Search results for: cerebral ischemia

Authors: Magdy Al Shourbagi

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Diabetes mellitus is the commonest cause of neuropathy. The common pattern is a distal symmetrical sensory polyneuropathy, associated with autonomic disturbances. Less often, Diabetes mellitus is responsible for a focal or multifocal neuropathy. Common causes for non-healing of diabetic foot are the infection and ischemia. Diabetes mellitus is associated with a defective cellular and humoral immunity. Particularly, decreased phagocytosis, decreased chemotaxis, impaired bacterial killing and abnormal lymphocytic function resulting in a reduced inflammatory reaction and defective wound healing. Hyperbaric oxygen therapy is defined by the Undersea and Hyperbaric Medical Society as a treatment in which a patient intermittently breathes 100% oxygen and the treatment chamber is pressurized to a pressure greater than sea level (1 atmosphere absolute). The pressure increase may be applied in mono-place (single person) or multi-place chambers. Multi-place chambers are pressurized with air, with oxygen given via face mask or endotracheal tube; while mono-place chambers are pressurized with oxygen. Oxygen gas plays an important role in the physiology of wound healing. Hyperbaric oxygen therapy can raise tissue oxygen tensions to levels where wound healing can be expected. HBOT increases the killing ability of leucocytes also it is lethal for certain anaerobic bacteria and inhibits toxin formation in many other anaerobes. Multiple anecdotal reports and studies in HBO therapy in diabetic patients report that HBO can be an effective adjunct therapy in the management of diabetic foot wounds and is associated with better functional outcomes.

Keywords: hyperbari oxygen therapy, diabetic foot, neuropathy, multiplace chambers

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Authors: Artem Kim, Clara Savary, Christele Dubourg, Wilfrid Carre, Houda Hamdi-Roze, Valerie Dupé, Sylvie Odent, Marie De Tayrac, Veronique David

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Holoprosencephaly (HPE) is a rare congenital brain malformation resulting from the incomplete separation of the two cerebral hemispheres. It is characterized by a wide phenotypic spectrum and a high degree of locus heterogeneity. Genetic defects in 16 genes have already been implicated in HPE, but account for only 30% of cases, suggesting that a large part of genetic factors remains to be discovered. HPE has been recently redefined as a complex multigenic disorder, requiring the joint effect of multiple mutational events in genes belonging to one or several developmental pathways. The onset of HPE may result from accumulation of the effects of multiple rare variants in functionally-related genes, each conferring a moderate increase in the risk of HPE onset. In order to decipher the genetic basis of HPE, unconventional patterns of inheritance involving multiple genetic factors need to be considered. The primary objective of this study was to uncover possible disease causing combinations of multiple rare variants underlying HPE by performing trio-based Whole Exome Sequencing (WES) of familial cases where no molecular diagnosis could be established. 39 families were selected with no fully-penetrant causal mutation in known HPE gene, no chromosomic aberrations/copy number variants and without any implication of environmental factors. As the main challenge was to identify disease-related variants among a large number of nonpathogenic polymorphisms detected by WES classical scheme, a novel variant prioritization approach was established. It combined WES filtering with complementary gene-level approaches: transcriptome-driven (RNA-Seq data) and clinically-driven (public clinical data) strategies. Briefly, a filtering approach was performed to select variants compatible with disease segregation, population frequency and pathogenicity prediction to identify an exhaustive list of rare deleterious variants. The exome search space was then reduced by restricting the analysis to candidate genes identified by either transcriptome-driven strategy (genes sharing highly similar expression patterns with known HPE genes during cerebral development) or clinically-driven strategy (genes associated to phenotypes of interest overlapping with HPE). Deeper analyses of candidate variants were then performed on a family-by-family basis. These included the exploration of clinical information, expression studies, variant characteristics, recurrence of mutated genes and available biological knowledge. A novel bioinformatics pipeline was designed. Applied to the 39 families, this final integrated workflow identified an average of 11 candidate variants per family. Most of candidate variants were inherited from asymptomatic parents suggesting a multigenic inheritance pattern requiring the association of multiple mutational events. The manual analysis highlighted 5 new strong HPE candidate genes showing recurrences in distinct families. Functional validations of these genes are foreseen.

Keywords: complex genetic disorder, holoprosencephaly, multiple rare variants, whole exome sequencing

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Authors: Vallejo Michael, Acuña Edgar, Roa Juan David, Peñuela Rosa, Parra Alejandra, Casallas Daniela, Rodriguez Sheyla

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Congenital Zika Virus Syndrome is an entity composed by a variety of birth defects presented in newborns that have been exposed to the Zika Virus during pregnancy. The syndrome characteristic features are severe microcephaly, cerebral tissue abnormalities, ophthalmological abnormalities such as uveitis and chorioretinitis, arthrogryposis, clubfoot deformity and muscular tone abnormalities. The confirmatory test is the Reverse transcription polymerase chain reaction (RT-PCR) associated to the physical findings. Here we present the case of a newborn with microcephaly whose mother presented a confirmed Zika Virus infection during the third trimester of pregnancy, despite of the evident findings and the history of Zika infection the RT-PCR in amniotic and cerebrospinal fluid of the newborn was negative. RT-PCR has demonstrated a low sensibility in samples with low viral loads, reason why, we propose a clinical diagnosis in patients with clinical history of Zika Virus infection during pregnancy accompanied by evident clinical manifestations of the child.

Keywords: congenital, Zika virus, microcephaly, reverse transcriptase polymerase chain reaction

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Authors: Reem Al-Garni

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Malnutrition is a global epidemic, but the under-weight or Failure-To-Thrive risk is increasing in rehabilitation setting and considered one of the contribution factor for developmental delay. Beside the consequences of malnutrition on children growth and development, there are other side-effects that might delay or hold the progress of rehabilitation. The awareness for malnutrition must be raised and discussed by the rehabilitation team, to promote the treatment and to optimize the client care. The solution can start from food supplements intake and / or Enteral Nutrition plan, depending on the malnutrition level and to reach the goal, the medical team should to work together in order to provide comprehensive treatment and to help the family to be able to manage their child condition. We have explore the outcomes of rehabilitation between the children with CP whose diagnosed with malnutrition and children with normal body Wight Over a period of 4 months who received 4-6 weeks of rehabilitation two hours daily by using WeeFIM score to measure rehabilitation outcomes. WeeFIM measures and covers various domains, such as: self-care, mobility, locomotion, communication and other psycho-social aspects. Our findings reported that children with normal body Wight has better outcomes and improvement comparing with children with malnutrition for the entire study sample.

Keywords: Cerebral Palsy (CP), pediatric Functional Independent Measure (WeeFIM), rehabilitation, malnutrition

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Authors: Eyad Talal Attar

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Epilepsy is a prevalent neurological condition that impacts a considerable population of around 50 million individuals globally, rendering it one of the most widespread neurological disorders. The condition is distinguished by recurring seizures, which are abrupt and transient disruptions in a cerebral activity that can induce alterations in perception, conduct, and awareness. Seizures can be classified as focal or generalized, based on the specific site and scope of the atypical brain activity. Focal seizures are identified by confinement to a particular brain area and can elicit localized manifestations. Generalized seizures are identified by extensive electrical activity throughout the brain, and they can appear in various symptoms such as convulsions, muscle rigidity, and loss of consciousness. This study represents seven individuals chosen according to the number of seizures in the range of three to five seizure and investigates the ability to detect brain seizure activity. The EEG recording Siena Scalp Database was used from PhysioNet databases. EEGLAB is a robust tool utilized for processing and analyzing electroencephalogram (EEG) data and is used to analyze the raw data. The efficacy of Independent Component Analysis ICA algorithms has been demonstrated in the separation of arterial EEG sources and neuronal-generated EEG sources.

Keywords: EEG, MATLAB software, power spectral density, PSD, signal analysis, attention, alpha, beta, gamma

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Authors: Y. Ruchi, A. Prerna, S. Deepshikha

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Amyotrophic lateral sclerosis (ALS), also known as “Lou Gehrig’s disease”. It is a neurodegenerative disease associated with degeneration of motor neurons in the cerebral cortex, brain stem, and spinal cord characterized by distal muscle weakness, atrophy, normal sensation, pyramidal signs and progressive muscular paralysis reflecting. ALS2 is a juvenile autosomal recessive disorder, slowly progressive, that maps to chromosome 2q33 and is associated with mutations in the alsin gene, a putative GTPase regulator. In this paper we have done homology modeling of alsin2 protein using multiple templates (3KCI_A, 4LIM_A, 402W_A, 4D9S_A, and 4DNV_A) designed using the Prime program in Schrödinger software. Further modeled structure is used to identify effective binding sites on the basis of structural and physical properties using sitemap program in Schrödinger software, structural and function analysis is done by using Prosite and ExPASy server that gives insight into conserved domains and motifs that can be used for protein classification. This paper summarizes the structural, functional and binding site property of alsin2 protein. These binding sites can be potential drug target sites and can be used for docking studies.

Keywords: ALS, binding site, homology modeling, neuronal degeneration

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Authors: Masaki Yamaguchi, Daimei Sasayama, Shinsuke Washizuka

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The goal of this study was to examine the possibility of salivary cytokines for the screening of attention deficit hyperactivity disorder (ADHD) in children. We carried out a case-control study, including 19 children with ADHD and 17 healthy children (controls). A multiplex bead array immunoassay was used to conduct a multi-analysis of 27 different salivary cytokines. Six salivary cytokines (interleukin (IL)-1β, IL-8, IL12p70, granulocyte colony-stimulating factor (G-CSF), interferon gamma (IFN-γ), and vascular endothelial growth factor (VEGF)) were significantly associated with the presence of ADHD (p < 0.05). An informative salivary cytokine panel was developed using VEGF by logistic regression analysis (odds ratio: 0.251). Receiver operating characteristic analysis revealed that assessment of a panel using VEGF showed “good” capability for discriminating between ADHD patients and controls (area under the curve: 0.778). ADHD has been hypothesized to be associated with reduced cerebral blood flow in the frontal cortex, due to reduced VEGF levels. Our study highlights the possibility of utilizing differential salivary cytokine levels for point-of-care testing (POCT) of biomarkers in children with ADHD.

Keywords: cytokine, saliva, attention deficit hyperactivity disorder, child

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Authors: Somojit Saha, Rohit K. Chatterjee, Sarit K. Das, Avijit Kar

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A new force field is designed for propagation of the parametric contour into deep narrow cortical fold in the application of knowledge based reconstruction of cerebral cortex from MR image of brain. Designing of this force field is highly inspired by the Generalized Gradient Vector Flow (GGVF) model and markedly differs in manipulation of image information in order to determine the direction of propagation of the contour. While GGVF uses edge map as its main driving force, the newly designed force field uses the map of distance between zero valued pixels and their nearest non-zero valued pixel as its main driving force. Hence, it is called Zero-Non-Zero Distance (ZNZD) force field. The objective of this force field is forceful propagation of the contour beyond spurious convergence due to partial volume effect (PVE) in to narrow sulcal fold. Being function of the corresponding non-zero pixel value, the force field has got an inherent property to determine spuriousness of the edge automatically. It is effectively applied along with some morphological processing in the application of cortical reconstruction to breach the hindrance of PVE in narrow sulci where conventional GGVF fails.

Keywords: deformable model, external force field, partial volume effect, cortical reconstruction, MR image of brain

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Authors: Arezou Hajhashemi, Karim Asgari, Masoud Etemadifar, Maryam Keyvani, Ali Hekmatnia

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Multiple Sclerosis (MS) is one of the most prevalent demyelinating diseases in CNS. As in other chronic cerebral diseases, impairment in cognitive functioning and in memory is popular. Because of the inflammatory and demyelinating nature of the disease, the localization of plaques in different parts of the Prefrontal and Limbic System, may lead to memorial symptoms. This investigation was intended to study relationship between frequency of plaques and memorial symptoms arising from dysfunction limbic system and prefrontal of patients with MS. The sample was selected randomly from patients with MS with memory problem, who have been referred to Isfahan Multiple Sclerosis Society. Brain System Test and Memory Test was administered to the sample, and their MRI's were analyzed by specialist in order to indentify two different parts of plaques. The data was analyzed by SPSS. The results showed that there were significant relationship between MS plaques and prefrontal's dysfunction and memorial symptom related to prefrontal area; however, there were no significant relationship between MS plaques and limbic system's dysfunction and memorial symptoms related to limbic system area. The results of this study suggest that memorial symptoms due to injury regions of the brain have the most significant relationship to prefrontal. Better judgment about these results needs more studies in future.

Keywords: multiple sclerosis, magnetic image, brain injury, behavior disorder

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Authors: Hye Jin Kim, Hwa Sung Shin

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Ischemic stroke means the caused brain damage due to neurological defects, occurring occlusion of cerebral vascular resulting in thrombus or embolism. t-PA (tissue Plasminogen Activator) is the only thrombolytic agent passed the FDA (Food and Drug Administration). However, t-PA directly dissolves the thrombus (direct activity) through fibrinolysis, showing side effects such as re-occlusion. In this study, we evaluated the thrombolytic activities of the serine protease extracted from lugworms inhabiting tidal flats. The new serine protease identified as 38 kDa by SDS-PAGE was not toxic to brain endothelial cells line (hCMEC/D3). Also, the plasmin synthesis inhibition activity (indirect activity) of the new serine protease was confirmed through fibrin zymography assay and fibrin plate assay. It was higher than direct activity as compared to u-PA (urokinase Plasminogen Activator). The activities were found to be maintained at a wide range of temperature (4-70 ℃) and pH 7-10 compared to previous thrombolytic agents from the azocasein assay. In addition, the new serine protease has shown anticoagulant activity from fibrinogenolytic activity assay. In conclusion, the serine protease in lug worms inhabiting the tidal flats could be considered a promising thrombolytic candidate for the treatment of ischemic stroke.

Keywords: alkaline serine protease, bifunctional thrombolytic activity, fibrinolytic activity, ischemic stroke, lug worms

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Authors: Hsiao-Wen Tsai

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Motor vehicle accident is the first cause of head injury in the world; severe head injury cases may cause conscious disturbance and death. This is a report about a case of a young adult patient suffering from motor vehicle accident leading to severe head injury who passed through three time surgical procedures, and his mother (who is the informal caregiver). This case was followed from 28th January to 15th February 2011 by using Gordon’s 11 functional health patterns. Patient’s cognitive-perceptual and self-perception-self-concept patterns were altered. Anxiety was also noted on his informal caregiver due to patients’ condition. During the intensive care period, maintaining patient’s vital signs and cerebral perfusion pressure were essential to avoid secondary neuronal injury. Multi-sensory stimulation, caring accompanying, supporting, listening and encouraging patient’s family involved in patient care were very important to reduce informal caregiver anxiety. Finally, the patient consciousness improved from GCS 4 to GCS 11 before discharging from ICU. Patient’s primary informal caregiver, his mother, also showed anxiety improvement. This is was successful case with traumatic brain injury recovered from coma.

Keywords: anxiety, multi-sensory stimulation, reduce intracranial adaptive capacity, traumatic brain injury

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Authors: Maryam Vaezjalali, Foad Davoodbeglou, Mehrnaz Mesdaghi, Hossein Goudarzi, Fariba Shojaei, Hourieh Aram

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Introduction: Hepatitis B virus (HBV) infection causes chronic infection in human population, with high mortality. Some people are more susceptible to this infection. One of the high risk communities is mentally retarded children, who are institutionalized. Special conditions in these centers predispose children for HBV infection and transmission to healthy people. In this study our objective was to determine the prevalence of HBV infection among institutionalized mentally retarded children and study its associated risk factors. Materials and methods: In this study, 250 mentally retarded children (younger than 14 years old) were included. They were living in 5 nursing institutions, located in different parts of Tehran. HBsAg was measured in the sera of these patients by ELISA method. Results: Among 250 children, 20 children (8%) were HBsAg positive. HBV infection in girls was more than boys (11% to 5.6%). Among the types of mental retardation, children with cerebral palsy had the highest positive result for HBsAg. The most HBV infection (28.5%) was seen in children with longest duration of being institutionalized (10 to 11 years). Vaccinated children were more HBsAg positive (8.7%) than non-vaccinated children (5.3%). However, no significant relationship was observed between any of these factors and HBsAg positivity. Conclusion: Despite improvement of people’s health condition and implementation of HBV vaccination, the prevalence of HBV infection is high in institutionalized mentally retarded children, which highlights the need for active measures to reduce this infection among this high risk population.

Keywords: hepatitis B virus, HBV vaccine, intellectually disabled children, mentally retarded

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Authors: W. Ling, Mohamed Saufi Bin Awang

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Introduction: Mycobacterium tuberculosis post a major health problem worldwide. Central nervous system (CNS) infection by mycobacterium tuberculosis is one of the most devastating complications of tuberculosis. Although with advancement in medical fields, we are yet to understand the pathophysiology of how mycobacterium tuberculosis was able to cross the blood-brain barrier (BBB) and infect the CNS. CNS TB may present with nonspecific clinical symptoms which can mimic other diseases/conditions; this is what makes the diagnosis relatively difficult and challenging. Public health has to be informed and educated about the spread of TB, and early identification of TB is important as it is a curable disease. Case Report: A young 21-year-old Malay gentleman was initially presented to us with symptoms of ear discharge, tinnitus, and right-sided headache for the past one year. Further history reveals that the symptoms have been mismanaged and neglected over the period of 1 year. Initial investigation reveals features of inflammation of the ear. Further imaging showed the feature of chronic inflammation of the otitis media and atypical right cerebral abscess, which has the same characteristic features and consistency. He further underwent a biopsy, and results reveal positive Mycobacterium tuberculosis of the otitis media. With the results and the available imaging, we were certain that this is likely a case of disseminated tuberculosis causing CNS TB. Conclusion: We aim to highlight the challenge and difficult face in our health care system and public health in early identification and treatment.

Keywords: central nervous system tuberculosis, intracranial tuberculosis, tuberculous encephalopathy, tuberculous meningitis

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Authors: Mai M. Farid, Ximeng Yang, Tomoharu Kuboyama, Yuna Inada, Chihiro Tohda

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Intro: Trigonella foenum-graecum (Fenugreek), from Fabaceae family is a well-known plant traditionally used as food and medicine. Many pharmacological effects of Trigonella foenum- graecum seeds extract (TF extract) were evaluated such as anti-diabetic, anti-tumor and anti-dementia effects using in vivo models. Regarding the anti-dementia effects of TF extract, diabetic rats, aluminum chloride-induced amnesia rats and scopolamine-injected mice were used previously for evaluation, which are not well established as Alzheimer’s disease models. In addition, those previous studies, active constituents in TF extract for memory function were not identified. Method: This study aimed to clarify the effect of TF extract on Alzheimer’s disease model, 5XFAD mouse that overexpresses mutated APP and PS1 genes and determine the major active constituent in the brain after oral intake of TF extract. Results: Trigonelline was detected in the cerebral cortex of 5XFAD mice after 24 hours of oral administration of TF extract by LC-MS/MS. Oral administration of TF extract for 17 days improved object location memory in 5XFAD mice. Conclusion: These results suggest that TF extract and its active constituents could be an expected therapeutic candidate for Alzheimer’s disease.

Keywords: Alzheimer's disease, LC-MS/MS, memory recovery, Trigonella foenum-graecum Seeds, 5XFAD mice

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Authors: Fanniyah Anis, Bram Kilapong

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Myocardial reperfusion injury is defined as the cellular damage that results from a period of ischemia, followed by the reestablishment of the blood supply to the infarcted tissue. Ventricular tachycardia is one of the most commonly encountered reperfusion arrhythmia as one of the types of myocardial perfusion injury. Prompt and early treatment can reduce mortality, despite limited resources of the hospital in high risk patients with history of triple vessel disease. Case report, Male 53 years old has been diagnosed with NSTEMI with 3VD and comorbid disease of Hypertension and has undergone revascularization management with Percutaneous coronary intervention. Ventricular tachycardia leading to cardiac arrest occurred right after the stent was inserted. Resuscitation was performed for almost 2 hours until spontaneous circulation returned. Patient admitted in ICU with refractory cardiac shock despite using combination of ionotropic and vasopressor agents under standard non-invasive monitoring due to the limitation of the hospital. Angiography was performed again 5 hours later to exclude other possibilities of blockage of coronary arteries and conclude diagnosis of myocardial reperfusion injury. Patient continually managed with combination of antiplatelet agents and maintenance dose of anti-arrhythmia agents. The handling of the patient was to focus more on supportive and preventive from further deteriorating of the condition. Patient showed clinically improvement and regained consciousness within 24 hours. Patient was successfully discharged from ICU within 3 days without any neurological sequela and was discharge from hospital after 3 days observation in general ward. Limited Resource of hospital did not refrain the physician from attaining a good outcome for this myocardial reperfusion injury case and angiography alone can be used to confirm the diagnosis of myocardial reperfusion injury.

Keywords: limited resources hospital, myocardial reperfusion injury, prolonged resuscitation, refractory cardiogenic shock, reperfusion arrhythmia, revascularization, triple-vessel disease

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Authors: Yu-Wen Cheng, Jau-Der Ho, Liang-Huan Wu, Fan-Li Lin, Li-Huei Chen, Hung-Ming Chang, Yueh-Hsiung Kuo, George Hsiao

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Retina glial activation and neuroinflammation have been confirmed to cause devastating responses in retinodegenerative diseases. The expression and activation of matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase (iNOS) could be exerted as the crucial pathological factors in glaucoma- and blue light-induced retinal injuries. The present study aimed to investigate the retinoprotective effects and mechanisms of fungal ingredient 3,4-dihydroxybenzalacetone (DBL) isolated from Phellinus linteus in the retinal glial activation and retinodegenerative animal models. According to the cellular studies, DBL significantly and concentration-dependently abrogated MMP-9 activation and expression in TNFα-stimulated retinal Müller (rMC-1) cells. We found the inhibitory activities of DBL were strongly through the STAT- and ERK-dependent pathways. Furthermore, DBL dramatically attenuated MMP-9 activation in the stimulated Müller cells exposed to conditioned media from LPS-stimulated microglia BV-2 cells. On the other hand, DBL strongly suppressed LPS-induced production of NO and ROS and expression of iNOS in microglia BV-2 cells. Consistently, the phosphorylation of STAT was substantially blocked by DBL in LPS-stimulated microglia BV-2 cells. In the evaluation of retinoprotective functions, the high IOP-induced scotopic electroretinographic (ERG) deficit and blue light-induced abnormal pupillary light response (PLR) were assessed. The deficit scotopic ERG responses markedly recovered by DBL in a rat model of glaucoma-like ischemia/reperfusion (I/R)-injury. DBL also reduced the aqueous gelatinolytic activity and retinal MMP-9 expression in high IOP-injured conditions. Additionally, DBL could restore the abnormal PLR and reduce retinal MMP-9 activation. In summary, DBL could ameliorate retinal neuroinflammation and MMP-9 activation by predominantly inhibiting STAT3 activation in the retinal Müller cells and microglia, which exhibits therapeutic potential for glaucoma and other retinal degenerative diseases.

Keywords: glaucoma, blue light, DBL, retinal Müller cell, MMP-9, STAT, Microglia, iNOS, ERG, PLR

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Authors: Devendra Gupta, S. P. Ambesh, P. K Singh

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Introduction: Minimally invasive coronary artery bypass grafting (MICABG) is a less invasive method of performing surgical revascularization. Minimally invasive direct coronary artery bypass (MIDCAB) provides many anesthetic challenges including one lung ventilation (OLV), managing myocardial ischemia, and pain. We present an early and midterm result of the use of this technique with OLV. Method: We enrolled 62 patients for analysis operated between 2008 and 2012. Patients were anesthetized and left endobronchial tube was placed. During the procedure left lung was isolated and one lung ventilation was maintained through right lung. Operation was performed utilizing off pump technique of coronary artery bypass grafting through a minimal invasive incision. Left internal mammary artery graft was done for single vessel disease and radial artery was utilized for other grafts if required. Postoperative ventilation was done with single lumen endotracheal tube. Median follow-up is 2.5 years (6 months to 4 years). Results: Median age was 58.5 years (41-77) and all were male. Single vessel disease was present in 36, double vessel in 24 and triple vessel disease in 2 patients. All the patients had normal left ventricular size and function. In 2 cases difficulty were encounter in placement of endobronchial tube. In 1 case cuff of endobronchial tube was ruptured during intubation. High airway pressure was developed on OLV in 1 case and surgery was accomplished with two lung anesthesia with low tidal volume. Mean postoperative ventilation time was 14.4 hour (11-22). There was no perioperative and 30 day mortality. Conversion to median sternotomy to complete the operation was done in 3.23% (2 out of 62 patients). One patient had acute myocardial infarction postoperatively and there were no deaths during follow-up. Conclusion: MICABG is a safe and effective method of revascularization with OLV in low risk candidates for coronary artery bypass grafting.

Keywords: MIDCABG, one lung ventilation, coronary artery bypass grafting, endobronchial tube

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Authors: Sheng Yu Chen, Shi-Heng Wang

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Aim: Based on human, animal experiments, and genetic studies, cysteinyl leukotrienes, LTC4, LTD4, and LTE4, are inflammatory substances that are metabolized by 5-lipooxygenase from arachidonic acid, and these substances trigger asthma. In addition, the synthetic pathway of cysteinyl leukotriene is relevant to the increase in cardiovascular diseases such as myocardial ischemia and stroke. Given the situation, we aim to investigate whether cysteinyl leukotrienes receptor antagonist (LTRA), montelukast which cures those who have asthma has potential protective effects on cardiovascular diseases. Method: We conducted a cohort study, and enrolled participants which are newly diagnosed with asthma (ICD-9 CM code 493. X) between 2002 to 2011. The data source is from Taiwan National Health Insurance Research Database Patients with a previous history of myocardial infarction or ischemic stroke were excluded. Among the remaining participants, every montelukast user was matched with two randomly non-users by sex, and age. The incident cardiovascular diseases, including myocardial infarction and ischemic stroke, were regarded as outcomes. We followed the participants until outcomes come first or the end of the following period. To explore the protective effect of montelukast on the risk of cardiovascular disease, we use multivariable Cox regression to estimate the hazard ratio with adjustment for potential confounding factors. Result: There are 55876 newly diagnosed asthma patients who had at least one claim of inpatient admission or at least three claims of outpatient records. We enrolled 5350 montelukast users and 10700 non-users in this cohort study. The following mean (±SD) time of the Montelukast group is 5 (±2.19 )years, and the non-users group is 6.2 5.47 (± 2.641) years. By using multivariable Cox regression, our analysis indicated that the risk of incident cardiovascular diseases between montelukast users (n=43, 0.8%) and non-users (n=111, 1.04%) is approximately equal. [adjusted hazard ratio 0.992; P-value:0.9643] Conclusion: In this population-based study, we found that the use of montelukast is not associated with a decrease in incident MI or IS.

Keywords: asthma, inflammation, montelukast, insurance research database, cardiovascular diseases

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Authors: James Patrick A. Diaz, Raul E. Ramboyong

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Background: Hypertensive response during maximal exercise test provides important information on the level of blood pressure control and evaluation of treatment. Method: A single center retrospective descriptive study was conducted among 117 young (aged 20 to 40) and middle age (aged 40 to 65) hypertensive patients, who underwent treadmill stress test. Currently on maintenance frontline medication either monotherapy (Angiotensin-converting enzyme inhibitor/Angiotensin receptor blocker [ACEi/ARB], Calcium channel blocker [CCB], Diuretic - Hydrochlorthiazide [HCTZ]) or combination therapy (ARB+CCB, ARB+HCTZ), who attained a maximal exercise on treadmill stress test (TMST) with hypertensive response (systolic blood pressure: male >210 mm Hg, female >190 mm Hg, diastolic blood pressure >100 mmHg, or increase of >10 mm Hg at any time during the test), on Bruce and Modified Bruce protocol. Exaggerated blood pressure response during exercise (systolic [SBP] and diastolic [DBP]), peak exercise blood pressure (SBP and DBP), recovery period (SBP and DBP) and test for ischemia and their antihypertensive medication/s were investigated. Analysis of variance and chi-square test were used for statistical analysis. Results: Hypertensive responses on maximal exercise test were seen mostly among female population (P < 0.000) and middle age (P < 0.000) patients. Exaggerated diastolic blood pressure responses were significantly lower in patients who were taking CCB (P < 0.004). A longer recovery period that showed a delayed decline in SBP was observed in patients taking ARB+HCTZ (P < 0.036). There were no significant differences in the level of exaggerated systolic blood pressure response and during peak exercise (both systolic and diastolic) in patients using either monotherapy or combination antihypertensives. Conclusion: Calcium channel blockers provided lower exaggerated diastolic BP response during maximal exercise test in hypertensive middle age patients. Patients on combination therapy using ARB+HCTZ exhibited a longer recovery period of systolic blood pressure.

Keywords: antihypertensive, exercise test, hypertension, hyperytensive response

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Authors: Tsung-yin Lin, Yi-yu Lee, Ching-hua Hung

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Snoring, the lay term for obstructive breathing during sleep, is one of the most prevalent of obnoxious human habits. Loud snoring usually makes others feel noisy and uncomfortable. Snoring also influences the sleep quality of snorers’ bed partners, because of the noise they do not get to sleep easily. Snoring causes the reduce of sleep quality leading to several medical problems, such as excessive daytime sleepiness, high blood pressure, increased risk for cardiovascular disease and cerebral vascular accident, and etc. There are many non-prescription devices offered for sale on the market, but very limited data are available to support a beneficial effect of these devices on snoring and use in treating obstructive sleep apnea (OSA). Mandibular advancement devices (MADs), also termed as the Mandibular reposition devices (MRDs) are removable devices which are worn at night during sleep. Most devices require dental impression, bite registration, and fabrication by a dental laboratory. Those devices are fixed to upper and lower teeth and are adjusted to advance the mandible. The amount of protrusion is adjusted to meet the therapeutic requirements, comfort, and tolerance. Many devices have a fixed degree of advancement. Some are adjustable in a limited degree. This study focuses on the stress analysis of Mandibular Advancement Devices (MADs), which are considered as a standard treatment of snoring that promoted by American Academy of Sleep Medicine (AASM). This paper proposes a new MAD design, and the finite element analysis (FEA) is introduced to precede the stress simulation for this MAD.

Keywords: finite element analysis, mandibular advancement devices, mechanical stress, snoring

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Authors: Berredjem Hajira, Benlaifa Meriem, Becheker Imene, Bardi Rafika, Djebar Med Reda

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Recent acquired or reactivation T.gondii infection is a serious complication in HIV patients. Classical serological diagnosis relies on the detection of anti-Toxoplasma immunoglobulin ; however, serology may be unreliable in HIV immunodeficient patients who fail to produce significant titers of specific antibodies. PCR assays allow a rapid diagnosis of Toxoplasma infection. In this study, we compared the value of the PCR for diagnosing active toxoplasmosis in cerebrospinal fluid and blood samples from HIV patients. Anti-Toxoplasma antibodies IgG and IgM titers were determined by ELISA. In parallel, nested PCR targeting B1 gene and conventional PCR-ELISA targeting P30 gene were used to detect T. gondii DNA in 25 blood samples and 12 cerebrospinal fluid samples from patients in whom toxoplasmic encephalitis was confirmed by clinical investigations. A total of 15 negative controls were used. Serology did not contribute to confirm toxoplasmic infection, as IgG and IgM titers decreased early. Only 8 out 25 blood samples and 5 out 12 cerebrospinal fluid samples PCRs yielded a positive result. 5 patients with confirmed toxoplasmosis had positive PCR results in either blood or cerebrospinal fluid samples. However, conventional nested B1 PCR gave best results than the P30 gene one for the detection of T.gondii DNA in both samples. All samples from control patients were negative. This study demonstrates the unusefulness of the serological tests and the high sensitivity and specificity of PCR in the diagnosis of toxoplasmic encephalitis in HIV patients.

Keywords: cerebrospinal fluid, HIV, Toxoplasmosis, PCR

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Authors: M. Klimova, O. Semyachkina-Glushkovskaya, J. Kurts, E. Zinchenko, N. Navolokin, A. Shirokov, A. Dubrovsky, A. Abdurashitov, A. Terskov, A. Mamedova, I. Agranovich, T. Antonova, I. Blokhina

Abstract:

The direction for research of Alzheimer's disease is to find an effective non-invasive and non-pharmacological way of treatment. Here we tested our hypothesis that the opening of the blood-brain barrier (BBB) induces activation of lymphatic drainage and clearing functions that can be used as a method for non-invasive stimulation of clearance of beta-amyloid and therapy of Alzheimer’s disease (AD). To test our hypothesis, in this study on healthy male mice we analyzed the interaction between BBB opening by repeated loud music (100-10000 Hz, 100 dB, duration 2 h: 60 sec – sound; 60 sec - pause) and functional changes in the meningeal lymphatic vessels (MLVs). We demonstrate clearance of dextran 70 kDa (i.v. injection), fluorescent beta-amyloid (intrahippocampal injection) and gold nanorods (intracortical injection) via MLV that significantly increased after the opening of BBB. Our studies also demonstrate that the BBB opening was associated with the improvement of neurocognitive status in mice with AD. Thus, we uncover therapeutic effects of BBB opening by loud music, such as non-invasive stimulation of lymphatic clearance of beta-amyloid in mice with AD, accompanied by improvement of their neurocognitive status. Our data are consistent with other results suggesting the therapeutic effect of BBB opening by focused ultrasound without drugs for patients with AD. This research was supported by a grant from RSF 18-75-10033

Keywords: Alzheimer's disease, beta-amyloid, blood-brain barrier, meningeal lymphatic vessels, repeated loud music

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Authors: Kyou Hee Shim, Hwa Sung Shin

Abstract:

When a thrombolysis agent is administered to treat ischemic stroke, excessive reactive oxygen species are generated due to a sudden provision of oxygen and occurs secondary damage cell necrosis. Thus, it is necessary to administrate adjuvant as well as thrombolysis agent to protect and reduce damaged tissue. As cerebral blood vessels have specific structure called blood-brain barrier (BBB), it is not easy to transfer substances from blood to tissue. Therefore, development of a drug carrier is required to increase drug delivery efficiency to brain tissue. In this study, cyanobacterial pigment from the blue-green algae known for having neuroprotective effect as well as antioxidant effect was nasally administrated for bypassing BBB. In order to deliver cyanobacterial pigment efficiently, the nano-sized liposome was used as a carrier. Liposomes were coated with a positive charge of chitosan since negative residues are present at the nasal mucosa the first gateway of nasal administration. Characteristics of liposome including morphology, size and zeta potential were analyzed by transmission electron microscope (TEM) and zeta analyzer. As a result of cytotoxic test, the liposomes were not harmful. Also, being administered a drug to the ischemic stroke animal model, we could confirm that the pharmacological effect of the pigment delivered by chitosan coated liposome was enhanced compared to that of non-coated liposome. Consequently, chitosan coated liposome could be considered as an optimized drug delivery system for the treatment of acute ischemic stroke.

Keywords: ischemic stroke, cyanobacterial pigment, liposome, chitosan, nasal administration

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Authors: Deepanjali Gurav, Kun Qian

Abstract:

In-vitro metabolic diagnosis relies on designed materials-based analytical platforms for detection of selected metabolites in biological samples, which has a key role in disease detection and therapeutic evaluation in clinics. However, the basic challenge deals with developing a simple approach for metabolic analysis in bio-samples with high sample complexity and low molecular abundance. In this work, we report a designer plasmonic nanoshells based platform for direct detection of small metabolites in clinical samples for in-vitro metabolic diagnostics. We first synthesized a series of plasmonic core-shell particles with tunable nanoshell structures. The optimized plasmonic nanoshells as new matrices allowed fast, multiplex, sensitive, and selective LDI MS (Laser desorption/ionization mass spectrometry) detection of small metabolites in 0.5 μL of bio-fluids without enrichment or purification. Furthermore, coupling with isotopic quantification of selected metabolites, we demonstrated the use of these plasmonic nanoshells for disease detection and therapeutic evaluation in clinics. For disease detection, we identified patients with postoperative brain infection through glucose quantitation and daily monitoring by cerebrospinal fluid (CSF) analysis. For therapeutic evaluation, we investigated drug distribution in blood and CSF systems and validated the function and permeability of blood-brain/CSF-barriers, during therapeutic treatment of patients with cerebral edema for pharmacokinetic study. Our work sheds light on the design of materials for high-performance metabolic analysis and precision diagnostics in real cases.

Keywords: plasmonic nanoparticles, metabolites, fingerprinting, mass spectrometry, in-vitro diagnostics

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Authors: Alexandre H. Okano, Pedro M. D. Agrícola, Daniel G. Da S. Machado, Luiz I. Do N. Neto, Luiz F. Farias Junior, Paulo H. D. Nascimento, Rickson C. Mesquita, John F. Araujo, Eduardo B. Fontes, Hassan M. Elsangedy, Shinsuke Shimojo, Li M. Li

Abstract:

The prefrontal cortex is involved in the reward system and the insular cortex integrates the afferent inputs arriving from the body’ systems and turns into feelings. Therefore, modulating neuronal activity in these regions may change individuals’ perception in a given situation such as exercise. We tested whether transcranial direct current stimulation (tDCS) change cerebral oxygenation and pleasure during exercise. Fourteen volunteer healthy adult men were assessed into five different sessions. First, subjects underwent to a maximum incremental test on a cycle ergometer. Then, subjects were randomly assigned to a transcranial direct current stimulation (2mA for 15 min) intervention in a cross over design in four different conditions: anode and cathode electrodes on T3 and Fp2 targeting the insular cortex, and Fpz and F4 targeting prefrontal cortex, respectively; and their respective sham. These sessions were followed by 30 min of moderate intensity exercise. Brain oxygenation was measured in prefrontal cortex with a near infrared spectroscopy. Perceived exertion and pleasure were also measured during exercise. The asymmetry in prefrontal cortex oxygenation before the stimulation decreased only when it was applied over this region which did not occur after insular cortex or sham stimulation. Furthermore, pleasure was maintained during exercise only after prefrontal cortex stimulation (P > 0.7), while there was a decrease throughout exercise (P < 0.03) during the other conditions. We conclude that tDCS over the prefrontal cortex changes brain oxygenation in ventromedial prefrontal cortex and maintains perceived pleasure during exercise. Therefore, this technique might be used to enhance effective responses related to exercise.

Keywords: affect, brain stimulation, dopamine neuromodulation, pleasure, reward, transcranial direct current stimulation

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Authors: S. Shafiee Ardestani, A. Najafi, N. Valizadeh, E. Payani, H. Karimian

Abstract:

Objectives: Treatment of mild traumatic brain injury in emergency ward patients with any type of traumatic intracranial hemorrhage is flexible. The aim of this study is to assess the clinical outcomes of mild traumatic brain injury patients who had acute traumatic intracranial hemorrhage on initial emergency ward neuroimaging. Materials-Methods: From March 2011 to November 2012 in a retrospective cohort study we enrolled emergency ward patients with mild traumatic brain injury with Glasgow Coma Scale (GCS) scores of 14 or 15 and who had stable vital signs. Patients who had any type of intracranial hemorrhage on first head CT and repeat head CT within 24 hours were included. Patients with initial GCS < 14, injury > 24 hours old, pregnancy, concomitant non-minor injuries, and coagulopathy were excluded. Primary endpoints were neurosurgical procedures and/or death and for discharged patients, return to the emergency ward during one week. Results: Among 755 patients who were referred to the emergency ward and underwent two head CTs during first 24 hours, 302 (40%) were included. The median interval between CT scans was 6 hours (ranging 4 to 8 hours). Consequently, 135 (45%) patients had subarachnoid hemorrhage, 124 (41%) patients had subdural hemorrhage, 15 (5%) patients had epidural hemorrhage, 28 (9%) patients had cerebral contusions, and 54 (18%) patients had intra-parenchymal hemorrhage. Six of 302 patients died within 15 days of injury. 200 patients (66%) have been discharged from the emergency ward, 25 (12%) of whom returned to the emergency ward after one week. Conclusion: Discharge of the head trauma patients after a repeat head CT and brief period of observation in the emergency ward lead to early discharge of mild traumatic brain injury patients with traumatic ICH without adverse events.

Keywords: clinical outcomes, emergency ward, mild traumatic intracranial hemorrhage, Glasgow Coma Scale (GCS)

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Authors: Basma Hassabo, Sarah Ahmed, Aisha Hameed

Abstract:

Aims and Objectives: To determine the incidence of maternal mortality amongst pregnant women with sickle cell disease (SCD) in the United Kingdom and to determine exact cause of death in these women. Background: SCD is caused by the ‘sickle’ gene and is characterized by episodes of severe bone pain and other complications like acute chest syndrome, chronic pulmonary hypertension, stroke, retinopathy, chronic renal failure, hepato-splenic crises, avascular bone necrosis, sepsis and leg ulcers. SCD is a continual cause of maternal mortality and fetal complications, and it comprises 1.5% of all Direct and Indirect deaths in the UK. Sepsis following premature rupture of membranes with ascending infection, post-partum infection and pre-labour overwhelming septic shock is one of its leading causes of death. Over the last fifty years of maternal mortality reports in UK, between 1 to 4 pregnant women died in each triennium. Material and Method: This is a retrospective study that involves pregnant women who died from SCD complications in the UK between 1952-2012. Data were collected from the UK Confidential Enquiries into Maternal Death and its causes between 1952–2012. Prior to 1985, exact cause of death in this cohort was not recorded. Results: 33 deaths reported between 1964 and 1984. 17 deaths were reported due to sickle cell disease between 1985 and 2012. Five women in this group died of sickle cell crisis, one woman had liver sequestration crisis, two women died of venous thromboembolism, two had myocardial fibrosis and three died of sepsis. Remaining women died of amniotic fluid embolism, SUDEP, myocardial ischemia and intracranial haemorrhage. Conclusion: The leading causes of death in sickle cell sick pregnant women are sickle cell crises, sepsis, venous thrombosis and thromboembolism. Prenatal care for women with SCD should be managed by a multidisciplinary team that includes an obstetrician, nutritionist, primary care physician, and haematologist. In every sick Sickle Cell woman Sickle Cell crises should be on the top of the list of differential diagnosis. Aggressive treatment of complications with low threshold to commence broad-spectrum antibiotics and LMWH contribute to better outcomes.

Keywords: incidence, maternal mortality, sickle cell disease (SCD), uk

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Authors: Ranjith Menon, Abathar Aladi, Hans-Christean Nahser, Maneesh Bhojak, Sacha Nevin, Paul Eldridge

Abstract:

Background: Spontaneous subarachnoid haemorrhage (SAH) accounts for approximately 5% of all strokes. Patients with spontaneous SAH (as shown by CT or lumbar puncture) undergo investigations to identify or exclude an underlying structural cause, typically cerebral aneurysm. However in 10 - 20% of cases, no structural cause is found. This includes more than one imaging modality (intracranial MRA, CTA, 4DCTA and/or DSA) and in some spinal MRI. Objective: To determine; 1) If an underlying structural or vascular cause can be identified in non-aneurysmal SAH patients by comparing different imaging modalities at presentation and at follow-up. 2) If MRI spine in patients with non-aneurysmal SAH reveals an underlying SAH cause. 3)The functional outcome at discharge. Results: We performed a retrospective analysis of all non-traumatic SAH patients admitted to the Walton centre from January 2009 to December 2015. There were 1457 patients with non-traumatic SAH admitted to the Walton centre of whom 21.8% (n=300) patients were diagnosed with non-aneurysmal SAH. Males were 65.6% and females were 43.3%. The presenting symptoms were sudden onset headache (93.6%), the focal neurological deficit (12%), loss of consciousness (10.6%) and others (6%). About 285 patients received 2 modalities of imaging (CTA & DSA), 192 received 3 modalities of imaging (CTA, MRA & DSA) and 137 received MRI spine (51/137 whole spine). The modified Rankin Score at discharge were: mRS 0 = 292 (97.33%), mRS 1-2 = 6, mRS 6 = 1 (cardiac arrest in IHD patient) and unknown in 1. Follow-up imaging at 3 to 6 months in 190 (63.3%) patients did not identify an underlying cause. Conclusion: This retrospective analysis concludes that non-aneurysmal SAH has a good functional outcome. A single imaging modality (CTA (4DCTA) or MRA or DSA) was adequate to exclude an underlying cause of SAH and a delayed imaging failed to identify a cause. Routinely performing MRI spine in this group of patients appears not to be necessary according to this evidence.

Keywords: stroke, non-aneurysmal subarachnoid haemorrhage, neuroimaging, modified rankin score

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Authors: Dinoo Kirthinanda, Sujani Wijeratne

Abstract:

Pseudohyperkalaemia is a common benign in vitro phenomenon caused by the release of potassium ions (K+) from cells during specimen processing. Analysis of haemolysed blood samples for predominantly intracellular electrolytes may lead to re-investigation and potentially harmful interventions. We report a case of a 52-year male with myeloproliferative disease manifested as Polycythaemia Rubra Vera, Hypertension and hypertensive nephropathy with stage 3 chronic kidney disease admitted to Neuro-intensive care unit (NICU) with an intra-cerebral haemorrhage secondary to hypertensive bleed. His initial blood investigations showed hyperkalemia with serum K+ 6.2 mmol/L yet the bedside arterial blood gas analysis yielded K+ of 4.6 mmol/L. The patient was however given hyperkalemia regime twice based on venous electrolyte analysis. The discrepancy between the bedside electrolyte analysis using arterial blood and venous blood prompted further evaluation. The 12 lead Electrocardiogram showed U waves and sinus bradycardia corresponding to the serum K+ of 2.8 mmol/L on arterial blood gas analysis. Immediate K+ replacement ensured the patient did not develop life-threatening cardiac complications. Pseudohyperkalaemia may pose diagnostic challenges in the absence of detectable haemolysis and should be suspected in susceptible patients with normal Electrocardiogram and Glomerular Filtration Rate to avoid potentially life-threatening interventions. When in doubt, rapid analysis of arterial blood gas may be useful for accurate quantification of potassium.

Keywords: patient safety, pseudohyperkalaemia, haemolysis, myeloproliferative disorder

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Authors: H. Hadjeris, R. B. Ghoul, Lekhlaf, M. Nebbal

Abstract:

Introduction: Adenoid cystic carcinomas of the lacrimal gland or orbital cylindroma constitute the second cause of epithelial tumors of this gland. It is a malignant tumor usually developed at the expense of the salivary glands; its orbital location is exceptional. It is a rare clinical entity, formidable by its malignancy and local aggressiveness; the recurrence rate is high. Materials and methods: Clinical case: 63 years old woman who presents with irreducible no pulsatile painful left exophthalmos with inflammatory chemosis and a decrease in visual acuity with a moderate intracranial hypertension syndrome that has been evolving for 03 months. Antecedent; a biopsy of the tumor was made; the histological examination was in favor of an adenoid cystic carcinoma of the lacrimal gland. Lesion assessment: computed tomography and brain MRI: show an intra and extra-conical mass; with sinus (ethmoido-frontal) and cerebral (left frontal) extension strongly enhanced after injection of contrast product surrounded by edema around the lesion, associated with left frontal bone lysis extension assessment: unremarkable treatment: Patient operated by left frontotemporal approach, a total exenteration was performed with macroscopically complete excision of the frontal lesion and wide frontal craniectomy with craniofacial reconstruction, followed by complementary radiotherapy. Results: The patient was seen again after 3 months in consultation; she does not present any signs in favor of a recurrence. Conclusion: Adenoid cystic carcinomas of the lacrimal gland are rare malignant tumors; they are very infiltrating and invasive. The prognosis is strongly linked to the treatment time.

Keywords: adenoid cystic, lacrimal gland, orbital location, fronto-temporal approac

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