On a doubly reduced model for dynamics of heterogeneous mixtures of stiffened gases, its regularizations and their implementations.

We deal with the reduced four-equation model for the dynamics of heterogeneous compressible binary mixtures with the stiffened gas equations of state. We study its further reduced form, with the excluded volume concentrations, and with a quadratic equation for the common pressure of the components; this form can be called a quasi-homogeneous form. We prove new properties of the equation, derive simple formulas for the squared speed of sound, and present an alternative proof for a formula that relates it to the squared Wood speed of sound; also, a short derivation of the pressure balance equation is given. For the first time, we introduce regularizations of the heterogeneous model (in the quasi-homogeneous form). Previously, regularizations of such types were developed only for the homogeneous mixtures of perfect polytropic gases, and it was unclear how to cover the case considered here. In the 1D case, based on these regularizations, we construct new explicit two-level in time and symmetric three-point in space finite-difference schemes without limiters and provide numerical results for various flows with shock waves.

The incidence of hyperthermia during cochlear implant surgery in children.

BACKGROUND: Inadvertent hyperthermia during anaesthesia is a rare but life-threatening complication. We have encountered several cases of severe hyperthermia in paediatric patients undergoing anaesthesia for cochlear implantation. METHODS: This study aimed to describe the clinical characteristics of children who developed hyperthermia while undergoing cochlear implantation, and to explore possible mechanisms and predisposing factors. The anaesthetic charts of all patients aged under 18 years who underwent cochlear implantation, or mastoid or ophthalmic surgery, between 1 January 2006 and 31 December 2009, at Soroka Medical Center in Beer Sheva, Israel, were reviewed. Patients undergoing mastoid and ophthalmic surgical procedures were used as controls. RESULTS: A larger percentage of patients who underwent cochlear implant surgery (10 per cent) developed hyperthermia compared to controls (0.7 per cent, p < 0.05). In five of the seven cases, hyperthermia appeared in combination with tachycardia and hypercapnia, adhering to the clinical triad of malignant hyperthermia. CONCLUSION: Patients undergoing cochlear implantation are susceptible to developing intra-operative hyperthermia. This article describes the hyperthermic events that occur during paediatric cochlear implantation, and attempts to identify potential triggers of hyperthermia.

Puerperal ventral epidural hematoma after epidural labor analgesia.

Serious complications in obstetric anesthesia are a rare occurrence. High neuraxial block, respiratory arrest in labor and delivery, and an unrecognized spinal catheter are among the most frequently reported serious complications. A serious complication occurs in approximately 1:3000 obstetric patients. Neuraxial hematoma after obstetric epidural analgesia or anesthesia is extremely rare. We present a case of a puerperal spinal epidural hematoma following epidural labor analgesia. The patient presented with foot drop, which resolved after conservative treatment. We reviewed the epidemiology, clinical manifestations and treatment options for this rare complication.

Tspan33 is Expressed in Transitional and Memory B Cells, but is not Responsible for High ADAM10 Expression.

Tetraspanins are a family of transmembrane proteins that form membrane microdomains. They play important roles in migration, adhesion and other cellular processes. TspanC8, a subfamily of tetraspanins, was found to associate and promote ADAM10 trafficking and cell surface localization. One of its members, Tspan33, is expressed in activated B cells. Using RT-PCR and flow cytometry, we analysed the pattern of expression of Tspan33 in B cells from healthy donors. We found Tspan33 expression in early and late stages of B cell development. However, Tspan33 expression did not correlate with ADAM10 surface expression. We also found expression of Tspan33 early in the activation process. Given its predominant expression in activated B cells and in several lymphomas, but not in naive B cells, we hypothesize that Tspan33 could be a potential target for therapeutic purposes.

Allergic sensitization to pegylated interferon-α results in drug eruptions.

BACKGROUND: The introduction of pegylated interferon (PEG-IFN)-α in the treatment of chronic hepatitis C has led to an increase in sustained virological response. Despite reduced immunogenicity of the pegylated form in comparison with native interferon (IFN)-α, a high frequency of adverse cutaneous reactions has been reported with pegylated IFN-α. Here, we aimed to investigate the immunological mechanisms underlying pegylated IFN-α-induced drug eruptions. METHODS: Hepatitis C patients suffering from drug eruptions in association with administration of pegylated interferons were enrolled in the study (n = 22). Subjects were tested for sensitivity to pegylated IFN-α2a , pegylated IFN-α2b , or ribavirin using intradermal, scratch, and/or patch tests, as well as lymphocyte activation tests (LATs). Skin biopsies obtained from pegylated IFN-α-associated exanthemas, as well as from localized inflammatory skin reactions at pegylated IFN-α injection sites, were analyzed for the expression of relevant chemokines by quantitative real-time PCR and immunohistochemistry. RESULTS: A subset of patients suffering from pegylated IFN-α-associated exanthemas displayed positive intradermal tests to PEG-IFNs but not to conventional IFN (11/22). In selected patients, this observation correlated with the presence of pegylated IFN-specific T cells (3/11). Chemokine profiles of inflammatory skin reactions at the injection sites reflected an IFN-α-signature, whereas lesional skin of exanthemas showed induction of TH2-associated chemokines. CONCLUSIONS: Our results indicate that specific sensitizations are one cause of exanthemas under therapy with PEG-IFNs. Clinical proof-of-concept analyses demonstrate that affected patients may benefit from a switch to conventional, nonpegylated drugs, enabling IFN-α therapy continuation without drug-associated skin eruptions.

Neutrophil functions in morbidly obese subjects.

The present study aimed to determine different peripheral blood neutrophil functions in 18 morbidly obese subjects with body mass index (BMI) ranging between 35 and 69 kg/m(2) in parallel with age- and gender-matched lean controls. Peripheral blood neutrophil functions of obese subjects and matched lean controls were determined. Neutrophils of obese subjects showed significant elevation of the release of basal superoxides (P < 0.0001), formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated superoxides (P < 0.0001) and opsonized zymosan (OZ)-stimulated superoxides (P < 0.045) compared with lean controls. Interestingly, there were no differences in phorbol myristate acetate (PMA)-stimulated superoxide production by neutrophils of the obese subjects and controls. There was also a significant elevation of chemotactic (P < 0.0003) and random (P < 0.0001) migration of neutrophils from obese subjects compared with lean controls. Phagocytosis, CD11b surface expression and adherence of neutrophils from obese subjects were not significantly different from those of the lean controls. The elevated superoxide production and chemotactic activity, together with the normal phagocytosis and adherence, suggest that neutrophils from obese subjects are primed and have the capability to combat infections. However, neutrophils in the priming state may participate in the pathogenesis of obesity-related diseases.

A comparison between amylase levels from peritonsillar, dental and neck abscesses.

OBJECTIVES: Pus of peritonsillar abscess (PTA) contains very high amylase levels in some patients. The objective of this study was to further test this finding and to check whether high amylase levels in peritonsillar abscess originate from contamination by saliva during aspiration. STUDY DESIGN: Prospective study. SETTING: Tertiary care university hospital. PARTICIPANTS: The study includes 64 patients with PTA, 8 patients with a neck abscess and 12 patients with a dental abscess. MAIN OUTCOME MEASURE: Amylase levels of pus and serum were compared between the groups. Clinical data regarding hospitalisation length, recurrence rate and previous antibiotic treatment were also collected. RESULTS: Mean amylase levels in the pus of the PTA group were 3045 U/L (median 59 U/L), 13 U/L in the neck abscess group (P = 0.001) and 22 U/L in the dental abscess group (P = 0.001). Mean serum amylase was higher in the PTA group; PTA - 50 U/L, neck abscess - 37 U/L (P = 0.002) and dental abscess - 26 U/L (P < 0.002). All of the patients with amylase levels above 65 U/L had a first episode of PTA. In contrast, 40% of patients with amylase lower than 65 U/L had recurrent PTA (P = 0.003). CONCLUSION: A clear association is seen between minor salivary glands and peritonsillar abscess. The high amylase level in peritonsillar pus is not from contamination with saliva.

Iodine-induced hyperthyroidism-an old clinical entity that is still relevant to daily ICU practice: a case report.

Objective. Hyperthyroidism has been described as elevated serum free T3 and/or free T4 levels with decreased thyrotropin (TSH) concentrations. The main causes are related to autoimmune and neoplastic pathology. However, it might be caused due to a long-term topical exposure (iodine solution dressing) or by intravenous administration of iodine-containing substances. Both clinical and laboratory features might be presented. The main management is based on interruption of all exposures with iodine solutions and also antithyroid medicine in case of severe laboratory and clinical disturbances. Data Sources. We present a case of iodine-induced hyperthyroidism in a critically ill ICU patient caused by excessive iodine containing antiseptic solution washes and contrast agent administration. The patient was successfully treated by discontinuing iodine exposure and beta-blocker administration. Conclusions. In patients with underlying thyroid gland pathology, thyroid-function tests and clinical observation in the ICU are of critical importance.

Civilian injuries due to unexploded ordnance in military training areas in southern Israel.

BACKGROUND: The problem of unexploded ordnance (UXO) is global and is usually associated with active or former war zones. Civilian injuries due to UXO in military training areas are not common. METHODS: This is a retrospective case series study based on prospectively collected data on patients who sustained injuries from UXO explosions and were admitted to the Soroka University Trauma Center during a five-year period. RESULTS: Twelve patients were included in this series. All patients were Bedouin and the distribution of injuries was concentrated around the head and upper and lower extremities, with sparing of the torso. CONCLUSION: Awareness and implementation of preventive measures are expected to reduce the incidence of this type of injury.

Traumatic page kidney induced hypertension in critical care: immediately resolved or long-term resistant problem.

Page kidney is a well-known phenomenon causing hypertension, due to compression of renal parenchyma by a subcapsular hematoma, of either traumatic or non-traumatic origin. The main therapeutic approach is based on surgical approach (nephrectomy or hematoma evacuation) and antihypertensive treatment. In this paper we present a post-traumatic case of Page Kidney in a Critical Care unit. We discuss different therapeutical opportunities to extremely elevated systemic blood pressure resistant to traditional drug therapy.

Homeostasis of glutamate in brain fluids: an accelerated brain-to-blood efflux of excess glutamate is produced by blood glutamate scavenging and offers protection from neuropathologies.

L-Glutamate (Glu) homeostasis in brain extracellular fluids and its maintenance at low micromolar concentrations in the face of the extremely high Glu concentrations present in brain cells and synaptic vesicles have been commonly attributed to the very effective action of glutamate transporters present on neuronal and glial cells. This view however does not take into account the fact that the brain is highly vascularized and that the vasculature harbors a high density of glutamate transporters. In this article, we review the accumulated data establishing the existence of an efflux of excess Glu from brain extracellular fluids into blood. We describe plausible mechanisms accounting for this efflux and present evidence that the brain-to-blood Glu efflux is modulated by blood Glu levels and can be accelerated by blood Glu scavenging. The latter procedure shown here to afford brain neuroprotection in a rat model of closed head injury could be applicable, as a first-line therapy, in the various acute brain insults characterized by excess Glu in brain fluids.

New insights on the role of CXCR4 in cancer metastasis.

The evolutionarily conserved chemokine superfamily encodes small peptide molecules that bind G-protein-coupled receptors. In humans, this superfamily includes at least 46 ligands and 18 receptors. In general, chemokines and their receptors form a chemotactic network that regulates the migration of cells to specific micro-anatomical destinations within an organism in an organized and non-random manner. Recent studies place chemokine-chemokine receptor pairs at the centre of not only physiological cell migration, but also pathological processes such as metastasis. This mini review considers some recent data on how chemokines regulate tumour cells during metastasis. These observations suggest novel ways for pharmacological intervention.

Gene array analysis comparison between rat collagen-induced arthritis and human rheumatoid arthritis.

Collagen-induced arthritis (CIA) is an experimental arthritis model used to study the inflammatory processes in this disease and test potential therapeutics. In order to better characterize this model, we conducted the first comprehensive gene expression analysis of rat CIA. To evaluate how closely the rat model reflects human rheumatoid arthritis (RA), we also analysed gene expression in human RA, using genome-wide Affymetrix gene arrays. By applying multiple strategies, including comparison of the highest induced genes, expression of immunological-associated genes as well as Ingenuity Pathway Analysis (IPA), we were able to compare the two expression profiles. Among the highest induced genes in RA were several B-cell-associated genes, including immunoglobulins, B-cell markers such as CD20, and cytokines and chemokines that act on B cells such as TNFSF13b/BLyS and CXCL13, none of which was upregulated in CIA. The latter was instead characterized by the upregulation of genes expressed primarily in macrophages and dendritic cells. Of the 22 pathways identified as significant in both diseases by IPA, only three (IL6, chemokine signalling and antigen presentation) were present in both settings. We conclude that there are significant differences in the inflammatory mechanisms between human RA and rat CIA, and that genome-wide comparative gene expression analyses are useful tools to evaluate the relevance of animal models to human disease.

Acoustic monitoring of lung sounds for the detection of one-lung intubation.

INTRODUCTION: Monitoring methods for the early diagnosis of one-lung intubation (OLI) are nonspecific and controversial. In this study, we evaluated a new acoustic monitoring system for the detection of OLI. METHODS: Lung sounds were collected from 24 adult surgical patients scheduled for routine surgical procedures. Four piezoelectric microphones attached to the patients' backs were used to sample lung sounds during induction of anesthesia and endotracheal tube positioning. To achieve OLI, the endotracheal tube was inserted and advanced down the airway so that diminished or no breath sounds were heard on the left side of the chest. The tube was then withdrawn stepwise until equal breath sounds were heard. Fiberoptic bronchoscopy confirmed the tube's final position. Acoustic analyses were preformed by a new algorithm which assumes a Multiple Input Multiple Output system, in which a multidimensional Auto-Regressive model relates the input (lungs) and the output (recorded sounds) and a classifier, based on a Generalized Likelihood Ratio Test, indicates the number of ventilated lungs without reconstructing the original lung sounds from the recorded samples. RESULTS: This algorithm achieved an OLI detection probability of 95.2% with a false alarm probability of 4.8%. CONCLUSION: Higher detection values can be achieved at the price of a higher incidence of false alarms.

Molecular characterization of human adenomyosis.

Adenomyosis is a common gynaecological disorder characterized by the abnormal growth of endometrium into the myometrium and myometrial hypertrophy/hyperplasia. Uterine fibroids are benign neoplasms of the myometrium, and they represent a diagnostic pitfall for adenomyosis. In this study, we have used the genome-wide Affymetrix U133 Plus 2.0 microarray platform to compare the gene expression patterns of adenomyosis, uterine fibroids, normal endometrium and myometrium. Unsupervised principal component analysis (PCA) revealed that these four tissue types could be segregated from one another solely based on their gene expression profiles. Analysis of variance (ANOVA), followed by Tukey means separation test, significance analysis of microarrays (SAM) and 2-fold change threshold, identified 7415 probe sets as differentially expressed among the four groups of samples. Supervised cluster analysis based on these probe sets clustered adenomyosis most closely with endometrium and uterine fibroids with myometrium, consistent with the anatomic origin of these two diseases. The Tukey means separation post hoc testing found 2073 probe sets altered between adenomyosis and normal endometrium or myometrium, and 2327 probe sets altered in expression when comparing uterine fibroids with myometrium. Using Ingenuity Pathways Analysis (IPA), we found 9 highly significant functional networks in adenomyosis and 10 in uterine fibroids. Notably, the top network in both cases was associated with functions implicated in cancer and cell death. Finally, we compared the gene expression profiles of adenomyosis and uterine fibroids and identified 471 differentially expressed probe sets that may represent potential biomarkers for the differential diagnosis of these diseases.

Experimental autoimmune encephalomyelitis develops in CC chemokine receptor 7-deficient mice with altered T-cell responses.

CC chemokine receptor 7 (CCR7) is involved in the initiation of immune responses by mediating the migration of naïve T cells and mature dendritic cells to T-cell-rich zones of secondary lymphoid organs where antigen presentation occurs. To address whether CCR7 plays a role in the development of autoimmunity, we induced experimental autoimmune encephalomyelitis in CCR7-deficient mice on a C57BL/6 background (CCR7(-/-)) using the neuroantigen, myelin oligodendrocyte glycoprotein 35-55 amino acid peptide (MOG((35-55))) and Bordetella pertussis toxin (PTX). CCR7(-/-) mice acquired disease with an intensity similar to wild-type littermates. MOG((35-55))-specific lymphocyte responses were dominant in the spleen of CCR7(-/-) mice, rather than in lymph nodes as observed in wild-type mice. These results indicate that effective immune responses (with altered kinetics) can develop in the absence of CCR7 but develop in the spleen rather than lymph nodes as CCR7 is necessary for T and dendritic cells to enter lymph nodes.

CCL18/DC-CK-1/PARC up-regulation in hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is a lung inflammatory disorder characterized by accumulation of T lymphocytes. However, the mechanisms implicated in this process remain undefined. We examined the expression of dendritic cell (DC)-derived CC chemokine 1 (CK1)/CCL18, a chemokine putatively involved in naive T cell recruitment, in lungs from 10 patients with HP, 9 patients with idiopathic pulmonary fibrosis (IPF), and 20 healthy lungs. CCL18 was measured by real-time quantitative PCR and localized in lungs by in situ hybridization and immunohistochemistry. CCL18 expression was significantly increased in lungs affected by HP in comparison with lungs affected by IPF (2,085+/-393 vs. 1,023+/-110; P<0.05) and controls (2,085+/-393 vs. 467+/-94; P<0.01). Macrophages, DCs, and alveolar epithelial cells were the main sources of CCL18. There was a direct correlation between the levels of tissue CCL18 and the number of lymphocytes in the bronchoalveolar lavage fluids. High levels of CCL18 were detected in the subacute rather than the chronic phase of HP. These findings suggest a role for CCL18 in the pathogenesis of HP.

Involvement of chemokine receptors in breast cancer metastasis.

Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1alpha and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells.

Aberrant in vivo T helper type 2 cell response and impaired eosinophil recruitment in CC chemokine receptor 8 knockout mice.

Chemokine receptors transduce signals important for the function and trafficking of leukocytes. Recently, it has been shown that CC chemokine receptor (CCR)8 is selectively expressed by Th2 subsets, but its functional relevance is unclear. To address the biological role of CCR8, we generated CCR8 deficient (-/-) mice. Here we report defective T helper type 2 (Th2) immune responses in vivo in CCR8(-/)- mice in models of Schistosoma mansoni soluble egg antigen (SEA)-induced granuloma formation as well as ovalbumin (OVA)- and cockroach antigen (CRA)-induced allergic airway inflammation. In these mice, the response to SEA, OVA, and CRA showed impaired Th2 cytokine production that was associated with aberrant type 2 inflammation displaying a 50 to 80% reduction in eosinophils. In contrast, a prototypical Th1 immune response, elicited by Mycobacteria bovis purified protein derivative (PPD) was unaffected by CCR8 deficiency. Mechanistic analyses indicated that Th2 cells developed normally and that the reduction in eosinophil recruitment was likely due to systemic reduction in interleukin 5. These results indicate an important role for CCR8 in Th2 functional responses in vivo.