverse population of 3-5 year old underserved children were recruited from two Harris County Department of Education (HCDE) Head Start centers. For 2 days at baseline and 2 days at post-test, 75 children enrolled wore MVP-4 pedometers for approximately 6-hours per observation day and were observed using SOFIT-P during predominantly active times. Statistical analyses used Pearson "r" correlation coefficients to determine mean minutes of PA and MVPA, convergent and criterion validity, and reliability. Significance was set at p = <0.05. Feasibility was determined through process evaluation information collected during this study via observations from data collectors and teacher input. Results show mean minutes of PA and MVPA ranged between 30-42 and 11-14 minutes, respectively. Convergent validity comparing BMI percentiles with MVP-4 PA outcomes show no significance at pre-test; however, each measurement at post-test showed significance for MVPA (p = 0.0247, p = 0.0056), respectively. Criterion validity comparing percent MVPA time between SOFIT-P and MVP-4 pedometers was determined; however, results deemed insufficient due to inconsistency in observation times while using the newly developed SOFIT-P. Reliability measures show no significance at pre-test, yet show significant results for all PA outcomes at post-test (p = 0.001, p = 0.001, p = 0.0010, p = 0.003), respectively. Finally, MVP-4 pedometers lacked feasibility due to logistical barriers in design. Researchers feel the significant results at post-test are secondary to increased familiarity and more accurate placement of pedometers across time. Researchers suggest manufacturers of MVP-4 pedometers further modify the instrument for ease of use with this population, following which future studies ought to determine validity using objective measures or all-day direct observation techniques.^

Molecular epidemiological studies on genetic predispositions to squamous cell carcinoma of the head and neck

Two molecular epidemiological studies were conducted to examine associations between genetic variation and risk of squamous cell carcinoma of the head and neck (SCCHN). In the first study, we hypothesized that genetic variation in p53 response elements (REs) may play roles in the etiology of SCCHN. We selected and genotyped five polymorphic p53 REs as well as a most frequently studied p53 codon 72 (Arg72Pro, rs1042522) polymorphism in 1,100 non-Hispanic White SCCHN patients and 1,122 age-and sex-matched cancer-free controls recruited at The University of Texas M. D. Anderson Cancer Center. In multivariate logistic regression analysis with adjustment for age, sex, smoking and drinking status, marital status and education level, we observed that the EOMES rs3806624 CC genotype had a significant effect of protection against SCCHN risk (adjusted odds ratio= 0.79, 95% confidence interval =0.64–0.98), compared with the -838TT+CT genotypes. Moreover, a significantly increased risk associated with the combined genotypes of p53 codon 72CC and EOMES -838TT+CT was observed, especially in the subgroup of non-oropharyneal cancer patients. The values of false-positive report probability were also calculated for significant findings. In the second study, we assessed the association between SCCHN risk and four potential regulatory single nucleotide polymorphisms (SNPs) of DEC1 (deleted in esophageal cancer 1) gene, a candidate tumor suppressor gene for esophageal cancer. After adjustment for age, sex, and smoking and drinking status, the variant -606CC (i.e., -249CC) homozygotes had a significantly reduced SCCHN risk (adjusted odds ratio = 0.71, 95% confidence interval = 0.52–0.99), compared with the -606TT homozygotes. Stratification analyses showed that a reduced risk associated with the -606CC genotype was more pronounced in subgroups of non-smokers, non-drinkers, younger subjects (defined as ≤ 57 years), carriers of TP53 Arg/Arg (rs1042522) genotype, patients with oropharyngeal cancer or late-stage SCCHN. Further in silico analysis revealed that the -249 T-to-C change led to a gain of a transcription factor binding site. Additional functional analysis showed that the -249T-to-C change significantly enhanced transcriptional activity of the DEC1 promoter and the DNA-protein binding activity. We conclude that the DEC1 promoter -249 T>C (rs2012775) polymorphism is functional, modulating susceptibility to SCCHN among non-Hispanic Whites. Additional large-scale, preferably population-based studies are needed to validate our findings.^