Neural correlates of olfactory and visual memory performance in 3D-simulated mazes after intranasal insulin application.

Science.gov (United States)

Brünner, Yvonne F; Rodriguez-Raecke, Rea; Mutic, Smiljana; Benedict, Christian; Freiherr, Jessica

2016-10-01

This fMRI study intended to establish 3D-simulated mazes with olfactory and visual cues and examine the effect of intranasally applied insulin on memory performance in healthy subjects. The effect of insulin on hippocampus-dependent brain activation was explored using a double-blind and placebo-controlled design. Following intranasal administration of either insulin (40IU) or placebo, 16 male subjects participated in two experimental MRI sessions with olfactory and visual mazes. Each maze included two separate runs. The first was an encoding maze during which subjects learned eight olfactory or eight visual cues at different target locations. The second was a recall maze during which subjects were asked to remember the target cues at spatial locations. For eleven included subjects in the fMRI analysis we were able to validate brain activation for odor perception and visuospatial tasks. However, we did not observe an enhancement of declarative memory performance in our behavioral data or hippocampal activity in response to insulin application in the fMRI analysis. It is therefore possible that intranasal insulin application is sensitive to the methodological variations e.g. timing of task execution and dose of application. Findings from this study suggest that our method of 3D-simulated mazes is feasible for studying neural correlates of olfactory and visual memory performance. Copyright © 2016 Elsevier Inc. All rights reserved.

Intranasal insulin modulates intrinsic reward and prefrontal circuitry of the human brain in lean women.

Science.gov (United States)

Kullmann, Stephanie; Frank, Sabine; Heni, Martin; Ketterer, Caroline; Veit, Ralf; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

2013-01-01

There is accumulating evidence that food consumption is controlled by a wide range of brain circuits outside of the homeostatic system. Activation in these brain circuits may override the homeostatic system and also contribute to the enormous increase of obesity. However, little is known about the influence of hormonal signals on the brain's non-homeostatic system. Thus, selective insulin action in the brain was investigated by using intranasal application. We performed 'resting-state' functional magnetic resonance imaging in 17 healthy lean female subjects to assess intrinsic brain activity by fractional amplitude of low-frequency fluctuations (fALFF) before, 30 and 90 min after application of intranasal insulin. Here, we showed that insulin modulates intrinsic brain activity in the hypothalamus and orbitofrontal cortex. Furthermore, we could show that the prefrontal and anterior cingulate cortex response to insulin is associated with body mass index. This demonstrates that hormonal signals as insulin may reduce food intake by modifying the reward and prefrontal circuitry of the human brain, thereby potentially decreasing the rewarding properties of food. Due to the alarming increase in obesity worldwide, it is of great importance to identify neural mechanisms of interaction between the homeostatic and non-homeostatic system to generate new targets for obesity therapy. Copyright © 2012 S. Karger AG, Basel.

Cortisol, but not intranasal insulin, affects the central processing of visual food cues.

Science.gov (United States)

Ferreira de Sá, Diana S; Schulz, André; Streit, Fabian E; Turner, Jonathan D; Oitzl, Melly S; Blumenthal, Terry D; Schächinger, Hartmut

2014-12-01

Stress glucocorticoids and insulin are important endocrine regulators of energy homeostasis, but little is known about their central interaction on the reward-related processing of food cues. According to a balanced group design, healthy food deprived men received either 40IU intranasal insulin (n=13), 30mg oral cortisol (n=12), both (n=15), or placebo (n=14). Acoustic startle responsiveness was assessed during presentation of food and non-food pictures. Cortisol enhanced startle responsiveness during visual presentation of "high glycemic" food pictures, but not during presentation of neutral and pleasant non-food pictures. Insulin had no effect. Based on the "frustrative nonreward" model these results suggest that the reward value of high glycemic food items is specifically increased by cortisol. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of superfused insulin on cerebral cortical glucose utilization in awake goats

International Nuclear Information System (INIS)

Pelligrino, D.A.; Miletich, D.J.; Albrecht, R.F.

1987-01-01

The effect on cortical cerebral glucose utilization (CMR glu ) of intracerebral insulin administration in awake goats was studied. The insulin was superfused in a mock cerebrospinal fluid (CSF) employing chronically implanted cranial windows. Two windows were implanted bilaterally: one window over an equivalent portion of each parietal cortex. With one window used to deliver insulin/CSF and the other used to simultaneously deliver CSF alone (control), changes in CMR glu were assessed using a modification of a sequential 2-[ 3 H]- then 2[ 14 C]deoxy-D-glucose (2DG) technique originally described by Altenau and Agranoff. Initial experiments employing 125 I-insulin demonstrated that the superfusion procedure increased insulin levels only in the outer 1 mm of cortical tissue exposed to insulin containing perfusate. Additional preliminary evaluations, using conditions known to alter CMR glu , generally established that present methods were adequate to induce and detect CMR glu changes. However, it was also shown experimentally and using a mathematical model that 2-[ 3 H]DG test/control tissue ratios could be influenced by subsequent changes in CMR glu and the dephosphorylation rate. Thus 3 H ratios could not be used to establish preexperimental test/control CMR glu relationships as the originally devised model assumed but could be employed to indicate changes in dephosphorylation. The mathematical model allowed for improved estimates of CMR glu changes from 2[ 14 C]DG/2-[ 3 H]DG test over control tissue ratios. Even with these corrections, insulin was estimated to cause no more than an 8-15% increase in cortical CMR glu . A very limited role for insulin, at least in cerebral cortical metabolic regulation, is thus indicated

Intranasal insulin influences the olfactory performance of patients with smell loss, dependent on the body mass index: A pilot study.

Science.gov (United States)

Schöpf, V; Kollndorfer, K; Pollak, M; Mueller, C A; Freiherr, J

2015-12-01

The application of intranasal insulin in healthy humans has been linked to improved memory function, reduced food intake, and increased olfactory thresholds. There has also been some correlation between the morbidities associated with central nervous system (CNS) insulin resistance, such as type II diabetes mellitus, Alzheimer's disease, obesity, and impaired odour recognition. Given that impaired odour recognition is an important component of olfactory performance, mechanisms that govern these effects may account for impaired olfactory functions in anosmic patients. Ten patients with post-infectious olfactory loss received intranasal administration of 40 IU insulin or a placebo solution, as well as olfactory performance tests before and after administration. When administered insulin, patients exhibited an immediate performance improvement with regard to olfactory sensitivity and olfactory intensity ratings. In addition, more odours were correctly identified. Furthermore, an improvement in the odour identification task was detected in patients with higher body mass index. Results of this pilot study shed light on the link between cerebral insulin level and an impaired sense of smell. This research line might provide a better understanding of olfactory loss in relation to eating and dietary behavior, and could offer opportunities to develop faster therapeutic intervention for patients with olfactory dysfunction.

Effects of intranasal insulin application on the hypothalamic BOLD response to glucose ingestion

DEFF Research Database (Denmark)

van Opstal, Anna M.; Akintola, Abimbola A.; Elst, Marjan van der

2017-01-01

The hypothalamus is a crucial structure in the brain that responds to metabolic cues and regulates energy homeostasis. Patients with type 2 diabetes demonstrate a lack of hypothalamic neuronal response after glucose ingestion, which is suggested to be an underlying cause of the disease. In this s......The hypothalamus is a crucial structure in the brain that responds to metabolic cues and regulates energy homeostasis. Patients with type 2 diabetes demonstrate a lack of hypothalamic neuronal response after glucose ingestion, which is suggested to be an underlying cause of the disease...... effect. Our data provide proof of concept for future experiments testing the potential of intranasal application of insulin to ameliorate defective homeostatic control in patients with type 2 diabetes....

Nose-to-Brain delivery of insulin for Alzheimer’s disease

Directory of Open Access Journals (Sweden)

Martina Stützle

2015-09-01

Full Text Available The transport of small molecules, peptides and proteins via the olfactory epithelium and along olfactory and trigeminal nerve pathways from the nasal cavity to the brain is very well known and clinically established for central nervous system (CNS active drugs like oxytocin, sumatriptan or insulin. Insulin is a clinically well-established biopharmaceutical with a validated function in cognition. Central supply with insulin via intranasal administration improves cognition in animal models and in human, making insulin a so-called cognitive enhancer. Furthermore, dysregulation of insulin is implicated in the pathogenesis of Alzheimer’s disease, which is associated with lower levels of insulin in the cerebrospinal fluid and is involved in amyloid-beta (Ab regulation. Clinical trials with intranasal insulin implicate positive effects on learning and memory, but a massive lack of pharmacokinetic and efficacy data hamper a pharmacokinetic – pharmcodynamic relation and a possible clinical development as cognition enhancer. A lack of such data also prevents resolving the mechanisms involved in directing insulin to the central or to the peripheral compartment. Here we discuss the basic mechanism of Nose-to-Brain delivery, evidences for intranasal insulin as cognition enhancer, medical devices for intranasal delivery and safety aspects.

Central Nervous Insulin Signaling in Sleep-Associated Memory Formation and Neuroendocrine Regulation

OpenAIRE

Feld, Gordon B; Wilhem, Ines; Benedict, Christian; Rüdel, Benjamin; Klameth, Corinna; Born, Jan; Hallschmid, Manfred

2016-01-01

The neurochemical underpinnings of sleep's contribution to the establishment and maintenance of memory traces are largely unexplored. Considering that intranasal insulin administration to the CNS improves memory functions in healthy and memory-impaired humans, we tested whether brain insulin signaling and sleep interact to enhance memory consolidation in healthy participants. We investigated the effect of intranasal insulin on sleep-associated neurophysiological and neuroendocrine parameters ...

Insulin and the brain.

Science.gov (United States)

Derakhshan, Fatemeh; Toth, Cory

2013-03-01

Mainly known for its role in peripheral glucose homeostasis, insulin has also significant impact within the brain, functioning as a key neuromodulator in behavioral, cellular, biochemical and molecular studies. The brain is now regarded as an insulin-sensitive organ with widespread, yet selective, expression of the insulin receptor in the olfactory bulb, hypothalamus, hippocampus, cerebellum, amygdala and cerebral cortex. Insulin receptor signaling in the brain is important for neuronal development, glucoregulation, feeding behavior, body weight, and cognitive processes such as with attention, executive functioning, learning and memory. Emerging evidence has demonstrated insulin receptor signaling to be impaired in several neurological disorders. Moreover, insulin receptor signaling is recognized as important for dendritic outgrowth, neuronal survival, circuit development, synaptic plasticity and postsynaptic neurotransmitter receptor trafficking. We review the multiple roles of insulin in the brain, as well as its endogenous trafficking to the brain or its exogenous intervention. Although insulin can be directly targeted to the brain via intracerebroventricular (ICV) or intraparenchymal delivery, these invasive techniques are with significant risk, necessitating repeated surgical intervention and providing potential for systemic hypoglycemia. Another method, intranasal delivery, is a non-invasive, safe, and alternative approach which rapidly targets delivery of molecules to the brain while minimizing systemic exposure. Over the last decades, the delivery of intranasal insulin in animal models and human patients has evolved and expanded, permitting new hope for associated neurodegenerative and neurovascular disorders.

Central insulin administration improves odor-cued reactivation of spatial memory in young men.

Science.gov (United States)

Brünner, Yvonne F; Kofoet, Anja; Benedict, Christian; Freiherr, Jessica

2015-01-01

Insulin receptors are ubiquitously found in the human brain, comprising the olfactory bulb, essential for odor processing, and the hippocampus, important for spatial memory processing. The present study aimed at examining if intranasal insulin, which is known to transiently increase brain insulin levels in humans, would improve odor-cued reactivation of spatial memory in young men. We applied a double-blind, placebo-controlled, counterbalanced within-subject design. The study was conducted at the research unit of a university hospital. Interventions/Participants/Main Outcome Measures: Following intranasal administration of either insulin (40 I.U.) or placebo, male subjects (n = 18) were exposed to eight odors. During each odor exposure, a green-colored field was presented on a 17-in. computer screen. During immediate recall (comprising 3 runs), the participants were re-exposed to each odor cue, and were asked to select the corresponding field (with visual feedback after each response). The delayed recall was scheduled ∼10 min later (without feedback). To test if insulin's putative effect on odor-place memory would be domain-specific, participants also performed a separate place and odor recognition task. Intranasal insulin improved the delayed but not immediate odor-cued recall of spatial memory. This effect was independent of odor type and in the absence of systemic side effects (eg, fasting plasma glucose levels remained unaltered). Place and odor recognition were unaffected by the insulin treatment. These findings suggest that acute intranasal insulin improves odor-cued reactivation of spatial memory in young men.

Brain insulin signaling and Alzheimer's disease: current evidence and future directions.

Science.gov (United States)

Schiöth, Helgi B; Craft, Suzanne; Brooks, Samantha J; Frey, William H; Benedict, Christian

2012-08-01

Insulin receptors in the brain are found in high densities in the hippocampus, a region that is fundamentally involved in the acquisition, consolidation, and recollection of new information. Using the intranasal method, which effectively bypasses the blood-brain barrier to deliver and target insulin directly from the nose to the brain, a series of experiments involving healthy humans has shown that increased central nervous system (CNS) insulin action enhances learning and memory processes associated with the hippocampus. Since Alzheimer's disease (AD) is linked to CNS insulin resistance, decreased expression of insulin and insulin receptor genes and attenuated permeation of blood-borne insulin across the blood-brain barrier, impaired brain insulin signaling could partially account for the cognitive deficits associated with this disease. Considering that insulin mitigates hippocampal synapse vulnerability to amyloid beta and inhibits the phosphorylation of tau, pharmacological strategies bolstering brain insulin signaling, such as intranasal insulin, could have significant therapeutic potential to deter AD pathogenesis.

Insulin in the nervous system and the mind: Functions in metabolism, memory, and mood.

Science.gov (United States)

Lee, Seung-Hwan; Zabolotny, Janice M; Huang, Hu; Lee, Hyon; Kim, Young-Bum

2016-08-01

Insulin, a pleotrophic hormone, has diverse effects in the body. Recent work has highlighted the important role of insulin's action in the nervous system on glucose and energy homeostasis, memory, and mood. Here we review experimental and clinical work that has broadened the understanding of insulin's diverse functions in the central and peripheral nervous systems, including glucose and body weight homeostasis, memory and mood, with particular emphasis on intranasal insulin. Implications for the treatment of obesity, type 2 diabetes, dementia, and mood disorders are discussed in the context of brain insulin action. Intranasal insulin may have potential in the treatment of central nervous system-related metabolic disorders.

Visualization and Quantitative Assessment of the Brain Distribution of Insulin through Nose-to-Brain Delivery Based on the Cell-Penetrating Peptide Noncovalent Strategy.

Science.gov (United States)

Kamei, Noriyasu; Shingaki, Tomotaka; Kanayama, Yousuke; Tanaka, Misa; Zochi, Riyo; Hasegawa, Koki; Watanabe, Yasuyoshi; Takeda-Morishita, Mariko

2016-03-07

Our recent work suggested that intranasal coadministration with the cell-penetrating peptide (CPP) penetratin increased the brain distribution of the peptide drug insulin. The present study aimed to distinctly certify the ability of penetratin to facilitate the nose-to-brain delivery of insulin by quantitatively evaluating the distribution characteristics in brain using radioactive (64)Cu-NODAGA-insulin. Autoradiography and analysis using a gamma counter of brain areas demonstrated that the accumulation of radioactivity was greatest in the olfactory bulb, the anterior part of the brain closest to the administration site, at 15 min after intranasal administration of (64)Cu-NODAGA-insulin with l- or d-penetratin. The brain accumulation of (64)Cu-NODAGA-insulin with penetratin was confirmed by ELISA using unlabeled insulin in which intact insulin was delivered to the brain after intranasal coadministration with l- or d-penetratin. By contrast, quantification of cerebrospinal fluid (CSF) samples showed increased insulin concentration in only the anterior portion of the CSF at 15 min after intranasal coadministration with l-penetratin. This study gives the first concrete proof that penetratin can accelerate the direct transport of insulin from the nasal cavity to the brain parenchyma. Further optimization of intranasal administration with CPP may increase the efficacy of delivery of biopharmaceuticals to the brain while reducing the risk of systemic drug exposure.

Impact of Single or Repeated Dose Intranasal Zinc-free Insulin in Young and Aged F344 Rats on Cognition, Signaling, and Brain Metabolism.

Science.gov (United States)

Anderson, Katie L; Frazier, Hilaree N; Maimaiti, Shaniya; Bakshi, Vikas V; Majeed, Zana R; Brewer, Lawrence D; Porter, Nada M; Lin, Ai-Ling; Thibault, Olivier

2017-02-01

Novel therapies have turned to delivering compounds to the brain using nasal sprays, bypassing the blood brain barrier, and enriching treatment options for brain aging and/or Alzheimer's disease. We conducted a series of in vivo experiments to test the impact of intranasal Apidra, a zinc-free insulin formulation, on the brain of young and aged F344 rats. Both single acute and repeated daily doses were compared to test the hypothesis that insulin could improve memory recall in aged memory-deficient animals. We quantified insulin signaling in different brain regions and at different times following delivery. We measured cerebral blood flow (CBF) using MRI and also characterized several brain metabolite levels using MR spectroscopy. We show that neither acute nor chronic Apidra improved memory or recall in young or aged animals. Within 2 hours of a single dose, increased insulin signaling was seen in ventral areas of the aged brains only. Although chronic Apidra was able to offset reduced CBF with aging, it also caused significant reductions in markers of neuronal integrity. Our data suggest that this zinc-free insulin formulation may actually hasten cognitive decline with age when used chronically. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Changes in insulin and insulin signaling in Alzheimer’s disease: cause or consequence?

Science.gov (United States)

Stanley, Molly; Macauley, Shannon L.

2016-01-01

Individuals with type 2 diabetes have an increased risk for developing Alzheimer’s disease (AD), although the causal relationship remains poorly understood. Alterations in insulin signaling (IS) are reported in the AD brain. Moreover, oligomers/fibrils of amyloid-β (Aβ) can lead to neuronal insulin resistance and intranasal insulin is being explored as a potential therapy for AD. Conversely, elevated insulin levels (ins) are found in AD patients and high insulin has been reported to increase Aβ levels and tau phosphorylation, which could exacerbate AD pathology. Herein, we explore whether changes in ins and IS are a cause or consequence of AD. PMID:27432942

Intranasal siRNA administration reveals IGF2 deficiency contributes to impaired cognition in Fragile X syndrome mice.

Science.gov (United States)

Pardo, Marta; Cheng, Yuyan; Velmeshev, Dmitry; Magistri, Marco; Eldar-Finkelman, Hagit; Martinez, Ana; Faghihi, Mohammad A; Jope, Richard S; Beurel, Eleonore

2017-03-23

Molecular mechanisms underlying learning and memory remain imprecisely understood, and restorative interventions are lacking. We report that intranasal administration of siRNAs can be used to identify targets important in cognitive processes and to improve genetically impaired learning and memory. In mice modeling the intellectual deficiency of Fragile X syndrome, intranasally administered siRNA targeting glycogen synthase kinase-3β (GSK3β), histone deacetylase-1 (HDAC1), HDAC2, or HDAC3 diminished cognitive impairments. In WT mice, intranasally administered brain-derived neurotrophic factor (BDNF) siRNA or HDAC4 siRNA impaired learning and memory, which was partially due to reduced insulin-like growth factor-2 (IGF2) levels because the BDNF siRNA- or HDAC4 siRNA-induced cognitive impairments were ameliorated by intranasal IGF2 administration. In Fmr1 -/- mice, hippocampal IGF2 was deficient, and learning and memory impairments were ameliorated by IGF2 intranasal administration. Therefore intranasal siRNA administration is an effective means to identify mechanisms regulating cognition and to modulate therapeutic targets.

Central Nervous Insulin Signaling in Sleep-Associated Memory Formation and Neuroendocrine Regulation.

Science.gov (United States)

Feld, Gordon B; Wilhem, Ines; Benedict, Christian; Rüdel, Benjamin; Klameth, Corinna; Born, Jan; Hallschmid, Manfred

2016-05-01

The neurochemical underpinnings of sleep's contribution to the establishment and maintenance of memory traces are largely unexplored. Considering that intranasal insulin administration to the CNS improves memory functions in healthy and memory-impaired humans, we tested whether brain insulin signaling and sleep interact to enhance memory consolidation in healthy participants. We investigated the effect of intranasal insulin on sleep-associated neurophysiological and neuroendocrine parameters and memory consolidation in 16 men and 16 women (aged 18-30 years), who learned a declarative word-pair task and a procedural finger sequence tapping task in the evening before intranasal insulin (160 IU) or placebo administration and 8 h of nocturnal sleep. On the subsequent evening, they learned interfering word-pairs and a new finger sequence before retrieving the original memories. Insulin increased growth hormone concentrations in the first night-half and EEG delta power during the second 90 min of non-rapid-eye-movement sleep. Insulin treatment impaired the acquisition of new contents in both the declarative and procedural memory systems on the next day, whereas retrieval of original memories was unchanged. Results indicate that sleep-associated memory consolidation is not a primary mediator of insulin's acute memory-improving effect, but that the peptide acts on mechanisms that diminish the subsequent encoding of novel information. Thus, by inhibiting processes of active forgetting during sleep, central nervous insulin might reduce the interfering influence of encoding new information.

Study of Preinduction Sedation with Intranasal Midazolam in Children

Directory of Open Access Journals (Sweden)

A. Rostaminejad

2010-04-01

Full Text Available Introduction & Objectives: Surgical procedures are the most stressful expreiences in life, specially in children. Different methods are used before operation to decrease the stress. Intranasal midazolam is an effective way of preparing before operation and to prevent the separation irritability.Materials & Methods: In a double blind experimental trial study , 60 patients aged 2-6 years with ASAI who had no elective surgery in the past were randomly chosen and divided into two groups.For the patients in group I intranasal midazolam 0.2 mg/kg was administerated and for the patients in group II the equal volume of normal saline was used. The patients’ crying was considered as mild, moderate, and severe. The irritability of their hands shaking during IV canula insertion,consciousness before the induction of anesthesia and cooperation during the mask ventilation were also evaluated.Results: The result of our study determined that 93.3% of the children in group I didn’t cry or they did mildly when separated from their parents but 90% of the children of group II cried moderately and some severely and 90% of the patients in group I cooperated well when separated from their parents. The resistance in group II was moderate or severe in 76.6%. Before induction of anesthesia 73.4% of group I were asleep but woke up with stimulation. 93.3% of the patients in group II were awake and irritated.90% of group I shook their hands steadily during iv cannula insertion but their hands shaking increased in 83.3% of group II..100% of group I cooperated well during face mask ventilation but 76.6% of group II did not. Conclusion: The above mentioned experiences showed that the intranasal midazolam is an effective way of preinduction sedation in children.

Morphology and Anatomy Characteristic of Pisang Awak (Musa paradisiaca cv. Awak in West Kalimantan

Directory of Open Access Journals (Sweden)

Ari Sunandar

2017-12-01

Full Text Available Indonesia is the origin and center of diversity of banana. One of an edible banana in Indonesia is Pisang Awak (Musa paradisiaca cv. Awak . In West Kalimantan, the ripe Pisang Awak has been processed into sale (dried banana. The aims of this research were to describe the morphological and anatomical character of Pisang Awak in West Kalimantan, Indonesia. In this study, Pisang Awak were collected from Padang Tikar I village, Batu Ampar Sub-district, Kubu Raya district, West Kalimantan. Morphological characterizations were conducted by following the instruction on Descriptors for Banana (Musa spp. from IPGRI. The root, leaf blade, and petiole were fixed in FAA solution. Root, leaf, and petiole anatomy preparats were made by paraffin method. The lamina of Pisang Awak consisted of adaxial epidermis, two hypodermis layers, two palisade layers, spongy layer, bundle sheath cell, abaxial epidermis, laticifer. The petiole of Pisang Awak composed of three tissue systems, i.e., epidermis layer, parenchyma tissue and vascular tissue. The root of Pisang Awak consists of two epidermis layers, parenchyma and vascular cylinder. In the future, morphological and anatomical character in Pisang Awak could be applied as the basis of information for breeding programs of banana cultivars and classification.

INTRANASAL DEXMEDETOMIDINE VS. INTRANASAL MIDAZOLAM FOR PREMEDICATION OF PAEDIATRIC SURGERY PATIENTS

Directory of Open Access Journals (Sweden)

Revi N

2016-06-01

Full Text Available AIM Preoperative anxiety is one of the most common problems faced by anyone practising paediatric anaesthesia. Various drugs have been used in various routes to get a calm but cooperative child before induction of anaesthesia. Midazolam and dexmedetomidine have already proved their value in paediatric premedication. This study was conducted to compare the effects of these two drugs given intranasally. MATERIALS AND METHODS 100 children falling under the inclusion criteria were assigned to groups of 50 each. They received either intranasal midazolam 0.2 mg/kg (group M or intranasal dexmedetomidine 2 mcg/kg (Group D as premedication. They were compared with regards to the sedation status, anxiety levels and cardiovascular status every 10 minutes, at parental separation and at face mask application. RESULTS The mean sedation score obtained at all-time intervals, at parental separation and more importantly at mask induction were much lower for the midazolam group compared to the dexmedetomidine group. The mean anxiety levels, in general, were lower in the midazolam group, but they attained statistical significance only at 10 minutes and at mask induction. The heart rate measured up to 20 minutes after drug administration did not show much difference between both groups, but at 30 minutes, 40 minutes and at parental separation, heart rate was found to be lower in the dexmedetomidine group. CONCLUSION Intranasal dexmedetomidine and intranasal midazolam are equally effective in providing satisfactory parental separation, but intranasal midazolam produced superior conditions for mask acceptance than intranasal dexmedetomidine.

Hypothalamic and Striatal Insulin Action Suppresses Endogenous Glucose Production and May Stimulate Glucose Uptake During Hyperinsulinemia in Lean but Not in Overweight Men.

Science.gov (United States)

Heni, Martin; Wagner, Robert; Kullmann, Stephanie; Gancheva, Sofiya; Roden, Michael; Peter, Andreas; Stefan, Norbert; Preissl, Hubert; Häring, Hans-Ulrich; Fritsche, Andreas

2017-07-01

Intranasal spray application facilitates insulin delivery to the human brain. Although brain insulin modulates peripheral metabolism, the mechanisms involved remain elusive. Twenty-one men underwent two hyperinsulinemic-euglycemic clamps with d-[6,6- 2 H 2 ]glucose infusion to measure endogenous glucose production and glucose disappearance. On two separate days, participants received intranasal insulin or placebo. Insulin spillover into circulation after intranasal insulin application was mimicked by an intravenous insulin bolus on placebo day. On a different day, brain insulin sensitivity was assessed by functional MRI. Glucose infusion rates (GIRs) had to be increased more after nasal insulin than after placebo to maintain euglycemia in lean but not in overweight people. The increase in GIRs was associated with regional brain insulin action in hypothalamus and striatum. Suppression of endogenous glucose production by circulating insulin was more pronounced after administration of nasal insulin than after placebo. Furthermore, glucose uptake into tissue tended to be higher after nasal insulin application. No such effects were detected in overweight participants. By increasing insulin-mediated suppression of endogenous glucose production and stimulating peripheral glucose uptake, brain insulin may improve glucose metabolism during systemic hyperinsulinemia. Obese people appear to lack these mechanisms. Therefore, brain insulin resistance in obesity may have unfavorable consequences for whole-body glucose homeostasis. © 2017 by the American Diabetes Association.

[Awake craniotomy for brain tumours].

Science.gov (United States)

Milos, Peter; Metcalf, Kerstin; Vigren, Patrick; Lindehammar, Hans; Nilsson, Malin; Boström, Sverre

2016-10-11

Awake craniotomy for brain tumours  Awake neurosurgery is a useful method in lesions near eloquent brain areas, particularly low-grade gliomas.The aim is to maximise tumour resection and preserve neurological function. We performed 40 primary awake surgeries and 8 residual surgeries. Patients were operated awake throughout the procedure or with a laryngeal mask and general anaesthesia during the opening stage and then awake during intracerebral surgery. Language and motor function were mapped with direct cortical stimulation, motor evoked potential and standardised neurological testing. Radiologically, complete resection was achieved in 18 out of 40 patients in the primary surgeries. Full neurological recovery at three months was observed in 29 patients. Of the 11 patients with persisting neurological deficits at three months, symptoms were present preoperatively in 9 patients. We conclude that awake surgery, combined with intraoperative neurophysiological methods, is a safe method to improve treatment for low-grade gliomas.

The asleep-awake technique using propofol-remifentanil anaesthesia for awake craniotomy for cerebral tumours

DEFF Research Database (Denmark)

Olsen, Karsten Skovgaard

2008-01-01

Background and objective: We retrospectively reviewed the first 25 planned cases of awake craniotomies using the 'asleep-awake' technique, an alternative to the often-used 'asleep-awake-asleep' technique. Methods: The patients were anaesthetized using propofol/remifentanil anaesthesia, a laryngeal...... mask and controlled ventilation according to a protocol defined before the start of this series of patients. The patients were awakened before the brain mapping and were kept awake throughout the rest of the procedure allowing for additional mapping and modification of the resection of the turnout...... to obtain a tight laryngeal mask. All of the 23 patients were awake as from when the mapping session began and throughout the rest of the operation. In five cases the resection of the tumour was modified as symptoms emerged. These symptoms all subsided in due course. No case of hypoxia was recorded...

Insulin in the nervous system and the mind: Functions in metabolism, memory, and mood

Directory of Open Access Journals (Sweden)

Seung-Hwan Lee

2016-08-01

Major conclusions: Implications for the treatment of obesity, type 2 diabetes, dementia, and mood disorders are discussed in the context of brain insulin action. Intranasal insulin may have potential in the treatment of central nervous system-related metabolic disorders.

[Anesthesiological management of awake craniotomy : Asleep-awake-asleep technique or without sedation].

Science.gov (United States)

Seemann, M; Zech, N; Graf, B; Hansen, E

2015-02-01

Awake craniotomy is indicated in deep brain stimulation (DBS) for treatment of certain movement disorders, such as in Parkinson disease patients or in the surgery of brain tumors in close vicinity to the language area. The standard procedure is the asleep-awake-asleep technique where general anesthesia or analgosedation is intermittently interrupted for neurological testing. In DBS the intraoperative improvement of symptoms, stereotactic navigation and microelectrode reading guide to the optimal position. In brain tumor resection, reversible functional impairments during electrical stimulation on the brain surface (brain mapping) show the exact individual position of eloquent or motoric areas that should be protected.The anesthesiology procedures used are very variable. It is a balancing act between overdosing of anesthetics with impairment of respiration and alertness and underdosing with pain, strain and stress for the patient. For the asleep-awake-asleep technique high acceptance but also frequent and partly severe complications have been reported. The psychological stress for the patient can be immense. Obviously, a feeling of being left alone and being at someone's mercy is not adequately treated by drugs and performance of the neurological tests is undoubtedly better and more reliable with less pharmacological impairment. Cranial nerve blocks can reduce the amount of anesthetics as they provide analgesia of the scalp more efficiently than local infiltration. With these nerve blocks, a strong therapeutic relationship and a specific communication, sedatives can be avoided and the need for opioids markedly reduced or abolished. The suggestive communication promotes for instance dissociation to an inner safe refuge, as well as reframing of disturbing noises and sensations. Each of the methods applied for awake craniotomy can profit from the principles of this awake-awake-awake technique.

Surgeon-patient communication during awake procedures.

Science.gov (United States)

Smith, Claire S; Guyton, Kristina; Pariser, Joseph J; Siegler, Mark; Schindler, Nancy; Langerman, Alexander

2017-06-01

Surgeons are increasingly performing procedures on awake patients. Communication during such procedures is complex and underexplored in the literature. Surgeons were recruited from the faculty of 2 hospitals to participate in an interview regarding their approaches to communication during awake procedures. Three researchers used the constant comparative method to transcribe, code, and review interviews until saturation was reached. Twenty-three surgeons described the advantages and disadvantages of awake procedures, their communication with the awake patient, their interactions with staff and with trainees, the environment of awake procedures, and how communication in this context is taught and learned. Surgeons recognized communication during awake procedures as important and reported varied strategies for ensuring patient comfort in this context. However, they also acknowledged challenges with multiparty communication during awake procedures, especially in balancing commitments to teaching with their duty to comfort the patient. Copyright © 2016 Elsevier Inc. All rights reserved.

Demonstration of analgesic effect of intranasal ketamine and intranasal fentanyl for postoperative pain after pediatric tonsillectomy.

Science.gov (United States)

Yenigun, Alper; Yilmaz, Sinan; Dogan, Remzi; Goktas, Seda Sezen; Calim, Muhittin; Ozturan, Orhan

2018-01-01

Tonsillectomy is one of the oldest and most commonly performed surgical procedure in otolaryngology. Postoperative pain management is still an unsolved problem. In this study, our aim is to demonstrate the efficacy of intranasal ketamine and intranasal fentanyl for postoperative pain relief after tonsillectomy in children. This randomized-controlled study was conducted to evaluate the effects of intranasal ketamine and intranasal fentanyl in children undergoing tonsillectomy. Tonsillectomy performed in 63 children were randomized into three groups. Group I received: Intravenous paracetamol (10 mg/kg), Group II received intranasal ketamine (1.5 mg/kg ketamine), Group III received intranasal fentanyl (1.5 mcg/kg). The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and Wilson sedation scale scores were recorded at 15, 30, 60 min, 2 h, 6hr, 12 h and 24 h postoperatively. Patients were interviewed on the day after surgery to assess the postoperative pain, nightmares, hallucinations, nausea, vomiting and bleeding. Intranasal ketamine and intranasal fentanyl provided significantly stronger analgesic affects compared to intravenous paracetamol administration at postoperative 15, 30, 60 min and at 2, 6, 12 and 24 h in CHEOPS (p ketamine administration group. No such sedative effect was seen in the groups that received intranasal fentanyl and intravenous paracetamol in Wilson Sedation Scale (p ketamine and intranasal fentanyl were more effective than paracetamol for postoperative analgesia after pediatric tonsillectomy. Sedative effects were observed in three patients with the group of intranasal ketamine. There was no significant difference in the efficacy of IN Ketamine and IN Fentanyl for post-tonsillectomy pain. Copyright © 2017 Elsevier B.V. All rights reserved.

Anaesthesia for awake craniotomy

Directory of Open Access Journals (Sweden)

Girija Prasad Rath

2014-01-01

Full Text Available Awake craniotomy is a neurosurgical procedure during which the patient remains awake as a whole or during some part of the surgery. Although not a new procedure, it has regained its importance since last two decades following the advent of newer drugs along with improvised techniques. The role of anesthesiologist during this procedure is of paramount importance. In this review, we discussed the anesthetic management during awake craniotomy and re-emphasized on the avoidance of intraoperative untoward events with appropriate patient selection.

Awake craniotomy for tumor resection.

Science.gov (United States)

Attari, Mohammadali; Salimi, Sohrab

2013-01-01

Surgical treatment of brain tumors, especially those located in the eloquent areas such as anterior temporal, frontal lobes, language, memory areas, and near the motor cortex causes high risk of eloquent impairment. Awake craniotomy displays major rule for maximum resection of the tumor with minimum functional impairment of the Central Nervous System. These case reports discuss the use of awake craniotomy during the brain surgery in Alzahra Hospital, Isfahan, Iran. A 56-year-old woman with left-sided body hypoesthesia since last 3 months and a 25-year-old with severe headache of 1 month duration were operated under craniotomy for brain tumors resection. An awake craniotomy was planned to allow maximum tumor intraoperative testing for resection and neurologic morbidity avoidance. The method of anesthesia should offer sufficient analgesia, hemodynamic stability, sedation, respiratory function, and also awake and cooperative patient for different neurological test. Airway management is the most important part of anesthesia during awake craniotomy. Tumor surgery with awake craniotomy is a safe technique that allows maximal resection of lesions in close relationship to eloquent cortex and has a low risk of neurological deficit.

Awake craniotomy for tumor resection

Directory of Open Access Journals (Sweden)

Mohammadali Attari

2013-01-01

Full Text Available Surgical treatment of brain tumors, especially those located in the eloquent areas such as anterior temporal, frontal lobes, language, memory areas, and near the motor cortex causes high risk of eloquent impairment. Awake craniotomy displays major rule for maximum resection of the tumor with minimum functional impairment of the Central Nervous System. These case reports discuss the use of awake craniotomy during the brain surgery in Alzahra Hospital, Isfahan, Iran. A 56-year-old woman with left-sided body hypoesthesia since last 3 months and a 25-year-old with severe headache of 1 month duration were operated under craniotomy for brain tumors resection. An awake craniotomy was planned to allow maximum tumor intraoperative testing for resection and neurologic morbidity avoidance. The method of anesthesia should offer sufficient analgesia, hemodynamic stability, sedation, respiratory function, and also awake and cooperative patient for different neurological test. Airway management is the most important part of anesthesia during awake craniotomy. Tumor surgery with awake craniotomy is a safe technique that allows maximal resection of lesions in close relationship to eloquent cortex and has a low risk of neurological deficit.

Awake fiberoptic or awake video laryngoscopic tracheal intubation in patients with anticipated difficult airway management

DEFF Research Database (Denmark)

Rosenstock, Charlotte Vallentin; Thøgersen, Bente; Afshari, Arash

2012-01-01

Awake flexible fiberoptic intubation (FFI) is the gold standard for management of anticipated difficult tracheal intubation. The purpose of this study was to compare awake FFI to awake McGrath® video laryngoscope, (MVL), (Aircraft Medical, Edinburgh, Scotland, United Kingdom) intubation in patients...... with an anticipated difficult intubation. The authors examined the hypothesis that MVL intubation would be faster than FFI....

[Awake craniotomy].

Science.gov (United States)

Kobyakov, G L; Lubnin, A Yu; Kulikov, A S; Gavrilov, A G; Goryaynov, S A; Poddubskiy, A A; Lodygina, K S

2016-01-01

Awake craniotomy is a neurosurgical intervention aimed at identifying and preserving the eloquent functional brain areas during resection of tumors located near the cortical and subcortical language centers. This article provides a review of the modern literature devoted to the issue. The anatomical rationale and data of preoperative functional neuroimaging, intraoperative electrophysiological monitoring, and neuropsychological tests as well as the strategy of active surgical intervention are presented. Awake craniotomy is a rapidly developing technique aimed at both preserving speech and motor functions and improving our knowledge in the field of speech psychophysiology.

Brain Insulin Signaling and Alzheimer's Disease: Current Evidence and Future Directions

OpenAIRE

Schiöth, Helgi B.; Craft, Suzanne; Brooks, Samantha J.; Frey, William H.; Benedict, Christian

2011-01-01

Insulin receptors in the brain are found in high densities in the hippocampus, a region that is fundamentally involved in the acquisition, consolidation, and recollection of new information. Using the intranasal method, which effectively bypasses the blood–brain barrier to deliver and target insulin directly from the nose to the brain, a series of experiments involving healthy humans has shown that increased central nervous system (CNS) insulin action enhances learning and memory processes as...

AWAKE starts the equipment installation phase

CERN Multimedia

Antonella Del Rosso

2015-01-01

AWAKE is the proof-of-principle experiment whose aim is to use protons to generate powerful wakefields to accelerate an electron beam. With accelerator gradients hundreds of times higher than those used in current systems, this technique could revolutionise the field of particle acceleration. Installed in the tunnel previously used by the CNGS facility, AWAKE is completing the service installation phase and will receive the plasma cell in the coming months.   The AWAKE proton line with all the magnets installed. (Image: AWAKE collaboration.) AWAKE is the world’s first proton-driven plasma wakefield acceleration experiment. In AWAKE, a beam of protons from the SPS will be travelling through a plasma cell and this will generate a wakefield that, in turn, will accelerate an electron beam. A laser will ionise the gas in the plasma cell and seed the self-modulation instability that will trigger the wakefield in the plasma. The project aims to prove that the plasma wakefield can be driv...

Awake right hemisphere brain surgery.

Science.gov (United States)

Hulou, M Maher; Cote, David J; Olubiyi, Olutayo I; Smith, Timothy R; Chiocca, E Antonio; Johnson, Mark D

2015-12-01

We report the indications and outcomes of awake right hemispheric brain surgery, as well as a rare patient with crossed aphasia. Awake craniotomies are often performed to protect eloquent cortex. We reviewed the medical records for 35 of 96 patients, in detail, who had awake right hemisphere brain operations. Intraoperative cortical mapping of motor and/or language function was performed in 29 of the 35 patients. A preoperative speech impairment and left hand dominance were the main indicators for awake right-sided craniotomies in patients with right hemisphere lesions. Four patients with lesion proximity to eloquent areas underwent awake craniotomies without cortical mapping. In addition, one patient had a broncho-pulmonary fistula, and another had a recent major cardiac procedure that precluded awake surgery. An eloquent cortex representation was identified in 14 patients (48.3%). Postoperatively, seven of 17 patients (41.1%) who presented with weakness, experienced improvements in their motor functions, 11 of 16 (68.7%) with seizures became seizure-free, and seven of nine (77.7%) with moderate to severe headaches and one of two with a visual field deficit improved significantly. There were also improvements in speech and language functions in all patients who presented with speech difficulties. A right sided awake craniotomy is an excellent option for left handed patients, or those with right sided cortical lesions that result in preoperative speech impairments. When combined with intraoperative cortical mapping, both speech and motor function can be well preserved. Copyright © 2015 Elsevier Ltd. All rights reserved.

The clinical management of awake bruxism.

Science.gov (United States)

Goldstein, Ronald E; Auclair Clark, Wendy

2017-06-01

Awake bruxism is a common clinical condition that often goes undetected, often leading to pain or damaged teeth and restorations. The authors searched electronic databases regarding the treatment and effects of awake bruxism compared with those of sleep bruxism. The authors used the search terms diurnal bruxism and oral parafunction. The authors combined information from relevant literature with clinical experience to establish a recommended protocol for diagnosis and treatment. The authors found articles regarding the diagnosis and treatment of bruxism. The authors combined information from the articles with a review of clinical cases to establish a treatment protocol for awake bruxism. Literature and clinical experience indicate a lack of patient awareness and, thus, underreporting of awake bruxism. As a result, myriad dental consequences can occur from bruxism. The authors propose a need for increased awareness, for both patients and professionals, particularly of the number of conditions related to awake bruxism. Clinicians should look for clinical signs and symptoms of awake bruxism and use minimally invasive treatment modalities. Copyright © 2017 American Dental Association. Published by Elsevier Inc. All rights reserved.

How I do it: Awake craniotomy.

Science.gov (United States)

Hill, Ciaran Scott; Severgnini, Flavio; McKintosh, Edward

2017-01-01

Awake craniotomy allows continuous assessment of a patient's clinical and neurological status during open brain surgery. This facilitates early detection of interference with eloquent cortex, and hence can allow a surgeon to maximize resection margins without compromising neurological function. Awake craniotomy requires an effective scalp blockade, intraoperative assessment, and a carefully co-ordinated theatre team. A variety of clinical and electrophysiological techniques can be used to assess cortical function. Effective scalp blockade and awake craniotomy provides the opportunity to intraoperatively assess cortical function in the awake patient, thus providing an important neurosurgical option for lesions near eloquent cortex.

Anaesthetic management for awake craniotomy in brain glioma ...

African Journals Online (AJOL)

The awake brain surgery is an innovative approach in the treatment of tumors in the functional areas of the brain. There are various anesthetic techniques for awake craniotomy (AC), including asleep-awake-asleep technique, monitored anesthesia care, and the recent introduced awakeawake- awake method. We describe ...

Awake craniotomy: improving the patient's experience.

Science.gov (United States)

Potters, Jan-Willem; Klimek, Markus

2015-10-01

Awake craniotomy patients are exposed to various stressful stimuli while their attention and vigilance is important for the success of the surgery. We describe several recent findings on the perception of awake craniotomy patients and address nonpharmacological perioperative factors that enhance the experience of awake craniotomy patients. These factors could also be applicable to other surgical patients. Proper preoperative counseling gives higher patient satisfaction and should be individually tailored to the patient. Furthermore, there is a substantial proportion of patients who have significant pain or fear during an awake craniotomy procedure. There is a possibility that this could induce post-traumatic stress disorder or related symptoms. Preoperative preparation is of utmost importance in awake craniotomy patients, and a solid doctor-patient relationship is an important condition. Nonpharmacological intraoperative management should focus on reduction of fear and pain by adaptation of the environment and careful and well considered communication.

Predicting sleepiness during an awake craniotomy.

Science.gov (United States)

Itoi, Chihiro; Hiromitsu, Kentaro; Saito, Shoko; Yamada, Ryoji; Shinoura, Nobusada; Midorikawa, Akira

2015-12-01

An awake craniotomy is a safe neurological surgical technique that minimizes the risk of brain damage. During the course of this surgery, the patient is asked to perform motor or cognitive tasks, but some patients exhibit severe sleepiness. Thus, the present study investigated the predictive value of a patient's preoperative neuropsychological background in terms of sleepiness during an awake craniotomy. Thirty-seven patients with brain tumor who underwent awake craniotomy were included in this study. Prior to craniotomy, the patient evaluated cognitive status, and during the surgery, each patient's performance and attitude toward cognitive tasks were recorded by neuropsychologists. The present findings showed that the construction and calculation abilities of the patients were moderately correlated with their sleepiness. These results indicate that the preoperative cognitive functioning of patients was related to their sleepiness during the awake craniotomy procedure and that the patients who exhibited sleepiness during an awake craniotomy had previously experienced reduced functioning in the parietal lobe. Copyright © 2015 Elsevier B.V. All rights reserved.

The Effects of Peripheral and Central High Insulin on Brain Insulin Signaling and Amyloid-β in Young and Old APP/PS1 Mice.

Science.gov (United States)

Stanley, Molly; Macauley, Shannon L; Caesar, Emily E; Koscal, Lauren J; Moritz, Will; Robinson, Grace O; Roh, Joseph; Keyser, Jennifer; Jiang, Hong; Holtzman, David M

2016-11-16

Hyperinsulinemia is a risk factor for late-onset Alzheimer's disease (AD). In vitro experiments describe potential connections between insulin, insulin signaling, and amyloid-β (Aβ), but in vivo experiments are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving APP swe /PS1 dE9 transgenic mice. Both a postprandial and supraphysiological insulin clamp significantly increased interstitial fluid (ISF) and plasma Aβ compared with controls. We could detect no increase in brain, ISF, or CSF insulin or brain insulin signaling in response to peripheral hyperinsulinemia, despite detecting increased signaling in the muscle. Next, we delivered insulin directly into the hippocampus of young APP/PS1 mice via reverse microdialysis. Brain tissue insulin and insulin signaling was dose-dependently increased, but ISF Aβ was unchanged by central insulin administration. Finally, to determine whether peripheral and central high insulin has differential effects in the presence of significant amyloid pathology, we repeated these experiments in older APP/PS1 mice with significant amyloid plaque burden. Postprandial insulin clamps increased ISF and plasma Aβ, whereas direct delivery of insulin to the hippocampus significantly increased tissue insulin and insulin signaling, with no effect on Aβ in old mice. These results suggest that the brain is still responsive to insulin in the presence of amyloid pathology but increased insulin signaling does not acutely modulate Aβ in vivo before or after the onset of amyloid pathology. Peripheral hyperinsulinemia modestly increases ISF and plasma Aβ in young and old mice, independent of neuronal insulin signaling. The transportation of insulin from blood to brain is a saturable process relevant to understanding the link between hyperinsulinemia and AD. In vitro experiments have found direct connections

Manipulating central nervous mechanisms of food intake and body weight regulation by intranasal administration of neuropeptides in man.

Science.gov (United States)

Hallschmid, Manfred; Benedict, Christian; Born, Jan; Fehm, Horst-Lorenz; Kern, Werner

2004-10-30

Maintaining a stable body weight set-point is assumed to rely on a homeostatic central nervous system (CNS) regulation of body fat with the particular involvement of hypothalamic pathways. The peripheral adiposity signals insulin and leptin convey information on the amount of energy stored as body fat to the arcuate nucleus of the hypothalamus, where anabolic/orexigenic and catabolic/anorexigenic pathways interact to regulate food intake and energy expenditure. One of the most prominent orexigenic messengers is neuropeptide Y (NPY), whereas melanocortins, including alpha-melanocyte-stimulating hormone (alpha-MSH), are essential for inducing anorexigenic effects. The melanocortin receptor 4 (MC4-R) plays the most important role in mediating catabolic effects of alpha-MSH. In this review, we present a series of own studies on NPY, insulin and MSH/ACTH4-10, an MC4-R agonist. The studies were all based on the intranasal route of administration which enables a direct access of the peptides to hypothalamic functions. NPY acutely attenuated electrocortical signs of meal-related satiety. Prolonged intranasal administration of insulin as well as of MSH induced weight loss in healthy human subjects. However, overweight subjects did not lose body fat after MSH administration. The results corroborate in humans the significance of all three messengers for the central nervous regulation of adiposity and might contribute to the future development of medical strategies against body-weight-related disorders.

Ethical challenges with awake craniotomy for tumor.

Science.gov (United States)

Kirsch, Brandon; Bernstein, Mark

2012-01-01

Awake brain surgery is useful for the treatment of a number of conditions such as epilepsy and brain tumor, as well as in functional neurosurgery. Several studies have been published regarding clinical results and outcomes of patients who have undergone awake craniotomy but few have dealt with related ethical issues. The authors undertake to explore broadly the ethical issues surrounding awake brain surgery for tumor resection to encourage further consideration and discussion. Based on a review of the literature related to awake craniotomy and in part from the personal experience of the senior author, we conducted an assessment of the ethical issues associated with awake brain tumor surgery. The major ethical issues identified relate to: (1) lack of data; (2) utilization; (3) conflict of interest; (4) informed consent; (5) surgical innovation; and (6) surgical training. The authors respectfully suggest that the selection of patients for awake craniotomy needs to be monitored according to more consistent, objective standards in order to avoid conflicts of interest and potential harm to patients.

Bioavailability of intranasal metoclopramide.

OpenAIRE

Ward, M J; Buss, D C; Ellershaw, J; Nash, A; Routledge, P A

1989-01-01

After intranasal administration of metoclopramide, (5 mg in 0.5 ml sterile water) the maximum plasma concentration of 13.5 +/- 7.3 (mean +/- s.d.) ng ml-1 was achieved. Absolute bioavailability was 50.5 +/- 29.5%, 110 +/- 41 min later. We conclude that the intranasal route does not allow rapid absorption of the drug and is not associated with greater bioavailability than the oral route.

Pediatric Awake Craniotomy for Brain Lesions.

Science.gov (United States)

Akay, Ali; Rükşen, Mete; Çetin, H Yurday; Seval, H Özer; İşlekel, Sertaç

2016-01-01

Awake craniotomy is a special method to prevent motor deficits during the resection of lesions that are located in, or close to, functional areas. Although it is more commonly performed in adult patients, reports of pediatric cases undergoing awake craniotomy are limited in the literature. In our clinic, where we frequently use awake craniotomy in adult patients, we performed this method in 2 selected pediatric cases for lesion surgery. At an early age, these 2 cases diagnosed with epilepsy presented cerebral lesions, but since the lesions enclosed functional areas, surgical resection was not regarded as a treatment option at this time. In these 2 pediatric cases, we successfully completed lesion surgery with awake craniotomy. The method and the techniques employed during surgery are presented concomitant with other reports in the literature. © 2016 S. Karger AG, Basel.

Nasal insulin changes peripheral insulin sensitivity simultaneously with altered activity in homeostatic and reward-related human brain regions.

Science.gov (United States)

Heni, M; Kullmann, S; Ketterer, C; Guthoff, M; Linder, K; Wagner, R; Stingl, K T; Veit, R; Staiger, H; Häring, H-U; Preissl, H; Fritsche, A

2012-06-01

Impaired insulin sensitivity is a major factor leading to type 2 diabetes. Animal studies suggest that the brain is involved in the regulation of insulin sensitivity. We investigated whether insulin action in the human brain regulates peripheral insulin sensitivity and examined which brain areas are involved. Insulin and placebo were given intranasally. Plasma glucose, insulin and C-peptide were measured in 103 participants at 0, 30 and 60 min. A subgroup (n = 12) was also studied with functional MRI, and blood sampling at 0, 30 and 120 min. For each time-point, the HOMA of insulin resistance (HOMA-IR) was calculated as an inverse estimate of peripheral insulin sensitivity. Plasma insulin increased and subsequently decreased. This excursion was accompanied by slightly decreased plasma glucose, resulting in an initially increased HOMA-IR. At 1 h after insulin spray, the HOMA-IR subsequently decreased and remained lower up to 120 min. An increase in hypothalamic activity was observed, which correlated with the increased HOMA-IR at 30 min post-spray. Activity in the putamen, right insula and orbitofrontal cortex correlated with the decreased HOMA-IR at 120 min post-spray. Central insulin action in specific brain areas, including the hypothalamus, may time-dependently regulate peripheral insulin sensitivity. This introduces a potential novel mechanism for the regulation of peripheral insulin sensitivity and underlines the importance of cerebral insulin action for the whole organism.

Anaesthesia for awake craniotomy is safe and well-tolerated

DEFF Research Database (Denmark)

Andersen, Jakob Hessel; Olsen, Karsten Skovgaard

2010-01-01

Awake craniotomy for tumour resection has been performed at Glostrup Hospital since 2004. We describe and discuss the various anaesthetic approaches for such surgery and retrospectively analyse the 44 planned awake craniotomies performed at Glostrup Hospital. The surgery falls into four phases......: craniotomy, mapping, tumour resection and closing. Three methods are being used: monitored anaesthetic care, asleep-awake-asleep and asleep-awake (AA)....

[Awake craniotomy: analysis of complicated cases].

Science.gov (United States)

Kulikov, A S; Kobyakov, G L; Gavrilov, A G; Lubnin, A Yu

2015-01-01

Awake craniotomy is recognized as method that can decrease the frequency of neurological complications after surgery for gliomas located near eloquent brain regions. Unfortunately good neurological outcome can't be ensured even by using of this technique. This paper discusses reasons and possible ways of prevention of such complications. 162 awake craniotomies were performed in our clinic. 152 of patients were discharged from the clinic with good outcome. In 10 (6%) cases sustained severe neurological deficit was noted. These complications were associated with anatomic or ischemic injury of subcortical pathways and internal capsule. Awake craniotomy is effective instrument of brain language mapping and prevention of neurological deterioration. Severe neurological complications of awake craniotomy are associated with underestimate neurosurgical risks, especially in terms of blood vessel injury and depth of resection. The main way of prevention of such complications is meticulous planning of operation and adequate using of mapping facilities.

Awake Craniotomy: First-Year Experiences and Patient Perception.

Science.gov (United States)

Joswig, Holger; Bratelj, Denis; Brunner, Thomas; Jacomet, Alfred; Hildebrandt, Gerhard; Surbeck, Werner

2016-06-01

Awake craniotomy for brain lesions in or near eloquent brain regions enables neurosurgeons to assess neurologic functions of patients intraoperatively, reducing the risk of permanent neurologic deficits and increasing the extent of resection. A retrospective review was performed of a consecutive series of patients with awake craniotomies in the first year of their introduction to our tertiary non-university-affiliated neurosurgery department. Operation time, complications, and neurologic outcome were assessed, and patient perception of awake craniotomy was surveyed using a mailed questionnaire. There were 24 awake craniotomies performed in 22 patients for low-grade/high-grade gliomas, cavernomas, and metastases (average 2 cases per month). Mean operation time was 205 minutes. Failure of awake craniotomy because of intraoperative seizures with subsequent postictal impaired testing or limited cooperation occurred in 2 patients. Transient neurologic deficits occurred in 29% of patients; 1 patient sustained a permanent neurologic deficit. Of the 18 patients (82%) who returned the questionnaire, only 2 patients recalled significant fear during surgery. Introducing awake craniotomy to a tertiary non-university-affiliated neurosurgery department is feasible and resulted in reasonable operation times and complication rates and high patient satisfaction. Copyright © 2016 Elsevier Inc. All rights reserved.

Awake craniotomy. A patient`s perspective.

Science.gov (United States)

Bajunaid, Khalid M; Ajlan, Abdulrazag M

2015-07-01

To report the personal experiences of patients undergoing awake craniotomy for brain tumor resection. We carried out a qualitative descriptive survey of patients` experiences with awake craniotomies for brain tumor resection. The survey was conducted through a standard questionnaire form after the patient was discharged from the hospital. Of the 9 patients who met the inclusion criteria and underwent awake craniotomy, 3 of those patients reported no recollection of the operation. Five patients had auditory recollections from the operation. Two-thirds (6/9) reported that they did not perceive pain. Five patients remembered the head clamp fixation, and 2 of those patients classified the pain from the clamp as moderate. None of the patients reported that the surgery was more difficult than anticipated. Awake craniotomy for surgical resection of brain tumors was well tolerated by patients. Most patients reported that they do not recall feeling pain during the operation. However, we feel that further work and exploration are needed in order to achieve better control of pain and discomfort during these types of operations.

Awake Craniotomy: A New Airway Approach.

Science.gov (United States)

Sivasankar, Chitra; Schlichter, Rolf A; Baranov, Dimitry; Kofke, W Andrew

2016-02-01

Awake craniotomies have been performed regularly at the University of Pennsylvania since 2004. Varying approaches to airway management are described for this procedure, including intubation with an endotracheal tube and use of a laryngeal mask airway, simple facemask, or nasal cannula. In this case series, we describe the successful use (i.e., no need for endotracheal intubation related to inadequate gas exchange) of bilateral nasopharyngeal airways in 90 patients undergoing awake craniotomies. The use of nasopharyngeal airways can ease the transition between the asleep and awake phases of the craniotomy without the need to stimulate the airway. Our purpose was to describe our experience and report adverse events related to this technique.

Patient response to awake craniotomy - a summary overview.

Science.gov (United States)

Milian, Monika; Tatagiba, Marcos; Feigl, Guenther C

2014-06-01

Awake craniotomy is a valuable procedure since it allows brain mapping and live monitoring of eloquent brain functions. The advantage of minimizing resource utilization is also emphasized by some physicians in North America. Data on how well an awake craniotomy is tolerated by patients and how much stress it creates is available from different studies, but this topic has not consequently been summarized in a review of the available literature. Therefore, it is the purpose of this review to shed more light on the still controversially discussed aspect of an awake craniotomy. We reviewed the available English literature published until December 2013 searching for studies that investigated patients' responses to awake craniotomies. Twelve studies, published between 1998 and 2013, including 396 patients with awake surgery were identified. Eleven of these 12 studies set the focus on the perioperative time, one study focused on the later postoperative time. The vast majority of patients felt well prepared and overall satisfaction with the procedure was high. In the majority of studies up to 30 % of the patients recalled considerable pain and 10-14 % experienced strong anxiety during the procedure. The majority of patients reported that they would undergo an awake craniotomy again. A post traumatic stress disorder was present neither shortly nor years after surgery. However, a normal human response to such an exceptional situation can for instance be the delayed appearance of unintentional distressing recollections of the event despite the patients' satisfaction concerning the procedure. For selected patients, an awake craniotomy presents the best possible way to reduce the risk of surgery related neurological deficits. However, benefits and burdens of this type of procedure should be carefully considered when planning an awake craniotomy and the decision should serve the interests of the patient.

Awake craniotomy for tumor resection

OpenAIRE

Mohammadali Attari; Sohrab Salimi

2013-01-01

Surgical treatment of brain tumors, especially those located in the eloquent areas such as anterior temporal, frontal lobes, language, memory areas, and near the motor cortex causes high risk of eloquent impairment. Awake craniotomy displays major rule for maximum resection of the tumor with minimum functional impairment of the Central Nervous System. These case reports discuss the use of awake craniotomy during the brain surgery in Alzahra Hospital, Isfahan, Iran. A 56-year-old woman with le...

Patient acceptance of awake craniotomy.

Science.gov (United States)

Wrede, Karsten H; Stieglitz, Lennart H; Fiferna, Antje; Karst, Matthias; Gerganov, Venelin M; Samii, Madjid; von Gösseln, Hans-Henning; Lüdemann, Wolf O

2011-12-01

The aim of this study was to objectively assess the patients' acceptance for awake craniotomy in a group of neurosurgical patients, who underwent this procedure for removal of lesions in or close to eloquent brain areas. Patients acceptance for awake craniotomy under local anesthesia and conscious sedation was assessed by a formal questionnaire (PPP33), initially developed for general surgery patients. The results are compared to a group of patients who had brain surgery under general anesthesia and to previously published data. The awake craniotomy (AC) group consisted of 37 male and 9 female patients (48 craniotomies) with age ranging from 18 to 71 years. The general anesthesia (GA) group consisted of 26 male and 15 female patients (43 craniotomies) with age ranging from 26 to 83 years. All patients in the study were included in the questionnaire analysis. In comparison to GA the overall PPP33 score for AC was higher (p=0.07), suggesting better overall acceptance for AC. The subscale scores for AC were also significantly better compared to GA for the two subscales "postoperative pain" (p=0.02) and "physical disorders" (p=0.01) and equal for the other 6 subscales. The results of the overall mean score and the scores for the subscales of the PPP33 questionnaire verify good patients' acceptance for AC. Previous studies have shown good patients' acceptance for awake craniotomy, but only a few times using formal approaches. By utilizing a formal questionnaire we could verify good patient acceptance for awake craniotomy for the treatment of brain tumors in or close to eloquent areas. This is a novel approach that substantiates previously published experiences. Copyright © 2011 Elsevier B.V. All rights reserved.

Awake Craniotomy Anesthesia: A Comparison of the Monitored Anesthesia Care and Asleep-Awake-Asleep Techniques.

Science.gov (United States)

Eseonu, Chikezie I; ReFaey, Karim; Garcia, Oscar; John, Amballur; Quiñones-Hinojosa, Alfredo; Tripathi, Punita

2017-08-01

Commonly used sedation techniques for an awake craniotomy include monitored anesthesia care (MAC), using an unprotected airway, and the asleep-awake-asleep (AAA) technique, using a partially or totally protected airway. We present a comparative analysis of the MAC and AAA techniques, evaluating anesthetic management, perioperative outcomes, and complications in a consecutive series of patients undergoing the removal of an eloquent brain lesion. Eighty-one patients underwent awake craniotomy for an intracranial lesion over a 9-year period performed by a single-surgeon and a team of anesthesiologists. Fifty patients were treated using the MAC technique, and 31 were treated using the AAA technique. A retrospective analysis evaluated anesthetic management, intraoperative complications, postoperative outcomes, pain management, and complications. The MAC and AAA groups had similar preoperative patient and tumor characteristics. Mean operative time was shorter in the MAC group (283.5 minutes vs. 313.3 minutes; P = 0.038). Hypertension was the most common intraoperative complication seen (8% in the MAC group vs. 9.7% in the AAA group; P = 0.794). Intraoperative seizure occurred at a rate of 4% in the MAC group and 3.2% in the AAA group (P = 0.858). Awake cases were converted to general anesthesia in no patients in the MAC group and in 1 patient (3.2%) in the AAA group (P = 0.201). No cases were aborted in either group. The mean hospital length of stay was 3.98 days in the MAC group and 3.84 days in the AAA group (P = 0.833). Both the MAC and AAA sedation techniques provide an efficacious and safe method for managing awake craniotomy cases and produce similar perioperative outcomes, with the MAC technique associated with shorter operative time. Copyright © 2017 Elsevier Inc. All rights reserved.

Awake craniotomy for supratentorial gliomas: why, when and how?

Science.gov (United States)

Ibrahim, George M; Bernstein, Mark

2012-09-01

Awake craniotomy has become an increasingly utilized procedure in the treatment of supratentorial intra-axial tumors. The popularity of this procedure is partially attributable to improvements in intraoperative technology and anesthetic techniques. The application of awake craniotomy to the field of neuro-oncology has decreased iatrogenic postoperative neurological deficits, allowed for safe maximal tumor resection and improved healthcare resource stewardship by permitting early patient discharge. In this article, we review recent evidence for the utility of awake craniotomy in the resection of gliomas and describe the senior author's experience in performing this procedure. Furthermore, we explore innovative applications of awake craniotomy to outpatient tumor resections and the conduct of neurosurgery in resource-poor settings. We conclude that awake craniotomy is an effective and versatile neurosurgical procedure with expanding applications in neuro-oncology.

Teaching and sustainably implementing awake craniotomy in resource-poor settings.

Science.gov (United States)

Howe, Kathryn L; Zhou, Guosheng; July, Julius; Totimeh, Teddy; Dakurah, Thomas; Malomo, Adefolarin O; Mahmud, Muhammad R; Ismail, Nasiru J; Bernstein, Mark A

2013-12-01

Awake craniotomy for brain tumor resection has the benefit of avoiding a general anesthetic and decreasing associated costs (e.g., intensive care unit beds and intravenous line insertion). In low- and middle-income countries, significant resource limitations for the system and individual make awake craniotomy an ideal tool, yet it is infrequently used. We sought to determine if awake craniotomy could be effectively taught and implemented safely and sustainably in low- and middle-income countries. A neurosurgeon experienced in the procedure taught awake craniotomy to colleagues in China, Indonesia, Ghana, and Nigeria during the period 2007-2012. Patients were selected on the basis of suspected intraaxial tumor, absence of major dysphasia or confusion, and ability to tolerate the positioning. Data were recorded by the local surgeons and included preoperative imaging, length of hospital admission, final pathology, postoperative morbidity, and mortality. Awake craniotomy was performed for 38 cases of suspected brain tumor; most procedures were completed independently. All patients underwent preoperative computed tomography or magnetic resonance imaging. In 64% of cases, patients remained in the hospital Awake craniotomy was successfully taught and implemented in 6 neurosurgical centers in China, Indonesia, Ghana, and Nigeria. Awake craniotomy is safe, resource-sparing, and sustainable. The data suggest awake craniotomy has the potential to significantly improve access to neurosurgical care in resource-challenged settings. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of an Enhanced Nose-to-Brain Delivery of Insulin on Mild and Progressive Memory Loss in the Senescence-Accelerated Mouse.

Science.gov (United States)

Kamei, Noriyasu; Tanaka, Misa; Choi, Hayoung; Okada, Nobuyuki; Ikeda, Takamasa; Itokazu, Rei; Takeda-Morishita, Mariko

2017-03-06

Insulin is now considered to be a new drug candidate for treating dementias, such as Alzheimer's disease, whose pathologies are linked to insulin resistance in the brain. Our recent work has clarified that a noncovalent strategy involving cell-penetrating peptides (CPPs) can increase the direct transport of insulin from the nasal cavity into the brain parenchyma. The present study aimed to determine whether the brain insulin level increased by intranasal coadministration of insulin with the CPP penetratin has potential for treating dementia. The pharmacological actions of insulin were investigated at different stages of memory impairment using a senescence-accelerated mouse-prone 8 (SAMP8) model. The results of spatial learning tests suggested that chronic intranasal administration of insulin with l-penetratin to SAMP8 slowed the progression of memory loss in the early stage of memory impairment. However, contrary to expectations, this strategy using penetratin was ineffective in recovering the severe cognitive dysfunction in the progressive stage, which involves brain accumulation of amyloid β (Aβ). Immunohistological examination of hippocampal regions of samples from SAMP8 in the progressive stage suggested that accelerated nose-to-brain insulin delivery had a partial neuroprotective function but unexpectedly increased Aβ plaque deposition in the hippocampus. These findings suggest that the efficient nose-to-brain delivery of insulin combined with noncovalent CPP strategy has different effects on dementia during the mild and progressive stages of cognitive dysfunction.

Nonopioid anesthesia for awake craniotomy: a case report.

Science.gov (United States)

Wolff, Diane L; Naruse, Robert; Gold, Michele

2010-02-01

Awake craniotomy is becoming more popular as a neurosurgical technique that allows for increased tumor resection and decreased postoperative neurologic morbidity. This technique, however, presents many challenges to both the neurosurgeon and anesthetist. An ASA class II, 37-year-old man with recurrent oligodendroglioma presented for repeated craniotomy. Prior craniotomy under general anesthesia resulted in residual neurologic deficits. An awake craniotomy was planned to allow for intraoperative testing for maximum tumor resection and avoidance of neurologic morbidity. The patient was sedated with propofol, and bupivacaine was infiltrated for placement of Mayfield tongs and skin incision. Following exposure of brain tissue, propofol infusion was discontinued to allow for patient cooperation during the procedure. Speech, motor, and sensory testing occurred during tumor resection until resection stopped after onset of weakness in the right arm. The propofol infusion was resumed while the cranium was closed and Mayfield tongs removed. The patient was awake, alert, oriented, and able to move all extremities but had residual weakness in the right forearm. Awake craniotomy requires appropriate patient selection, knowledge of the surgeon's skill, and a thorough anesthesia plan. This case report discusses the clinical and anesthetic management for awake craniotomy and reviews the literature.

Insulin and Brain Injury: Memory, Metabolism and Microglia

Science.gov (United States)

2016-05-20

circular craniotomy was performed over the left motor cortex at -2.5 mm lateral and -3.0 mm posterior from Bregma. Following the craniotomy, the CCI...injury on a beam /peg board walking motor function test as previously described. (226) Briefly, rats were trained to walk across beams of...18F]- FDG uptake as a result of treatment (data not shown). Intranasal insulin improved aspects of motor and cognitive function Rats were trained on

Anaesthesia for awake craniotomy is safe and well-tolerated.

Science.gov (United States)

Andersen, Jakob Hessel; Olsen, Karsten Skovgaard

2010-10-01

Awake craniotomy for tumour resection has been performed at Glostrup Hospital since 2004. We describe and discuss the various anaesthetic approaches for such surgery and retrospectively analyse the 44 planned awake craniotomies performed at Glostrup Hospital. The surgery falls into four phases: craniotomy, mapping, tumour resection and closing. Three methods are being used: monitored anaesthetic care, asleep-awake-asleep and asleep-awake (AA). Anaesthesia is induced and maintained with propofol and remifentanil. A laryngeal mask (LM) is used as an airway during the craniotomy phase. In the AA method, patients are mapped and the tumour is resected while the patient is awake. A total of 41 of 44 planned AA craniotomies were performed. Three had to be converted into general anaesthesia (GA) due to tight brain, leaking LM and tumour haemorrhage, respectively. The following complications were observed: bradycardia 10%, leaking LM 5%, nausea 10%, vomiting 5%, focal seizures 28%, generalized seizures 10%, hypoxia 2%, hypotension 5% and hypertension 2%. Our results comply well with the international literature in terms of complications related to haemodynamics, respiration, seizures, vomiting and nausea and in terms of patient satisfaction. Awake craniotomy is a well-tolerated procedure with potential benefits. More prospective randomized studies are required.

Ammonia encephalopathy and awake craniotomy for brain language mapping: cause of failed awake craniotomy.

Science.gov (United States)

Villalba Martínez, G; Fernández-Candil, J L; Vivanco-Hidalgo, R M; Pacreu Terradas, S; León Jorba, A; Arroyo Pérez, R

2015-05-01

We report the case of an aborted awake craniotomy for a left frontotemporoinsular glioma due to ammonia encephalopathy on a patient taking Levetiracetam, valproic acid and clobazam. This awake mapping surgery was scheduled as a second-stage procedure following partial resection eight days earlier under general anesthesia. We planned to perform the surgery with local anesthesia and sedation with remifentanil and propofol. After removal of the bone flap all sedation was stopped and we noticed slow mentation and excessive drowsiness prompting us to stop and control the airway and proceed with general anesthesia. There were no post-operative complications but the patient continued to exhibit bradypsychia and hand tremor. His ammonia level was found to be elevated and was treated with an infusion of l-carnitine after discontinuation of the valproic acid with vast improvement. Ammonia encephalopathy should be considered in patients treated with valproic acid and mental status changes who require an awake craniotomy with patient collaboration. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Evaluation of Language Function under Awake Craniotomy

Science.gov (United States)

KANNO, Aya; MIKUNI, Nobuhiro

2015-01-01

Awake craniotomy is the only established way to assess patients’ language functions intraoperatively and to contribute to their preservation, if necessary. Recent guidelines have enabled the approach to be used widely, effectively, and safely. Non-invasive brain functional imaging techniques, including functional magnetic resonance imaging and diffusion tensor imaging, have been used preoperatively to identify brain functional regions corresponding to language, and their accuracy has increased year by year. In addition, the use of neuronavigation that incorporates this preoperative information has made it possible to identify the positional relationships between the lesion and functional regions involved in language, conduct functional brain mapping in the awake state with electrical stimulation, and intraoperatively assess nerve function in real time when resecting the lesion. This article outlines the history of awake craniotomy, the current state of pre- and intraoperative evaluation of language function, and the clinical usefulness of such functional evaluation. When evaluating patients’ language functions during awake craniotomy, given the various intraoperative stresses involved, it is necessary to carefully select the tasks to be undertaken, quickly perform all examinations, and promptly evaluate the results. As language functions involve both input and output, they are strongly affected by patients’ preoperative cognitive function, degree of intraoperative wakefulness and fatigue, the ability to produce verbal articulations and utterances, as well as perform synergic movement. Therefore, it is essential to appropriately assess the reproducibility of language function evaluation using awake craniotomy techniques. PMID:25925758

Evaluation of Language Function under Awake Craniotomy.

Science.gov (United States)

Kanno, Aya; Mikuni, Nobuhiro

2015-01-01

Awake craniotomy is the only established way to assess patients' language functions intraoperatively and to contribute to their preservation, if necessary. Recent guidelines have enabled the approach to be used widely, effectively, and safely. Non-invasive brain functional imaging techniques, including functional magnetic resonance imaging and diffusion tensor imaging, have been used preoperatively to identify brain functional regions corresponding to language, and their accuracy has increased year by year. In addition, the use of neuronavigation that incorporates this preoperative information has made it possible to identify the positional relationships between the lesion and functional regions involved in language, conduct functional brain mapping in the awake state with electrical stimulation, and intraoperatively assess nerve function in real time when resecting the lesion. This article outlines the history of awake craniotomy, the current state of pre- and intraoperative evaluation of language function, and the clinical usefulness of such functional evaluation. When evaluating patients' language functions during awake craniotomy, given the various intraoperative stresses involved, it is necessary to carefully select the tasks to be undertaken, quickly perform all examinations, and promptly evaluate the results. As language functions involve both input and output, they are strongly affected by patients' preoperative cognitive function, degree of intraoperative wakefulness and fatigue, the ability to produce verbal articulations and utterances, as well as perform synergic movement. Therefore, it is essential to appropriately assess the reproducibility of language function evaluation using awake craniotomy techniques.

Intranasal sedatives in pediatric dentistry

Science.gov (United States)

AlSarheed, Maha A.

2016-01-01

Objectives: To identify the intranasal (IN) sedatives used to achieve conscious sedation during dental procedures amongst children. Methods: A literature review was conducted by identifying relevant studies through searches on Medline. Search included IN of midazolam, ketamine, sufentanil, dexmedetomidine, clonidine, haloperidol and loranzepam. Studies included were conducted amongst individuals below 18 years, published in English, and were not restricted by year. Exclusion criteria were articles that did not focus on pediatric dentistry. Results: Twenty studies were included. The most commonly used sedatives were midazolam, followed by ketamine and sufentanil. Onset of action for IN midazolam was 5-15 minutes (min), however, IN ketamine was faster (mean 5.74 min), while both IN sufentanil (mean 20 min) and IN dexmedetomidine (mean 25 min) were slow in comparison. Midazolam was effective for modifying behavior in mild to moderately anxious children, however, for more invasive or prolonged procedures, stronger sedatives, such as IN ketamine, IN sufentanil were recommended. In addition, ketamine fared better in overall success rate (89%) when compared with IN midazolam (69%). Intranasal dexmedetomidine was only used as pre-medication amongst children. While its’ onset of action is longer when compared with IN midazolam, it produced deeper sedation at the time of separation from the parent and at the time of anesthesia induction. Conclusion: Intranasal midazolam, ketamine and sufentanil are effective and safe for conscious sedation, while intranasal midazolam, dexmedetomidine and sufentanil have proven to be effective premedications. PMID:27570849

Anesthesia for awake craniotomy: case report

Directory of Open Access Journals (Sweden)

Nelson Davi Bolzani

2013-11-01

Full Text Available Background and objectives: Some intracranial procedures are achievable with patients awake, however, there are challenges ranging from patient compliance to homeostasis. The aim of this study is to present a case of intracranial surgery for removal of a tumor in the left parietal lobe with the patient awake during the procedure. Case report: After patient selection and psychological preparation, the proposed excision of the left parietal lobe lesion in the waking state was clarified and accepted. Continuous infusion of propofol and remifentanil was administered to maintain a Ramsay score of 2-3. The bilateral scalp blockade was performed with ropivacaine. The Mayfield head fixation device was installed and drapes adjusted to maintain the airway and eyes accessible for mapping with electrical stimulation and tumor excision. For dura mater incision, a pad with 2% lidocaine was applied for 3 minutes. The surgery was uneventful. The patient was discharged on the seventh day of hospitalization without presenting complication. Conclusion: Although the maintenance of analgesia and hemodynamic stability was a challenge with the patient awake, the target-controlled infusion of propofol provided the desired level of consciousness, remifentanil titrated analgesia and sedation without drug accumulation, and the blockade with ropivacaine provided satisfactory analgesia. We conclude that the anesthetic technique was satisfactory for our patient. Keywords: Craniotomy awake, Neurosurgery, Propofol, Remifentanil, Ropivacaine

The Rationale for Insulin Therapy in Alzheimer’s Disease

Directory of Open Access Journals (Sweden)

Samo Ribarič

2016-05-01

Full Text Available Alzheimer’s disease (AD is the most common form of dementia, with a prevalence that increases with age. By 2050, the worldwide number of patients with AD is projected to reach more than 140 million. The prominent signs of AD are progressive memory loss, accompanied by a gradual decline in cognitive function and premature death. AD is the clinical manifestation of altered proteostasis. The initiating step of altered proteostasis in most AD patients is not known. The progression of AD is accelerated by several chronic disorders, among which the contribution of diabetes to AD is well understood at the cell biology level. The pathological mechanisms of AD and diabetes interact and tend to reinforce each other, thus accelerating cognitive impairment. At present, only symptomatic interventions are available for treating AD. To optimise symptomatic treatment, a personalised therapy approach has been suggested. Intranasal insulin administration seems to open the possibility for a safe, and at least in the short term, effective symptomatic intervention that delays loss of cognition in AD patients. This review summarizes the interactions of AD and diabetes from the cell biology to the patient level and the clinical results of intranasal insulin treatment of cognitive decline in AD.

Non-clinical safety evaluation of intranasal iota-carrageenan.

Science.gov (United States)

Hebar, Alexandra; Koller, Christiane; Seifert, Jan-Marcus; Chabicovsky, Monika; Bodenteich, Angelika; Bernkop-Schnürch, Andreas; Grassauer, Andreas; Prieschl-Grassauer, Eva

2015-01-01

Carrageenan has been widely used as food additive for decades and therefore, an extended oral data set is available in the public domain. Less data are available for other routes of administration, especially intranasal administration. The current publication describes the non-clinical safety and toxicity of native (non-degraded) iota-carrageenan when applied intranasally or via inhalation. Intranasally applied iota-carrageenan is a topically applied, locally acting compound with no need of systemic bioavailability for the drug's action. Animal experiments included repeated dose local tolerance and toxicity studies with intranasally applied 0.12% iota-carrageenan for 7 or 28 days in New Zealand White rabbits and nebulized 0.12% iota-carrageenan administered to F344 rats for 7 days. Permeation studies revealed no penetration of iota-carrageenan across nasal mucosa, demonstrating that iota-carrageenan does not reach the blood stream. Consistent with this, no relevant toxic or secondary pharmacological effects due to systemic exposure were observed in the rabbit or rat repeated dose toxicity studies. Data do not provide any evidence for local intolerance or toxicity, when carrageenan is applied intranasally or by inhalation. No signs for immunogenicity or immunotoxicity have been observed in the in vivo studies. This is substantiated by in vitro assays showing no stimulation of a panel of pro-inflammatory cytokines by iota-carrageenan. In conclusion, 0.12% iota-carrageenan is safe for clinical use via intranasal application.

Non-clinical safety evaluation of intranasal iota-carrageenan.

Directory of Open Access Journals (Sweden)

Alexandra Hebar

Full Text Available Carrageenan has been widely used as food additive for decades and therefore, an extended oral data set is available in the public domain. Less data are available for other routes of administration, especially intranasal administration. The current publication describes the non-clinical safety and toxicity of native (non-degraded iota-carrageenan when applied intranasally or via inhalation. Intranasally applied iota-carrageenan is a topically applied, locally acting compound with no need of systemic bioavailability for the drug's action. Animal experiments included repeated dose local tolerance and toxicity studies with intranasally applied 0.12% iota-carrageenan for 7 or 28 days in New Zealand White rabbits and nebulized 0.12% iota-carrageenan administered to F344 rats for 7 days. Permeation studies revealed no penetration of iota-carrageenan across nasal mucosa, demonstrating that iota-carrageenan does not reach the blood stream. Consistent with this, no relevant toxic or secondary pharmacological effects due to systemic exposure were observed in the rabbit or rat repeated dose toxicity studies. Data do not provide any evidence for local intolerance or toxicity, when carrageenan is applied intranasally or by inhalation. No signs for immunogenicity or immunotoxicity have been observed in the in vivo studies. This is substantiated by in vitro assays showing no stimulation of a panel of pro-inflammatory cytokines by iota-carrageenan. In conclusion, 0.12% iota-carrageenan is safe for clinical use via intranasal application.

The neurolinguistic approach to awake surgery reviewed.

Science.gov (United States)

De Witte, Elke; Mariën, Peter

2013-02-01

Intraoperative direct electrical stimulation (DES) is increasingly used in patients operated on for tumours in critical language areas. Although a positive impact of DES on postoperative linguistic outcome is generally advocated, the literature is only scantily documented with information about the linguistic methods applied in awake surgery. This article critically reviews the neurolinguistic procedures currently used in awake studies. Based on an extensive review of the literature, an overview is given of the language mapping techniques applied in brain tumour surgery. Studies investigating linguistic testing and outcome in awake surgery were analysed. Information about the timing of the assessment(s), the linguistic tasks, the linguistic stimuli and the indication for awake surgery was also discussed. Intraoperative DES remains the 'gold standard' for language mapping, but pre- and postoperative non-invasive mapping methods are important adjuncts. In the pre- and postoperative phase, standardised linguistic test batteries are generally used to assess language function. In the intraoperative phase, only naming and number counting are commonly applied. Most often no detailed information about the linguistic stimuli is provided and no standardised protocols measuring different linguistic levels have been described. Awake surgery with DES is a useful tool for preserving linguistic functions in patients undergoing surgery in critical brain regions. However, no studies exist that apply a well-balanced and standardised linguistic protocol to reliably identify the critical language zones. The availability of a standardised linguistic protocol might substantially increase intraoperative comfort and might improve outcome and quality of life. Copyright © 2012 Elsevier B.V. All rights reserved.

New twist on neuronal insulin receptor signaling in health, disease, and therapeutics.

Science.gov (United States)

Wada, Akihiko; Yokoo, Hiroki; Yanagita, Toshihiko; Kobayashi, Hideyuki

2005-10-01

Long after the pioneering studies documenting the existence of insulin (year 1967) and insulin receptor (year 1978) in brain, the last decade has witnessed extraordinary progress in the understanding of brain region-specific multiple roles of insulin receptor signalings in health and disease. In the hypothalamus, insulin regulates food intake, body weight, peripheral fat deposition, hepatic gluconeogenesis, reproductive endocrine axis, and compensatory secretion of counter-regulatory hormones to hypoglycemia. In the hippocampus, insulin promotes learning and memory, independent of the glucoregulatory effect of insulin. Defective insulin receptor signalings are associated with the dementia in normal aging and patients with age-related neurodegenerative diseases (e.g., Alzheimer's disease); the cognitive impairment can be reversed with systemic administration of insulin in the euglycemic condition. Intranasal administration of insulin enhances memory and mood and decreases body weight in healthy humans, without causing hypoglycemia. In the hypothalamus, insulin-induced activation of the phosphoinositide 3-kinase pathway followed by opening of ATP-sensitive K+ channel has been shown to be related to multiple effects of insulin. However, the precise molecular mechanisms of insulin's pleiotropic effects still remain obscure. More importantly, much remains unknown about the quality control mechanisms ensuring correct conformational maturation of the insulin receptor, and the cellular mechanisms regulating density of cell surface functional insulin receptors.

Intranasal dexmedetomidine for adrenergic crisis in familial dysautonomia.

Science.gov (United States)

Spalink, Christy L; Barnes, Erin; Palma, Jose-Alberto; Norcliffe-Kaufmann, Lucy; Kaufmann, Horacio

2017-08-01

To report the use of intranasal dexmedetomidine, an α 2 -adrenergic agonist for the acute treatment of refractory adrenergic crisis in patients with familial dysautonomia. Case series. Three patients with genetically confirmed familial dysautonomia (case 1: 20-year-old male; case 2: 43-year-old male; case 3: 26-year-old female) received intranasal dexmedetomidine 2 mcg/kg, half of the dose in each nostril, for the acute treatment of adrenergic crisis. Within 8-17 min of administering the intranasal dose, the adrenergic crisis symptoms abated, and blood pressure and heart rate returned to pre-crises values. Adrenergic crises eventually resumed, and all three patients required hospitalization for investigation of the cause of the crises. Intranasal dexmedetomidine is a feasible and safe acute treatment for adrenergic crisis in patients with familial dysautonomia. Further controlled studies are required to confirm the safety and efficacy in this population.

A Retrospective Study of Success, Failure, and Time Needed to Perform Awake Intubation.

Science.gov (United States)

Joseph, Thomas T; Gal, Jonathan S; DeMaria, Samuel; Lin, Hung-Mo; Levine, Adam I; Hyman, Jaime B

2016-07-01

Awake intubation is the standard of care for management of the anticipated difficult airway. The performance of awake intubation may be perceived as complex and time-consuming, potentially leading clinicians to avoid this technique of airway management. This retrospective review of awake intubations at a large academic medical center was performed to determine the average time taken to perform awake intubation, its effects on hemodynamics, and the incidence and characteristics of complications and failure. Anesthetic records from 2007 to 2014 were queried for the performance of an awake intubation. Of the 1,085 awake intubations included for analysis, 1,055 involved the use of a flexible bronchoscope. Each awake intubation case was propensity matched with two controls (1:2 ratio), with similar comorbidities and intubations performed after the induction of anesthesia (n = 2,170). The time from entry into the operating room until intubation was compared between groups. The anesthetic records of all patients undergoing awake intubation were also reviewed for failure and complications. The median time to intubation for patients intubated post induction was 16.0 min (interquartile range: 13 to 22) from entrance into the operating room. The median time to intubation for awake patients was 24.0 min (interquartile range: 19 to 31). The complication rate was 1.6% (17 of 1,085 cases). The most frequent complications observed were mucous plug, endotracheal tube cuff leak, and inadvertent extubation. The failure rate for attempted awake intubation was 1% (n = 10). Awake intubations have a high rate of success and low rate of serious complications and failure. Awake intubations can be performed safely and rapidly.

Anaesthesia for awake craniotomy: A retrospective study of 54 cases.

Science.gov (United States)

Sokhal, Navdeep; Rath, Girija Prasad; Chaturvedi, Arvind; Dash, Hari Hara; Bithal, Parmod Kumar; Chandra, P Sarat

2015-05-01

The anaesthetic challenge of awake craniotomy is to maintain adequate sedation, analgesia, respiratory and haemodynamic stability in an awake patient who should be able to co-operate during intraoperative neurological assessment. The current literature, sharing the experience on awake craniotomy, in Indian context, is minimal. Hence, we carried out a retrospective study with the aim to review and analyse the anaesthetic management and perioperative complications in patients undergoing awake craniotomy, at our centre. Medical records of 54 patients who underwent awake craniotomy for intracranial lesions over a period of 10 years were reviewed, retrospectively. Data regarding anaesthetic management, intraoperative complications and post-operative course were recorded. Propofol (81.5%) and dexmedetomidine (18.5%) were the main agents used for providing conscious sedation to facilitate awake craniotomy. Hypertension (16.7%) was the most commonly encountered complication during intraoperative period, followed by seizures (9.3%), desaturation (7.4%), tight brain (7.4%), and shivering (5.6%). The procedure had to be converted to general anaesthesia in one of patients owing to refractory brain bulge. The incidence of respiratory and haemodynamic complications were comparable in the both groups (P > 0.05). There was less incidence of intraoperative seizures in patients who received propofol (P = 0.03). In post-operative period, 20% of patients developed new motor deficit. Mean intensive care unit stay was 2.8 ± 1.9 day (1-14 days) and mean hospital stay was 7.0 ± 5.0 day (3-30 days). 'Conscious sedation' was the technique of choice for awake craniotomy, at our institute. Fentanyl, propofol, and dexmedetomidine were the main agents used for this purpose. Patients receiving propofol had less incidence of intraoperative seizure. Appropriate selection of patients, understanding the procedure of surgery, and judicious use of sedatives or anaesthetic agents are key to the

Comparison of Conscious Sedation and Asleep-Awake-Asleep Techniques for Awake Craniotomy.

Science.gov (United States)

Dilmen, Ozlem Korkmaz; Akcil, Eren Fatma; Oguz, Abdulvahap; Vehid, Hayriye; Tunali, Yusuf

2017-01-01

Since awake craniotomy (AC) has become a standard of care for supratentorial tumour resection, especially in the motor and language cortex, determining the most appropriate anaesthetic protocol is very important. The aim of this retrospective study is to compare the effectiveness of conscious sedation (CS) to "awake-asleep-awake" (AAA) techniques for supratentorial tumour resection. Forty-two patients undergoing CS and 22 patients undergoing AAA were included in the study. The primary endpoint was to compare the CS and AAA techniques with respect to intraoperative pain and agitation in patients undergoing supratentorial tumour resection. The secondary endpoint was comparison of the other intraoperative complications. This study results show that the incidence of intraoperative agitation and seizure were lower in the AAA group than in the CS group. Intraoperative blood pressures were significantly higher in the CS group than in the AAA group during the pinning and incision, but the level of blood pressures did not need antihypertensive treatment. Otherwise, blood pressures were significantly higher in the AAA group than in the CS group during the neurological examination and the severity of hypertension needed statistically significant more antihypertensive treatment in the AAA group. As a result of hypertension, the amount of intraoperative bleeding was higher in the AAA group than in the CS group. In conclusion, the AAA technique may provide better results with respect to agitation and seizure, but intraoperative hypertension needed a vigilant follow-up especially in the wake-up period. Copyright © 2016 Elsevier Ltd. All rights reserved.

The SAMP8 mouse for investigating memory and the role of insulin in the brain.

Science.gov (United States)

Rhea, Elizabeth M; Banks, William A

2017-08-01

SAMP8 mice exhibit changes that commonly occur with normal aging late in life, but do so at a much earlier age. These changes include impairments in learning and memory as early as 8months of age and so the SAMP8 is a useful model to investigate those age-related brain changes that may affect cognition. As brain insulin signaling and memory decline with aging, the SAMP8 model is useful for investigating these changes and interventions that might prevent the decline. This review will summarize the SAMP8 mouse model, highlight changes in brain insulin signaling and its role in memory, and discuss intranasal insulin delivery in investigating effects on insulin metabolism and memory in the SAMP8 mice. Published by Elsevier Inc.

Comparison of jaw muscle EMG activity in awake and sleep bruxers

DEFF Research Database (Denmark)

Castrillon, Eduardo; Dreyer Nielsen, Patricia; Haugland, Morten

2015-01-01

, Scandinavian Center for Orofacial Neuroscience (SCON), Aarhus, DENMARK; M. Haugland, DELTA, Copenhagen, DENMARK; W. Yachida, T. Arima, Hokkaido University, Hokkaido, JAPAN; Group Author Abstracts: ABSTRACT: Objectives: Background: Bruxism has two different circadian manifestations (awake and sleep) that have...... been proposed to have different underlying pathophysiology. Objectives: To compare the characteristics of multiple days EMG assessment of the anterior temporalis muscles between patients with self-reported awake bruxism, sleep bruxism and healthy individuals. Methods: Methods: Participants...... with possible sleep bruxism (n=9) or awake bruxism (n=9) bruxism were included in an open study and compared with healthy individuals during awake (n=9) and sleep (n=7) states. All participants were assessed for a minimum of 4 days (awake or sleep) with a portable single-channel EMG recorder. The outcome...

Awake insertion of a Laryngeal Mask Airway-Proseal™ as alternative to awake fiberoptic intubation in management of anticipated difficult airway in ambulatory surgery

Directory of Open Access Journals (Sweden)

Matilde Zaballos

Full Text Available Abstract Background and objectives The decision whether to manage an ambulatory patient with a previously documented difficult airway with a supraglottic device remain controversial. We report an awake insertion of a Laryngeal Mask Airway Proseal™ in a patient with known difficult airway scheduled for ambulatory surgery. Case report A 46-yr-old woman was programmed as a day case surgery for breast nodule resection. Her anesthetic record included an impossible intubation with cancelation of surgery and subsequent awake fibroscopic intubation. She reported emotional distress with the previous experience and declined this approach. In view of the previous experience, an awake airway control with a Laryngeal Mask Airway Proseal™ was planned after explaining and reassuring the patient. After adequate topicalisation, a size 4 Laryngeal Mask Airway Proseal™ was successfully inserted after two attempts, and their patency was confirmed by capnography. Anesthesia was induced intravenously and the surgery was uneventful. Conclusion We describe a feasible alternative strategy to awake intubation in a patient with known difficult airway undergoing ambulatory surgery. In this specific clinical situation, if tracheal intubation is deemed unnecessary, awake supraglottic airway might allow adequate ventilation and their use should be considered.

Awake craniotomy in a depressed and agitated patient

Science.gov (United States)

Al Shuaibi, Khalid M.

2010-01-01

Depressed patients with brain tumors are often not referred to awake craniotomy because of concern of uncooperation which may increase the risk of perioperative complications. This report describes an interesting case of awake craniotomy for frontal lobe glioma in a 41-year-old woman undergoing language and motor mapping intraoperatively. As she was fearful and apprehensive and was on antidepressant therapy to control depression, the author adopted general anesthesia with laryngeal mask airway during initial stage of skull pinning and craniotomy procedures. Then, the patient reverted to awake state to continue the intended neurosurgical procedure. The patient tolerated the situation satisfactorily and was cooperative till the finish, without any event. PMID:25885087

Transethmoidal intranasal meningoencephalocele in an adult with recurrent meningitis.

Science.gov (United States)

Hasegawa, Takafumi; Sugeno, Naoto; Shiga, Yusei; Takeda, Atsushi; Karibe, Hiroshi; Tominaga, Teiji; Itoyama, Yasuto

2005-08-01

Intranasal meningoencephalocele is a rarely encountered congenital malformation. We report a case of transethmoidal intranasal meningoencephalocele in a 52-year old man with recurrent purulent meningitis. After treatment of the acute meningitis, frontal craniotomy followed by the removal of the stalk of the meningoencephalocele and repair of the bony defect was successfully performed. He has had no further meningitis or CSF rhinorrhea post-operatively. Detailed neuroradiological examination and appropriate surgical treatment are important to prevent fatal neurological complications of intranasal meningoencephalocele.

The History of Awake Craniotomy in Hospital Universiti Sains Malaysia

Science.gov (United States)

WAN HASSAN, Wan Mohd Nazaruddin

2013-01-01

Awake craniotomy is a brain surgery performed on awake patients and is indicated for certain intracranial pathologies. These include procedures that require an awake patient for electrocorticographic mapping or precise electrophysiological recordings, resection of lesions located close to or in the motor and speech of the brain, or minor intracranial procedures that aim to avoid general anaesthesia for faster recovery and earlier discharge. This type of brain surgery is quite new and has only recently begun to be performed in a few neurosurgical centres in Malaysia. The success of the surgery requires exceptional teamwork from the neurosurgeon, neuroanaesthesiologist, and neurologist. The aim of this article is to briefly describe the history of awake craniotomy procedures at our institution. PMID:24643321

Awake Craniotomy and Coaching

NARCIS (Netherlands)

Ruis, Carla; Huenges Wajer, Irene; Robe, Pierre; van Zandvoort, Martine

2014-01-01

Background: The importance of monitoring cognition during awake craniotomy has been well described in previous studies. The relevance of being coached during such a procedure has received less attention and questions still remain unanswered about what factors are the most important herein.

Anaesthesia for awake craniotomy: A retrospective study of 54 cases

Directory of Open Access Journals (Sweden)

Navdeep Sokhal

2015-01-01

Full Text Available Background and Aims: The anaesthetic challenge of awake craniotomy is to maintain adequate sedation, analgesia, respiratory and haemodynamic stability in an awake patient who should be able to co-operate during intraoperative neurological assessment. The current literature, sharing the experience on awake craniotomy, in Indian context, is minimal. Hence, we carried out a retrospective study with the aim to review and analyse the anaesthetic management and perioperative complications in patients undergoing awake craniotomy, at our centre. Methods: Medical records of 54 patients who underwent awake craniotomy for intracranial lesions over a period of 10 years were reviewed, retrospectively. Data regarding anaesthetic management, intraoperative complications and post-operative course were recorded. Results: Propofol (81.5% and dexmedetomidine (18.5% were the main agents used for providing conscious sedation to facilitate awake craniotomy. Hypertension (16.7% was the most commonly encountered complication during intraoperative period, followed by seizures (9.3%, desaturation (7.4%, tight brain (7.4%, and shivering (5.6%. The procedure had to be converted to general anaesthesia in one of patients owing to refractory brain bulge. The incidence of respiratory and haemodynamic complications were comparable in the both groups (P > 0.05. There was less incidence of intraoperative seizures in patients who received propofol (P = 0.03. In post-operative period, 20% of patients developed new motor deficit. Mean intensive care unit stay was 2.8 ± 1.9 day (1-14 days and mean hospital stay was 7.0 ± 5.0 day (3-30 days. Conclusions: ′Conscious sedation′ was the technique of choice for awake craniotomy, at our institute. Fentanyl, propofol, and dexmedetomidine were the main agents used for this purpose. Patients receiving propofol had less incidence of intraoperative seizure. Appropriate selection of patients, understanding the procedure of surgery, and

Descriptive Study: Anesthesia for Awake Craniotomy in Siriraj Hospital

Directory of Open Access Journals (Sweden)

Saipin Muangman

2016-03-01

Full Text Available Background: The purpose of awake craniotomy is to test neurological functions to ensure accurate lesion surgery and lessen postoperative neurological complications. There are several methods to provide anesthesia during awake craniotomy including local anesthesia infiltration, local anesthesia plus conscious sedation, general anesthesia and wake-up during surgery and sleep again (asleep-awake-asleep or AAA. Each method has its pro and con with different complications. In Siriraj Hospital, there was no prior study of anesthetic techniques and complications of awake craniotomy. Methods: The retrospective descriptive study of awake craniotomy was carried out with 60 patients in Siriraj Hospital 2007-2011. Results: There were 35 males (58.3% with average age 40.7±12.6 years and weight 64.2±12 kilograms undergoing awake craniotomy. Twenty patients (33.3% presented with seizure before surgery. Most diagnosis was oligodendroglioma in 25 patients (41.7%, mostly at the frontal lobe (44 patients or 73.3%. The most common position was supine(46patientsor76.7%. ICU lengthof stay was1.4±0.9(0,6days. Hospital stay was11.1±9 (4,55days. Total intravenous anesthesia (TIVA was mostlyused(52patientsor90% while18patients (30% received scalp block. Most patients (85% did not require nasal airways while 8 patients (13.3% did, and only 1 patient (1.7% required laryngeal mask airway (LMA to help open up air passage. The drugs used during asleep1 and asleep2 were propofol together with dexmedetomidine and fentanyl in 34 patients (56.7% and 23 patients (38.3%, respectively. Whilebeingawake (15patientsor20%,dexmedetomidine and/or fentanyl were administered. Complications during anesthesia were hypertension (33.3%, hypotension (26.7%, upper airway obstruction(23.3%, bradycardia (15%, tachycardia (10%, seizure (1.7% andnausea (1.7%. Conclusion: The most common anesthesia method inSiriraj Hospital for awake craniotomy was TIVA (90%, using propofol together with

Intranasal tumors in dogs: diagnosis and treatment

International Nuclear Information System (INIS)

Theisen, S.K.; Lewis, D.D.; Hosgood, G.

1996-01-01

Intranasal tumors are rare in dogs and occur mostly in middle-aged and old dogs. The malignant behavior of these tumors is reflected more by their tendency to invade local tissue than by a tendency to produce distant metastasis. Distant metastasis may, however, become more important as success in treatment of the initial lesion improves. The history and clinical signs (sneezing, nasal discharge, and facial deformity) of intranasal tumor in dogs often reflect intranasal disease but are usually nonspecific. Diagnostics should include at least the minimum data base, high-detail radiographs of the nasal cavity obtained while the dog is anesthetized, and biopsy of nasal cavity tissue. Radiotherapy with or without aggressive cytoreduction is the only treatment that significantly extends survival of these dogs. Ortho-voltage, megavoltage, or brachytherapy (implantation of (192)lridium) has been used

Awake craniotomy for brain tumor: indications, technique and benefits.

Science.gov (United States)

Dziedzic, Tomasz; Bernstein, Mark

2014-12-01

Increasing interest in the quality of life of patients after treatment of brain tumors has led to the exploration of methods that can improve intraoperative assessment of neurological status to avoid neurological deficits. The only method that can provide assessment of all eloquent areas of cerebral cortex and white matter is brain mapping during awake craniotomy. This method helps ensure that the quality of life and the neuro-oncological result of treatment are not compromised. Apart from the medical aspects of awake surgery, its economic issues are also favorable. Here, we review the main aspects of awake brain tumor surgery. Neurosurgical, neuropsychological, neurophysiological and anesthetic issues are briefly discussed.

[AWAKE CRANIOTOMY: IN SEARCH FOR OPTIMAL SEDATION].

Science.gov (United States)

Kulikova, A S; Sel'kov, D A; Kobyakov, G L; Shmigel'skiy, A V; Lubnin, A Yu

2015-01-01

Awake craniotomy is a "gold standard"for intraoperative brain language mapping. One of the main anesthetic challenge of awake craniotomy is providing of optimal sedation for initial stages of intervention. The goal of this study was comparison of different technics of anesthesia for awake craniotomy. Materials and methods: 162 operations were divided in 4 groups: 76 cases with propofol sedation (2-4mg/kg/h) without airway protection; 11 cases with propofol sedation (4-5 mg/kg/h) with MV via LMA; 36 cases of xenon anesthesia; and 39 cases with dexmedetomidine sedation without airway protection. Results and discussion: brain language mapping was successful in 90% of cases. There was no difference between groups in successfulness of brain mapping. However in the first group respiratory complications were more frequent. Three other technics were more safer Xenon anesthesia was associated with ultrafast awakening for mapping (5±1 min). Dexmedetomidine sedation provided high hemodynamic and respiratory stability during the procedure.

Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge.

Directory of Open Access Journals (Sweden)

Alex J Mann

Full Text Available We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments or intranasally (CSN adjuvanted and placebo treatments only with clade 1 HPAI A/Vietnam/1194/2004 (H5N1 virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant

Randomized Controlled Feasibility Trial of Intranasal Ketamine Compared to Intranasal Fentanyl for Analgesia in Children with Suspected Extremity Fractures.

Science.gov (United States)

Reynolds, Stacy L; Bryant, Kathleen K; Studnek, Jonathan R; Hogg, Melanie; Dunn, Connell; Templin, Megan A; Moore, Charity G; Young, James R; Walker, Katherine Rivera; Runyon, Michael S

2017-12-01

We compared the tolerability and efficacy of intranasal subdissociative ketamine to intranasal fentanyl for analgesia of children with acute traumatic pain and investigated the feasibility of a larger noninferiority trial that could investigate the potential opioid-sparing effects of intranasal ketamine. This randomized controlled trial compared 1 mg/kg intranasal ketamine to 1.5 μg/kg intranasal fentanyl in children 4 to 17 years old with acute pain from suspected isolated extremity fractures presenting to an urban Level II pediatric trauma center from December 2015 to November 2016. Patients, parents, treating physicians, and outcome assessors were blinded to group allocation. The primary outcome, a tolerability measure, was the frequency of cumulative side effects and adverse events within 60 minutes of drug administration. The secondary outcomes included the difference in mean pain score reduction at 20 minutes, the proportion of patients achieving a clinically significant reduction in pain in 20 minutes, total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the emergency department (ED) stay, and the feasibility of enrolling children presenting to the ED in acute pain into a randomized trial conducted under U.S. regulations. All patients were monitored until 6 hours after their last dose of study drug or until admission to the hospital ward or operating room. Of 629 patients screened, 87 received the study drug and 82 had complete data for the primary outcome (41 patients in each group). The median (interquartile range) age was 8 (6-11) years and 62% were male. Baseline pain scores were similar among patients randomized to receive ketamine (73 ± 26) and fentanyl (69 ± 26; mean difference [95% CI] = 4 [-7 to 15]). The cumulative number of side effects was 2.2 times higher in the ketamine group, but there were no serious adverse events and no patients in either group required intervention. The most

Implantable electrode for recording nerve signals in awake animals

Science.gov (United States)

Ninomiya, I.; Yonezawa, Y.; Wilson, M. F.

1976-01-01

An implantable electrode assembly consisting of collagen and metallic electrodes was constructed to measure simultaneously neural signals from the intact nerve and bioelectrical noises in awake animals. Mechanical artifacts, due to bodily movement, were negligibly small. The impedance of the collagen electrodes, measured in awake cats 6-7 days after implantation surgery, ranged from 39.8-11.5 k ohms at a frequency range of 20-5 kHz. Aortic nerve activity and renal nerve activity, measured in awake conditions using the collagen electrode, showed grouped activity synchronous with the cardiac cycle. Results indicate that most of the renal nerve activity was from postganglionic sympathetic fibers and was inhibited by the baroceptor reflex in the same cardiac cycle.

Long-term imaging in awake mice using removable cranial windows

Science.gov (United States)

Glickfeld, Lindsey L.; Kerlin, Aaron M.; Reid, R. Clay; Bonin, Vincent; Schafer, Dorothy P.; Andermann, Mark L.

2015-01-01

Cranial window implants in head-fixed rodents are becoming a preparation of choice for stable optical access to large areas of cortex over extended periods of time. Here, we provide a highly detailed and reliable surgical protocol for a cranial window implantation procedure for chronic widefield and cellular imaging in awake, head-fixed mice, which enables subsequent window removal and replacement in the weeks and months following the initial craniotomy. This protocol has facilitated awake, chronic imaging in adolescent as well as adult mice over several months from a large number of cortical brain regions; targeted virus and tracer injections from data obtained using prior awake functional mapping; and functionally-targeted two-photon imaging across all cortical layers in awake mice using a microprism attachment to the cranial window. Collectively, these procedures extend the reach of chronic imaging of cortical function and dysfunction in behaving animals. PMID:25275789

Awake craniotomy: A qualitative review and future challenges

Science.gov (United States)

Ghazanwy, Mahmood; Chakrabarti, Rajkalyan; Tewari, Anurag; Sinha, Ashish

2014-01-01

Neurosurgery in awake patients incorporates newer technologies that require the anesthesiologists to update their skills and evolve their methodologies. They need effective communication skills and knowledge of selecting the right anesthetic drugs to ensure adequate analgesia, akinesia, along with patient satisfaction with the anesthetic conduct throughout the procedure. The challenge of providing adequate anesthetic care to an awake patient for intracranial surgery requires more than routine vigilance about anesthetic management. PMID:25422613

Awake craniotomy: A qualitative review and future challenges

Directory of Open Access Journals (Sweden)

Mahmood Ghazanwy

2014-01-01

Full Text Available Neurosurgery in awake patients incorporates newer technologies that require the anesthesiologists to update their skills and evolve their methodologies. They need effective communication skills and knowledge of selecting the right anesthetic drugs to ensure adequate analgesia, akinesia, along with patient satisfaction with the anesthetic conduct throughout the procedure. The challenge of providing adequate anesthetic care to an awake patient for intracranial surgery requires more than routine vigilance about anesthetic management.

Failed awake craniotomy: a retrospective analysis in 424 patients undergoing craniotomy for brain tumor.

Science.gov (United States)

Nossek, Erez; Matot, Idit; Shahar, Tal; Barzilai, Ori; Rapoport, Yoni; Gonen, Tal; Sela, Gal; Korn, Akiva; Hayat, Daniel; Ram, Zvi

2013-02-01

Awake craniotomy for removal of intraaxial tumors within or adjacent to eloquent brain regions is a well-established procedure. However, awake craniotomy failures have not been well characterized. In the present study, the authors aimed to analyze and assess the incidence and causes for failed awake craniotomy. The database of awake craniotomies performed at Tel Aviv Medical Center between 2003 and 2010 was reviewed. Awake craniotomy was considered a failure if conversion to general anesthesia was required, or if adequate mapping or monitoring could not have been achieved. Of 488 patients undergoing awake craniotomy, 424 were identified as having complete medical, operative, and anesthesiology records. The awake craniotomies performed in 27 (6.4%) of these 424 patients were considered failures. The main causes of failure were lack of intraoperative communication with the patient (n = 18 [4.2%]) and/or intraoperative seizures (n = 9 [2.1%]). Preoperative mixed dysphasia (p awake craniotomy group, a significantly lower rate of gross-total resection was achieved (83% vs 54%, p = 0.008), there was a higher incidence of short-term speech deterioration postoperatively (6.1% vs 23.5%, p = 0.0017) as well as at 3 months postoperatively (2.3% vs 15.4%, p = 0.0002), and the hospitalization period was longer (4.9 ± 6.2 days vs 8.0 ± 10.1 days, p awake craniotomy were associated with a lower incidence of gross-total resection and increased postoperative morbidity. The majority of awake craniotomy failures were preventable by adequate patient selection and avoiding side effects of drugs administered during surgery.

Influenza (Flu) vaccine (Live, Intranasal): What you need to know

Science.gov (United States)

... is taken in its entirety from the CDC Influenza Live, Intranasal Flu Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... flulive.html . CDC review information for Live, Intranasal Influenza VIS: Vaccine Information Statement Influenza Page last reviewed: ...

Path to AWAKE: Evolution of the concept

Energy Technology Data Exchange (ETDEWEB)

Caldwell, A. [Max Planck Institute for Physics, Föhringer Ring 6, 80805 München (Germany); Adli, E. [University of Oslo, 0316 Oslo (Norway); Amorim, L. [GoLP/Instituto de Plasmas e Fusão Nuclear, Instituto Superior Técnico, Universidade de Lisboa, Lisbon (Portugal); Apsimon, R. [Cockcroft Institute, Warrington WA4 4AD (United Kingdom); Lancaster University, Lancaster LA1 4YR (United Kingdom); Argyropoulos, T. [CERN, Geneva (Switzerland); Assmann, R. [DESY, Notkestrasse 85, 22607 Hamburg (Germany); Bachmann, A.-M.; Batsch, F. [Max Planck Institute for Physics, Föhringer Ring 6, 80805 München (Germany); Bauche, J. [CERN, Geneva (Switzerland); Berglyd Olsen, V.K. [University of Oslo, 0316 Oslo (Norway); Bernardini, M. [CERN, Geneva (Switzerland); Bingham, R. [STFC Rutherford Appleton Laboratory, Didcot OX11 0QX (United Kingdom); Biskup, B. [CERN, Geneva (Switzerland); Czech Technical University, Zikova 1903/4, 166 36 Praha 6 (Czech Republic); Bohl, T.; Bracco, C. [CERN, Geneva (Switzerland); Burrows, P.N. [John Adams Institute for Accelerator Science, Oxford (United Kingdom); University of Oxford, Oxford OX1 2JD (United Kingdom); Burt, G. [Cockcroft Institute, Warrington WA4 4AD (United Kingdom); Lancaster University, Lancaster LA1 4YR (United Kingdom); Buttenschön, B. [Max Planck Institute for Plasma Physics, Wendelsteinstr. 1, 17491 Greifswald (Germany); Butterworth, A. [CERN, Geneva (Switzerland); Cascella, M. [UCL, Gower Street, London WC1E 6BT (United Kingdom); and others

2016-09-01

This paper describes the conceptual steps in reaching the design of the AWAKE experiment currently under construction at CERN. We start with an introduction to plasma wakefield acceleration and the motivation for using proton drivers. We then describe the self-modulation instability – a key to an early realization of the concept. This is then followed by the historical development of the experimental design, where the critical issues that arose and their solutions are described. We conclude with the design of the experiment as it is being realized at CERN and some words on the future outlook. A summary of the AWAKE design and construction status as presented in this conference is given in Gschwendtner et al. [1]. - Highlights: • Proton-driven plasma wakefield acceleration is proposed to bring electron bunches to high energies. • The self-modulation instability allows the use of existing proton bunches. • Schemes for overcoming the varying wake phase velocity were developed. • AWAKE will demonstrate proton-driven plasma wakefield acceleration for the first time.

Anaesthetic management of supratentorial tumor craniotomy using awake-throughout approach

International Nuclear Information System (INIS)

Shafiq, F.; Salim, F.; Parkash, J.

2017-01-01

The authors are reporting an anaesthetic management of patient presenting with left parietal lobe space occupying lesion and scheduled for Awake-craniotomy. Awake-throughout approach using scalp block was planned. Among techniques reported for keeping patient awake during the surgery, this one is really underutilized. The successful conduct requires thorough preoperative assessment and psychological preparation. We used powerpoint presentation as a preoperative teaching tool. The anatomical landmark technique was used to institute scalp block, where individual nerves were targeted bilaterally. Patient remained stable throughout and participated actively in intraoperative neurological monitoring. Postoperative period showed remarkable recovery, better pain control, and shorter length of stay in hospital. (author)

Anaesthetic Management of Supratentorial Tumor Craniotomy Using Awake-Throughout Approach.

Science.gov (United States)

Shafiq, Faraz; Salim, Fahad; Enam, Ather; Parkash, Jai; Faheem, Mohammad

2017-12-01

The authors are reporting an anaesthetic management of patient presenting with left parietal lobe space occupying lesion and scheduled for Awake-craniotomy. Awake-throughout approach using scalp block was planned. Among techniques reported for keeping patient awake during the surgery, this one is really underutilized. The successful conduct requires thorough preoperative assessment and psychological preparation. We used powerpoint presentation as a preoperative teaching tool. The anatomical landmark technique was used to institute scalp block, where individual nerves were targeted bilaterally. Patient remained stable throughout and participated actively in intraoperative neurological monitoring. Postoperative period showed remarkable recovery, better pain control, and shorter length of stay in hospital.

Outcome of elderly patients undergoing awake-craniotomy for tumor resection.

Science.gov (United States)

Grossman, Rachel; Nossek, Erez; Sitt, Razi; Hayat, Daniel; Shahar, Tal; Barzilai, Ori; Gonen, Tal; Korn, Akiva; Sela, Gal; Ram, Zvi

2013-05-01

Awake-craniotomy allows maximal tumor resection, which has been associated with extended survival. The feasibility and safety of awake-craniotomy and the effect of extent of resection on survival in the elderly population has not been established. The aim of this study was to compare surgical outcome of elderly patients undergoing awake-craniotomy to that of younger patients. Outcomes of consecutive patients younger and older than 65 years who underwent awake-craniotomy at a single institution between 2003 and 2010 were retrospectively reviewed. The groups were compared for clinical variables and surgical outcome parameters, as well as overall survival. A total of 334 young (45.4 ± 13.2 years, mean ± SD) and 90 elderly (71.7 ± 5.1 years) patients were studied. Distribution of gender, mannitol treatment, hemodynamic stability, and extent of tumor resection were similar. Significantly more younger patients had a better preoperative Karnofsky Performance Scale score (>70) than elderly patients (P = 0.0012). Older patients harbored significantly more high-grade gliomas (HGG) and brain metastases, and fewer low-grade gliomas (P Awake-craniotomy is a well-tolerated and safe procedure, even in elderly patients. Gross total tumor resection in elderly patients with HGG was associated with prolonged survival. The data suggest that favorable prognostic factors for patients with malignant brain tumors are also valid in elderly patients.

Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies.

Science.gov (United States)

Walum, Hasse; Waldman, Irwin D; Young, Larry J

2016-02-01

Over the last decade, oxytocin (OT) has received focus in numerous studies associating intranasal administration of this peptide with various aspects of human social behavior. These studies in humans are inspired by animal research, especially in rodents, showing that central manipulations of the OT system affect behavioral phenotypes related to social cognition, including parental behavior, social bonding, and individual recognition. Taken together, these studies in humans appear to provide compelling, but sometimes bewildering, evidence for the role of OT in influencing a vast array of complex social cognitive processes in humans. In this article, we investigate to what extent the human intranasal OT literature lends support to the hypothesis that intranasal OT consistently influences a wide spectrum of social behavior in humans. We do this by considering statistical features of studies within this field, including factors like statistical power, prestudy odds, and bias. Our conclusion is that intranasal OT studies are generally underpowered and that there is a high probability that most of the published intranasal OT findings do not represent true effects. Thus, the remarkable reports that intranasal OT influences a large number of human social behaviors should be viewed with healthy skepticism, and we make recommendations to improve the reliability of human OT studies in the future. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Patients' perceptions of awake and outpatient craniotomy for brain tumor: a qualitative study.

Science.gov (United States)

Khu, Kathleen Joy; Doglietto, Francesco; Radovanovic, Ivan; Taleb, Faisal; Mendelsohn, Daniel; Zadeh, Gelareh; Bernstein, Mark

2010-05-01

Routine and nonselective use of awake and outpatient craniotomy for supratentorial tumors has been shown to be safe and effective from a medical standpoint. In this study the authors aim was to explore patients' perceptions about awake and outpatient craniotomy. Qualitative research methodology was used. Two semistructured, open-ended interviews were conducted with 27 participants, who were ambulatory adult patients who underwent craniotomy for brain tumor excision between October 2008 and April 2009. The participants were each assigned to one of the following categories: 1) awake outpatient; 2) awake inpatient; 3) outpatient under general anesthesia; and 4) inpatient under general anesthesia. Interviews were audiotaped and transcribed, and the data were subjected to thematic analysis. The following 6 overarching themes emerged from the data: 1) patients had a positive experience with awake craniotomy; 2) patient satisfaction with outpatient surgery was high; 3) patients understood the rationale behind awake surgery; 4) patients were surprised that brain surgery can be done on an outpatient basis; 5) trust in one's surgeon was important; and 6) patients were more concerned about the disease than the procedure. The results reflected positively on the patients' awake and outpatient surgery experience, but there were some areas that require improvement, specifically perioperative pain control and postoperative care. These insights on patients' perspectives can lead to better delivery of care, and ultimately, improved health outcomes.

Awake craniotomy using electromagnetic navigation technology without rigid pin fixation.

Science.gov (United States)

Morsy, Ahmed A; Ng, Wai Hoe

2015-11-01

We report our institutional experience using an electromagnetic navigation system, without rigid head fixation, for awake craniotomy patients. The StealthStation® S7 AxiEM™ navigation system (Medtronic, Inc.) was used for this technique. Detailed preoperative clinical and neuropsychological evaluations, patient education and contrast-enhanced MRI (thickness 1.5mm) were performed for each patient. The AxiEM Mobile Emitter was typically placed in a holder, which was mounted to the operating room table, and a non-invasive patient tracker was used as the patient reference device. A monitored conscious sedation technique was used in all awake craniotomy patients, and the AxiEM Navigation Pointer was used for navigation during the procedure. This offers the same accuracy as optical navigation, but without head pin fixation or interference with intraoperative neurophysiological techniques and surgical instruments. The application of the electromagnetic neuronavigation technology without rigid head fixation during an awake craniotomy is accurate, and offers superior patient comfort. It is recommended as an effective adjunctive technique for the conduct of awake surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anesthesia for awake craniotomy: case report.

Science.gov (United States)

Bolzani, Nelson Davi; Junqueira, Daisy de Oliveira Pollon; Ferrari, Paulo André Pinheiro Fernandes; Ferrari, Antonio Fernandes; Gaia, Felipe; Tapajós, Caroline Moraes; Junior, José Francisco Cursino de Moura; Neto, Edmundo Pereira de Souza

2013-01-01

Some intracranial procedures are achievable with patients awake, however, there are challenges ranging from patient compliance to homeostasis. The aim of this study is to present a case of intracranial surgery for removal of a tumor in the left parietal lobe with the patient awake during the procedure. After patient selection and psychological preparation, the proposed excision of the left parietal lobe lesion in the waking state was clarified and accepted. Continuous infusion of propofol and remifentanil was administered to maintain a Ramsay score of 2-3. The bilateral scalp blockade was performed with ropivacaine. The Mayfield head fixation device was installed and drapes adjusted to maintain the airway and eyes accessible for mapping with electrical stimulation and tumor excision. For dura mater incision, a pad with 2% lidocaine was applied for 3 minutes. The surgery was uneventful. The patient was discharged on the seventh day of hospitalization without presenting complication. Although the maintenance of analgesia and hemodynamic stability was a challenge with the patient awake, the target-controlled infusion of propofol provided the desired level of consciousness, remifentanil titrated analgesia and sedation without drug accumulation, and the blockade with ropivacaine provided satisfactory analgesia. We conclude that the anesthetic technique was satisfactory for our patient. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Glucose turnover during insulin-induced hypoglycemia in liver-denervated rats

DEFF Research Database (Denmark)

Mikines, K J; Sonne, B; Richter, Erik

1985-01-01

The role of hepatic autonomic nerves in glucose production during hypoglycemia was studied. Selective, surgical denervation of the liver was performed in rats, which reduced hepatic norepinephrine concentrations by 96%. Hypoglycemia was induced by 250 mU of insulin intra-arterially in anesthetized...... as well as in chronically catheterized, awake rats. Half of the anesthetized denervated or sham-operated rats had previously been adrenodemedullated. Glucose turnover was measured by primed, constant intravenous infusion of [3-3H]glucose. Before as well as during hypoglycemia the arterial glucose...

P10.05 Establishment of team work awake craniotomy: clinical experience in Taiwan

Science.gov (United States)

Chen, P.; Chang, W.; Chao, Y.; Toh, C.; Wei, K.

2017-01-01

Abstract Introduction: Awake craniotomy provides the opportunity to maximize both extent of resection and preservation of neurological function. Serial preoperative and postoperative neurobehavial evaluation, magnetic resonance image examination and intraoperative task investigation need multidisciplinary experts to cooperate. Materials and Methods: From 2013, we gradually establish our team for awake craniotomy. Patient who had brain tumor with the symptom of aphasia or hemiparesis and are willing to cooperate would be entered the protocol of awake craniotomy. Patients would receive complete preoperative neurobehavial examination by psychologists and speech therapists and magnetic resonance image included diffuse tensor image. During operation, Patients went through asleep-awake-asleep anesthetic techniques. Direct electric stimulation was used for both cortical and subcortical mapping. Navigation included information of lesion and important fiber tract guided the direction of excision. Rehabilitation doctor performed the tasks and decided the positive response caused by stimulation or excisional procedure. After operation, post-operative image and neurobehavial examination would be performed within one week, 3 months, 6 months and one year later Results: We scheduled awake craniotomy on almost every Tuesday. In recent 89 patients who received awake craniotomy, Twenty-five participants with recurrent tumor underwent the operation. Seven patients received twice and one patient received three times of awake craniotomy. Two patients had controllable intraoperative seizure attack. Early termination of awake status was found in two patients due to general discomfort. Patients with modest preoperative performance status still benefit from the operation. Neurobehavioral functions improved over time and some specific feature correlate to certain aspect of quality of life. The grading of tumor and the extension of resection influence the recovery of neurobehavioral

CT of intranasal pleomorphic adenoma

Energy Technology Data Exchange (ETDEWEB)

Clark, M.; Fatterpekar, G.M.; Mukherji, S.K.; Buenting, J. [Department of Radiology, 3324 Infirmary CB F 7510, University of North Carolina, School of Medicine, Chapel Hill, NC 27599-7510 (United States)

1999-08-01

Intranasal pleomorphic adenoma is rare. We report the CT features this tumor in a 41-year-old woman who presented to us with right nasal obstruction and a 2-day history of epistaxis. (orig.) With 3 figs., 9 refs.

Awake craniotomy, electrophysiologic mapping, and tumor resection with high-field intraoperative MRI.

Science.gov (United States)

Parney, Ian F; Goerss, Stephan J; McGee, Kiaran; Huston, John; Perkins, William J; Meyer, Frederic B

2010-05-01

Awake craniotomy and electrophysiologic mapping (EPM) is an established technique to facilitate the resection of near eloquent cortex. Intraoperative magnetic resonance imaging (iMRI) is increasingly used to aid in the resection of intracranial lesions. Standard draping protocols in high-field iMRI units make awake craniotomies challenging, and only two groups have previously reported combined EPM and high-field iMRI. We present an illustrative case describing a simple technique for combining awake craniotomy and EPM with high-field iMRI. A movable platter is used to transfer the patient from the operating table to a transport trolley and into the adjacent MRI and still maintaining the patient's surgical position. This system allows excess drapes to be removed, facilitating awake craniotomy. A 57-year-old right-handed man presented with new onset seizures. Magnetic resonance imaging demonstrated a large left temporal mass. The patient underwent an awake, left frontotemporal craniotomy. The EPM demonstrated a single critical area for speech in his inferior frontal gyrus. After an initial tumor debulking, the scalp flap was loosely approximated, the wound was covered with additional drapes, and the excess surrounding drapes were trimmed. An iMRI was obtained. The image-guidance system was re-registered and the patient was redraped. Additional resection was performed, allowing extensive removal of what proved to be an anaplastic astrocytoma. The patient tolerated this well without any new neurological deficits. Standard protocols for positioning and draping in high-field iMRI units make awake craniotomies problematic. This straightforward technique for combined awake EPM and iMRI may facilitate safe removal of large lesions in eloquent cortex. Copyright © 2010 Elsevier Inc. All rights reserved.

Anaesthesia for awake craniotomy: A report of two cases in national ...

African Journals Online (AJOL)

Anaesthesia for neurosurgery while the patient remains awake requires a highly motivated patient and provision of high safety standard. Resection of brain tumours may cause neurological sequelae especially in the eloquent cortex depending on the site and size of tumour. Awake craniotomy which allows monitoring and ...

Organic and Non-Organic Language Disorders after Awake Brain Surgery

Directory of Open Access Journals (Sweden)

Elke De Witte

2014-04-01

Full Text Available INTRODUCTION: Awake surgery with Direct Electrical Stimulation (DES is considered the ‘gold standard’ to resect brain tumours in the language dominant hemisphere (De Witte & Mariën, 2013. Although transient language impairments are common in the immediate postoperative phase, permanent postoperative language deficits seem to be rare (Duffau, 2007. Milian et al. (2014 stated that most patients tolerate the awake procedure well and would undergo a similar procedure again. However, postoperative psychological symptoms including recurrent distressing dreams and persistent avoidance of stimuli have been recorded following awake surgery (Goebel, Nabavi, Schubert, & Mehdorn, 2010; Milian et al., 2014. To the best of our knowledge, psychogenic language disturbances have never been described after awake surgery. In general, only a handful of non-organic, psychogenic language disorders have been reported in the literature (De Letter et al., 2012. We report three patients with left brain tumours (see table 1 who presented linguistic symptoms after awake surgery that were incompatible with the lesion location, suggesting a psychogenic origin. METHODS: Neurocognitive (language, memory, executive functions investigations were carried out before, during and after awake surgery (6 weeks, 6 months postsurgery on the basis of standardised tests. Pre- and postoperative (fMRI images, DTI results and intraoperative DES findings were analysed. A selection of tasks was used to map language intraoperatively (De Witte et al., 2013. In the postoperative phase spontaneous speech and behavioural phenomena to errors were video-recorded. RESULTS: Preoperative language tests did not reveal any speech or language problems. Intraoperatively, eloquent sites were mapped and preserved enabling good language skills at the end of the awake procedure. However, assessments in the first weeks postsurgery disclosed language and behavioural symptoms that support the hypothesis of a

The Association of Industry Payments to Physicians with Prescription of Brand-Name Intranasal Corticosteroids.

Science.gov (United States)

Morse, Elliot; Fujiwara, Rance J T; Mehra, Saral

2018-06-01

Objectives To examine the association of industry payments for brand-name intranasal corticosteroids with prescribing patterns. Study Design Cross-sectional retrospective analysis. Setting Nationwide. Subjects and Methods We identified physicians prescribing intranasal corticosteroids to Medicare beneficiaries 2014-2015 and physicians receiving payment for the brand-name intranasal corticosteroids Dymista and Nasonex. Prescription and payment data were linked by physician, and we compared the proportion of prescriptions written for brand-name intranasal corticosteroids in industry-compensated vs non-industry-compensated physicians. We associated the number and dollar amount of industry payments with the relative frequency of brand-name prescriptions. Results In total, 164,587 physicians prescribing intranasal corticosteroids were identified, including 7937 (5%) otolaryngologists; 10,800 and 3886 physicians received industry compensation for Dymista and Nasonex, respectively. Physicians receiving industry payment for Dymista prescribed more Dymista as a proportion of total intranasal corticosteroid prescriptions than noncompensated physicians (3.1% [SD = 9.6%] vs 0.2% [SD = 2.5%], respectively, P association was stronger in otolaryngologists than general practitioners ( P brand-name intranasal corticosteroids is significantly associated with prescribing patterns. The magnitude of association may depend on physician specialty and the drug's time on the market.

Anaesthetic management for awake craniotomy in brain glioma resection: initial experience in Military Hospital Mohamed V of Rabat.

Science.gov (United States)

Meziane, Mohammed; Elkoundi, Abdelghafour; Ahtil, Redouane; Guazaz, Miloudi; Mustapha, Bensghir; Haimeur, Charki

2017-01-01

The awake brain surgery is an innovative approach in the treatment of tumors in the functional areas of the brain. There are various anesthetic techniques for awake craniotomy (AC), including asleep-awake-asleep technique, monitored anesthesia care, and the recent introduced awake-awake-awake method. We describe our first experience with anesthetic management for awake craniotomy, which was a combination of these techniques with scalp nerve block, and propofol/rémifentanil target controlled infusion. A 28-year-oldmale underwent an awake craniotomy for brain glioma resection. The scalp nerve block was performed and a low sedative state was maintained until removal of bone flap. During brain glioma resection, the patient awake state was maintained without any complications. Once, the tumorectomy was completed, the level of anesthesia was deepened and a laryngeal mask airway was inserted. A well psychological preparation, a reasonable choice of anesthetic techniques and agents, and continuous team communication were some of the key challenges for successful outcome in our patient.

Path to AWAKE: Evolution of the concept

CERN Document Server

Caldwell, A.; Amorim, L.; Apsimon, R.; Argyropoulos, T.; Assmann, R.; Bachmann, A.-M.; Batsch, F.; Bauche, J.; Berglyd Olsen, V.K.; Bernardini, M.; Bingham, R.; Biskup, B.; Bohl, T.; Bracco, C.; Burrows, P.N.; Burt, G.; Buttenschön, B.; Butterworth, A.; Cascella, M.; Chattopadhyay, S.; Chevallay, E.; Cipiccia, S.; Damerau, H.; Deacon, L.; Dirksen, P.; Doebert, S.; Dorda, U.; Elsen, E.; Farmer, J.; Fartoukh, S.; Fedosseev, V.; Feldbaumer, E.; Fiorito, R.; Fonseca, R.; Friebel, F.; Geschonke, G.; Goddard, B.; Gorn, A.A.; Grulke, O.; Gschwendtner, E.; Hansen, J.; Hessler, C.; Hillenbrand, S.; Hofle, W.; Holloway, J.; Huang, C.; Hüther, M.; Jaroszynski, D.; Jensen, L.; Jolly, S.; Joulaei, A.; Kasim, M.; Keeble, F.; Kersevan, R.; Kumar, N.; Li, Y.; Liu, S.; Lopes, N.; Lotov, K.V.; Lu, W.; Machacek, J.; Mandry, S.; Martin, I.; Martorelli, R.; Martyanov, M.; Mazzoni, S.; Meddahi, M.; Merminga, L.; Mete, O.; Minakov, V.A.; Mitchell, J.; Moody, J.; Müller, A.-S.; Najmudin, Z.; Noakes, T.C.Q.; Norreys, P.; Osterhoff, J.; Öz, E.; Pardons, A.; Pepitone, K.; Petrenko, A.; Plyushchev, G.; Pozimski, J.; Pukhov, A.; Reimann, O.; Rieger, K.; Roesler, S.; Ruhl, H.; Rusnak, T.; Salveter, F.; Savard, N.; Schmidt, J.; von der Schmitt, H.; Seryi, A.; Shaposhnikova, E.; Sheng, Z.M.; Sherwood, P.; Silva, L.; Simon, F.; Soby, L.; Sosedkin, A.P.; Spitsyn, R.I.; Tajima, T.; Tarkeshian, R.; Timko, H.; Trines, R.; Tückmantel, T.; Tuev, P.V.; Turner, M.; Velotti, F.; Verzilov, V.; Vieira, J.; Vincke, H.; Wei, Y.; Welsch, C.P.; Wing, M.; Xia, G.; Yakimenko, V.; Zhang, H.; Zimmermann, F.

2016-09-01

This report describes the conceptual steps in reaching the design of the AWAKE experiment currently under construction at CERN. We start with an introduction to plasma wakefield acceleration and the motivation for using proton drivers. We then describe the self-modulation instability --- a key to an early realization of the concept. This is then followed by the historical development of the experimental design, where the critical issues that arose and their solutions are described. We conclude with the design of the experiment as it is being realized at CERN and some words on the future outlook. A summary of the AWAKE design and construction status as presented in this conference is given in [1].

Intraoperative seizures and seizures outcome in patients underwent awake craniotomy.

Science.gov (United States)

Yuan, Yang; Peizhi, Zhou; Xiang, Wang; Yanhui, Liu; Ruofei, Liang; Shu, Jiang; Qing, Mao

2016-11-25

Awake craniotomies (AC) could reduce neurological deficits compared with patients under general anesthesia, however, intraoperative seizure is a major reason causing awake surgery failure. The purpose of the study was to give a comprehensive overview the published articles focused on seizure incidence in awake craniotomy. Bibliographic searches of the EMBASE, MEDLINE,were performed to identify articles and conference abstracts that investigated the intraoperative seizure frequency of patients underwent AC. Twenty-five studies were included in this meta-analysis. Among the 25 included studies, one was randomized controlled trials and 5 of them were comparable studies. The pooled data suggested the general intraoperative seizure(IOS) rate for patients with AC was 8%(fixed effect model), sub-group analysis identified IOS rate for glioma patients was 8% and low grade patients was 10%. The pooled data showed early seizure rates of AC patients was 11% and late seizure rates was 35%. This systematic review and meta-analysis shows that awake craniotomy is a safe technique with relatively low intraoperative seizure occurrence. However, few RCTs were available, and the acquisition of further evidence through high-quality RCTs is highly recommended.

The influence of awake craniotomy on postoperative neuropsychology

Directory of Open Access Journals (Sweden)

YANG Ming-yuan

2012-12-01

Full Text Available Objective To assess the neuropsychological function and quality of life of the patients after awake craniotomy (AC. Methods A case-control study was conducted among 81 patients who underwent awake craniotomy, and a 1-to-1 control group (matched by age, gender, degree of education, tumor location and characteristic undergoing general anesthesia (GA in glioma resections was assembled. The incidence of postoperative neurological deficits, psychological disorders and recurrence were investigated during telephone follow-ups, and Medical Outcomes Study Short Form 36 (SF-36 was adopted to evaluate the life quality of patients. Results Almost 73 pairs of patients fulfilled the survey of AC and GA group respectively. There were 21 patients and 28 patients with postoperative neurological deficits, and 12 patients and 8 patients with psychological disorders in AC and GA group respectively. Thirty patients of AC group had the recollection of being awake during the surgery. There were 9 patients in CA group having long-term ( > 6 months neurological deficits, which was less than the number of GA group (18 patients, P = 0.038. According to the assessment in short-term, medium-term and long-term postoperative neurological deficits, there was no significant difference in the quality-of-life scores between the two groups (P > 0.05, for all. Conclusion Awake craniotomy can be the main method for removing the lesions located in or close to functional areas with lower incidence of long?term postoperative neurological deficits, and it has no significant impact on the psychological status and the quality of life postoperatively．

Development of a safe and pragmatic awake craniotomy program at Maine Medical Center.

Science.gov (United States)

Rughani, Anand I; Rintel, Theodor; Desai, Rajiv; Cushing, Deborah A; Florman, Jeffrey E

2011-01-01

Awake craniotomy offers an excellent means of performing intraoperative mapping and optimizing surgical resection of brain tumors. Awake craniotomy relies on a strong collaboration between anesthesiologists, neurosurgeons, and operating room staff. The authors recently introduced awake craniotomy for tumor resection at the Maine Medical Center and propose that it can be performed safely, effectively, and efficiently in a high-volume community hospital. We describe a practical approach to performing awake craniotomy involving streamlined anesthetic protocols and simplified intraoperative testing parameters in a carefully selected group of patients. Our first 25 patients are retrospectively reviewed with particular attention to the anesthetic protocol, the extent of resection, the operative time, post-operative complications, the length of hospitalization, and their functional status at follow-up. The authors established an anesthetic protocol based primarily on midazolam, fentanyl, propofol, and local anesthetic. The authors note that all but one patient was able to tolerate the awake procedure. Gross total resection was achieved in nearly 80% of patients with a glial tumor. Operative time was short, averaging 159 minutes of entire anesthesia care. Length of stay averaged 3.7 days. Persistent new post-operative deficits were noted in 2 of 25 patients. There was no substantial difference in total hospital charges for patients undergoing awake craniotomy when compared to a matched historical control. With attention focused on patient selection and a streamlined anesthetic protocol, the authors were able to successfully implement an awake craniotomy protocol in a community setting with satisfying results, including low operative morbidity, short operative times, low anesthetic complications, and excellent patient tolerance.

Awake, Offline Processing during Associative Learning.

Science.gov (United States)

Bursley, James K; Nestor, Adrian; Tarr, Michael J; Creswell, J David

2016-01-01

Offline processing has been shown to strengthen memory traces and enhance learning in the absence of conscious rehearsal or awareness. Here we evaluate whether a brief, two-minute offline processing period can boost associative learning and test a memory reactivation account for these offline processing effects. After encoding paired associates, subjects either completed a distractor task for two minutes or were immediately tested for memory of the pairs in a counterbalanced, within-subjects functional magnetic resonance imaging study. Results showed that brief, awake, offline processing improves memory for associate pairs. Moreover, multi-voxel pattern analysis of the neuroimaging data suggested reactivation of encoded memory representations in dorsolateral prefrontal cortex during offline processing. These results signify the first demonstration of awake, active, offline enhancement of associative memory and suggest that such enhancement is accompanied by the offline reactivation of encoded memory representations.

Central nervous insulin resistance: a promising target in the treatment of metabolic and cognitive disorders?

Science.gov (United States)

Hallschmid, M; Schultes, B

2009-11-01

Research on functions and signalling pathways of insulin has traditionally focused on peripheral tissues such as muscle, fat and liver, while the brain was commonly believed to be insensitive to the effects of this hormone secreted by pancreatic beta cells. However, since the discovery some 30 years ago that insulin receptors are ubiquitously found in the central nervous system, an ever-growing research effort has conclusively shown that circulating insulin accesses the brain, which itself does not synthesise insulin, and exerts pivotal functions in central nervous networks. As an adiposity signal reflecting the amount of body fat, insulin provides direct negative feedback to hypothalamic nuclei that control whole-body energy and glucose homeostasis. Moreover, insulin affects distinct cognitive processes, e.g. by triggering the formation of psychological memory contents. Accordingly, metabolic and cognitive disorders such as obesity, type 2 diabetes mellitus and Alzheimer's disease are associated with resistance of central nervous structures to the effects of insulin, which may derive from genetic polymorphisms as well as from long-term exposure to excess amounts of circulating insulin due to peripheral insulin resistance. Thus, overcoming central nervous insulin resistance, e.g. by pharmacological interventions, appears to be an attractive strategy in the treatment and prevention of these disorders. Enhancement of central nervous insulin signalling by administration of intranasal insulin, insulin analogues and insulin sensitisers in basic research approaches has yielded encouraging results that bode well for the successful translation of these effects into future clinical practice.

Glucose recovery after intranasal glucagon during hypoglycaemia in man

DEFF Research Database (Denmark)

Hvidberg, A; Djurup, R; Hilsted, J

1994-01-01

to exceed 3 mmol.l-1 was significantly shorter for i.m. glucagon. The mean plasma glucagon level increased faster after i.m. glucagon than after intranasal glucagon, and the levels remained higher throughout the study period. We conclude that glucose recovery was significantly better after i...... endogenous glucose counterregulation, and glucose turnover was estimated by a 3-[3H]-glucose infusion. When hypoglycaemia was reached, the subjects received either i.m. glucagon of pancreatic extraction (1 mg) or intranasal genetically engineered glucagon (2 mg). The incremental values for plasma glucose...... concentrations 15 min after intranasal and i.m. administration of glucagon differed marginally. However, after 5 min the glucose appearance rate, as well as the incremental values for plasma glucose, were significantly higher for the i.m. glucagon treatment. The mean time taken for incremental plasma glucose...

Awake craniotomy anesthetic management using dexmedetomidine, propofol, and remifentanil.

Science.gov (United States)

Prontera, Andrea; Baroni, Stefano; Marudi, Andrea; Valzania, Franco; Feletti, Alberto; Benuzzi, Francesca; Bertellini, Elisabetta; Pavesi, Giacomo

2017-01-01

Awake craniotomy allows continuous monitoring of patients' neurological functions during open surgery. Anesthesiologists have to sedate patients in a way so that they are compliant throughout the whole surgical procedure, nevertheless maintaining adequate analgesia and anxiolysis. Currently, the use of α2-receptor agonist dexmedetomidine as the primary hypnotic-sedative medication is increasing. Nine patients undergoing awake craniotomy were treated with refined monitored anesthesia care (MAC) protocol consisting of a combination of local anesthesia without scalp block, low-dose infusion of dexmedetomidine, propofol, and remifentanil, without the need of airways management. The anesthetic protocol applied in our study has the advantage of decreasing the dose of each drug and thus reducing the occurrence of side effects. All patients had smooth and rapid awakenings. The brain remained relaxed during the entire procedure. In our experience, this protocol is safe and effective during awake brain surgery. Nevertheless, prospective randomized trials are necessary to confirm the optimal anesthetic technique to be used.

Iatrogenic Cushing's syndrome caused by intranasal steroid use.

Science.gov (United States)

Dursun, Fatma; Kirmizibekmez, Heves

2017-01-01

Cushing's syndrome (CS) is common after oral steroid use and has also been reported following topical or inhaled use, but it is extremely uncommon after intranasal administration. This is the case of a 6-year-old child who developed Cushing's syndrome after intranasal application of dexamethasone sodium phosphate for a period of 6 months. Pediatricians and other clinical practitioners should be aware that high-dose and long-term nasal steroid administration may cause iatrogenic Cushing's syndrome characterized by complications of glucocorticoid excess as well as serious and even life-threatening complications of adrenal insufficiency.

The Potential Benefits of Awake Craniotomy for Brain Tumor Resection: An Anesthesiologist's Perspective.

Science.gov (United States)

Meng, Lingzhong; Berger, Mitchel S; Gelb, Adrian W

2015-10-01

Awake craniotomy for brain tumor resection is becoming a standard of care for lesions residing within or in close proximity to regions presumed to have language or sensorimotor function. Evidence shows an improved outcome including greater extent of resection, fewer late neurological deficits, shorter hospital stay, and longer survival after awake brain tumor resection compared with surgery under general anesthesia. The surgeon's ability to maximize tumor resection within the constraint of preserving neurological function by intraoperative stimulation mapping in an awake patient is credited for this advantageous result. It is possible that the care provided by anesthesiologists, especially the avoidance of certain components of general endotracheal anesthesia, may also be important in the outcome of awake brain tumor resection. We present our interpretation of the evidence that we believe substantiates this proposition. However, due to the lack of direct evidence based on randomized-controlled trials and the heterogeneity of anesthetic techniques used for awake craniotomy, our perspective is largely speculative and hypothesis generating that needs to be validated or refuted by future quality research.

Patients' perspective on awake craniotomy for brain tumors-single center experience in Brazil.

Science.gov (United States)

Leal, Rafael Teixeira Magalhaes; da Fonseca, Clovis Orlando; Landeiro, Jose Alberto

2017-04-01

Awake craniotomy with brain mapping is the gold standard for eloquent tissue localization. Patients' tolerability and satisfaction have been shown to be high; however, it is a matter of debate whether these findings could be generalized, since patients across the globe have their own cultural backgrounds and may perceive and accept this procedure differently. We conducted a prospective qualitative study about the perception and tolerability of awake craniotomy in a population of consecutive brain tumor patients in Brazil between January 2013 and April 2015. Seventeen patients were interviewed using a semi-structured model with open-ended questions. Patients' thoughts were grouped into five categories: (1) overall perception: no patient considered awake craniotomy a bad experience, and most understood the rationale behind it. They were positively surprised with the surgery; (2) memory: varied from nothing to the entire surgery; (3) negative sensations: in general, it was painless and comfortable. Remarks concerning discomfort on the operating table were made; (4) postoperative recovery: perception of the postoperative period was positive; (5) previous surgical experiences versus awake craniotomy: patients often preferred awake surgery over other surgery under general anesthesia, including craniotomies. Awake craniotomy for brain tumors was well tolerated and yielded high levels of satisfaction in a population of patients in Brazil. This technique should not be avoided under the pretext of compromising patients' well-being.

Awake tracheal intubation using Pentax airway scope in 30 patients: A Case series

Directory of Open Access Journals (Sweden)

Payal Kajekar

2014-01-01

Full Text Available Background and Aims: Pentax airway scope (AWS has been successfully used for managing difficult intubations. In this case series, we aimed to evaluate the success rate and time taken to complete intubation, when AWS was used for awake tracheal intubation. Methods: We prospectively evaluated the use of AWS for awake tracheal intubation in 30 patients. Indication for awake intubation, intubation time, total time to complete tracheal intubation, laryngoscopic view (Cormack and Lehane grade, total dose of local anaesthetic used, anaesthetists rating and patient′s tolerance of the procedure were recorded. Results: The procedure was successful in 25 out of the 30 patients (83%. The mean (standard deviation intubation time and total time to complete the tracheal intubation was 5.4 (2.4 and 13.9 (3.7 min, respectively in successful cases. The laryngeal view was grade 1 in 24 and grade 2 in one of 25 successful intubations. In three out of the five patients where the AWS failed, awake tracheal intubation was successfully completed with the assistance of flexible fibre optic scope (FOS. Conclusion: Awake tracheal intubation using AWS was successful in 83% of patients. Success rate can be further improved using a combination of AWS and FOS. Anaesthesiologists who do not routinely use FOS may find AWS easier to use for awake tracheal intubation using an oral route.

Awake, Offline Processing during Associative Learning.

Directory of Open Access Journals (Sweden)

James K Bursley

Full Text Available Offline processing has been shown to strengthen memory traces and enhance learning in the absence of conscious rehearsal or awareness. Here we evaluate whether a brief, two-minute offline processing period can boost associative learning and test a memory reactivation account for these offline processing effects. After encoding paired associates, subjects either completed a distractor task for two minutes or were immediately tested for memory of the pairs in a counterbalanced, within-subjects functional magnetic resonance imaging study. Results showed that brief, awake, offline processing improves memory for associate pairs. Moreover, multi-voxel pattern analysis of the neuroimaging data suggested reactivation of encoded memory representations in dorsolateral prefrontal cortex during offline processing. These results signify the first demonstration of awake, active, offline enhancement of associative memory and suggest that such enhancement is accompanied by the offline reactivation of encoded memory representations.

Effects of intranasal medicines on microcirculatory blood flow of nasal cavity

Directory of Open Access Journals (Sweden)

Svistunov A.A.

2012-09-01

Full Text Available The article describes the new method of assessment of microcirculatory blood perfusion and introduction of this method into the study of intranasal drugs effects on mucosal blood flow in the nasal cavity. The research work presents some different groups of drugs — decongestants, physical solutions for irrigation therapy and local corticosteroids. It has been revealed that intranasal decongestants have a significant effect on the intranasal blood flow, but their intake affects the mucosal membrane of the nasal cavity. Other drugs have not shown such negative effects and have not caused tachyphylaxis. Therefore these medicines may be recommended for more common use in ENT-practice.

Humidification of inspired oxygen is increased with pre-nasal cannula, compared to intranasal cannula.

Science.gov (United States)

Dellweg, Dominic; Wenze, Markus; Hoehn, Ekkehard; Bourgund, Olaf; Haidl, Peter

2013-08-01

Oxygen therapy is usually combined with a humidification device, to prevent mucosal dryness. Depending on the cannula design, oxygen can be administered pre- or intra-nasally (administration of oxygen in front of the nasal ostia vs cannula system inside the nasal vestibulum). The impact of cannula design on intra-nasal humidity, however, has not been investigated to date. First, to develop a system, that samples air from the nasal cavity and analyzes the humidity of these samples. Second, to investigate nasal humidity during pre-nasal and intra-nasal oxygen application, with and without humidification. We first developed and validated a sampling and analysis system to measure humidity from air samples. By means of this system we measured inspiratory air samples from 12 subjects who received nasal oxygen with an intra-nasal and pre-nasal cannula at different flows, with and without humidification. The sampling and analysis system showed good correlation to a standard hygrometer within the tested humidity range (r = 0.99, P humidification (P = .001, P humidification. With the addition of humidification we observed no significant change in humidity at any flow, and independent of pre- or intranasal oxygen administration. Pre-nasal administration of dry oxygen achieves levels of intranasal humidity similar to those achieved by intranasal administration in combination with a bubble through humidifier. Pre-nasal oxygen simplifies application and may reduce therapy cost.

Awake craniotomy anesthetic management using dexmedetomidine, propofol, and remifentanil

Directory of Open Access Journals (Sweden)

Prontera A

2017-03-01

Full Text Available Andrea Prontera,1 Stefano Baroni,2 Andrea Marudi,2 Franco Valzania,3 Alberto Feletti,1 Francesca Benuzzi,4 Elisabetta Bertellini,2 Giacomo Pavesi1 1Department of Neurosurgery, Nuovo Ospedale Civile SAgostino-Estense, 2Department of Anesthesiology, Nuovo Ospedale Civile SAgostino-Estense, 3Department of Neurology, Nuovo Ospedale Civile S Agostino-Estense, 4Department of Neuroscience, University of Modena and Reggio Emilia, Modena, Italy Introduction: Awake craniotomy allows continuous monitoring of patients’ neurological functions during open surgery. Anesthesiologists have to sedate patients in a way so that they are compliant throughout the whole surgical procedure, nevertheless maintaining adequate analgesia and anxiolysis. Currently, the use of α2-receptor agonist dexmedetomidine as the primary hypnotic–sedative medication is increasing.Methods: Nine patients undergoing awake craniotomy were treated with refined monitored anesthesia care (MAC protocol consisting of a combination of local anesthesia without scalp block, low-dose infusion of dexmedetomidine, propofol, and remifentanil, without the need of airways management.Results: The anesthetic protocol applied in our study has the advantage of decreasing the dose of each drug and thus reducing the occurrence of side effects. All patients had smooth and rapid awakenings. The brain remained relaxed during the entire procedure.Conclusion: In our experience, this protocol is safe and effective during awake brain surgery. Nevertheless, prospective randomized trials are necessary to confirm the optimal anesthetic technique to be used. Keywords: dexmedetomidine, awake surgery, anesthesia

Awake craniotomy and multilingualism: language testing during anaesthesia for awake craniotomy in a bilingual patient.

Science.gov (United States)

Costello, T G

2014-08-01

An awake craniotomy for epilepsy surgery is presented where a bilingual patient post-operatively reported temporary aphasia of his first language (Spanish). This case report discusses the potential causes for this clinical presentation and methods to prevent the occurrence of this in future patients undergoing this form of surgery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Awake craniotomy and electrophysiological mapping for eloquent area tumours.

Science.gov (United States)

Chacko, Ari George; Thomas, Santhosh George; Babu, K Srinivasa; Daniel, Roy Thomas; Chacko, Geeta; Prabhu, Krishna; Cherian, Varghese; Korula, Grace

2013-03-01

An awake craniotomy facilitates radical excision of eloquent area gliomas and ensures neural integrity during the excision. The study describes our experience with 67 consecutive awake craniotomies for the excision of such tumours. Sixty-seven patients with gliomas in or adjacent to eloquent areas were included in this study. The patient was awake during the procedure and intraoperative cortical and white matter stimulation was performed to safely maximize the extent of surgical resection. Of the 883 patients who underwent craniotomies for supratentorial intraaxial tumours during the study period, 84 were chosen for an awake craniotomy. Sixty-seven with a histological diagnosis of glioma were included in this study. There were 55 men and 12 women with a median age of 34.6 years. Forty-two (62.6%) patients had positive localization on cortical stimulation. In 6 (8.9%) patients white matter stimulation was positive, five of whom had responses at the end of a radical excision. In 3 patients who developed a neurological deficit during tumour removal, white matter stimulation was negative and cessation of the surgery did not result in neurological improvement. Sixteen patients (24.6%) had intraoperative neurological deficits at the time of wound closure, 9 (13.4%) of whom had persistent mild neurological deficits at discharge, while the remaining 7 improved to normal. At a mean follow-up of 40.8 months, only 4 (5.9%) of these 9 patients had persistent neurological deficits. Awake craniotomy for excision of eloquent area gliomas enable accurate mapping of motor and language areas as well as continuous neurological monitoring during tumour removal. Furthermore, positive responses on white matter stimulation indicate close proximity of eloquent cortex and projection fibres. This should alert the surgeon to the possibility of postoperative deficits to change the surgical strategy. Thus the surgeon can resect tumour safely, with the knowledge that he has not damaged

Association of temporomandibular disorder pain with awake and sleep bruxism in adults.

Science.gov (United States)

Sierwald, Ira; John, Mike T; Schierz, Oliver; Hirsch, Christian; Sagheri, Darius; Jost-Brinkmann, Paul-Georg; Reissmann, Daniel R

2015-07-01

Parafunctional habits such as clenching or grinding (bruxism) during daytime and at night are considered to have a great impact on the etiopathogenesis of temporomandibular disorders (TMD). However, the size of the effect and how daytime activities interact with nocturnal activities is not yet clear. The aim of this study was to assess the association of TMD pain with both awake and sleep bruxism in adults. In this case-control study, data of a consecutive sample of 733 TMD patients (cases; mean age ± SD: 41.4 ± 16.3 years; 82% women) with at least one pain-related TMD diagnosis according to the German version of the Research Diagnostic Criteria for TMD (RDC/TMD) and of a community-based probability sample of 890 subjects (controls; mean age ± SD: 40.4 ± 11.8 years; 57% female) without TMD were evaluated. Clenching or grinding while awake and/or asleep was assessed with self-reports. Association of TMD pain with awake and sleep bruxism was analyzed using multiple logistic regression analyses and controlled for potential confounders. Odds ratios (OR) with corresponding 95% confidence intervals (CI) were calculated. While 11.2% of the controls reported clenching or grinding while awake, this proportion was significantly higher in TMD patients (33.9%; p bruxism (OR 1.8; CI 1.4-2.4). However, risk for TMD pain substantially increased in cases of simultaneous presence of awake and sleep bruxism (OR 7.7; CI 5.4-11.1). When occurring separately, awake and sleep bruxism are significant risk factors for TMD pain. In case of simultaneous presence, the risk for TMD pain is even higher.

Pain during awake craniotomy for brain tumor resection. Incidence, causes, consequences and management.

Science.gov (United States)

Fontaine, D; Almairac, F

2017-06-01

Awake craniotomy for brain tumor resection is usually well-tolerated and most of the patients are satisfied. However, in studies reporting the patients' postoperative perception of the awake craniotomy procedure, about half of them have experienced some degree of intraoperative pain. Pain was mild (intensity between 1 and 2 on the visual analogical score) short lasting in most cases, and did not challenge the procedure. Pain was reported as moderate in about 25% and exceptionally severe. We conducted a preliminary survey among French centers (n=9) routinely performing awake craniotomy. Neurosurgeons' opinions were concordant with patient's reports. Intraoperative pain exceptionally challenged the awake craniotomy procedure or led to changes in the resection strategy. For neurosurgeons, the most challenging causes of intraoperative pain were the patient's inadequate installation, the contact of surgical tools with pain-sensitive intracranial structures, especially the dura mater of the skull base, falx cerebri, and the leptomeninges of the lateral fissure and neighboring sulci. Strategies to deal with these causes included focusing the patient on the intraoperative functional tests to distract their attention away from the pain, and avoiding contacts with the pain-sensitive intracranial structures during the awake phase. Adequate preoperative patient information and preparation, trained anesthesiologists and application of recommendations for awake craniotomy procedures as well as adaptation of surgical technique to avoid contact with pain-sensitive intracranial structures are key factors to prevent intraoperative pain and ensure patient's postoperative satisfaction. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Awake craniotomy for assisting placement of auditory brainstem implant in NF2 patients.

Science.gov (United States)

Zhou, Qiangyi; Yang, Zhijun; Wang, Zhenmin; Wang, Bo; Wang, Xingchao; Zhao, Chi; Zhang, Shun; Wu, Tao; Li, Peng; Li, Shiwei; Zhao, Fu; Liu, Pinan

2018-06-01

Auditory brainstem implants (ABIs) may be the only opportunity for patients with NF2 to regain some sense of hearing sensation. However, only a very small number of individuals achieved open-set speech understanding and high sentence scores. Suboptimal placement of the ABI electrode array over the cochlear nucleus may be one of main factors for poor auditory performance. In the current study, we present a method of awake craniotomy to assist with ABI placement. Awake surgery and hearing test via the retrosigmoid approach were performed for vestibular schwannoma resections and auditory brainstem implantations in four patients with NF2. Auditory outcomes and complications were assessed postoperatively. Three of 4 patients who underwent awake craniotomy during ABI surgery received reproducible auditory sensations intraoperatively. Satisfactory numbers of effective electrodes, threshold levels and distinct pitches were achieved in the wake-up hearing test. In addition, relatively few electrodes produced non-auditory percepts. There was no serious complication attributable to the ABI or awake craniotomy. It is safe and well tolerated for neurofibromatosis type 2 (NF2) patients using awake craniotomy during auditory brainstem implantation. This method can potentially improve the localization accuracy of the cochlear nucleus during surgery.

Awake craniotomy for excision of arteriovenous malformations? A qualitative comparison study with stereotactic radiosurgery.

Science.gov (United States)

Chan, David Yuen Chung; Chan, Danny Tat Ming; Zhu, Cannon Xian Lun; Kan, Patricia Kwok Yee; Ng, Amelia Yikjin; Hsieh, Yi-Pin Sonia; Abrigo, Jill; Poon, Wai Sang; Wong, George Kwok Chu

2018-05-01

Treatment of arteriovenous malformations (AVM) located at the eloquent area has been a challenge. Awake brain mapping allows identification of a non-eloquent gyrus for intervention and can potentially facilitate resection with preservation of functions. An alternative treatment option is stereotactic radiosurgery (SRS). The objective of this study was to perform a qualitative comparison of the treatment outcome of awake AVM excision versus SRS. We conducted a 13-year retrospective review of AVM excision under awake craniotomy performed at Prince of Wales Hospital, Hong Kong, from 2003 to 2016. Patients' presentation, Spetzler-Martin (SM) grading, rate of obliteration and complication were reviewed and analyzed with the modified radiosurgery-based AVM score (RS score). Six patients had excision of AVM under awake mapping during this period of time. Two were SM Grade II and four were SM Grade III. Five located at the peri-rolandic region while one at the temporal language area. None had failed mapping. Five out of six achieved complete obliteration (83.3%). Qualitative comparative analysis had revealed better treatment outcome with awake AVM excision as compared to SRS with the obliteration rate of 100% versus 96% for RS score ≤1.00, 100% versus 78% for RS score 1.01-1.50, and 66% versus 50% for RS score >2.00 respectively. In conclusion, awake mapping and excision of AVMs at the eloquent area is feasible. Qualitative comparative analysis had revealed higher obliteration rate with awake AVM excision as compared to SRS. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pediatric awake craniotomy for seizure focus resection with dexmedetomidine sedation-a case report.

Science.gov (United States)

Sheshadri, Veena; Chandramouli, B A

2016-08-01

Resection of lesions near the eloquent cortex of brain necessitates awake craniotomy to reduce the risk of permanent neurologic deficits during surgery. There are limited reports of anesthetic management of awake craniotomy in pediatric patients. This report is on use of dexmedetomidine sedation for awake craniotomy in a 11-year-old child, without any airway adjuncts throughout the procedure. Dexmedetomidine infusion administered at a dosage of 0.2 to 0.7μg kg(-1) h(-1) provided adequate sedation for the entire procedure. There were no untoward incidents or any interference with electrocorticography, intraoperative stimulation, and functional mapping. Adequate preoperative visits and counseling of patient and parents regarding course and nature of events along with well-planned intraoperative management are of utmost importance in a pediatric age group for successful intraoperative awake craniotomy. Copyright © 2016 Elsevier Inc. All rights reserved.

IS ATOMIZED INTRANASAL MIDAZOLAM A NOVEL SEDATIVE PREMEDICATION IN PAEDIATRIC PATIENTS?

Directory of Open Access Journals (Sweden)

Savitri D. Kabade

2017-06-01

Full Text Available BACKGROUND The successful conduct of anaesthesia in children depends on adequate premedication, which not only comforts the anxious child but also comforts the parents or guardians. Atomized Intranasal Midazolam is quickly absorbed through the nasal mucosa, resulting in a rapid and reliable onset of action. Clonidine has several applications in paediatric anaesthesia as a premedication and as an adjuvant in general as well as regional anaesthesia. Thus, in search of a novel premedication technique, we conducted a study to compare the effectiveness of atomized intranasal midazolam with intranasal clonidine for preoperative sedation in paediatric patients undergoing elective surgery. MATERIALS AND METHODS After obtaining Institutional Ethical Committee clearance and parent’s consent, a prospective, randomised, double-blinded clinical study was conducted in 78 children of ASA I and II, belonging to 2 - 10 years age, posted for various elective surgery. Group M (n= 39 received atomized intranasal midazolam (0.3 mg/kg and Group C (n= 39 received clonidine (4 mcg/kg instilled into both the nostrils. Sedation score (Ramsay, separation score, mask acceptance, recovery and vital parameters were recorded. Statistical analysis of data was done using IBM-SPSS version 21.0. RESULTS Mean sedation scores (± SD were higher in Group M than in Group C (at 5th minute 1.58 ± 0.55 in Group M and 1.15 ± 0.36 in Group C with P= 0.002, at 10th minute 2.34 ± 0.97 in Group M and 1.75 ± 0.71 in Group C with P= 0.008. Separation scores and mask acceptance were better with Group M than Group C. Haemodynamic parameters were similar in both the groups and no major adverse effects were noted. CONCLUSION Atomized intranasal midazolam produces superior sedation levels, child-parent separation and mask acceptance compared to intranasal clonidine in children.

The effect of single low-dose dexamethasone on vomiting during awake craniotomy.

Science.gov (United States)

Kamata, Kotoe; Morioka, Nobutada; Maruyama, Takashi; Komayama, Noriaki; Nitta, Masayuki; Muragaki, Yoshihiro; Kawamata, Takakazu; Ozaki, Makoto

2016-12-01

Intraoperative vomiting leads to serious respiratory complications that could influence the surgical decision-making process for awake craniotomy. However, the use of antiemetics is still limited in Japan. The aim of this study was to investigate the effect of prophylactically administered single low-dose dexamethasone on the incidence of vomiting during awake craniotomy. The frequency of hyperglycemia was also examined. We conducted a retrospective case review of awake craniotomy for glioma resection between 2012 and 2015. Of the 124 patients, 91 were included in the analysis. Dexamethasone was not used in 43 patients and the 48 remaining patients received an intravenous bolus of 4.95 mg dexamethasone at anesthetic induction. Because of stable operating conditions, no one required conscious sedation throughout functional mapping and tumor resection. Although dexamethasone pretreatment reduced the incidence of intraoperative vomiting (P = 0.027), the number of patients who complained of nausea was comparable (P = 0.969). No adverse events related to vomiting occurred intraoperatively. Baseline blood glucose concentration did not differ between each group (P = 0.143), but the samples withdrawn before emergence (P = 0.018), during the awake period (P awake craniotomy cases. However, as even a small dose of dexamethasone increases the risk for hyperglycemia, antiemetic prophylaxis with dexamethasone should be administered after careful consideration. Monitoring of perioperative blood glucose concentration is also necessary.

Engineering intranasal mRNA vaccines to enhance lymph node trafficking and immune responses.

Science.gov (United States)

Li, Man; Li, You; Peng, Ke; Wang, Ying; Gong, Tao; Zhang, Zhirong; He, Qin; Sun, Xun

2017-12-01

Intranasal mRNA vaccination provides immediate immune protection against pandemic diseases. Recent studies have shown that diverse forms of polyethyleneimine (PEI) have potent mucosal adjuvant activity, which could significantly facilitate the delivery of intranasal mRNA vaccines. Nevertheless, optimizing the chemical structure of PEI to maximize its adjuvanticity and decrease its toxicity remains a challenge. Here we show that the chemical structure of PEI strongly influences how well nanocomplexes of PEI and mRNA migrate to the lymph nodes and elicit immune responses. Conjugating cyclodextrin (CD) with PEI600 or PEI2k yielded CP (CD-PEI) polymers with different CD/PEI ratios. We analyzed the delivery efficacy of CP600, CP2k, and PEI25k as intranasal mRNA vaccine carriers by evaluating the lymph nodes migration and immune responses. Among these polymers, CP2k/mRNA showed significantly higher in vitro transfection efficiency, stronger abilities to migrate to lymph nodes and stimulate dendritic cells maturation in vivo, which further led to potent humoral and cellular immune responses, and showed lower local and systemic toxicity than PEI25k/mRNA. These results demonstrate the potential of CD-PEI2k/mRNA nanocomplex as a self-adjuvanting vaccine delivery vehicle that traffics to lymph nodes with high efficiency. As we face outbreaks of pandemic diseases such as Zika virus, intranasal mRNA vaccination provides instant massive protection against highly variant viruses. Various polymer-based delivery systems have been successfully applied in intranasal vaccine delivery. However, the influence of molecular structure of the polymeric carriers on the lymph node trafficking and dendritic cell maturation is seldom studied for intranasal vaccination. Therefore, engineering polymer-based vaccine delivery system and elucidating the relationship between molecular structure and the intranasal delivery efficiency are essential for maximizing the immune responses. We hereby

Deposition of intranasal glucocorticoids--preliminary study.

Science.gov (United States)

Rapiejko, Piotr; Sosnowski, Tomasz R; Sova, Jarosław; Jurkiewicz, Dariusz

2015-01-01

Intranasal glucocorticoids are the treatment of choice in the therapy of rhinitis. The differences in efficiency of particular medications proven by therapeutic index may result from differences in composition of particular formulations as well as from diverse deposition in nasal cavities. Intranasal formulations of glucocorticoids differ in volume of a single dose in addition to variety in density, viscosity and dispenser nozzle structure. The aim of this report was to analyze the deposition of most often used intranasal glucocorticoids in the nasal cavity and assessment of the usefulness of a nose model from a 3D printer reflecting anatomical features of a concrete patient. Three newest and most often used in Poland intranasal glucocorticoids were chosen to analysis; mometasone furoate (MF), fluticasone propionate (FP) and fluticasone furoate (FF). Droplet size distribution obtained from the tested formulations was determined by use of a laser aerosol spectrometer Spraytec (Malvern Instruments, UK). The model of the nasal cavity was obtained using a 3D printer. The printout was based upon a tridimensional reconstruction of nasal cavity created on the basis of digital processing of computed tomography of paranasal sinuses. The deposition of examined medications was established by a method of visualization combined with image analysis using commercial substance which colored itself intensively under the influence of water being the dominant ingredient of all tested preparations. On the basis of obtained results regions of dominating deposition of droplets of intranasal medication on the wall and septum of the nasal cavity were compared. Droplet size of aerosol of tested intranasal medications typically lies within the range of 25-150 µm. All tested medications deposited mainly on the anterior part of inferior turbinate. FP preparation deposited also on the anterior part of the middle nasal turbinate, marginally embracing a fragment of the central part of this

Pediatric awake craniotomy and intra-operative stimulation mapping.

Science.gov (United States)

Balogun, James A; Khan, Osaama H; Taylor, Michael; Dirks, Peter; Der, Tara; Carter Snead Iii, O; Weiss, Shelly; Ochi, Ayako; Drake, James; Rutka, James T

2014-11-01

The indications for operating on lesions in or near areas of cortical eloquence balance the benefit of resection with the risk of permanent neurological deficit. In adults, awake craniotomy has become a versatile tool in tumor, epilepsy and functional neurosurgery, permitting intra-operative stimulation mapping particularly for language, sensory and motor cortical pathways. This allows for maximal tumor resection with considerable reduction in the risk of post-operative speech and motor deficits. We report our experience of awake craniotomy and cortical stimulation for epilepsy and supratentorial tumors located in and around eloquent areas in a pediatric population (n=10, five females). The presenting symptom was mainly seizures and all children had normal neurological examinations. Neuroimaging showed lesions in the left opercular (n=4) and precentral or peri-sylvian regions (n=6). Three right-sided and seven left-sided awake craniotomies were performed. Two patients had a history of prior craniotomy. All patients had intra-operative mapping for either speech or motor or both using cortical stimulation. The surgical goal for tumor patients was gross total resection, while for all epilepsy procedures, focal cortical resections were completed without any difficulty. None of the patients had permanent post-operative neurologic deficits. The patient with an epileptic focus over the speech area in the left frontal lobe had a mild word finding difficulty post-operatively but this improved progressively. Follow-up ranged from 6 to 27 months. Pediatric awake craniotomy with intra-operative mapping is a precise, safe and reliable method allowing for resection of lesions in eloquent areas. Further validations on larger number of patients will be needed to verify the utility of this technique in the pediatric population. Copyright © 2014 Elsevier Ltd. All rights reserved.

Entropy-guided use of a unique cocktail in awake craniotomy

Directory of Open Access Journals (Sweden)

Itee Chowdhury

2016-01-01

Full Text Available The major benefit of awake craniotomy is to enable a tailored resection that can theoretically maximize the extent of the tumor resection and can minimize the neurological damages. There is still no consensus as to the best anesthetic technique. We describe here a case report where a combination of propofol infusion and dexmedetomidine along with intermittent doses of fentanyl, and fentanyl patch was used with entropy monitoring to assess the depth of sedation in a patient for awake craniotomy.

Gene therapy prospects--intranasal delivery of therapeutic genes.

Science.gov (United States)

Podolska, Karolina; Stachurska, Anna; Hajdukiewicz, Karolina; Małecki, Maciej

2012-01-01

Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.

[A Case of Psychogenic Tremor during Awake Craniotomy].

Science.gov (United States)

Kujirai, Kazumasa; Kamata, Kotoe; Uno, Toshihiro; Hamada, Keiko; Ozaki, Makoto

2016-01-01

A 31-year-old woman with a left frontal and parietal brain tumor underwent awake craniotomy. Propofol/remifentanil general anesthesia was induced. Following craniotomy, anesthetic administrations ceased. The level of consciousness was sufficient and she was not agitated. However, the patient complained of nausea 70 minutes into the awake phase. Considering the adverse effects of antiemetics and the upcoming surgical strategy, we did not give any medications. Nausea disappeared spontaneously while the operation was suspended. When surgical intervention extended to the left caudate nucleus, involuntary movement, classified as a tremor, with 5-6 Hz frequency, abruptly occurred on her left forearm. The patient showed emotional distress. Tremor appeared on her right forearm and subsequently spread to her lower extremities. Intravenous midazolam and fentanyl could not reduce her psychological stress. Since the tremor disturbed microscopic observation, general anesthesia was induced. Consequently, the tremor disappeared and did not recur. Based on the anatomical ground and the medication status, her involuntary movement was diagnosed as psychogenic tremor. Various factors can induce involuntary movements. In fact, intraoperative management of nausea and vomiting takes priority during awake craniotomy, but we should be reminded that some antiemetics potentially induce involuntary movement that could be caused by surgery around basal ganglia.

Sleep bruxism, awake bruxism and sleep quality among Brazilian dental students: a cross-sectional study.

Science.gov (United States)

Serra-Negra, Júnia Maria; Scarpelli, Ana Carolina; Tirsa-Costa, Débora; Guimarães, Flávia Helena; Pordeus, Isabela Almeida; Paiva, Saul Martins

2014-01-01

The aim of the study was to evaluate the association of sleep bruxism, awake bruxism and sleep quality among dental students of the Federal University of Minas Gerais, Belo Horizonte, Brazil. A cross-sectional study was performed including 183 Brazilian dental students aged from 17 to 46 years old. The complete course curriculum consists of 9 semesters. Students enrolled in the first semester, the middle semester and the final semester of the course participated in the survey. The PSQI-BR (the Brazilian version of the Pittsburgh Sleep Questionnaire Index) was used for data collection. The PSQI-BR was distributed during lecture classes. Sleep bruxism and awake bruxism diagnosis was based on self-reported data. Descriptive analysis, Kruskal-Wallis, Mann-Whitney and Poisson regression with robust estimator were the statistical tests used. Sleep bruxism prevalence was 21.5% and awake bruxism prevalence was 36.5%. Sleep duration components were associated with sleep bruxism (PR=1.540; 95% CI: 1.00-2.37) and awake bruxism (PR=1.344; 95% CI: 1,008-1,790). There was an association between awake bruxism and habitual sleep efficiency component (PR=1.323; 95% CI: 1.03-1.70). Sleep disturbance component and awake bruxism were associated (PR=1.533; 95% CI: 1.03-2.27). Poor sleep quality was an important factor among dental students, who reported sleep bruxism as well as among those who presented awake bruxism.

"Imagine your neighbor mows the lawn": a pilot study of psychological sequelae due to awake craniotomy: clinical article.

Science.gov (United States)

Milian, Monika; Luerding, Ralf; Ploppa, Annette; Decker, Karlheinz; Psaras, Tsambika; Tatagiba, Marcos; Gharabaghi, Alireza; Feigl, Guenther C

2013-06-01

Although it has been reported that awake neurosurgical procedures are well tolerated, the long-term occurrence of general psychological sequelae has not yet been investigated. This study assessed the frequency and effects of psychological symptoms after an awake craniotomy on health-related quality of life (HRQOL). Sixteen patients undergoing an awake surgery were surveyed with a self-developed questionnaire, the Posttraumatic Stress Disorder Inventory For Awake Surgery Patients, which adopts the core components of the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) posttraumatic stress disorder (PTSD) criteria. The mean time between surgery and data collection was 97.3 ± 93.2 weeks. Health-related quality of life was assessed with the 36-Item Short Form Health Survey. Forty-four percent of the patients stated that they had experienced either repetitive distressing recollections or dreams related to the awake surgery, 18.8% stated persistent avoidance of stimuli associated with the awake surgery, and symptoms of increased arousal occurred in 62.5%. Two patients presented with postoperative psychological sequelae resembling PTSD symptoms. Younger age at surgery and female sex were risk factors for symptoms of increased arousal. The experience of intense anxiety during awake surgery appears to favor the development of postsurgical PTSD symptoms, while recurrent distressing recollections particularly affect HRQOL negatively. In many cases awake craniotomy is necessary to preserve language and motor function. However, in some cases awake craniotomy can lead to postoperative psychological sequelae resembling PTSD symptoms. Therefore, possible long-term effects of an awake surgery should be considered and discussed with the patient when planning this type of surgery.

Out-of-Body Experience During Awake Craniotomy.

Science.gov (United States)

Bos, Eelke M; Spoor, Jochem K H; Smits, Marion; Schouten, Joost W; Vincent, Arnaud J P E

2016-08-01

The out-of-body experience (OBE), during which a person feels as if he or she is spatially removed from the physical body, is a mystical phenomenon because of its association with near-death experiences. Literature implicates the cortex at the temporoparietal junction (TPJ) as the possible anatomic substrate for OBE. We present a patient who had an out-of-body experience during an awake craniotomy for resection of low-grade glioma. During surgery, stimulation of subcortical white matter in the left TPJ repetitively induced OBEs, in which the patient felt as if she was floating above the operating table looking down on herself. We repetitively induced OBE by subcortical stimulation near the left TPJ during awake craniotomy. Diffusion tensor imaging tractography implicated the posterior thalamic radiation as a possible substrate for autoscopic phenomena. Copyright © 2016 Elsevier Inc. All rights reserved.

Awake craniotomy in a developmentally delayed blind man with cognitive deficits.

Science.gov (United States)

Burbridge, Mark; Raazi, Mateen

2013-04-01

To describe the complex perioperative considerations and anesthetic management of a cognitively delayed blind adult male who underwent awake craniotomy to remove a left anterior temporal lobe epileptic focus. A 28-yr-old left-handed blind cognitively delayed man was scheduled for awake craniotomy to resect a left anterior temporal lobe epileptic focus due to intractable epilepsy despite multiple medications. His medical history was also significant for retinopathy of prematurity that rendered him legally blind in both eyes and an intracerebral hemorrhage shortly after birth that resulted in a chronic brain injury and developmental delay. His cognitive capacity was comparable with that of an eight year old. Since patient cooperation was the primary concern during the awake electrocorticography phase of surgery, careful assessment of the patient's ability to tolerate the procedure was undertaken. There was extensive planning between surgeons and anesthesiologists, and a patient-specific pharmacological strategy was devised to facilitate surgery. The operation proceeded without complication, the patient has remained seizure-free since the procedure, and his quality of life has improved dramatically. This case shows that careful patient assessment, effective interdisciplinary communication, and a carefully tailored anesthetic strategy can facilitate an awake craniotomy in a potentially uncooperative adult patient with diminished mental capacity and sensory deficits.

Beam studies and experimental facility for the AWAKE experiment at CERN

International Nuclear Information System (INIS)

Bracco, Chiara; Gschwendtner, Edda; Petrenko, Alexey; Timko, Helga; Argyropoulos, Theodoros; Bartosik, Hannes; Bohl, Thomas; Esteban Müller, Juan; Goddard, Brennan; Meddahi, Malika; Pardons, Ans; Shaposhnikova, Elena; Velotti, Francesco M.; Vincke, Helmut

2014-01-01

A Proton Driven Plasma Wakefield Acceleration Experiment has been proposed as an approach to eventually accelerate an electron beam to the TeV energy range in a single plasma section. To verify this novel technique, a proof of principle R and D experiment, AWAKE, is planned at CERN using 400 GeV proton bunches from the SPS. An electron beam will be injected into the plasma cell to probe the accelerating wakefield. The AWAKE experiment will be installed in the CNGS facility profiting from existing infrastructure where only minor modifications need to be foreseen. The design of the experimental area and the proton and electron beam lines are shown. The achievable SPS proton bunch properties and their reproducibility have been measured and are presented. - Highlights: • A proton driven plasma wakefield experiment using the first time protons as drive beam is proposed. • The integration of AWAKE experiment, the proton, laser and electron beam line in an existing CERN facility is demonstrated. • The necessary modifications in the experimental facility are presented. • Proton beam optics and a new electron beam line are adapted to match with the required beam parameters. • Short high-intensity bunches were studied in the SPS to guide the design parameters of the AWAKE project

Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes.

Directory of Open Access Journals (Sweden)

Rasmus Mortensen

Full Text Available Streptococcus pyogenes (group A streptococcus, GAS is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future vaccine against GAS, it is therefore important to investigate how protective immunity is related to the route of vaccine administration. To explore this, we examined whether a parenterally administered anti-GAS vaccine could protect against an intranasal GAS infection or if this would require locally primed immunity. We foundd that a parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently protected against an intraperitoneal GAS infection. However, the same vaccine administered via the intranasal route was able to induce protection against repeated intranasal GAS infections in a murine challenge model. The lack of intranasal protection induced by the parenteral vaccine correlated with a reduced mucosal recall response at the site of infection. Taken together, our results demonstrate that locally primed immunity is important for the defense against intranasal infection with Streptococcus pyogenes.

AWAKE, The Advanced Proton Driven Plasma Wakefield Acceleration Experiment at CERN

CERN Document Server

Gschwendtner, E.; Amorim, L.; Apsimon, R.; Assmann, R.; Bachmann, A.M.; Batsch, F.; Bauche, J.; Berglyd Olsen, V.K.; Bernardini, M.; Bingham, R.; Biskup, B.; Bohl, T.; Bracco, C.; Burrows, P.N.; Burt, G.; Buttenschon, B.; Butterworth, A.; Caldwell, A.; Cascella, M.; Chevallay, E.; Cipiccia, S.; Damerau, H.; Deacon, L.; Dirksen, P.; Doebert, S.; Dorda, U.; Farmer, J.; Fedosseev, V.; Feldbaumer, E.; Fiorito, R.; Fonseca, R.; Friebel, F.; Gorn, A.A.; Grulke, O.; Hansen, J.; Hessler, C.; Hofle, W.; Holloway, J.; Huther, M.; Jaroszynski, D.; Jensen, L.; Jolly, S.; Joulaei, A.; Kasim, M.; Keeble, F.; Li, Y.; Liu, S.; Lopes, N.; Lotov, K.V.; Mandry, S.; Martorelli, R.; Martyanov, M.; Mazzoni, S.; Mete, O.; Minakov, V.A.; Mitchell, J.; Moody, J.; Muggli, P.; Najmudin, Z.; Norreys, P.; Oz, E.; Pardons, A.; Pepitone, K.; Petrenko, A.; Plyushchev, G.; Pukhov, A.; Rieger, K.; Ruhl, H.; Salveter, F.; Savard, N.; Schmidt, J.; Seryi, A.; Shaposhnikova, E.; Sheng, Z.M.; Sherwood, P.; Silva, L.; Soby, L.; Sosedkin, A.P.; Spitsyn, R.I.; Trines, R.; Tuev, P.V.; Turner, M.; Verzilov, V.; Vieira, J.; Vincke, H.; Wei, Y.; Welsch, C.P.; Wing, M.; Xia, G.; Zhang, H.

2016-01-01

The Advanced Proton Driven Plasma Wakefield Acceleration Experiment (AWAKE) aims at studying plasma wakefield generation and electron acceleration driven by proton bunches. It is a proof-of-principle R&D experiment at CERN and the world's first proton driven plasma wakefield acceleration experiment. The AWAKE experiment will be installed in the former CNGS facility and uses the 400 GeV/c proton beam bunches from the SPS. The first experiments will focus on the self-modulation instability of the long (rms ~12 cm) proton bunch in the plasma. These experiments are planned for the end of 2016. Later, in 2017/2018, low energy (~15 MeV) electrons will be externally injected to sample the wakefields and be accelerated beyond 1 GeV. The main goals of the experiment will be summarized. A summary of the AWAKE design and construction status will be presented.

Anesthetic approach to high-risk patients and prolonged awake craniotomy using dexmedetomidine and scalp block.

Science.gov (United States)

Garavaglia, Marco M; Das, Sunit; Cusimano, Michael D; Crescini, Charmagne; Mazer, C David; Hare, Gregory M T; Rigamonti, Andrea

2014-07-01

Awake craniotomy with intraoperative speech or motor testing is relatively contraindicated in cases requiring prolonged operative times and in patients with severe medical comorbidities including anxiety, anticipated difficult airway, obesity, large tumors, and intracranial hypertension. The anesthetic management of neurosurgical patients who possess these contraindications but would be optimally treated by an awake procedure remains unclear. We describe a new anesthetic approach for awake craniotomy that did not require any airway manipulation, utilizing a bupivacaine-based scalp nerve block, and dexmedetomidine as the primary hypnotic-sedative agent. Using this technique, we provided optimal operative conditions to perform awake craniotomy facilitating safe tumor resection, while utilizing intraoperative electrocorticography for motor and speech mapping in a cohort of 10 patients at a high risk for airway compromise and complications associated with patient comorbidities. All patients underwent successful awake craniotomy, intraoperative mapping, and tumor resection with adequate sedation for up to 9 hours (median 3.5 h, range 3 to 9 h) without any loss of neurological function, airway competency, or the need to provide any active rescue airway management. We report 4 of these cases that highlight our experience: 1 case required prolonged surgery because of the complexity of tumor resection and 3 patients had important medical comorbidities and/or relative contraindication for an awake procedure. Dexmedetomidine, with concurrent scalp block, is an effective and safe anesthetic approach for awake craniotomy. Dexmedetomidine facilitates the extension procedure complexity and duration in patients who might traditionally not be considered to be candidates for this procedure.

Surgery-Independent Language Function Decline in Patients Undergoing Awake Craniotomy.

Science.gov (United States)

Gonen, Tal; Sela, Gal; Yanakee, Ranin; Ram, Zvi; Grossman, Rachel

2017-03-01

Despite selection process before awake-craniotomy, some patients experience an unexpected decline in language functions in the operating room (OR), compared with their baseline evaluation, which may impair their functional monitoring. To investigate this phenomenon we prospectively compared language function the day before surgery and on entrance to the OR. Data were collected prospectively from consecutive patients undergoing awake-craniotomy with intraoperative cortical mapping for resection of gliomas affecting language areas. Language functions of 79 patients were evaluated and compared 1-2 days before surgery and after entering the OR. Changes in functional linguistic performance were analyzed with respect to demographic, clinical, and pathologic characteristics. There was a significant decline in language function, beyond sedation effect, after entering the OR, (from median/interquartile range: 0.94/0.72-0.98 to median/interquartile range: 0.86/0.51-0.94; Z = -7.19, P awake-craniotomy may experience a substantial decline in language functioning after entering the OR. Tumor grade and the presence of preoperative language deficits were significant risk factors for this phenomenon, suggesting a possible relation between cognitive reserve, psychobehavioral coping abilities and histologic features of a tumor involving language areas. Capturing and identifying this unique population of patients who are prone to experience such language decline may improve our ability in the future to select patients eligible for awake-craniotomy. Copyright © 2016 Elsevier Inc. All rights reserved.

Design and Efficacy of Nanogels Formulations for Intranasal Administration

Directory of Open Access Journals (Sweden)

Blessing A. Aderibigbe

2018-05-01

Full Text Available Nanogels are drug delivery systems that can bypass the blood-brain barrier and deliver drugs to the desired site when administered intranasally. They have been used as a drug delivery platform for the management of brain diseases such as Alzheimer disease, migraine, schizophrenia and depression. nanogels have also been developed as vaccine carriers for the protection of bacterial infections such as influenza, meningitis, pneumonia and as veterinary vaccine carriers for the protection of animals from encephalomyelitis and mouth to foot disease. It has been developed as vaccine carriers for the prevention of lifestyle disease such as obesity. Intranasal administration of therapeutics using nanogels for the management of brain diseases revealed that the drug transportation was via the olfactory nerve pathway resulting in rapid drug delivery to the brain with excellent neuroprotective effect. The application of nanogels as vaccine carriers also induced significant responses associated with protective immunity against selected bacterial and viral infections. This review provides a detailed information on the enhanced therapeutic effects, mechanisms and biological efficacy of nanogels for intranasal administration.

[Successful airway management using i-gel in 7 patients undergoing awake craniotomy].

Science.gov (United States)

Matsunami, Katsuaki; Sanuki, Michiyoshi; Yasuuji, Masakazu; Nakanuno, Ryuichi; Kato, Takahiro; Kawamoto, Masashi

2014-07-01

In order to secure airway during awake craniotomy, we used i-gel to perform positive-pressure ventilation in 7 patients for their anesthetic management. During removal of a tumor around the motor speech center, anesthetic management including asleep-awake-asleep technique was applied for speech testing. The technique, insertion and re-insertion of i-gel, was needed and it was easy in all the patients. During positive-pressure ventilation, peak pressure, tidal volume both for inspiration and expiration, and endtidal-CO2 were not markedly altered. Leakage around i-gel, and its differences between inspiration and expiration were negligible, while the tidal volume was adequate. We conclude that i-gel is useful for anesthetic management for awake craniotomy procedure for both securing airway and ventilation.

[Awake craniotomy. Considerations in special situations].

Science.gov (United States)

Solera Ruiz, I; Uña Orejón, R; Valero, I; Laroche, F

2013-01-01

Awake craniotomy was the earliest surgical procedure known, and it has become fashionable again. In the past it was used for the surgical management of intractable epilepsy, but nowadays, its indications are increasing, and it is a widely recognized technique for the resection of mass lesions involving the eloquent cortex, and for deep brain stimulation. The procedure is safe, provides excellent results, and saves money and resources. The anesthesiologist should know the principles underlying neuroanesthesia, the technique of scalp blockade, and the sedation protocols, as well as feeling comfortable with advanced airway management. The main anesthetic aim is to keep patients cooperating when required (analgesia-based anesthesia). This review attempts to summarize the most recent evidence from the clinical literature, a long as the number of patients undergoing craniotomies in the awake state are increasing, specifically in the pediatric population. Copyright © 2011 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

The AWAKE Experimental Facility at CERN

CERN Document Server

Gschwendtner, E; Bracco, C; Butterworth, A; Cipiccia, S; Doebert, S; Fedosseev, V; Feldbaumer, E; Hessler, C; Hofle, W; Martyanov, M; Meddahi, M; Osborne, J; Pardons, A; Petrenko, A; Vincke, H

2014-01-01

AWAKE, an Advanced Wakefield Experiment is launched at CERN to verify the proton driven plasma wakefield acceleration concept. Proton bunches at 400 GeV/c will be extracted from the CERN SPS and sent along a 750 m long proton line to a plasma cell, a Rubidium vapour source, where the proton beam drives wakefields reaching accelerating gradients of several gigavolts per meter. A high power laser pulse will copropagate within the proton bunch creating the plasma by ionizing the (initially) neutral gas. An electron beam will be injected into the plasma cell to probe the accelerating wakefield. The AWAKE experiment will be installed in the CNGS facility. First proton beam to the plasma cell is expected by end 2016. The installation planning and the baseline parameters of the experiment are shown. The design of the experimental area and the integration of the new beam-lines as well as the experimental equipment are presented. The needed modifications of the infrastructure in the facility and a few challenges are h...

A new minimal-stress freely-moving rat model for preclinical studies on intranasal administration of CNS drugs.

Science.gov (United States)

Stevens, Jasper; Suidgeest, Ernst; van der Graaf, Piet Hein; Danhof, Meindert; de Lange, Elizabeth C M

2009-08-01

To develop a new minimal-stress model for intranasal administration in freely moving rats and to evaluate in this model the brain distribution of acetaminophen following intranasal versus intravenous administration. Male Wistar rats received one intranasal cannula, an intra-cerebral microdialysis probe, and two blood cannulas for drug administration and serial blood sampling respectively. To evaluate this novel model, the following experiments were conducted. 1) Evans Blue was administered to verify the selectivity of intranasal exposure. 2) During a 1 min infusion 10, 20, or 40 microl saline was administered intranasally or 250 microl intravenously. Corticosterone plasma concentrations over time were compared as biomarkers for stress. 3) 200 microg of the model drug acetaminophen was given in identical setup and plasma, and brain pharmacokinetics were determined. In 96% of the rats, only the targeted nasal cavity was deeply colored. Corticosterone plasma concentrations were not influenced, neither by route nor volume of administration. Pharmacokinetics of acetaminophen were identical after intravenous and intranasal administration, although the Cmax in microdialysates was reached a little earlier following intravenous administration. A new minimal-stress model for intranasal administration in freely moving rats has been successfully developed and allows direct comparison with intravenous administration.

Intranasal vaccine trial for canine infectious tracheobronchitis (kennel cough).

Science.gov (United States)

Glickman, L T; Appel, M J

1981-08-01

Two field trials were conducted during periods of endemic (summer) and epizootic (winter) canine infectious tracheobronchitis activity to evaluate the efficacy of three intranasal vaccines in a closed commercial beagle breeding kennel. A trivalent vaccine containing Bordetella bronchiseptica, canine parainfluenza, and canine adenovirus-2 was administered at 3 weeks of age. The vaccine was 71.2% and 81.8% effective in decreasing the incidence of coughing during the winter and summer trials, respectively. The number of deaths was lower in each of the vaccine groups than in the placebo groups. No adverse reactions were observed with any of the intranasal vaccines.

ROLE OF INTRANASAL STEROIDAL SPRAY IN SEASONAL ALLERGIC RHINITIS WITH OCULAR SYMPTOMS

Directory of Open Access Journals (Sweden)

Vineel Muppidi

2017-06-01

Full Text Available BACKGROUND The eye is especially susceptible to the symptoms of allergic rhinitis, itching (pruritus, tearing (epiphora and redness (erythema because it lacks a mechanical barrier that could prevent the deposition of allergens, such as pollen on the conjunctival surface. These ocular symptoms have been described as examples of the type 1 immediate hypersensitivity reaction. A number of recently published clinical studies apparently support the positive effect of intranasal steroidal sprays on ocular allergy symptoms. The aim of the study is to evaluate the role of intranasal steroids in relieving ocular symptoms in allergic rhinitis. MATERIALS AND METHODS 60 subjects who had seasonal allergic rhinitis with ocular symptoms came to Outpatient Department of Chalmeda Anand Rao Hospital in the year 2015-2016. Randomly, each intranasal steroid is given to 12 patients to a total of 60 patients for 4 weeks 2 puffs in each nostril twice daily and the clinical response is observed. RESULTS A subjective improvement in ocular symptoms was observed in 11 of the 12 patients treated with fluticasone furoate, 8 of 12 patients with fluticasone propionate, 7 of the 12 patients with mometasone furoate, 6 of the 12 patients with beclomethasone and 6 of the 12 patients with budesonide. CONCLUSION Intranasal corticosteroids, which are used for seasonal allergic rhinitis with ocular symptoms are effective in controlling of ocular symptoms. Among these, intranasal corticosteroids, which are used for allergic rhinitis, fluticasone furoate is more effective in relieving ocular symptoms in our study.

Anaesthetic Considerations of Awake Craniotomy: An Upcoming Entity

Directory of Open Access Journals (Sweden)

Jui Lagoo

2014-08-01

Full Text Available Awake craniotomy was historically advocated for resistant epilepsy surgery. Presently, its role has widened for resection of lesions abutting or invading the eloquent cortex. It aims at maximizing resection while minimizing neurological damage. Anaesthetic challenges include providing sufficient depth of anaesthesia, full cooperation and consciousness during cortical mapping, smooth transition between anaesthesia and consciousness, airway protection, haemodynamic stability, patient immobility and co-operation. Communication and co-operation between the patient and surgical and anaesthesia teams is vital. We report safe conduct of monitored anaesthesia care by the combined use of dexmedetomidine and scalp nerve blocks for tumour resection. This technique ensured haemodynamic stability, decreased stress response to painful stimuli and improved patient tolerance. As awake craniotomy is an upcoming technique, knowledge about anaesthetic implications, challenges and techniques will help in optimum management.

Music is Beneficial for Awake Craniotomy Patients: A Qualitative Study.

Science.gov (United States)

Jadavji-Mithani, Radhika; Venkatraghavan, Lashmi; Bernstein, Mark

2015-01-01

Patients undergoing awake craniotomy may experience high levels of stress. Minimizing anxiety benefits patients and surgeons. Music has many therapeutic effects in altering human mood and emotion. Tonality of music as conveyed by composition in major or minor keys can have an impact on patients' emotions and thoughts. Assessing the effects of listening to major and minor key musical pieces on patients undergoing awake craniotiomy could help in the design of interventions to alleviate anxiety, stress and tension. Twenty-nine patients who were undergoing awake craniotomy were recruited and randomly assigned into two groups: Group 1 subjects listened to major key music and Group 2 listened to minor key compositions. Subjects completed a demographics questionnaire, a pre- and post-operative Beck Anxiety Inventory (BAI) and a semi-structured open-ended interview. RESULTS were analyzed using modified thematic analysis through open and axial coding. Overall, patients enjoyed the music regardless of the key distinctions and stated they benefitted from listening to the music. No adverse reactions to the music were found. Subjects remarked that the music made them feel more at ease and less anxious before, during and after their procedure. Patients preferred either major key or minor key music but not a combination of both. Those who preferred major key pieces said it was on the basis of tonality while the individuals who selected minor key pieces stated that tempo of the music was the primary factor. Overall, listening to music selections was beneficial for the patients. Future work should further investigate the effects of audio interventions in awake surgery through narrative means.

Preparing to perform an awake fiberoptic intubation.

LENUS (Irish Health Repository)

Walsh, M E

2012-02-03

Fiberoptically guided tracheal intubation represents one of the most important advances in airway management to occur in the past thirty years. Perhaps its most important role is in management of the anticipated difficult airway. This is a situation in which the dangers of encountering the life-threatening "can\\'t intubate, can\\'t ventilate" situation can be avoided by placement of an endotracheal tube while the patient is awake. Although skill at the procedure of endoscopy is obviously necessary in this setting, these authors hold that success or failure of the technique frequently depends on the adequacy of preparation. These measures include 1) pre-operative assessment of the patient; 2) careful explanation of what lies in store; 3) "setting the stage"; 4) preparing the equipment to be used; and 5) preparing the patient (antisialogue, sedation, application of topical anesthesia to the upper airway). If these preparatory measures are carried out meticulously, the likelihood of performing a successful and comfortable awake fiberoptic tracheal intubation is greatly increased.

Voluntary running enhances glymphatic influx in awake behaving, young mice

DEFF Research Database (Denmark)

von Holstein-Rathlou, Stephanie; Petersen, Nicolas Caesar; Nedergaard, Maiken

2018-01-01

that exercise would also stimulate glymphatic activity in awake, young mice with higher baseline glymphatic function. Therefore, we assessed glymphatic function in young female C57BL/6J mice following five weeks voluntary wheel running and in sedentary mice. The active mice ran a mean distance of 6km daily. We...... of the cortex, but also in the middle cerebral artery territory. While glymphatic activity was higher under ketamine/xylazine anesthesia, we saw a decrease in glymphatic function during running in awake mice after five weeks of wheel running. In summary, daily running increases CSF flux in widespread areas...

Intranasal immunization with protective antigen of Bacillus anthracis induces a long-term immunological memory response.

Science.gov (United States)

Woo, Sun-Je; Kang, Seok-Seong; Park, Sung-Moo; Yang, Jae Seung; Song, Man Ki; Yun, Cheol-Heui; Han, Seung Hyun

2015-10-01

Although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. Here, we investigated whether intranasal immunization with recombinant protective antigen (rPA) of Bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. Intranasal immunization with rPA plus cholera toxin (CT) sustained PA-specific antibody responses for 6 months in lung, nasal washes, and vaginal washes as well as serum. A significant induction of PA-specific memory B cells was observed in spleen, cervical lymph nodes (CLNs) and lung after booster immunization. Furthermore, intranasal immunization with rPA plus CT remarkably generated effector memory CD4(+) T cells in the lung. PA-specific CD4(+) T cells preferentially increased the expression of Th1- and Th17-type cytokines in lung, but not in spleen or CLNs. Collectively, the intranasal immunization with rPA plus CT promoted immunologic memory responses in the mucosal and systemic compartments, providing long-term immunity. Copyright © 2015 Elsevier Ltd. All rights reserved.

New opportunities in glioma therapy - awake craniotomy

Directory of Open Access Journals (Sweden)

Maria Golebiowska

2017-09-01

Study reveals the growing importance of awake surgery with simultaneous necessity for new pre-operative technologies, which can support the greater outcomes of the surgeries. Apart from that, the concerns of the ethical matter can be withdrawn if the valid algorythms and guidelines are applied for this procedure.

Inflammatory Profile of Awake Function-Controlled Craniotomy and Craniotomy under General Anesthesia

Science.gov (United States)

Klimek, Markus; Hol, Jaap W.; Wens, Stephan; Heijmans-Antonissen, Claudia; Niehof, Sjoerd; Vincent, Arnaud J.; Klein, Jan; Zijlstra, Freek J.

2009-01-01

Background. Surgical stress triggers an inflammatory response and releases mediators into human plasma such as interleukins (ILs). Awake craniotomy and craniotomy performed under general anesthesia may be associated with different levels of stress. Our aim was to investigate whether those procedures cause different inflammatory responses. Methods. Twenty patients undergoing craniotomy under general anesthesia and 20 patients undergoing awake function-controlled craniotomy were included in this prospective, observational, two-armed study. Circulating levels of IL-6, IL-8, and IL-10 were determined pre-, peri-, and postoperatively in both patient groups. VAS scores for pain, anxiety, and stress were taken at four moments pre- and postoperatively to evaluate physical pain and mental duress. Results. Plasma IL-6 level significantly increased with time similarly in both groups. No significant plasma IL-8 and IL-10 change was observed in both experimental groups. The VAS pain score was significantly lower in the awake group compared to the anesthesia group at 12 hours postoperative. Postoperative anxiety and stress declined similarly in both groups. Conclusion. This study suggests that awake function-controlled craniotomy does not cause a significantly different inflammatory response than craniotomy performed under general anesthesia. It is also likely that function-controlled craniotomy does not cause a greater emotional challenge than tumor resection under general anesthesia. PMID:19536349

Cilioretinal artery occlusion following intranasal cocaine insufflations

Directory of Open Access Journals (Sweden)

Balaji Kannan

2011-01-01

Full Text Available Cocaine is used to produce a euphoric effect by abusers, who may be unaware of the devastating systemic and ocular side effects of this drug. We describe the first known case of cilioretinal artery occlusion after intranasal cocaine abuse.

Rapid DNA vaccination against Burkholderia pseudomallei flagellin by tattoo or intranasal application.

Science.gov (United States)

Lankelma, Jacqueline M; Wagemakers, Alex; Birnie, Emma; Haak, Bastiaan W; Trentelman, Jos J A; Weehuizen, Tassili A F; Ersöz, Jasmin; Roelofs, Joris J T H; Hovius, Joppe W; Wiersinga, W Joost; Bins, Adriaan D

2017-11-17

Melioidosis is a severe infectious disease with a high mortality that is endemic in South-East Asia and Northern Australia. The causative pathogen, Burkholderia pseudomallei, is listed as potential bioterror weapon due to its high virulence and potential for easy dissemination. Currently, there is no licensed vaccine for prevention of melioidosis. Here, we explore the use of rapid plasmid DNA vaccination against B. pseudomallei flagellin for protection against respiratory challenge. We tested three flagellin DNA vaccines with different subcellular targeting designs. C57BL/6 mice were vaccinated via skin tattoo on day 0, 3 and 6 before intranasal challenge with B. pseudomallei on day 21. Next, the most effective construct was used as single vaccination on day 0 by tattoo or intranasal formulation. Mice were sacrificed 72 hours post-challenge to assess bacterial loads, cytokine responses, inflammation and microscopic lesions. A construct encoding a cellular secretion signal resulted in the most effective protection against melioidosis via tattooing, with a 10-fold reduction in bacterial loads in lungs and distant organs compared to the empty vector. Strikingly, a single intranasal administration of the same vaccine resulted in >1000-fold lower bacterial loads and increased survival. Pro-inflammatory cytokine responses were significantly diminished and strong reductions in markers for distant organ damage were observed. A rapid vaccination scheme using flagellin DNA tattoo provides significant protection against intranasal challenge with B. pseudomallei, markedly improved by a single administration via airway mucosa. Hence intranasal vaccination with flagellin-encoding DNA may be applicable when acute mass vaccination is indicated and warrants further testing.

Reduced phosphorylation of brain insulin receptor substrate and Akt proteins in apolipoprotein-E4 targeted replacement mice.

Science.gov (United States)

Ong, Qi-Rui; Chan, Elizabeth S; Lim, Mei-Li; Cole, Gregory M; Wong, Boon-Seng

2014-01-17

Human ApoE4 accelerates memory decline in ageing and in Alzheimer's disease. Although intranasal insulin can improve cognition, this has little effect in ApoE4 subjects. To understand this ApoE genotype-dependent effect, we examined brain insulin signaling in huApoE3 and huApoE4 targeted replacement (TR) mice. At 32 weeks, lower insulin receptor substrate 1 (IRS1) at S636/639 and Akt phosphorylation at T308 were detected in fasting huApoE4 TR mice as compared to fasting huApoE3 TR mice. These changes in fasting huApoE4 TR mice were linked to lower brain glucose content and have no effect on plasma glucose level. However, at 72 weeks of age, these early changes were accompanied by reduction in IRS2 expression, IRS1 phosphorylation at Y608, Akt phosphorylation at S473, and MAPK (p38 and p44/42) activation in the fasting huApoE4 TR mice. The lower brain glucose was significantly associated with higher brain insulin in the aged huApoE4 TR mice. These results show that ApoE4 reduces brain insulin signaling and glucose level leading to higher insulin content.

Enclosure for small animals during awake animal imaging

Science.gov (United States)

Goddard, Jr., James S

2013-11-26

An enclosure or burrow restrains an awake animal during an imaging procedure. A tubular body, made from a radiolucent material that does not attenuate x-rays or gamma rays, accepts an awake animal. A proximal end of the body includes an attachment surface that corresponds to an attachment surface of an optically transparent and optically uniform window. An anti-reflective coating may be applied to an inner surface, an outer surface, or both surfaces of the window. Since the window is a separate element of the enclosure and it is not integrally formed as part of the body, it can be made with optically uniform thickness properties for improved motion tracking of markers on the animal with a camera during the imaging procedure. The motion tracking information is then used to compensate for animal movement in the image.

Use of intranasal fentanyl in children undergoing myringotomy and tube placement during halothane and sevoflurane anesthesia.

Science.gov (United States)

Galinkin, J L; Fazi, L M; Cuy, R M; Chiavacci, R M; Kurth, C D; Shah, U K; Jacobs, I N; Watcha, M F

2000-12-01

Many children are restless, disoriented, and inconsolable immediately after bilateral myringotomy and tympanosotomy tube placement (BMT). Rapid emergence from sevoflurane anesthesia and postoperative pain may increase emergence agitation. The authors first determined serum fentanyl concentrations in a two-phase study of intranasal fentanyl. The second phase was a prospective, placebo-controlled, double-blind study to determine the efficacy of intranasal fentanyl in reducing emergence agitation after sevoflurane or halothane anesthesia. In phase 1, 26 children with American Society of Anesthesiologists (ASA) physical status I or II who were scheduled for BMT received intranasal fentanyl, 2 microg/kg, during a standardized anesthetic. Serum fentanyl concentrations in blood samples drawn at emergence and at postanesthesia care unit (PACU) discharge were determined by radioimmunoassay. In phase 2, 265 children with ASA physical status I or II were randomized to receive sevoflurane or halothane anesthesia along with either intranasal fentanyl (2 microg/kg) or saline. Postoperative agitation, Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores, and satisfaction of PACU nurses and parents with the anesthetic technique were evaluated. In phase 1, the mean fentanyl concentrations at 10 +/- 4 min (mean +/- SD) and 34 +/- 9 min after administering intranasal fentanyl were 0.80 +/- 0.28 and 0.64 +/- 0.25 ng/ml, respectively. In phase 2, the incidence of severe agitation, highest CHEOPS scores, and heart rate in the PACU were decreased with intranasal fentanyl. There were no differences between sevoflurane and halothane in these measures and in times to hospital discharge. The incidence of postoperative vomiting, hypoxemia, and slow respiratory rates were not increased with fentanyl. Serum fentanyl concentrations after intranasal administration exceed the minimum effective steady state concentration for analgesia in adults. The use of intranasal fentanyl during

Fluticasone furoate: A new intranasal corticosteroid

Directory of Open Access Journals (Sweden)

R Kumar

2012-01-01

Full Text Available Intranasal corticosteroids are recommended as one of the first-line therapies for the treatment of allergic rhinitis (AR, especially when associated with nasal congestion and recurrent symptoms. Fluticasone furoate is a novel enhanced-affinity glucocorticoid for the treatment of AR approved by the Food and Drug Administration in 2007 and recently introduced in India. Fluticasone furoate nasal spray is indicated for the treatment of the symptoms of seasonal and perennial AR in patients aged two years and older. This review summarizes the clinical data on fluticasone furoate nasal spray and discusses its role in the management of AR. Important attributes of fluticasone furoate include low systemic bioavailability (<0.5%, 24-h symptom relief with once-daily dosing, comprehensive coverage of both nasal and ocular symptoms, safety and tolerability with daily use, and availability in a side-actuated device that makes medication delivery simple and consistent. With these properties, fluticasone furoate nasal spray has the potential to enhance patient satisfaction and compliance, thus making it a good choice amongst available intranasal steroids.

AWAKE CRANIOTOMY USING DEXMEDETOMIDINE INFUSION AND SCALP BLOCK: OUR EXPERIENCE IN SERIES OF CASES

Directory of Open Access Journals (Sweden)

MSSV Prasad

2015-11-01

Full Text Available BACKGROUND: Awake craniotomy for removal of intracranial tumors is most challenging procedure. The critical aspect of awake craniotomy is to maintain adequate analgesia and sedation, hemodynamic stability, airway safety, while keeping the patient immobile for duration of surgery, cooperative for neurological testing. AIM OF THE STUDY: Dexmedetomidine is good analgesic, sedative and has anaesthetic-sparing properties without causing significant respiratory depression. [1] We are reporting cases series of awake craniotomy under monitored anesthesia care using dexmedetomidine infusion as an adjuvant to scalp block, titrating the sedation level by BIS monitoring. MATERIALS AND METHODS: after careful patient selection and psychological preparation Monitored Anesthesia care(MAC was provided by continuous infusion of Dexmedetomidine at a rate of 0.2-0.5 mcg/kg/min titrating sedation level to a BIS value of 70-90%. Bilateral scalp block was administered using 0.5% bupivacaine. For dura mater incision, a pad with 2% lidocaine was applied for 3 minutes. The tumor removal was complete with no neurological deficiency. All the patients were discharged on 5th postoperative day without complications and with full patient satisfaction. CONCLUSION: We conclude that monitored anesthesia care with dexmedetomidine infusion and scalp block for awake craniotomy is a safe and efficacious. Absence of complications and high patient satisfaction score makes this technique close to an ideal technique for awake craniotomy.

Anaesthesia Management for Awake Craniotomy: Systematic Review and Meta-Analysis.

Science.gov (United States)

Stevanovic, Ana; Rossaint, Rolf; Veldeman, Michael; Bilotta, Federico; Coburn, Mark

2016-01-01

Awake craniotomy (AC) renders an expanded role in functional neurosurgery. Yet, evidence for optimal anaesthesia management remains limited. We aimed to summarise the latest clinical evidence of AC anaesthesia management and explore the relationship of AC failures on the used anaesthesia techniques. Two authors performed independently a systematic search of English articles in PubMed and EMBASE database 1/2007-12/2015. Search included randomised controlled trials (RCTs), observational trials, and case reports (n>4 cases), which reported anaesthetic approach for AC and at least one of our pre-specified outcomes: intraoperative seizures, hypoxia, arterial hypertension, nausea and vomiting, neurological dysfunction, conversion into general anaesthesia and failure of AC. Random effects meta-analysis was used to estimate event rates for four outcomes. Relationship with anaesthesia technique was explored using logistic meta-regression, calculating the odds ratios (OR) and 95% confidence intervals [95%CI]. We have included forty-seven studies. Eighteen reported asleep-awake-asleep technique (SAS), twenty-seven monitored anaesthesia care (MAC), one reported both and one used the awake-awake-awake technique (AAA). Proportions of AC failures, intraoperative seizures, new neurological dysfunction and conversion into general anaesthesia (GA) were 2% [95%CI:1-3], 8% [95%CI:6-11], 17% [95%CI:12-23] and 2% [95%CI:2-3], respectively. Meta-regression of SAS and MAC technique did not reveal any relevant differences between outcomes explained by the technique, except for conversion into GA. Estimated OR comparing SAS to MAC for AC failures was 0.98 [95%CI:0.36-2.69], 1.01 [95%CI:0.52-1.88] for seizures, 1.66 [95%CI:1.35-3.70] for new neurological dysfunction and 2.17 [95%CI:1.22-3.85] for conversion into GA. The latter result has to be interpreted cautiously. It is based on one retrospective high-risk of bias study and significance was abolished in a sensitivity analysis of only

Anaesthesia Management for Awake Craniotomy: Systematic Review and Meta-Analysis.

Directory of Open Access Journals (Sweden)

Ana Stevanovic

Full Text Available Awake craniotomy (AC renders an expanded role in functional neurosurgery. Yet, evidence for optimal anaesthesia management remains limited. We aimed to summarise the latest clinical evidence of AC anaesthesia management and explore the relationship of AC failures on the used anaesthesia techniques.Two authors performed independently a systematic search of English articles in PubMed and EMBASE database 1/2007-12/2015. Search included randomised controlled trials (RCTs, observational trials, and case reports (n>4 cases, which reported anaesthetic approach for AC and at least one of our pre-specified outcomes: intraoperative seizures, hypoxia, arterial hypertension, nausea and vomiting, neurological dysfunction, conversion into general anaesthesia and failure of AC. Random effects meta-analysis was used to estimate event rates for four outcomes. Relationship with anaesthesia technique was explored using logistic meta-regression, calculating the odds ratios (OR and 95% confidence intervals [95%CI].We have included forty-seven studies. Eighteen reported asleep-awake-asleep technique (SAS, twenty-seven monitored anaesthesia care (MAC, one reported both and one used the awake-awake-awake technique (AAA. Proportions of AC failures, intraoperative seizures, new neurological dysfunction and conversion into general anaesthesia (GA were 2% [95%CI:1-3], 8% [95%CI:6-11], 17% [95%CI:12-23] and 2% [95%CI:2-3], respectively. Meta-regression of SAS and MAC technique did not reveal any relevant differences between outcomes explained by the technique, except for conversion into GA. Estimated OR comparing SAS to MAC for AC failures was 0.98 [95%CI:0.36-2.69], 1.01 [95%CI:0.52-1.88] for seizures, 1.66 [95%CI:1.35-3.70] for new neurological dysfunction and 2.17 [95%CI:1.22-3.85] for conversion into GA. The latter result has to be interpreted cautiously. It is based on one retrospective high-risk of bias study and significance was abolished in a sensitivity analysis of

CSF and blood oxytocin concentration changes following intranasal delivery in macaque.

Directory of Open Access Journals (Sweden)

Olga Dal Monte

Full Text Available Oxytocin (OT in the central nervous system (CNS influences social cognition and behavior, making it a candidate for treating clinical disorders such as schizophrenia and autism. Intranasal administration has been proposed as a possible route of delivery to the CNS for molecules like OT. While intranasal administration of OT influences social cognition and behavior, it is not well established whether this is an effective means for delivering OT to CNS targets. We administered OT or its vehicle (saline to 15 primates (Macaca mulatta, using either intranasal spray or a nebulizer, and measured OT concentration changes in the cerebral spinal fluid (CSF and in blood. All subjects received both delivery methods and both drug conditions. Baseline samples of blood and CSF were taken immediately before drug administration. Blood was collected every 10 minutes after administration for 40 minutes and CSF was collected once post-delivery, at the 40 minutes time point. We found that intranasal administration of exogenous OT increased concentrations in both CSF and plasma compared to saline. Both delivery methods resulted in similar elevations of OT concentration in CSF, while the changes in plasma OT concentration were greater after nasal spray compared to nebulizer. In conclusion our study provides evidence that both nebulizer and nasal spray OT administration can elevate CSF OT levels.

Salivary Oxytocin Concentrations in Males following Intranasal Administration of Oxytocin: A Double-Blind, Cross-Over Study.

Science.gov (United States)

Daughters, Katie; Manstead, Antony S R; Hubble, Kelly; Rees, Aled; Thapar, Anita; van Goozen, Stephanie H M

2015-01-01

The use of intranasal oxytocin (OT) in research has become increasingly important over the past decade. Although researchers have acknowledged a need for further investigation of the physiological effects of intranasal administration, few studies have actually done so. In the present double-blind cross-over study we investigated the longevity of a single 24 IU dose of intranasal OT measured in saliva in 40 healthy adult males. Salivary OT concentrations were significantly higher in the OT condition, compared to placebo. This significant difference lasted until the end of testing, approximately 108 minutes after administration, and peaked at 30 minutes. Results showed significant individual differences in response to intranasal OT administration. To our knowledge this is the largest and first all-male within-subjects design study to demonstrate the impact of intranasal OT on salivary OT concentrations. The results are consistent with previous research in suggesting that salivary OT is a valid matrix for OT measurement. The results also suggest that the post-administration 'wait-time' prior to starting experimental tasks could be reduced to 30 minutes, from the 45 minutes typically used, thereby enabling testing during peak OT concentrations. Further research is needed to ascertain whether OT concentrations after intranasal administration follow similar patterns in females, and different age groups.

Salivary Oxytocin Concentrations in Males following Intranasal Administration of Oxytocin: A Double-Blind, Cross-Over Study.

Directory of Open Access Journals (Sweden)

Katie Daughters

Full Text Available The use of intranasal oxytocin (OT in research has become increasingly important over the past decade. Although researchers have acknowledged a need for further investigation of the physiological effects of intranasal administration, few studies have actually done so. In the present double-blind cross-over study we investigated the longevity of a single 24 IU dose of intranasal OT measured in saliva in 40 healthy adult males. Salivary OT concentrations were significantly higher in the OT condition, compared to placebo. This significant difference lasted until the end of testing, approximately 108 minutes after administration, and peaked at 30 minutes. Results showed significant individual differences in response to intranasal OT administration. To our knowledge this is the largest and first all-male within-subjects design study to demonstrate the impact of intranasal OT on salivary OT concentrations. The results are consistent with previous research in suggesting that salivary OT is a valid matrix for OT measurement. The results also suggest that the post-administration 'wait-time' prior to starting experimental tasks could be reduced to 30 minutes, from the 45 minutes typically used, thereby enabling testing during peak OT concentrations. Further research is needed to ascertain whether OT concentrations after intranasal administration follow similar patterns in females, and different age groups.

Intranasal and sublingual delivery of inactivated polio vaccine.

Science.gov (United States)

Kraan, Heleen; Soema, Peter; Amorij, Jean-Pierre; Kersten, Gideon

2017-05-09

Polio is on the brink of eradication. Improved inactivated polio vaccines (IPV) are needed towards complete eradication and for the use in the period thereafter. Vaccination via mucosal surfaces has important potential advantages over intramuscular injection using conventional needle and syringe, the currently used delivery method for IPV. One of them is the ability to induce both serum and mucosal immune responses: the latter may provide protection at the port of virus entry. The current study evaluated the possibilities of polio vaccination via mucosal surfaces using IPV based on attenuated Sabin strains. Mice received three immunizations with trivalent sIPV via intramuscular injection, or via the intranasal or sublingual route. The need of an adjuvant for the mucosal routes was investigated as well, by testing sIPV in combination with the mucosal adjuvant cholera toxin. Both intranasal and sublingual sIPV immunization induced systemic polio-specific serum IgG in mice that were functional as measured by poliovirus neutralization. Intranasal administration of sIPV plus adjuvant induced significant higher systemic poliovirus type 3 neutralizing antibody titers than sIPV delivered via the intramuscular route. Moreover, mucosal sIPV delivery elicited polio-specific IgA titers at different mucosal sites (IgA in saliva, fecal extracts and intestinal tissue) and IgA-producing B-cells in the spleen, where conventional intramuscular vaccination was unable to do so. However, it is likely that a mucosal adjuvant is required for sublingual vaccination. Further research on polio vaccination via sublingual mucosal route should include the search for safe and effective adjuvants, and the development of novel oral dosage forms that improve antigen uptake by oral mucosa, thereby increasing vaccine immunogenicity. This study indicates that both the intranasal and sublingual routes might be valuable approaches for use in routine vaccination or outbreak control in the period after

Tumor location and IDH1 mutation may predict intraoperative seizures during awake craniotomy.

Science.gov (United States)

Gonen, Tal; Grossman, Rachel; Sitt, Razi; Nossek, Erez; Yanaki, Raneen; Cagnano, Emanuela; Korn, Akiva; Hayat, Daniel; Ram, Zvi

2014-11-01

Intraoperative seizures during awake craniotomy may interfere with patients' ability to cooperate throughout the procedure, and it may affect their outcome. The authors have assessed the occurrence of intraoperative seizures during awake craniotomy in regard to tumor location and the isocitrate dehydrogenase 1 (IDH1) status of the tumor. Data were collected in 137 consecutive patients who underwent awake craniotomy for removal of a brain tumor. The authors performed a retrospective analysis of the incidence of seizures based on the tumor location and its IDH1 mutation status, and then compared the groups for clinical variables and surgical outcome parameters. Tumor location was strongly associated with the occurrence of intraoperative seizures. Eleven patients (73%) with tumor located in the supplementary motor area (SMA) experienced intraoperative seizures, compared with 17 (13.9%) with tumors in the other three non-SMA brain regions (p awake craniotomy compared with patients who have a tumor in non-SMA frontal areas and other brain regions. The IDH1 mutation was more common in SMA region tumors compared with other brain regions, and may be an additional risk factor for the occurrence of intraoperative seizures.

Awake craniotomy induces fewer changes in the plasma amino acid profile than craniotomy under general anesthesia.

Science.gov (United States)

Hol, Jaap W; Klimek, Markus; van der Heide-Mulder, Marieke; Stronks, Dirk; Vincent, Arnoud J; Klein, Jan; Zijlstra, Freek J; Fekkes, Durk

2009-04-01

In this prospective, observational, 2-armed study, we compared the plasma amino acid profiles of patients undergoing awake craniotomy to those undergoing craniotomy under general anesthesia. Both experimental groups were also compared with a healthy, age-matched and sex-matched reference group not undergoing surgery. It is our intention to investigate whether plasma amino acid levels provide information about physical and emotional stress, as well as pain during awake craniotomy versus craniotomy under general anesthesia. Both experimental groups received preoperative, perioperative, and postoperative dexamethasone. The plasma levels of 20 amino acids were determined preoperative, perioperative, and postoperatively in all groups and were correlated with subjective markers for pain, stress, and anxiety. In both craniotomy groups, preoperative levels of tryptophan and valine were significantly decreased whereas glutamate, alanine, and arginine were significantly increased relative to the reference group. Throughout time, tryptophan levels were significantly lower in the general anesthesia group versus the awake craniotomy group. The general anesthesia group had a significantly higher phenylalanine/tyrosine ratio, which may suggest higher oxidative stress, than the awake group throughout time. Between experimental groups, a significant increase in large neutral amino acids was found postoperatively in awake craniotomy patients, pain was also less and recovery was faster. A significant difference in mean hospitalization time was also found, with awake craniotomy patients leaving after 4.53+/-2.12 days and general anesthesia patients after 6.17+/-1.62 days; P=0.012. This study demonstrates that awake craniotomy is likely to be physically and emotionally less stressful than general anesthesia and that amino acid profiling holds promise for monitoring postoperative pain and recovery.

Clinical outcomes of asleep vs awake deep brain stimulation for Parkinson disease.

Science.gov (United States)

Brodsky, Matthew A; Anderson, Shannon; Murchison, Charles; Seier, Mara; Wilhelm, Jennifer; Vederman, Aaron; Burchiel, Kim J

2017-11-07

To compare motor and nonmotor outcomes at 6 months of asleep deep brain stimulation (DBS) for Parkinson disease (PD) using intraoperative imaging guidance to confirm electrode placement vs awake DBS using microelectrode recording to confirm electrode placement. DBS candidates with PD referred to Oregon Health & Science University underwent asleep DBS with imaging guidance. Six-month outcomes were compared to those of patients who previously underwent awake DBS by the same surgeon and center. Assessments included an "off"-levodopa Unified Parkinson's Disease Rating Scale (UPDRS) II and III, the 39-item Parkinson's Disease Questionnaire, motor diaries, and speech fluency. Thirty participants underwent asleep DBS and 39 underwent awake DBS. No difference was observed in improvement of UPDRS III (+14.8 ± 8.9 vs +17.6 ± 12.3 points, p = 0.19) or UPDRS II (+9.3 ± 2.7 vs +7.4 ± 5.8 points, p = 0.16). Improvement in "on" time without dyskinesia was superior in asleep DBS (+6.4 ± 3.0 h/d vs +1.7 ± 1.2 h/d, p = 0.002). Quality of life scores improved in both groups (+18.8 ± 9.4 in awake, +8.9 ± 11.5 in asleep). Improvement in summary index ( p = 0.004) and subscores for cognition ( p = 0.011) and communication ( p < 0.001) were superior in asleep DBS. Speech outcomes were superior in asleep DBS, both in category (+2.77 ± 4.3 points vs -6.31 ± 9.7 points ( p = 0.0012) and phonemic fluency (+1.0 ± 8.2 points vs -5.5 ± 9.6 points, p = 0.038). Asleep DBS for PD improved motor outcomes over 6 months on par with or better than awake DBS, was superior with regard to speech fluency and quality of life, and should be an option considered for all patients who are candidates for this treatment. NCT01703598. This study provides Class III evidence that for patients with PD undergoing DBS, asleep intraoperative CT imaging-guided implantation is not significantly different from awake microelectrode recording-guided implantation in improving motor outcomes at 6 months. © 2017

Pharmaceutical Product Development: Intranasal Scopolamine (INSCOP) Metered Dose Spray

Science.gov (United States)

Putcha, Lakshmi; Crady, Camille; Putcha, Lakshmi

2012-01-01

Motion sickness (MS) has been a problem associated with space flight, the modern military and commercial air and water transportation for many years. Clinical studies have shown that scopolamine is the most effective medication for the prevention of motion sickness (Dornhoffer et al, 2004); however, the two most common methods of administration (transdermal and oral) have performance limitations that compromise its utility. Intranasal administration offers a noninvasive treatment modality, and has been shown to counter many of the problems associated with oral and transdermal administration. With the elimination of the first pass effect by the liver, intranasal delivery achieves higher and more reliable bioavailability than an equivalent oral dose. This allows for the potential of enhanced efficacy at a reduced dose, thus minimizing the occurrence of untoward side effects. An Intranasal scopolamine (INSCOP) gel formulation was prepared and tested in four ground-based clinical trials under an active Investigational New Drug (IND) application with the Food and Drug Administration (FDA). Although there were early indicators that the intranasal gel formulation was effective, there were aspects of formulation viscosity and the delivery system that were less desirable. The INSCOP gel formulation has since been reformulated into an aqueous spray dosage form packaged in a precise, metered dose delivery system; thereby enhancing dose uniformity, increased user satisfaction and palatability, and a potentially more rapid onset of action. Recent reports of new therapeutic indications for scopolamine has prompted a wide spread interest in new scopolamine dosage forms. The novel dosage form and delivery system of INSCOP spray shows promise as an effective treatment for motion sickness targeted at the armed forces, spaceflight, and commercial sea, air, and space travel markets, as well as prospective psychotherapy for mental and emotional disorders.

Technical Aspects of Awake Craniotomy with Mapping for Brain Tumors in a Limited Resource Setting.

Science.gov (United States)

Leal, Rafael Teixeira Magalhaes; Barcellos, Bruno Mendonça; Landeiro, Jose Alberto

2018-05-01

Brain tumor surgery near or within eloquent regions is increasingly common and is associated with a high risk of neurologic injury. Awake craniotomy with mapping has been shown to be a valid method to preserve neurologic function and increase the extent of resection. However, the technique used varies greatly among centers. Most count on professionals such as neuropsychologists, speech therapists, neurophysiologists, or neurologists to help in intraoperative patient evaluation. We describe our technique with the sole participation of neurosurgeons and anesthesiologists. A retrospective review of 19 patients who underwent awake craniotomies for brain tumors between January 2013 and February 2017 at a tertiary university hospital was performed. We sought to identify and describe the most critical stages involved in this surgery as well as show the complications associated with our technique. Preoperative preparation, positioning, anesthesia, brain mapping, resection, and management of seizures and pain were stages deemed relevant to the accomplishment of an awake craniotomy. Sixteen percent of the patients developed new postoperative deficit. Seizures occurred in 24%. None led to awake craniotomy failure. We provide a thorough description of the technique used in awake craniotomies with mapping used in our institution, where the intraoperative patient evaluation is carried out solely by neurosurgeons and anesthesiologists. The absence of other specialized personnel and equipment does not necessarily preclude successful mapping during awake craniotomy. We hope to provide helpful information for those who wish to offer function-guided tumor resection in their own centers. Copyright © 2018 Elsevier Inc. All rights reserved.

Efficacy and safety of dexmedetomidine infusion for patients undergoing awake craniotomy: An observational study.

Science.gov (United States)

Mahajan, Charu; Rath, Girija Prasad; Singh, Gyaninder Pal; Mishra, Nitasha; Sokhal, Suman; Bithal, Parmod Kumar

2018-01-01

The goal of awake craniotomy is to maintain adequate sedation, analgesia, respiratory, and hemodynamic stability and also to provide a cooperative patient for neurologic testing. An observational study carried out to evaluate the efficacy of dexmedetomidine sedation for awake craniotomy. Adult patients with age >18 year who underwent awake craniotomy for intracranial tumor surgery were enrolled. Those who were uncooperative and had difficult airway were excluded from the study. In the operating room, the patients received a bolus dose of dexmedetomidine 1 μg/kg followed by an infusion of 0.2-0.7 μg/kg/h (bispectral index target 60-80). Once the patients were sedated, scalp block was given with bupivacaine 0.25%. The data on hemodynamics at various stages of the procedure, intraoperative complications, total amount of fentanyl used, intravenous fluids required, blood loss and transfusion, duration of surgery, Intensive Care Unit (ICU), and hospital stay were collected. The patients were assessed for Glasgow outcome scale (GOS) score and patient satisfaction score (PSS). A total of 27 patients underwent awake craniotomy during a period of 2 years. Most common intraoperative complication was seizures; observed in five patients (18.5%). None of these patients experienced any episode of desaturation. Two patients had tight brain for which propofol boluses were administered. The average fentanyl consumption was 161.5 ± 85.0 μg. The duration of surgery, ICU, and hospital stays were 231.5 ± 90.5 min, 14.5 ± 3.5 h, and 4.7 ± 1.5 days, respectively. The overall PSS was 8 and GOS was good in all the patients. The use of dexmedetomidine infusion with regional scalp block in patients undergoing awake craniotomy is safe and efficacious. The absence of major complications and higher PSS makes it close to an ideal agent for craniotomy in awake state.

Asleep-awake-asleep craniotomy: a comparison with general anesthesia for resection of supratentorial tumors.

Science.gov (United States)

Rajan, Shobana; Cata, Juan P; Nada, Eman; Weil, Robert; Pal, Rakhi; Avitsian, Rafi

2013-08-01

The anesthetic plan for patients undergoing awake craniotomy, when compared to craniotomy under general anesthesia, is different, in that it requires changes in states of consciousness during the procedure. This retrospective review compares patients undergoing an asleep-awake-asleep technique for craniotomy (group AW: n = 101) to patients undergoing craniotomy under general anesthesia (group AS: n = 77). Episodes of desaturation (AW = 31% versus AS = 1%, p awake-asleep craniotomies with propofol-dexmedetomidine infusion had less hemodynamic response to pinning and emergence, and less overall narcotic use compared to general anesthesia. Despite a higher incidence of temporary episodes of desaturation and hypoventilation, no adverse clinical consequences were seen. Copyright © 2013 Elsevier Ltd. All rights reserved.

Restricted sedation and absence of cognitive impairments after administration of intranasal scopolamine.

Science.gov (United States)

Weerts, Aurélie P; Pattyn, Nathalie; Putcha, Lakshmi; Hoag, Stephen W; Van Ombergen, Angelique; Hallgren, Emma; Van de Heyning, Paul H; Wuyts, Floris L

2015-12-01

Space motion sickness in astronauts during spaceflight causes significant discomfort, which might impede their functionality. Pharmacological treatment has been mainly restricted to promethazine. Transdermal and oral scopolamine have also been used in space; however, their use was reduced due to unpredictable effectiveness and side effects. Recently, intranasal scopolamine administration has gained much interest, since this route ensures fast and reliable absorption with a decreased incidence of undesirable side effects. The aim of this study was to evaluate the effect of intranasal scopolamine on cognitive performance and to determine its side effects. This double-blind, placebo controlled, repeated measures study evaluated vigilant attention, short-term memory, implicit memory and working memory. Side effects were reported on a 22-item questionnaire and sleepiness was assessed by the Karolinska, Stanford and Epworth Sleepiness Scales. Scopolamine had no effect on cognitive function. Only the Karolinska score was significantly increased for scopolamine compared to placebo. Participants reported a dry mouth and dizziness after receiving scopolamine. Results show that intranasal scopolamine did not impair cognitive performance. Intranasal scopolamine might be a good alternative to promethazine for the alleviation of space motion sickness, since the agent has minimal sedative effects and does not hamper cognitive performance. © The Author(s) 2015.

Influence of intranasal and carotid cooling on cerebral temperature balance and oxygenation

DEFF Research Database (Denmark)

Nybo, Lars; Wanscher, Michael; Secher, Niels H.

2014-01-01

temperatures were measured to assess the cerebral heat balance and corresponding paired blood samples were obtained to evaluate cerebral metabolism and oxygenation at rest, following 60 min of intranasal cooling, 5 min of nasal ventilation, and 15 min with carotid cooling. Intranasal cooling induced a parallel......The present study evaluated the influence of intranasal cooling with balloon catheters, increased nasal ventilation, or percutaneous cooling of the carotid arteries on cerebral temperature balance and oxygenation in six healthy male subjects. Aortic arch and internal jugular venous blood...... drop in jugular venous and arterial blood temperatures by 0.30 ± 0.08°C (mean ± SD), whereas nasal ventilation and carotid cooling failed to lower the jugular venous blood temperature. The magnitude of the arterio-venous temperature difference across the brain remained unchanged at -0.33 ± 0.05°C...

Awake percutaneous tracheostomy as an alternative to open ...

African Journals Online (AJOL)

Southern African Journal of Anaesthesia and Analgesia is co-published by Medpharm Publications, NISC (Pty) Ltd and Informa UK .... anaesthesiologist on call for emergency awake tracheostomy. ... to the intensive care unit (ICU) for further monitoring, ventilatory .... Advances in the field of ultrasound technology have made.

Emergent Awake tracheostomy--The five-year experience at an urban tertiary care center.

Science.gov (United States)

Fang, Christina H; Friedman, Remy; White, Priscilla E; Mady, Leila J; Kalyoussef, Evelyne

2015-11-01

There are few studies that discuss the issues surrounding emergent awake tracheostomy. We aim to review the indications, anesthesia used, complications, and outcomes of patients undergoing urgent awake tracheostomy. Chart review. Medical charts of patients who underwent an emergent awake tracheostomy at our institution-affiliated tertiary care center over a 5-year period from 2009 to 2014 were reviewed. Data were collected from inpatient, outpatient, and operative records. Sixty-eight patients underwent emergent awake tracheostomy. Over half presented with hoarseness (n=37, 54.4%) and/or stridor (n=37, 54.4%). Acute upper airway obstruction secondary to malignancy was the most common indication and accounted for 58 cases (85.3%). Thirty-nine (70.1%) of the 55 patients with squamous cell carcinoma presented with advanced disease (stage III or IV). Other indications included glottic or subglottic stenosis (4.4%), failure to intubate (2.9%), and other (7.4%). Local anesthesia was used alone in 35.3% of cases and in combination with conscious sedation in 64.7% of cases. Mild bleeding occurred postoperatively in five patients (7.4%). There were no other postoperative complications. Nineteen patients were lost to follow-up. The mean follow-up of 49 patients was 7.2 weeks, ranging from 2 to 261 weeks. Long-term complications occurred in three patients and included tracheitis 7.4% and suprastomal granuloma 2.9%. Eleven patients (22%) were decannulated at a mean of 11.8 months following tracheostomy. Emergent awake tracheostomy should be considered in patients with impeding airway obstruction and is a safe and effective method to secure an airway in these patients. 4. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Effects of intranasal and peripheral oxytocin or gastrin-releasing peptide administration on social interaction and corticosterone levels in rats.

Science.gov (United States)

Kent, Pamela; Awadia, Alisha; Zhao, Leah; Ensan, Donna; Silva, Dinuka; Cayer, Christian; James, Jonathan S; Anisman, Hymie; Merali, Zul

2016-02-01

The intranasal route of drug administration has gained increased popularity as it is thought to allow large molecules, such as peptide hormones, more direct access to the brain, while limiting systemic exposure. Several studies have investigated the effects of intranasal oxytocin administration in humans as this peptide is associated with prosocial behavior. There are, however, few preclinical studies investigating the effects of intranasal oxytocin administration in rodents. Oxytocin modulates hypothalamic-pituitary-adrenal (HPA) axis functioning and it has been suggested that oxytocin's ability to increase sociability may occur through a reduction in stress reactivity. Another peptide that appears to influence both social behavior and HPA axis activity is gastrin-releasing peptide (GRP), but it is not known if these GRP-induced effects are related. With this in mind, in the present study, we assessed the effects of intranasal and intraperitoneal oxytocin and GRP administration on social interaction and release of corticosterone in rats. Intranasal and intraperitoneal administration of 20, but not 5 μg, of oxytocin significantly increased social interaction, whereas intranasal and peripheral administration of GRP (20 but not 5 μg) significantly decreased levels of social interaction. In addition, while intranasal oxytocin (20 μg) had no effect on blood corticosterone levels, a marked increase in blood corticosterone levels was observed following intraperitoneal oxytocin administration. With GRP, intranasal (20 μg) but not peripheral administration increased corticosterone levels. These findings provide further evidence that intranasal peptide delivery can induce behavioral alterations in rodents which is consistent with findings from human studies. In addition, the peptide-induced changes in social interaction were not linked to fluctuations in corticosterone levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

A case of loss of consciousness with contralateral acute subdural haematoma during awake craniotomy

OpenAIRE

Kamata, Kotoe; Maruyama, Takashi; Nitta, Masayuki; Ozaki, Makoto; Muragaki, Yoshihiro; Okada, Yoshikazu

2014-01-01

We are reporting the case of a 56-year-old woman who developed loss of consciousness during awake craniotomy. A thin subdural haematoma in the contralateral side of the craniotomy was identified with intraoperative magnetic resonance imaging and subsequently removed. Our case indicates that contralateral acute subdural haematoma could be a cause of deterioration of the conscious level during awake craniotomy.

A case of loss of consciousness with contralateral acute subdural haematoma during awake craniotomy

Science.gov (United States)

Kamata, Kotoe; Maruyama, Takashi; Nitta, Masayuki; Ozaki, Makoto; Muragaki, Yoshihiro; Okada, Yoshikazu

2014-01-01

We are reporting the case of a 56-year-old woman who developed loss of consciousness during awake craniotomy. A thin subdural haematoma in the contralateral side of the craniotomy was identified with intraoperative magnetic resonance imaging and subsequently removed. Our case indicates that contralateral acute subdural haematoma could be a cause of deterioration of the conscious level during awake craniotomy. PMID:25301378

Intranasal Delivery of Granulocyte Colony-Stimulating Factor Enhances Its Neuroprotective Effects Against Ischemic Brain Injury in Rats.

Science.gov (United States)

Sun, Bao-Liang; He, Mei-Qing; Han, Xiang-Yu; Sun, Jing-Yi; Yang, Ming-Feng; Yuan, Hui; Fan, Cun-Dong; Zhang, Shuai; Mao, Lei-Lei; Li, Da-Wei; Zhang, Zong-Yong; Zheng, Cheng-Bi; Yang, Xiao-Yi; Li, Yang V; Stetler, R Anne; Chen, Jun; Zhang, Feng

2016-01-01

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor with strong neuroprotective properties. However, it has limited capacity to cross the blood-brain barrier and thus potentially limiting its protective capacity. Recent studies demonstrated that intranasal drug administration is a promising way in delivering neuroprotective agents to the central nervous system. The current study therefore aimed at determining whether intranasal administration of G-CSF increases its delivery to the brain and its neuroprotective effect against ischemic brain injury. Transient focal cerebral ischemia in rat was induced with middle cerebral artery occlusion. Our resulted showed that intranasal administration is 8-12 times more effective than subcutaneous injection in delivering G-CSF to cerebrospinal fluid and brain parenchyma. Intranasal delivery enhanced the protective effects of G-CSF against ischemic injury in rats, indicated by decreased infarct volume and increased recovery of neurological function. The neuroprotective mechanisms of G-CSF involved enhanced upregulation of HO-1 and reduced calcium overload following ischemia. Intranasal G-CSF application also promoted angiogenesis and neurogenesis following brain ischemia. Taken together, G-CSF is a legitimate neuroprotective agent and intranasal administration of G-CSF is more effective in delivery and neuroprotection and could be a practical approach in clinic.

Initial Experience with Awake Craniotomy In Sudan | Mohamed ...

African Journals Online (AJOL)

especially if the tumour is located in the anterior temporal or frontal lobes, near motor, language, or memory areas of the brain. Awake craniotomy has been proposed aiming for maximum resection with minimum impairment of neurological function. The technique should provide adequate sedation, analgesia, respiratory ...

Voluntary running enhances glymphatic influx in awake behaving, young mice.

Science.gov (United States)

von Holstein-Rathlou, Stephanie; Petersen, Nicolas Caesar; Nedergaard, Maiken

2018-01-01

Vascular pathology and protein accumulation contribute to cognitive decline, whereas exercise can slow vascular degeneration and improve cognitive function. Recent investigations suggest that glymphatic clearance measured in aged mice while anesthetized is enhanced following exercise. We predicted that exercise would also stimulate glymphatic activity in awake, young mice with higher baseline glymphatic function. Therefore, we assessed glymphatic function in young female C57BL/6J mice following five weeks voluntary wheel running and in sedentary mice. The active mice ran a mean distance of 6km daily. We injected fluorescent tracers in cisterna magna of awake behaving mice and in ketamine/xylazine anesthetized mice, and later assessed tracer distribution in coronal brain sections. Voluntary exercise consistently increased CSF influx during wakefulness, primarily in the hypothalamus and ventral parts of the cortex, but also in the middle cerebral artery territory. While glymphatic activity was higher under ketamine/xylazine anesthesia, we saw a decrease in glymphatic function during running in awake mice after five weeks of wheel running. In summary, daily running increases CSF flux in widespread areas of the mouse brain, which may contribute to the pro-cognitive effects of exercise. Copyright © 2017 Elsevier B.V. All rights reserved.

PERANCANGAN SISTEM TELE-NAVIGATION PADA PESAWAT TANPA AWAK (MICRO UAV

Directory of Open Access Journals (Sweden)

Agus Basukesti

2016-04-01

Full Text Available Sistem navigasi pada pengoperasian pesawat tanpa awak (Micro UAV saat ini terdapat 2 cara yaitu dengan cara pandangan manual (line of sight dan sistem autopilot. Sistem navigasi line of sight memiliki kelemahan jangkauan pesawat tanpa awak hanya pada radius 200 meter karena keterbatasan penglihatan dari pengendali. Metode autopilot adalah metode kendali pesawat dengan algoritma lock position and homing. Sistem autopilot bekerja dengan cara mencari koordinat posisi yang dituju kemudian kembali ke lokasi awal. Keunggulan teknologi ini adalah pesawat dapat menjangkau jarak yang cukup jauh. Akan tetapi metode ini memiliki kelemahan yaitu pesawat harus terbang tinggi dan pesawat belum bisa menghindari halangan seperti gedung pencakar langit maupun pepohonan tinggi. Dalam penelitian ini dirancang sebuah sistem tele-navigasi yang merupakan modifikasi sistem navigasi line of sight dan autopilot sehingga dapat menutupi kelemahan dari masing masing metode navigasi yang ada saat ini. metode penelitian yang digunakan dalam penelitian ini adalah metode eksperimen yaitu dengan membuat pilot plan sistem Tele-navigasi yang selanjutnya akan diuji dengan pesawat tanpa awak (micro UAV jenis flying wing. Metode dokumentasi dan metode studi pustaka juga digunakan untuk melengkapi data teknis alat yang digunakan sehingga dapat dilakukan analisis mendalam terhadap performa alat yang dirancang. Kata kunci: line of sight, lock position and homing, autopilot, micro UAV.

Long-term exposure to intranasal oxytocin in a mouse autism model.

Science.gov (United States)

Bales, K L; Solomon, M; Jacob, S; Crawley, J N; Silverman, J L; Larke, R H; Sahagun, E; Puhger, K R; Pride, M C; Mendoza, S P

2014-11-11

Oxytocin (OT) is a neuropeptide involved in mammalian social behavior. It is currently in clinical trials for the treatment of autism spectrum disorder (ASD). Previous studies in healthy rodents (prairie voles and C57BL/6J mice) have shown that there may be detrimental effects of long-term intranasal administration, raising the questions about safety and efficacy. To investigate the effects of OT on the aspects of ASD phenotype, we conducted the first study of chronic intranasal OT in a well-validated mouse model of autism, the BTBR T+ Itpr3tf/J inbred strain (BTBR), which displays low sociability and high repetitive behaviors. BTBR and C57BL/6J (B6) mice (N=94) were administered 0.8  IU/kg of OT intranasally, daily for 30 days, starting on day 21. We ran a well-characterized set of behavioral tasks relevant to diagnostic and associated symptoms of autism, including juvenile reciprocal social interactions, three-chambered social approach, open-field exploratory activity, repetitive self-grooming and fear-conditioned learning and memory, some during and some post treatment. Intranasal OT did not improve autism-relevant behaviors in BTBR, except for female sniffing in the three-chambered social interaction test. Male saline-treated BTBR mice showed increased interest in a novel mouse, both in chamber time and sniffing time, whereas OT-treated male BTBR mice showed a preference for the novel mouse in sniffing time only. No deleterious effects of OT were detected in either B6 or BTBR mice, except possibly for the lack of a preference for the novel mouse's chamber in OT-treated male BTBR mice. These results highlight the complexity inherent in understanding the effects of OT on behavior. Future investigations of chronic intranasal OT should include a wider dose range and early developmental time points in both healthy rodents and ASD models to affirm the efficacy and safety of OT.

Tailorable Trimethyl chitosans as adjuvant for intranasal immunization

NARCIS (Netherlands)

Verheul, R.J.

2010-01-01

Tailorable Trimethyl Chitosans as Adjuvant for Intranasal Immunization Active vaccination has proven to be the most (cost) effective tool in the fight against infectious diseases. Nowadays, most vaccines are administered via parenteral injection. However, the risk of contaminated needles and need

Combination of Continuous Dexmedetomidine Infusion with Titrated Ultra-Low-Dose Propofol-Fentanyl for an Awake Craniotomy

Science.gov (United States)

Das, Samaresh; Al-Mashani, Ali; Suri, Neelam; Salhotra, Neeraj; Chatterjee, Nilay

2016-01-01

An awake craniotomy is a continuously evolving technique used for the resection of brain tumours from the eloquent cortex. We report a 29-year-old male patient who presented to the Khoula Hospital, Muscat, Oman, in 2016 with a two month history of headaches and convulsions due to a space-occupying brain lesion in close proximity with the left motor cortex. An awake craniotomy was conducted using a scalp block, continuous dexmedetomidine infusion and a titrated ultra-low-dose of propofolfentanyl. The patient remained comfortable throughout the procedure and the intraoperative neuropsychological tests, brain mapping and tumour resection were successful. This case report suggests that dexmedetomidine in combination with titrated ultra-low-dose propofolfentanyl are effective options during an awake craniotomy, ensuring optimum sedation, minimal disinhibition and a rapid recovery. To the best of the authors’ knowledge, this is the first awake craniotomy conducted successfully in Oman. PMID:27606116

Comparison of dexmedetomidine versus midazolam for intranasal ...

African Journals Online (AJOL)

route; however, it is not as painful as the intramuscular route, and it is absorbed directly ... respiratory tract infection, any central nervous system disorder, refusal for intranasal administration or history of allergic reaction to dexmedetomidine ... and the calculated dose of drug diluted to a total volume of 1 ml was administered ...

Anaesthetic technique during awake craniotomy. Case report and literature review

Directory of Open Access Journals (Sweden)

M.M. Madriz-Godoy

2016-07-01

Results: This case was managed with a scalp nerve block as local anaesthesia plus intravenous sedation without airway instrumentation. We reviewed the literature about patient management during awake craniotomy.

Comparison of propofol pharmacokinetic and pharmacodynamic models for awake craniotomy: A prospective observational study.

Science.gov (United States)

Soehle, Martin; Wolf, Christina F; Priston, Melanie J; Neuloh, Georg; Bien, Christian G; Hoeft, Andreas; Ellerkmann, Richard K

2015-08-01

Anaesthesia for awake craniotomy aims for an unconscious patient at the beginning and end of surgery but a rapidly awakening and responsive patient during the awake period. Therefore, an accurate pharmacokinetic/pharmacodynamic (PK/PD) model for propofol is required to tailor depth of anaesthesia. To compare the predictive performances of the Marsh and the Schnider PK/PD models during awake craniotomy. A prospective observational study. Single university hospital from February 2009 to May 2010. Twelve patients undergoing elective awake craniotomy for resection of brain tumour or epileptogenic areas. Arterial blood samples were drawn at intervals and the propofol plasma concentration was determined. The prediction error, bias [median prediction error (MDPE)] and inaccuracy [median absolute prediction error (MDAPE)] of the Marsh and the Schnider models were calculated. The secondary endpoint was the prediction probability PK, by which changes in the propofol effect-site concentration (as derived from simultaneous PK/PD modelling) predicted changes in anaesthetic depth (measured by the bispectral index). The Marsh model was associated with a significantly (P = 0.05) higher inaccuracy (MDAPE 28.9 ± 12.0%) than the Schnider model (MDAPE 21.5 ± 7.7%) and tended to reach a higher bias (MDPE Marsh -11.7 ± 14.3%, MDPE Schnider -5.4 ± 20.7%, P = 0.09). MDAPE was outside of accepted limits in six (Marsh model) and two (Schnider model) of 12 patients. The prediction probability was comparable between the Marsh (PK 0.798 ± 0.056) and the Schnider model (PK 0.787 ± 0.055), but after adjusting the models to each individual patient, the Schnider model achieved significantly higher prediction probabilities (PK 0.807 ± 0.056, P = 0.05). When using the 'asleep-awake-asleep' anaesthetic technique during awake craniotomy, we advocate using the PK/PD model proposed by Schnider. Due to considerable interindividual variation, additional monitoring of anaesthetic depth is

Intranasal mesenchymal stem cell treatment for neonatal brain damage: long-term cognitive and sensorimotor improvement.

Directory of Open Access Journals (Sweden)

Vanessa Donega

Full Text Available Mesenchymal stem cell (MSC administration via the intranasal route could become an effective therapy to treat neonatal hypoxic-ischemic (HI brain damage. We analyzed long-term effects of intranasal MSC treatment on lesion size, sensorimotor and cognitive behavior, and determined the therapeutic window and dose response relationships. Furthermore, the appearance of MSCs at the lesion site in relation to the therapeutic window was examined. Nine-day-old mice were subjected to unilateral carotid artery occlusion and hypoxia. MSCs were administered intranasally at 3, 10 or 17 days after hypoxia-ischemia (HI. Motor, cognitive and histological outcome was investigated. PKH-26 labeled cells were used to localize MSCs in the brain. We identified 0.5 × 10(6 MSCs as the minimal effective dose with a therapeutic window of at least 10 days but less than 17 days post-HI. A single dose was sufficient for a marked beneficial effect. MSCs reach the lesion site within 24 h when given 3 or 10 days after injury. However, no MSCs were detected in the lesion when administered 17 days following HI. We also show for the first time that intranasal MSC treatment after HI improves cognitive function. Improvement of sensorimotor function and histological outcome was maintained until at least 9 weeks post-HI. The capacity of MSCs to reach the lesion site within 24 h after intranasal administration at 10 days but not at 17 days post-HI indicates a therapeutic window of at least 10 days. Our data strongly indicate that intranasal MSC treatment may become a promising non-invasive therapeutic tool to effectively reduce neonatal encephalopathy.

Scalp Block for Awake Craniotomy in a Patient With a Frontal Bone Mass: A Case Report

Science.gov (United States)

Amiri, Hamid Reza; Kouhnavard, Marjan; Safari, Saeid

2012-01-01

“Anesthesia” for awake craniotomy is a unique clinical condition that requires the anesthesiologist to provide changing states of sedation and analgesia, to ensure optimal patient comfort without interfering with electrophysiologic monitoring and patient cooperation, and also to manipulate cerebral and systemic hemodynamics while guaranteeing adequate ventilation and patency of airways. Awake craniotomy is not as popular in developing countries as in European countries. This might be due to the lack of information regarding awake craniotomy and its benefits among the neurosurgeons and anesthetists in developing countries. From the economic perspective, this procedure may decrease resource utilization by reducing the use of invasive monitoring, the duration of the operation, and the length of postoperative hospital stay. All these reasons also favor its use in the developing world, where the availability of resources still remains a challenge. In this case report we presented a successful awake craniotomy in patient with a frontal bone mass. PMID:24904791

Cardiovascular risk assessment with oxidised LDL measurement in postmenopausal women receiving intranasal estrogen replacement therapy.

Science.gov (United States)

Kurdoglu, Mertihan; Yildirim, Mulazim; Kurdoglu, Zehra; Erdem, Ahmet; Erdem, Mehmet; Bilgihan, Ayse; Goktas, Bulent

2011-08-01

To investigate the effect of intranasal estrogen replacement therapy administered to postmenopausal women alone or in combination with progesterone on markers of cardiovascular risk. The study was conducted with 44 voluntary postmenopausal women. In group I (n = 15), the patients were treated with only intranasal estradiol (300 μg/day estradiol hemihydrate). In group II (n = 11), the patients received cyclic progesterone (200 mg/day micronized progesterone) for 12 days in each cycle in addition to continuous intranasal estradiol. Group III (n = 18) was the controls. Serum lipid profiles, oxidised low-density lipoprotein (LDL) and other markers of cardiovascular risk were assessed at baseline and at the 3rd month of the treatment. Lipid profile, LDL apolipoprotein B, lipoprotein a, homocysteine, oxidised LDL values and oxidised LDL/LDL cholesterol ratio were not observed to change after 3 months compared to baseline values within each group (p > 0.016). In comparison to changes between the groups after the treatment, only oxidised LDL levels and oxidised LDL/LDL cholesterol ratios of group II were increased compared to control group (p < 0.05). Intranasal estradiol alone did not appear to have an effect on markers of cardiovascular risk in healthy postmenopausal women. However, the addition of cyclic oral micronized progesterone to intranasal estradiol influenced the markers of cardiovascular risk negatively in comparison to non-users in healthy postmenopausal women.

Saliva oxytocin measures do not reflect peripheral plasma concentrations after intranasal oxytocin administration in men.

Science.gov (United States)

Quintana, Daniel S; Westlye, Lars T; Smerud, Knut T; Mahmoud, Ramy A; Andreassen, Ole A; Djupesland, Per G

2018-05-16

Oxytocin plays an important role in social behavior. Thus, there has been significant research interest for the role of the oxytocin system in several psychiatric disorders, and the potential of intranasal oxytocin administration to treat social dysfunction. Measurement of oxytocin concentrations in saliva are sometimes used to approximate peripheral levels of oxytocin; however, the validity of this approach is unclear. In this study, saliva and plasma oxytocin was assessed after two doses of Exhalation Delivery System delivered intranasal oxytocin (8 IU and 24 IU), intravenous oxytocin (1 IU) and placebo in a double-dummy, within-subjects design with men. We found that intranasal oxytocin (8 IU and 24 IU) administration increased saliva oxytocin concentrations in comparison to saliva oxytocin concentration levels after intravenous and placebo administration. Additionally, we found that saliva oxytocin concentrations were not significantly associated with plasma oxytocin concentrations after either intranasal or intravenous oxytocin administration. Altogether, we suggest that saliva oxytocin concentrations do not accurately index peripheral oxytocin after intranasal or intravenous oxytocin administration, at least in men. The data indicates that elevated oxytocin saliva levels after nasal delivery primarily reflect exogenous administered oxytocin that is cleared from the nasal cavity to the oropharynx, and is therefore a weak surrogate for peripheral blood measurements. Copyright © 2018 Elsevier Inc. All rights reserved.

Awake language mapping and 3-Tesla intraoperative MRI-guided volumetric resection for gliomas in language areas.

Science.gov (United States)

Lu, Junfeng; Wu, Jinsong; Yao, Chengjun; Zhuang, Dongxiao; Qiu, Tianming; Hu, Xiaobing; Zhang, Jie; Gong, Xiu; Liang, Weimin; Mao, Ying; Zhou, Liangfu

2013-09-01

The use of both awake surgery and intraoperative MRI (iMRI) has been reported to optimize the maximal safe resection of gliomas. However, there has been little research into combining these two demanding procedures. We report our unique experience with, and methodology of, awake surgery in a movable iMRI system, and we quantitatively evaluate the contribution of the combination on the extent of resection (EOR) and functional outcome of patients with gliomas involving language areas. From March 2011 to November 2011, 30 consecutive patients who underwent awake surgery with iMRI guidance were prospectively investigated. The EOR was assessed by volumetric analysis. Language assessment was conducted before surgery and 1 week, 1 month, 3 months and 6 months after surgery using the Aphasia Battery of Chinese. Awake language mapping integrated with 3.0 Tesla iMRI was safely performed for all patients. An additional resection was conducted in 11 of 30 patients (36.7%) after iMRI. The median EOR significantly increased from 92.5% (range, 75.1-97.0%) to 100% (range, 92.6-100%) as a result of iMRI (p<0.01). Gross total resection was achieved in 18 patients (60.0%), and in seven of those patients (23.3%), the gross total resection could be attributed to iMRI. A total of 12 patients (40.0%) suffered from transient language deficits; however, only one (3.3%) patient developed a permanent deficit. This study demonstrates the potential utility of combining awake craniotomy with iMRI; it is safe and reliable to perform awake surgery using a movable iMRI. Copyright © 2013 Elsevier Ltd. All rights reserved.

Intranasal Delivery of pGDNF Nanoparticles for Parkinson's Disease

Science.gov (United States)

Harmon, Brendan Trevor

Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily affects the dopaminergic A9 nigrostriatal tract. For dopamine neurons specifically, glial cell-derived neurotrophic factor (GDNF) has been shown to promote their survival and proliferation both in culture and in vivo. GDNF has also proven to be neuroprotective and restorative in various animal models of PD and some human clinical trials. However, its delivery to the brain has required invasive surgical routes which are not clinically practical for many patients. The main objective of this project was to test intranasal delivery to the brain of a nanoparticle vector incorporating an expression plasmid for GDNF (pGDNF). The intranasal route circumvents the blood-brain barrier, allowing larger sized vectors into the central nervous system while avoiding peripheral distribution. This approach would provide a renewable source of GDNF within the target areas of the brain, the striatum and the substantia nigra (SN) without the need for surgical injections or frequent re-dosing. A PEGylated polylysine compacted plasmid nanoparticle vector (PEG-CK30), developed by Copernicus Therapeutics, Inc., has been shown to transfect neurons and glial cells in vivo while lacking the safety issues present with other vectors. The first goal of this work was to determine if these PEG-CK30 compacted plasmid nanoparticles can successfully transfect cells and express the reporter protein, enhanced green fluorescent protein (eGFP) in the rat brain after intranasal administration. Initial in vivo experiments utilized the expression plasmid pCG, expressing eGFP under the fast-acting cytomegalovirus (CMV) promoter. Intranasal administration of pCG nanoparticles resulted in evidence of transfection of brain cells, as shown both qualitatively, by GFP-immunohistochemistry, and quantitatively, by GFP-ELISA. Expression was detected throughout the rat brain two days post-administration. Following the proof

Prospective study of awake craniotomy used routinely and nonselectively for supratentorial tumors.

Science.gov (United States)

Serletis, Demitre; Bernstein, Mark

2007-07-01

The authors prospectively assessed the value of awake craniotomy used nonselectively in patients undergoing resection of supratentorial tumors. The demographic features, presenting symptoms, tumor location, histological diagnosis, outcomes, and complications were documented for 610 patients who underwent awake craniotomy for supratentorial tumor resection. Intraoperative brain mapping was used in 511 cases (83.8%). Mapping identified eloquent cortex in 115 patients (22.5%) and no eloquent cortex in 396 patients (77.5%). Neurological deficits occurred in 89 patients (14.6%). In the subset of 511 patients in whom brain mapping was performed, 78 (15.3%) experienced postoperative neurological worsening. This phenomenon was more common in patients with preoperative neurological deficits or in those individuals in whom mapping successfully identified eloquent tissue. Twenty-five (4.9%) of the 511 patients suffered intraoperative seizures, and two of these individuals required intubation and induction of general anesthesia after generalized seizures occurred. Four (0.7%) of the 610 patients developed wound complications. Postoperative hematomas developed in seven patients (1.1%), four of whom urgently required a repeated craniotomy to allow evacuation of the clot. Two patients (0.3%) required readmission to the hospital soon after being discharged. There were three deaths (0.5%). Awake craniotomy is safe, practical, and effective during resection of supratentorial lesions of diverse pathological range and location. It allows for intraoperative brain mapping that helps identify and protect functional cortex. It also avoids the complications inherent in the induction of general anesthesia. Awake craniotomy provides an excellent alternative to surgery of supratentorial brain lesions in patients in whom general anesthesia has been induced.

Selective insulin resistance in homeostatic and cognitive control brain areas in overweight and obese adults.

Science.gov (United States)

Kullmann, Stephanie; Heni, Martin; Veit, Ralf; Scheffler, Klaus; Machann, Jürgen; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

2015-06-01

Impaired brain insulin action has been linked to obesity, type 2 diabetes, and neurodegenerative diseases. To date, the central nervous effects of insulin in obese humans still remain ill defined, and no study thus far has evaluated the specific brain areas affected by insulin resistance. In 25 healthy lean and 23 overweight/obese participants, we performed magnetic resonance imaging to measure cerebral blood flow (CBF) before and 15 and 30 min after application of intranasal insulin or placebo. Additionally, participants explicitly rated pictures of high-caloric savory and sweet food 60 min after the spray for wanting and liking. In response to insulin compared with placebo, we found a significant CBF decrease in the hypothalamus in both lean and overweight/obese participants. The magnitude of this response correlated with visceral adipose tissue independent of other fat compartments. Furthermore, we observed a differential response in the lean compared with the overweight/obese group in the prefrontal cortex, resulting in an insulin-induced CBF reduction in lean participants only. This prefrontal cortex response significantly correlated with peripheral insulin sensitivity and eating behavior measures such as disinhibition and food craving. Behaviorally, we were able to observe a significant reduction for the wanting of sweet foods after insulin application in lean men only. Brain insulin action was selectively impaired in the prefrontal cortex in overweight and obese adults and in the hypothalamus in participants with high visceral adipose tissue, potentially promoting an altered homeostatic set point and reduced inhibitory control contributing to overeating behavior. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

The Effects of Oral d-Amphetamine on Impulsivity in Smoked and Intranasal Cocaine Users

Science.gov (United States)

Reed, Stephanie Collins; Evans, Suzette M.

2016-01-01

BACKGROUND Effective treatments for cocaine use disorders remain elusive. Two factors that may be related to treatment failures are route of cocaine used and impulsivity. Smoked cocaine users are more likely to have poorer treatment outcomes compared to intranasal cocaine users. Further, cocaine users are impulsive and impulsivity is associated with poor treatment outcomes. While stimulants are used to treat Attention Deficit Hyperactivity Disorder (ADHD) and attenuate certain cocaine-related behaviors, few studies have comprehensively examined whether stimulants can reduce behavioral impulsivity in cocaine users, and none examined route of cocaine use as a factor. METHODS The effects of immediate release oral d-amphetamine (AMPH) were examined in 34 cocaine users (13 intranasal, 21 smoked). Participants had three separate sessions where they were administered AMPH (0, 10, or 20 mg) and completed behavioral measures of impulsivity and risk-taking and subjective measures of abuse liability. RESULTS Smoked cocaine users were more impulsive on the Delayed Memory Task, the GoStop task and the Delay Discounting Task than intranasal cocaine users. Smoked cocaine users also reported more cocaine craving and negative mood than intranasal cocaine users. AMPH produced minimal increases on measures of abuse liability (e.g., Drug Liking). CONCLUSIONS Smoked cocaine users were more impulsive than intranasal cocaine users on measures of impulsivity that had a delay component. Additionally, although AMPH failed to attenuate impulsive responding, there was minimal evidence of abuse liability in cocaine users. These preliminary findings need to be confirmed in larger samples that control for route and duration of cocaine use. PMID:27114203

Inflammatory Profile of Awake Function-Controlled Craniotomy and Craniotomy under General Anesthesia

Directory of Open Access Journals (Sweden)

Markus Klimek

2009-01-01

Results. Plasma IL-6 level significantly increased with time similarly in both groups. No significant plasma IL-8 and IL-10 change was observed in both experimental groups. The VAS pain score was significantly lower in the awake group compared to the anesthesia group at 12 hours postoperative. Postoperative anxiety and stress declined similarly in both groups. Conclusion. This study suggests that awake function-controlled craniotomy does not cause a significantly different inflammatory response than craniotomy performed under general anesthesia. It is also likely that function-controlled craniotomy does not cause a greater emotional challenge than tumor resection under general anesthesia.

Effect of administration method, animal weight and age on the intranasal delivery of drugs to the brain.

Science.gov (United States)

Krishnan, Jishnu K S; Arun, Peethambaran; Chembukave, Bhadra; Appu, Abhilash P; Vijayakumar, Nivetha; Moffett, John R; Puthillathu, Narayanan; Namboodiri, Aryan M A

2017-07-15

The intranasal route of administration has proven to be an effective method for bypassing the blood brain barrier and avoiding first pass hepatic metabolism when targeting drugs to the brain. Most small molecules gain rapid access to CNS parenchyma when administered intranasally. However, bioavailability is affected by various factors ranging from the molecular weight of the drug to the mode of intranasal delivery. We examined the effects of animal posture, intranasal application method and animal weight and age on the delivery of radiolabeled pralidoxime ( 3 H-2-PAM) to the brain of rats. We found that using upright vs. supine posture did not significantly affect 3 H-2-PAM concentrations in different brain regions. Older animals with higher weights required increased doses to achieve the same drug concentration throughout the brain when compared to young animals with lower body weights. The use of an intranasal aerosol propelled delivery device mainly increased bioavailability in the olfactory bulbs, but did not reliably increase delivery of the drug to various other brain regions, and in some regions of the brain delivered less of the drug than simple pipette administration. In view of the emerging interest in the use of intranasal delivery of drugs to combat cognitive decline in old age, we tested effectiveness in very old rats and found the method to be as effective in the older rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Mapping oxygen concentration in the awake mouse brain

Science.gov (United States)

Lyons, Declan G; Parpaleix, Alexandre; Roche, Morgane; Charpak, Serge

2016-01-01

Although critical for brain function, the physiological values of cerebral oxygen concentration have remained elusive because high-resolution measurements have only been performed during anesthesia, which affects two major parameters modulating tissue oxygenation: neuronal activity and blood flow. Using measurements of capillary erythrocyte-associated transients, fluctuations of oxygen partial pressure (Po2) associated with individual erythrocytes, to infer Po2 in the nearby neuropil, we report the first non-invasive micron-scale mapping of cerebral Po2 in awake, resting mice. Interstitial Po2 has similar values in the olfactory bulb glomerular layer and the somatosensory cortex, whereas there are large capillary hematocrit and erythrocyte flux differences. Awake tissue Po2 is about half that under isoflurane anesthesia, and within the cortex, vascular and interstitial Po2 values display layer-specific differences which dramatically contrast with those recorded under anesthesia. Our findings emphasize the importance of measuring energy parameters non-invasively in physiological conditions to precisely quantify and model brain metabolism. DOI: http://dx.doi.org/10.7554/eLife.12024.001 PMID:26836304

Comparison of dexmedetomidine and propofol for conscious sedation in awake craniotomy: a prospective, double-blind, randomized, and controlled clinical trial.

Science.gov (United States)

Shen, She-liang; Zheng, Jia-yin; Zhang, Jun; Wang, Wen-yuan; Jin, Tao; Zhu, Jing; Zhang, Qi

2013-11-01

It has been reported that dexmedetomidine (DEX) can be used for conscious sedation in awake craniotomy, but few data exist to compare DEX versus propofol (PRO). To compare the efficacy and safety of DEX versus PRO for conscious sedation in awake craniotomy. Thirty patients of American Society of Anesthesiologists grade I-II scheduled for awake craniotomy, were randomized into 2 groups each containing 15 subjects. Group D received DEX and group P received PRO. Two minutes after tracheal intubation (T1), PRO (target plasma concentration) was titrated down to 1 to 4 µg/mL in group P. In group D, PRO was discontinued and DEX was administered 1.0 µg/kg followed by a maintenance dose of 0.2 to 0.7 µg/kg/h. The surgeon preset the anticipated awake point-in-time (T0) preoperatively. Ten minutes before T0 (T3), DEX was titrated down to 0.2 µg/kg/h in group D, PRO was discontinued and normal saline (placebo) 5 mL/h was infused in group P. Arousal time, quality of revival and adverse events during the awake period, degree of satisfaction from surgeons and patients were recorded. Arousal time was significantly shorter in group D than in group P (P awake period in group D was similar to that of group P (P = .68). The degree of satisfaction of surgeons was significantly higher in group D than in group P (P awake period (P > .05). Either DEX or PRO can be effectively and safely used for conscious sedation in awake craniotomy. Comparing the two, DEX produced a shorter arousal time and a higher degree of surgeon satisfaction.

Awake Craniotomy for Tumor Resection: Further Optimizing Therapy of Brain Tumors.

Science.gov (United States)

Mehdorn, H Maximilian; Schwartz, Felix; Becker, Juliane

2017-01-01

In recent years more and more data have emerged linking the most radical resection to prolonged survival in patients harboring brain tumors. Since total tumor resection could increase postoperative morbidity, many methods have been suggested to reduce the risk of postoperative neurological deficits: awake craniotomy with the possibility of continuous patient-surgeon communication is one of the possibilities of finding out how radical a tumor resection can possibly be without causing permanent harm to the patient.In 1994 we started to perform awake craniotomy for glioma resection. In 2005 the use of intraoperative high-field magnetic resonance imaging (MRI) was included in the standard tumor therapy protocol. Here we review our experience in performing awake surgery for gliomas, gained in 219 patients.Patient selection by the operating surgeon and a neuropsychologist is of primary importance: the patient should feel as if they are part of the surgical team fighting against the tumor. The patient will undergo extensive neuropsychological testing, functional MRI, and fiber tractography in order to define the relationship between the tumor and the functionally relevant brain areas. Attention needs to be given at which particular time during surgery the intraoperative MRI is performed. Results from part of our series (without and with ioMRI scan) are presented.

[Pre-anesthetic medication with intranasal dexmedetomidine and oral midazolam as an anxiolytic. A clinical trial].

Science.gov (United States)

Linares Segovia, B; García Cuevas, M A; Ramírez Casillas, I L; Guerrero Romero, J F; Botello Buenrostro, I; Monroy Torres, R; Ramírez Gómez, X S

2014-10-01

Dexmedetomidine is a pharmacological option for sedation in children. In this study, the efficacy of intranasal dexmedetomidine to reduce preoperative anxiety in pediatric patients is compared with that of oral midazolam. A prospective, randomized, double-blind, controlled trial was conducted on children 2-12 years of age, randomly assigned to one of the following two groups: group A received premedication with oral midazolam and intranasal placebo, group B received intranasal dexmedetomidine and oral placebo. Anxiety was assessed with the modified Yale scale, and a risk analysis and number needed to treat was performed. A total of 108 patients were included, 52 (48.1%) treated with dexmedetomidine, and 56 (51.9%) with midazolam. Anxiety was less frequent in the dexmedetomidine group at 60minutes (P=.001), induction (p=.04), and recovery (P=.0001). Risk analysis showed that dexmedetomidine reduced the risk of anxiety by 28% (RAR=0.28, 95% CI; 0.12 to 0.43) and to prevent one case of anxiety, four patients need to be treated with intranasal dexmedetomidine (NNT=4, 95% CI: 3-9).Changes in heart rate, mean arterial pressure, and oxygen saturation, were statistically significant in the dexmedetomidine group, with no clinical consequences. There were no cases of bradycardia, hypotension or oxygen desaturation. Intranasal dexmedetomidine premedication is more effective than oral midazolam to reduce preoperative anxiety in pediatric patients. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Assessment of the pharmacodynamics of intranasal, intravenous and oral scopolamine

Science.gov (United States)

Tietze, Karen J.

1990-01-01

Space motion sickness is an important issue in the space medical sciences program. One of the objectives of the ongoing clinical experimental protocol Pharmacokinetics of Intranasal Scopolamine in Normal Subjects is to evaluate the pharmacodynamics of scopolamine using salivary flow rate and pH profiles and cognitive performance tests as pharmacodynamic parameters. Normal volunteers collected saliva and performed the NTI Multiresource Performance Battery tests at designed time intervals to establish control saliva flow rates, salivary pH profiles, and the characteristics of the learning curve for the performance program under normal conditions. In the clinical part of the study, saliva samples and performance test scores are collected from healthy nonsmoking subjects after receiving a single 0.4 mg dose of either intranasal, intravenous, or oral scopolamine.

Impact of preoperative functional magnetic resonance imaging during awake craniotomy procedures for intraoperative guidance and complication avoidance.

Science.gov (United States)

Trinh, Victoria T; Fahim, Daniel K; Maldaun, Marcos V C; Shah, Komal; McCutcheon, Ian E; Rao, Ganesh; Lang, Frederick; Weinberg, Jeffrey; Sawaya, Raymond; Suki, Dima; Prabhu, Sujit S

2014-01-01

We wanted to study the role of functional MRI (fMRI) in preventing neurological injury in awake craniotomy patients as this has not been previously studied. To examine the role of fMRI as an intraoperative adjunct during awake craniotomy procedures. Preoperative fMRI was carried out routinely in 214 patients undergoing awake craniotomy with direct cortical stimulation (DCS). In 40% of our cases (n = 85) fMRI was utilized for the intraoperative localization of the eloquent cortex. In the other 129 cases significant noise distortion, poor task performance and nonspecific BOLD activation precluded the surgeon from using the fMRI data. Compared with DCS, fMRI had a sensitivity and specificity, respectively, of 91 and 64% in Broca's area, 93 and 18% in Wernicke's area and 100 and 100% in motor areas. A new intraoperative neurological deficit during subcortical dissection was predictive of a worsened deficit following surgery (p awake craniotomy procedures. © 2014 S. Karger AG, Basel.

Case report: Awake insertion of the intubating laryngeal mask ...

African Journals Online (AJOL)

Case report: Awake insertion of the intubating laryngeal mask airway using dexmedetomidine sedation. P Dhar, TR Tedore. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.1080/22201173.2003.10872999.

The Sleep Elaboration-Awake Pruning (SEAP) theory of memory: long term memories grow in complexity during sleep and undergo selection while awake. Clinical, psychopharmacological and creative implications.

Science.gov (United States)

Charlton, Bruce G; Andras, Peter

2009-07-01

Long term memory (LTM) systems need to be adaptive such that they enhance an organism's reproductive fitness and self-reproducing in order to maintain their complexity of communications over time in the face of entropic loss of information. Traditional 'representation-consolidation' accounts conceptualize memory adaptiveness as due to memories being 'representations' of the environment, and the longevity of memories as due to 'consolidation' processes. The assumption is that memory representations are formed while an animal is awake and interacting with the environment, and these memories are consolidated mainly while the animal is asleep. So the traditional view of memory is 'instructionist' and assumes that information is transferred from the environment into the brain. By contrast, we see memories as arising endogenously within the brain's LTM system mainly during sleep, to create complex but probably maladaptive memories which are then simplified ('pruned') and selected during the awake period. When awake the LTM system is brought into a more intense interaction with past and present experience. Ours is therefore a 'selectionist' account of memory, and could be termed the Sleep Elaboration-Awake Pruning (or SEAP) theory. The SEAP theory explains the longevity of memories in the face of entropy by the tendency for memories to grow in complexity during sleep; and explains the adaptiveness of memory by selection for consistency with perceptions and previous memories during the awake state. Sleep is therefore that behavioural state during which most of the internal processing of the system of LTM occurs; and the reason sleep remains poorly understood is that its primary activity is the expansion of long term memories. By re-conceptualizing the relationship between memory, sleep and the environment; SEAP provides a radically new framework for memory research, with implications for the measurement of memory and the design of empirical investigations in clinical

Layer-specific high-frequency spiking in the prefrontal cortex of awake rats

Directory of Open Access Journals (Sweden)

Zimbo Saroeni Raymond Maria Boudewijns

2013-06-01

Full Text Available Cortical pyramidal neurons show irregular in vivo action potential (AP spiking with high frequency bursts occurring on sparse background activity. Somatic APs can backpropagate from soma into basal and apical dendrites and locally generate dendritic calcium spikes. The critical AP frequency for generation of such dendritic calcium spikes can be very different depending on cell-type or brain area involved. Previously, it was shown in vitro that calcium electrogenesis can also be induced in L(ayer 5 pyramidal neurons of prefrontal cortex (PFC. It remains an open question whether somatic burst spiking and resulting dendritic calcium electrogenesis also occur in morphologically more compact L2/3 pyramidal neurons. Furthermore, it is not known whether critical frequencies that trigger dendritic calcium electrogenesis occur in PFC under awake conditions in vivo. Here, we addressed these issues and found that pyramidal neurons in both PFC L2/3 and L5 in awake rats spike APs in short bursts, but with different probabilities. The critical frequency for calcium electrogenesis in vitro was layer-specific and lower in L5 neurons compared to L2/3. Taking the in vitro critical frequency as predictive measure for dendritic electrogenesis during in vivo spontaneous activity, supracritical bursts in vivo were observed in a larger fraction of L5 neurons compared to L2/3 neurons but with similar incidence within these subpopulations. Together, these results show that in PFC of awake rats, AP spiking occurs at frequencies that are relevant for dendritic calcium electrogenesis and suggest that in awake rat PFC, dendritic calcium electrogenesis may be involved in neuronal computation.

Conditioned social preference, but not place preference, produced by intranasal oxytocin in female mice.

Science.gov (United States)

Kosaki, Yutaka; Watanabe, Shigeru

2016-04-01

Oxytocin (OT) has been implicated in a variety of mammalian reproductive and social behaviors, and the use of intranasal OT for clinical purposes is on the rise. However, basic actions of OT, including the rewarding or reinforcing properties of the drug, are currently not fully understood. In this study, the authors investigated whether intranasally administered OT has different reinforcing properties for social and nonsocial stimuli and whether such effects are variable between male and female subjects. Conditioned social preference (CSP) and conditioned place preference (CPP) paradigms were used to examine social and nonsocial reinforcing properties of OT. In CSP, the presence of a same-sex unfamiliar conspecific was repeatedly paired with intranasal OT, while a different conspecific was associated with saline. The reinforcing effect of OT was assessed in a postconditioning choice test under a drug-free condition. In CPP, the 2 conspecifics were replaced with nonsocial black and white compartments. The authors found that intranasal OT (12 μg) in females supported the formation of CSP (Experiment 1) but not CPP (Experiment 3). Neither CSP (Experiment 2) nor CPP (Experiment 4) was formed in males. Extended conditioning with higher dose OT (36 μg), however, abolished the initial CSP in females and produced an aversion to the OT-paired stimulus mouse. Experiment 5 indicated that it was the repeated administrations rather than the higher dose that produced the abolition of the original preference. Overall, the current results demonstrate for the first time a sex- and stimulus-dependent reinforcing property of intranasal OT in mice. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Intranasal tissue necrosis associated with opioid abuse: Case report and systematic review.

Science.gov (United States)

Morrison, Danielle A; Wise, Sarah K; DelGaudio, John M; Chowdhury, Naweed I; Levy, Joshua M

2017-12-27

Opioid abuse is a common disorder affecting over 2 million Americans. Intranasal tissue necrosis is a previously described sequela of nasal opioid inhalation, with a similar presentation to invasive fungal rhinosinusitis (IFRS). The goal of this case report and systematic review is to evaluate the evidence supporting this uncommon disease, with qualitative analysis of the presentation, management and treatment outcomes. MEDLINE, EMBASE, Google Scholar, Scopus, and Web of Science. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were utilized to identify English-language studies reporting intranasal mucosal injury associated with prescription opioid abuse. Primary outcomes included clinical presentation, treatment strategies, and outcomes. Systematic review identified 61 patients for qualitative analysis. Common clinical features include facial pain without a history of chronic sinusitis or known immunodeficiency. Diagnostic nasal endoscopy revealed superficial debris with underlying tissue necrosis, consistent with a preliminary diagnosis of IFRS. Characteristic pathologic findings include mucosal ulceration with an overlying acellular substrate, often with polarizable material. Fungal colonization is often reported, with several accounts of angiocentric invasion in immunocompetent patients. Complete symptom resolution is expected following surgical debridement with cessation of intranasal opioid inhalation, with 89% of identified patients experiencing a complete resolution of disease. Intranasal opioid abuse is a prevalent condition associated with chronic pain and tissue necrosis that is clinically concerning for invasive fungal disease. Whereas IFRS must be excluded, even in patients without known immunodeficiency, complete resolution of symptoms can be expected following surgical debridement with cessation of opioid abuse. Laryngoscope, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Guanidinylated Neomycin Conjugation Enhances Intranasal Enzyme Replacement in the Brain.

Science.gov (United States)

Tong, Wenyong; Dwyer, Chrissa A; Thacker, Bryan E; Glass, Charles A; Brown, Jillian R; Hamill, Kristina; Moremen, Kelley W; Sarrazin, Stéphane; Gordts, Philip L S M; Dozier, Lara E; Patrick, Gentry N; Tor, Yitzhak; Esko, Jeffrey D

2017-12-06

Iduronidase (IDUA)-deficient mice accumulate glycosaminoglycans in cells and tissues and exhibit many of the same neuropathological symptoms of patients suffering from Mucopolysaccharidosis I. Intravenous enzyme-replacement therapy for Mucopolysaccharidosis I ameliorates glycosaminoglycan storage and many of the somatic aspects of the disease but fails to treat neurological symptoms due to poor transport across the blood-brain barrier. In this study, we examined the delivery of IDUA conjugated to guanidinoneomycin (GNeo), a molecular transporter. GNeo-IDUA and IDUA injected intravenously resulted in reduced hepatic glycosaminoglycan accumulation but had no effect in the brain due to fast clearance from the circulation. In contrast, intranasally administered GNeo-IDUA entered the brain rapidly. Repetitive intranasal treatment with GNeo-IDUA reduced glycosaminoglycan storage, lysosome size and number, and neurodegenerative astrogliosis in the olfactory bulb and primary somatosensory cortex, whereas IDUA was less effective. The enhanced efficacy of GNeo-IDUA was not the result of increased nose-to-brain delivery or enzyme stability, but rather due to more efficient uptake into neurons and astrocytes. GNeo conjugation also enhanced glycosaminoglycan clearance by intranasally delivered sulfamidase to the brain of sulfamidase-deficient mice, a model of Mucopolysaccharidosis IIIA. These findings suggest the general utility of the guanidinoglycoside-based delivery system for restoring missing lysosomal enzymes in the brain. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Beam studies and experimental facility for the AWAKE experiment at CERN

CERN Document Server

Bracco, Chiara; Petrenko, Alexey; Timko, Helga; Argyropoulos, Theodoros; Bartosik, Hannes; Bohl, Thomas; Esteban Müller, Juan; Goddard, Brennan; Meddahi, Malika; Pardons, Ans; Shaposhnikova, Elena; Velotti, Francesco M; Vincke, Helmut

2014-01-01

A Proton Driven Plasma Wakefield Acceleration Experiment has been proposed as an approach to eventually accelerate an electron beam to the TeV energy range in a single plasma section. To verify this novel technique, a proof of principle R&D experiment, AWAKE, is planned at CERN using 400 GeV proton bunches from the SPS. An electron beam will be injected into the plasma cell to probe the accelerating wakefield. The AWAKE experiment will be installed in the CNGS facility profiting from existing infrastructure where only minor modifications need to be foreseen. The design of the experimental area and the proton and electron beam lines are shown. The achievable SPS proton bunch properties and their reproducibility have been measured and are presented.

Infection of growing swine with porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae — Effects on growth, serum metabolites, and insulin-like growth factor-I.

OpenAIRE

Roberts, N. Elizabeth; Almond, Glen W.

2003-01-01

This study evaluated the influence of concomitant infections with porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae on growth performance, serum metabolite concentrations, and serum insulin-like growth factor-I (IGF-I) in growing pigs. Twenty-two barrows (10 weeks of age) were treated with either an intranasal administration of PRRSV and an intratracheal infusion of M. hyopneumoniae (treatment; n = 8) or a sham inoculation with medium (sham; n = 8), or w...

[BETA-ADRENERGIC REGULATION OF THE ADENYLYL CYCLASE SIGNALING SYSTEM IN MYOCARDIUM AND BRAIN OF RATS WITH OBESITY AND TYPES 2 DIABETES MELLITUS AND THE EFFECT OF LONG-TERM INTRANASAL INSULIN TREATMENT].

Science.gov (United States)

Kuznetsova, L A; Sharova, T S; Pertseva, M N; Shpakov, A O

2015-01-01

The stimulating effect of norepinephrine, isoproterenol and selective β-adrenoceptor (β3-AR) agonists BRL 37344 and CL 316.243 on the adenylyl cyclase signaling system (ACSS) in the brain and myocardium of young and mature rats (disease induction at 2 and 4 months, respectively) with experimental obesity and type 2 diabetes mellitus (DM2), and the influence of long-term treatment of animals with intranasal insulin (I-I) were studied. The AC stimulatory effects of β-agonist isoproterenol in animals with obesity and DM2 was shown to be practically unchanged. The respective effects of norepinephrine on the AC activity were attenuated in the brain of young and mature rats and in the myocardium if mature rats, and the I-I treatment led to their partial recovery. In the brain and myocardium of mature rats with obesity and DM2, the enhancement of the AC stimulatory effects of β3-AR agonists was observed, white in young rats the influence of the same pathological conditions was lacking. The I-I treatment decreased the AC stimulatory effects of β3-agonists to their levels in the control. Since functional disruption of the adrenergic agonist-sensitive ACSS can lead to metabolic syndrome and DM2, the recovery of this system by the I-I treatment offers one of the ways to correct these diseases and their complications in the nervous and cardiovascular systems.

Intranasal immunization with chitosan/pCETP nanoparticles inhibits atherosclerosis in a rabbit model of atherosclerosis.

Science.gov (United States)

Yuan, Xiying; Yang, Xiaorong; Cai, Danning; Mao, Dan; Wu, Jie; Zong, Li; Liu, Jingjing

2008-07-04

In search of a convenient and pain-free route of administration of DNA vaccine against atherosclerosis, the plasmid pCR-X8-HBc-CETP (pCETP) encoding B-cell epitope of cholesteryl ester transfer protein C-terminal fragment displayed by Hepatitis B virus core particle was condensed with chitosan to form chitosan/pCETP nanoparticles. Cholesterol-fed rabbits were then intranasally immunized with the chitosan/pCETP nanoparticles to evaluate antiatherogenic effects. The results showed that significant serum antibodies against CETP were detected by enzyme-linked immunosorbent analysis and verified by Western blot analysis. The significant anti-CETP IgG lasted for 21 weeks in the rabbits immunized intranasally. Moreover, the atherogenic index was significantly lower compared with the saline control (5.95 versus 2.39, pnanoparticles was 59.2% less than those treated with saline (29.0+/-10.9% versus 71.0+/-14.4%, pintramuscularly injected with pCETP solution (29.0+/-10.9% versus 21.2+/-14.2%, p>0.05). Thus, chitosan/pCETP nanoparticles could significantly attenuate the progression of atherosclerosis by intranasal immunization. The results suggested that intranasal administration could be potentially developed as a vaccination route against atherosclerosis.

Combination of Continuous Dexmedetomidine Infusion with Titrated Ultra-Low-Dose Propofol-Fentanyl for an Awake Craniotomy; Case report

Directory of Open Access Journals (Sweden)

Samaresh Das

2016-08-01

Full Text Available An awake craniotomy is a continuously evolving technique used for the resection of brain tumours from the eloquent cortex. We report a 29-year-old male patient who presented to the Khoula Hospital, Muscat, Oman, in 2016 with a two month history of headaches and convulsions due to a space-occupying brain lesion in close proximity with the left motor cortex. An awake craniotomy was conducted using a scalp block, continuous dexmedetomidine infusion and a titrated ultra-low-dose of propofol-fentanyl. The patient remained comfortable throughout the procedure and the intraoperative neuropsychological tests, brain mapping and tumour resection were successful. This case report suggests that dexmedetomidine in combination with titrated ultra-low-dose propofolfentanyl are effective options during an awake craniotomy, ensuring optimum sedation, minimal disinhibition and a rapid recovery. To the best of the authors’ knowledge, this is the first awake craniotomy conducted successfully in Oman.

Comparison of desmopressin (DDAVP tablet and intranasal spray in the treatment of central diabetes insipidus

Directory of Open Access Journals (Sweden)

"Bagher Larijani

2005-07-01

Full Text Available Desmoperssin is the drug of choice for treatment of central diabetes insipidus and most commonly it is used as intranasal spray. In this study, efficacy and side effects of oral desmopressin was compared with the intranasal spray. This study was before -after clinical trial on 14 outpatients (9 F, 5 M, age 14 -50 Y with central diabetes insipidus who had been treated with intranasal spray of desmopressin previously. Weight, pulse rate and blood pressure (sitting -standing, biochemical profile, serum electrolytes, 24h urine volume, specific gravity of urine and LFT was measured before and after 1 month study. Starting dose for each patient was one oral tablet of DDAVP (0.1 mg per 8 hours. Paired Samples T-Test was used for data analysis. No clinically significant changes were found as regard to weight, pulse rate, blood pressure, blood chemistry, electrolyte and urinalysis. Single reported adverse effect was headache (43% in tablet group and dyspnea (7% in spray group. Both dosage forms were able to control diurnal polyuria and nocturnal polyuria. The antidiuretic dose - equivalence ratio for intranasal to oral desmopressin was 1: 18. Spray was superior in terms of rapid onset of action and duration of antidiuretic action in 100% and 78% of cases (not significant, respectively. Tablets were more available and much more easily consumed as reported by patients, in 86% (P=0.0006. Treatment with tablets offers a good alternative to the intranasal route, especially in patients with chronic rhinitis or common cold and similar conditions.

[Difficult Ventilation Requiring Emergency Endotracheal Intubation during Awake Craniotomy Managed by Laryngeal Mask Airway].

Science.gov (United States)

Matsuda, Asako; Mizota, Toshiyuki; Tanaka, Tomoharu; Segawa, Hajime; Fukuda, Kazuhiko

2016-04-01

We report a case of difficult ventilation requiring emergency endotracheal intubation during awake craniotomy managed by laryngeal mask airway (LMA). A 45-year-old woman was scheduled to receive awake craniotomy for brain tumor in the frontal lobe. After anesthetic induction, airway was secured using ProSeal LMA and patient was mechanically ventilated in pressure-control mode. Patient's head was fixed with head-pins at anteflex position, and the operation started. About one hour after the start of the operation, tidal volume suddenly decreased. We immediately started manual ventilation, but the airway resistance was extremely high and we could not adequately ventilate the patient. We administered muscle relaxant for suspected laryngospasm, but ventilatory status did not improve; so we decided to conduct emergency endotracheal intubation. We tried to intubate using Airwayscope or LMA-Fastrach, but they were not effective in our case. Finally trachea was intubated using transnasal fiberoptic bronchoscopy. We discuss airway management during awake craniotomy, focusing on emergency endotracheal intubation during surgery.

Laser pulse propagation in a meter scale rubidium vapor/plasma cell in AWAKE experiment

Energy Technology Data Exchange (ETDEWEB)

Joulaei, A. [Max-Planck Institute for Physics, Munich (Germany); University of Mazandaran (Iran, Islamic Republic of); Moody, J. [Max-Planck Institute for Physics, Munich (Germany); Berti, N.; Kasparian, J. [University of Geneva (Switzerland); Mirzanejhad, S. [University of Mazandaran (Iran, Islamic Republic of); Muggli, P. [Max-Planck Institute for Physics, Munich (Germany)

2016-09-01

We present the results of numerical studies of laser pulse propagating in a 3.5 cm Rb vapor cell in the linear dispersion regime by using a 1D model and a 2D code that has been modified for our special case. The 2D simulation finally aimed at finding laser beam parameters suitable to make the Rb vapor fully ionized to obtain a uniform, 10 m-long, at least 1 mm in radius plasma in the next step for the AWAKE experiment. - Highlights: • Discussion the AWAKE plasma source based on photoionization of rubidium vapor with a TW/cm^2 Intensity laser with a spectrum across valence ground state transition resonances. • Examines the propagation of the AWAKE ionization laser through rubidium vapor at design density on a small scale and reduced intensity with a linear numerical model compared to experimental results. • Discusses physics of pulse propagation through the vapor at high intensity regime where strong ionization occurs within the laser pulse.

[Non-verbal communication of patients submitted to heart surgery: from awaking after anesthesia to extubation].

Science.gov (United States)

Werlang, Sueli da Cruz; Azzolin, Karina; Moraes, Maria Antonieta; de Souza, Emiliane Nogueira

2008-12-01

Preoperative orientation is an essential tool for patient's communication after surgery. This study had the objective of evaluating non-verbal communication of patients submitted to cardiac surgery from the time of awaking from anesthesia until extubation, after having received preoperative orientation by nurses. A quantitative cross-sectional study was developed in a reference hospital of the state of Rio Grande do Sul, Brazil, from March to July 2006. Data were collected in the pre and post operative periods. A questionnaire to evaluate non-verbal communication on awaking from sedation was applied to a sample of 100 patients. Statistical analysis included Student, Wilcoxon, and Mann Whittney tests. Most of the patients responded satisfactorily to non-verbal communication strategies as instructed on the preoperative orientation. Thus, non-verbal communication based on preoperative orientation was helpful during the awaking period.

Conscious sedation for awake craniotomy in intraoperative magnetic resonance imaging operating theater

Science.gov (United States)

Takrouri, Mohamad Said Maani; Shubbak, Firas A.; Al Hajjaj, Aisha; Maestro, Rolando F. Del; Soualmi, Lahbib; Alkhodair, Mashael H.; Alduraiby, Abrar M.; Ghanem, Najeeb

2010-01-01

This case report describes the first case in intraoperative magnetic resonance imaging operating theater (iMRI OT) (BrainSuite®) of awake craniotomy for frontal lobe glioma excision in a 24-year-old man undergoing eloquent cortex language mapping intraoperatively. As he was very motivated to take pictures of him while being operated upon, the authors adapted conscious sedation technique with variable depth according to Ramsey's scale, in order to revert to awake state to perform the intended neurosurgical procedure. The patient tolerated the situation satisfactorily and was cooperative till the finish, without any event. We elicit in this report the special environment of iMRI OT for lengthy operation in pinned fixed patient having craniotomy. PMID:25885085

Anxiety in the preoperative phase of awake brain tumor surgery

NARCIS (Netherlands)

Ruis, Carla; Huenges Wajer, I.M.C.; Robe, Pierre; van Zandvoort, Martine

OBJECTIVE: Awake surgery emerges as a standard of care for brain tumors located in or near eloquent areas. Levels of preoperative anxiety in patients are important, because anxiety can influence cognitive performance and participation, hence altering the outcome of the procedure. In this study we

Anxiety in the preoperative phase of awake brain tumor surgery

NARCIS (Netherlands)

Ruis, C.; Huenges Wajer, I.M.C.; Robe, Pierre; van Zandvoort, M.J.E.

Objective Awake surgery emerges as a standard of care for brain tumors located in or near eloquent areas. Levels of preoperative anxiety in patients are important, because anxiety can influence cognitive performance and participation, hence altering the outcome of the procedure. In this study we

Assessment of insulin resistance in fructose-fed rats with 125I-6-deoxy-6-iodo-D-glucose, a new tracer of glucose transport

International Nuclear Information System (INIS)

Perret, Pascale; Slimani, Lotfi; Briat, Arnaud; Villemain, Daniele; Fagret, Daniel; Ghezzi, Catherine; Halimi, Serge; Demongeot, Jacques

2007-01-01

Insulin resistance, characterised by an insulin-stimulated glucose transport defect, is an important feature of the pre-diabetic state that has been observed in numerous pathological disorders. The purpose of this study was to assess variations in glucose transport in rats using 125 I-6-deoxy-6-iodo-D-glucose (6DIG), a new tracer of glucose transport proposed as an imaging tool to assess insulin resistance in vivo. Two protocols were performed, a hyperinsulinaemic-euglycaemic clamp and a normoinsulinaemic-normoglycaemic protocol, in awake control and insulin-resistant fructose-fed rats. The tracer was injected at steady state, and activity in 11 tissues and the blood was assessed ex vivo at several time points. A multicompartmental mathematical model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the organs. Insulin sensitivity of fructose-fed rats, estimated by the glucose infusion rate, was reduced by 40% compared with control rats. At steady state, 6DIG uptake was significantly stimulated by insulin in insulin-sensitive tissues of control rats (basal versus insulin: diaphragm, p < 0.01; muscle, p < 0.05; heart, p < 0.001), whereas insulin did not stimulate 6DIG uptake in insulin-resistant fructose-fed rats. Moreover, in these tissues, the fractional transfer coefficients of entrance were significantly increased with insulin in control rats (basal vs insulin: diaphragm, p < 0.001; muscle, p < 0.001; heart, p < 0.01) whereas no significant changes were observed in fructose-fed rats. This study sets the stage for the future use of 6DIG as a non-invasive means for the evaluation of insulin resistance by nuclear imaging. (orig.)

Assessment of insulin resistance in fructose-fed rats with 125I-6-deoxy-6-iodo-D-glucose, a new tracer of glucose transport

Science.gov (United States)

Perret, Pascale; Slimani, Lotfi; Briat, Arnaud; Villemain, Danièle; Halimi, Serge; Demongeot, Jacques; Fagret, Daniel; Ghezzi, Catherine

2007-01-01

Purpose Insulin resistance, characterised by an insulin-stimulated glucose transport defect, is an important feature of the pre-diabetic state and it has been observed in numerous pathological disorders. The purpose of this study was to assess variations in glucose transport in rats with 125I-6-Deoxy-6-Iodo-D-glucose (6DIG), a new tracer of glucose transport proposed as an imaging tool to assess insulin resistance in vivo. Methods Two protocols were performed, a hyperinsulinaemic-euglycaemic clamp and a normoinsulinaemic normoglycaemic protocol, in awake control and insulin-resistant fructose-fed rats. The tracer was injected at steady state, and activity in 11 tissues and the blood were assessed ex vivo at several time points. A multicompartmental mathematical model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the organs. Results Insulin sensitivity of fructose-fed rats, estimated by the glucose infusion rate, was reduced by 40% compared with control rats. At steady-state, 6DIG uptake was significantly stimulated by insulin in insulin-sensitive tissues of control rats (basal versus insulin: diaphragm, p<0.01; muscle, p<0.05; heart, p<0.001), whereas insulin did not stimulate 6DIG uptake in insulin-resistant fructose-fed rats. Moreover, in these tissues, the fractional transfer coefficients of entrance were significantly increased with insulin in control rats (basal vs insulin: diaphragm, p<0.001; muscle, p<0.001; heart, p<0.01) and whereas no significant changes were observed in fructose-fed rats. Conclusion This study sets the stage for the future use of 6DIG as a non-invasive means for the evaluation of insulin resistance by nuclear imaging. PMID:17171359

Early Experience with Combining Awake Craniotomy and Intraoperative Navigable Ultrasound for Resection of Eloquent Region Gliomas.

Science.gov (United States)

Moiyadi, Aliasgar; Shetty, Prakash

2017-03-01

Introduction  Optimal resection of tumors in eloquent locations requires a combination of intraoperative imaging and functional monitoring during surgery. Combining awake surgery with intraoperative magnetic resonanceis logistically challenging. Navigable ultrasound (US) is a useful alternative in such cases. Methods  A total of 22 subjects with eloquent tumors were operated on (1 intended biopsy and 21 intended radical resections) using combined modality three-dimensional (3D) US and awake craniotomy with intraoperative clinical monitoring. We describe the technical details for these cases specifically addressing the feasibility of combining the two modalities. Results  US was used for resection control in 18 cases. There were technical limitations in three cases. Transient intraoperative worsening was encountered in eight, necessitating premature termination of the procedure. All patients tolerated the awake procedure well. Mean duration of the surgery was 3.2 hours. Radical resections were obtained in 14 of 18 where this was intended and in 12 of the 13 where there was no adverse intraoperative monitoring event prompting premature termination of the resection. Conclusions  Combining awake surgery with 3DUS is feasible and beneficial. It does not entail any additional surgical workflow modification or patient discomfort. This combined modality intraoperative monitoring can be beneficial for eloquent region tumors. Georg Thieme Verlag KG Stuttgart · New York.

Intraoperative Subcortical Electrical Mapping of the Optic Tract in Awake Surgery Using a Virtual Reality Headset.

Science.gov (United States)

Mazerand, Edouard; Le Renard, Marc; Hue, Sophie; Lemée, Jean-Michel; Klinger, Evelyne; Menei, Philippe

2017-01-01

Brain mapping during awake craniotomy is a well-known technique to preserve neurological functions, especially the language. It is still challenging to map the optic radiations due to the difficulty to test the visual field intraoperatively. To assess the visual field during awake craniotomy, we developed the Functions' Explorer based on a virtual reality headset (FEX-VRH). The impaired visual field of 10 patients was tested with automated perimetry (the gold standard examination) and the FEX-VRH. The proof-of-concept test was done during the surgery performed on a patient who was blind in his right eye and presenting with a left parietotemporal glioblastoma. The FEX-VRH was used intraoperatively, simultaneously with direct subcortical electrostimulation, allowing identification and preservation of the optic radiations. The FEX-VRH detected 9 of the 10 visual field defects found by automated perimetry. The patient who underwent an awake craniotomy with intraoperative mapping of the optic tract using the FEX-VRH had no permanent postoperative visual field defect. Intraoperative visual field assessment with the FEX-VRH during direct subcortical electrostimulation is a promising approach to mapping the optical radiations and preventing a permanent visual field defect during awake surgery for epilepsy or tumor. Copyright © 2016 Elsevier Inc. All rights reserved.

Is a wake-up call in order? Review of the evidence for awake craniotomy.

Science.gov (United States)

Paldor, Iddo; Drummond, Katharine J; Awad, Mohammed; Sufaro, Yuval Z; Kaye, Andrew H

2016-01-01

Awake craniotomy (AC) has been used in increasing frequency in the past few decades. It has mainly been used for resection of intrinsic tumors, but also, rarely, for other pathologies. The vast majority of reports specific to one pathology, however, have focused on resection of low grade glioma in the awake setting. Tumors in eloquent areas have mainly been resected when the patient is awake for the purpose of preservation of function. Motor function is the most documented, and most successfully preserved function. Other functions are harder to localize with direct electrical stimulation (DES), and thus more difficult to preserve. The success rate of DES localization correlates to the rate of function preservation. The effect of AC on extent of resection is inconsistent in the literature. Other functions, such as sensory and visuospatial recognition, have been protected during AC, but this is best performed in large, referral centers that have experience with the procedure. Other benefits to AC, such as cost-effectiveness and reduction in patient pain and anxiety, have also been reported. Copyright © 2015 Elsevier Ltd. All rights reserved.

Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury.

Science.gov (United States)

Donega, Vanessa; Nijboer, Cora H; van Tilborg, Geralda; Dijkhuizen, Rick M; Kavelaars, Annemieke; Heijnen, Cobi J

2014-11-01

Previous work from our group has shown that intranasal MSC-treatment decreases lesion volume and improves motor and cognitive behavior after hypoxic-ischemic (HI) brain damage in neonatal mice. Our aim was to determine the kinetics of MSC migration after intranasal administration, and the early effects of MSCs on neurogenic processes and gliosis at the lesion site. HI brain injury was induced in 9-day-old mice and MSCs were administered intranasally at 10days post-HI. The kinetics of MSC migration were investigated by immunofluorescence and MRI analysis. BDNF and NGF gene expression was determined by qPCR analysis following MSC co-culture with HI brain extract. Nestin, Doublecortin, NeuN, GFAP, Iba-1 and M1/M2 phenotypic expression was assessed over time. MRI and immunohistochemistry analyses showed that MSCs reach the lesion site already within 2h after intranasal administration. At 12h after administration the number of MSCs at the lesion site peaks and decreases significantly at 72h. The number of DCX(+) cells increased 1 to 3days after MSC administration in the SVZ. At the lesion, GFAP(+)/nestin(+) and DCX(+) expression increased 3 to 5days after MSC-treatment. The number of NeuN(+) cells increased within 5days, leading to a dramatic regeneration of the somatosensory cortex and hippocampus at 18days after intranasal MSC administration. Interestingly, MSCs expressed significantly more BDNF gene when exposed to HI brain extract in vitro. Furthermore, MSC-treatment resulted in the resolution of the glial scar surrounding the lesion, represented by a decrease in reactive astrocytes and microglia and polarization of microglia towards the M2 phenotype. In view of the current lack of therapeutic strategies, we propose that intranasal MSC administration is a powerful therapeutic option through its functional repair of the lesion represented by regeneration of the cortical and hippocampal structure and decrease of gliosis. Copyright © 2014. Published by Elsevier Inc.

Anesthetic management with scalp nerve block and propofol/remifentanil infusion during awake craniotomy in an adolescent patient -A case report-

Science.gov (United States)

Sung, Bohyun; Park, Jin-Woo; Byon, Hyo-Jin; Kim, Jin-Tae; Kim, Chong Sung

2010-01-01

Despite of various neurophysiologic monitoring methods under general anesthesia, functional mapping at awake state during brain surgery is helpful for conservation of speech and motor function. But, awake craniotomy in children or adolescents is worrisome considering their emotional friabilities. We present our experience on anesthetic management for awake craniotomy in an adolescent patient. The patient was 16 years old male who would undergo awake craniotomy for removal of brain tumor. Scalp nerve block was done with local anesthetics and we infused propofol and remifentanil with target controlled infusion. The patient endured well and was cooperative before scalp suture, but when surgeon sutured scalp, he complained of pain and was suddenly agitated. We decided change to general anesthesia. Neurosurgeon did full neurologic examinations and there was no neurologic deficit except facial palsy of right side. Facial palsy had improved with time. PMID:21286435

Assessment of insulin resistance in fructose-fed rats with {sup 125}I-6-deoxy-6-iodo-D-glucose, a new tracer of glucose transport

Energy Technology Data Exchange (ETDEWEB)

Perret, Pascale; Slimani, Lotfi; Briat, Arnaud; Villemain, Daniele; Fagret, Daniel; Ghezzi, Catherine [INSERM, E340, 38000 Grenoble, (France); Univ Grenoble, 38000 Grenoble, (France); Halimi, Serge [CHRU Grenoble, Hopital Michallon, Service de Diabetologie, 38000 Grenoble, (France); Demongeot, Jacques [Univ Grenoble, 38000 Grenoble, (France); CNRS, UMR 5525, 38000 Grenoble, (France)

2007-05-15

Insulin resistance, characterised by an insulin-stimulated glucose transport defect, is an important feature of the pre-diabetic state that has been observed in numerous pathological disorders. The purpose of this study was to assess variations in glucose transport in rats using {sup 125}I-6-deoxy-6-iodo-D-glucose (6DIG), a new tracer of glucose transport proposed as an imaging tool to assess insulin resistance in vivo. Two protocols were performed, a hyperinsulinaemic-euglycaemic clamp and a normoinsulinaemic-normoglycaemic protocol, in awake control and insulin-resistant fructose-fed rats. The tracer was injected at steady state, and activity in 11 tissues and the blood was assessed ex vivo at several time points. A multicompartmental mathematical model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the organs. Insulin sensitivity of fructose-fed rats, estimated by the glucose infusion rate, was reduced by 40% compared with control rats. At steady state, 6DIG uptake was significantly stimulated by insulin in insulin-sensitive tissues of control rats (basal versus insulin: diaphragm, p < 0.01; muscle, p < 0.05; heart, p < 0.001), whereas insulin did not stimulate 6DIG uptake in insulin-resistant fructose-fed rats. Moreover, in these tissues, the fractional transfer coefficients of entrance were significantly increased with insulin in control rats (basal vs insulin: diaphragm, p < 0.001; muscle, p < 0.001; heart, p < 0.01) whereas no significant changes were observed in fructose-fed rats. This study sets the stage for the future use of 6DIG as a non-invasive means for the evaluation of insulin resistance by nuclear imaging. (orig.)

Efektivitas Terapi Kortikosteroid Intranasal pada Hipertrofi Adenoid Usia Dewasa berdasarkan Pemeriksaan Narrow Band Imaging

Directory of Open Access Journals (Sweden)

Sinta Sari Ratunanda

2016-12-01

Full Text Available Adenoid hypertrophy is a process in which adenoid size becomes enlarged and causes clinical symptoms, especially nasal obstruction. Adenoid hypertrophy can be due to physiological, inflammatory, or malignancy processes. Adenoid inflammatory process can be assessed using a flexible fiberoptic nasoendoscopy with narrow band imaging (NBI. Intranasal corticosteroid is one of the choices to treat adenoid hypertrophy in children; however, more experiments are needed to use it in adults. This study was performed in the period of November 2012 to January 2013 at the outpatient clinic of the Otorhinolaryngology-Head and Neck Surgery Department of Dr. Hasan Sadikin General Hospital Bandung, using pre- and post-test open-labeled quasiexperimental design. Sample was selected through consecutive sampling, involving 11 subjects. Diagnosis was based on research subject’s anamnesis, ear nose and throat (ENT physical examination, NBI-equipped fiberoptic nasoendocopy examination, and adenoid mucosal biopsy. Subjects were given intranasal corticosteroid therapy for four weeks. NBI-equipped fiberoptic nasoendocopy examination and biopsy examination were performed after therapy. Data were analyzed using Wilcoxon test, showing significant improvement of the adenoid inflammation after intranasal corticosteroids therapy (p<0.05. McNemar test results showed a significant reduction in adenoid size (p<0.05. Spearman rank test showed a significant correlation between histopathologic findings and NBI examination result (p<0.05. In conclusion, intranasal corticosteroids are effective for adult adenoid hypertrophy treatment based on NBI examination. [MKB. 2016;48(4:228–33

Awake craniotomy may further improve neurological outcome of intraoperative MRI-guided brain tumor surgery.

Science.gov (United States)

Tuominen, Juho; Yrjänä, Sanna; Ukkonen, Anssi; Koivukangas, John

2013-10-01

Results of awake craniotomy are compared to results of resections done under general anesthesia in patients operated with IMRI control. We hypothesized that stimulation of the cortex and white matter during awake surgery supplements IMRI control allowing for safer resection of eloquent brain area tumors. The study group consisted of 20 consecutive patients undergoing awake craniotomy with IMRI control. Resection outcome of these patients was compared to a control group of 20 patients operated in the same IMRI suite but under general anesthesia without cortical stimulation. The control group was composed of those patients whose age, sex, tumor location, recurrence and histology best matched to patients in study group. Cortical stimulation identified functional cortex in eight patients (40 %). Postoperatively the neurological condition in 16 patients (80 %) in the study group was unchanged or improved compared with 13 patients (65 %) in the control group. In both groups, three patients (15 %) had transient impairment symptoms. There was one patient (5 %) with permanent neurological impairment in the study group compared to four patients (20 %) in the control group. These differences between groups were not statistically significant. There was no surgical mortality in either group and the overall infection rate was 5 %. Mean operation time was 4 h 45 min in the study group and 3 h 15 min in the control group. The study consisted of a limited patient series, but it implies that awake craniotomy with bipolar cortical stimulation may help to reduce the risk of postoperative impairment following resection of tumors located in or near speech and motor areas also under IMRI control.

An unusual case of repeated venous air embolism during awake ...

African Journals Online (AJOL)

Keywords: awake craniotomy, burr hole, deep brain stimulation, neurosurgery, venous air embolism. Introduction ... surgery started with the right burr hole and after the dura mater was opened, the ... opened. The patient was initially comfortable but then developed ... The surgery for the insertion of DBS on the left side was.

Short-term weight loss attenuates local tissue inflammation and improves insulin sensitivity without affecting adipose inflammation in obese mice.

Science.gov (United States)

Jung, Dae Young; Ko, Hwi Jin; Lichtman, Eben I; Lee, Eunjung; Lawton, Elizabeth; Ong, Helena; Yu, Kristine; Azuma, Yoshihiro; Friedline, Randall H; Lee, Ki Won; Kim, Jason K

2013-05-01

Obesity is a major cause of insulin resistance, and weight loss is shown to improve glucose homeostasis. But the underlying mechanism and the role of inflammation remain unclear. Male C57BL/6 mice were fed a high-fat diet (HFD) for 12 wk. After HFD, weight loss was induced by changing to a low-fat diet (LFD) or exercise with continuous HFD. The weight loss effects on energy balance and insulin sensitivity were determined using metabolic cages and hyperinsulinemic euglycemic clamps in awake mice. Diet and exercise intervention for 3 wk caused a modest weight loss and improved glucose homeostasis. Weight loss dramatically reduced local inflammation in skeletal muscle, liver, and heart but not in adipose tissue. Exercise-mediated weight loss increased muscle glucose metabolism without affecting Akt phosphorylation or lipid levels. LFD-mediated weight loss reduced lipid levels and improved insulin sensitivity selectively in liver. Both weight loss interventions improved cardiac glucose metabolism. These results demonstrate that a short-term weight loss with exercise or diet intervention attenuates obesity-induced local inflammation and selectively improves insulin sensitivity in skeletal muscle and liver. Our findings suggest that local factors, not adipose tissue inflammation, are involved in the beneficial effects of weight loss on glucose homeostasis.

Formulation and In-vivo Pharmacokinetic Consideration of Intranasal Microemulsion and Mucoadhesive Microemulsion of Rivastigmine for Brain Targeting.

Science.gov (United States)

Shah, Brijesh; Khunt, Dignesh; Misra, Manju; Padh, Harish

2018-01-02

Presence of tight junctions in blood brain barrier (BBB) pose a major hurdle for delivery of drug and severely affects adequate therapeutic concentration to reach the brain. In present work, we have selected Rivastigmine hydrogen tartrate (RHT), a reversible cholinesterase inhibitor, which exhibits extensive first-pass metabolism, resulting in limited absolute bioavailability (36%). RHT shows extremely low aqueous solubility and poor penetration, resulting in inadequate concentration reaching the brain, thus necessitating frequent oral dosing. To overcome these problems of RHT, microemulsion (ME) and mucoadhesive microemulsion (MME) of RHT were formulated for brain targeting via intranasal delivery route and compared on the basis of in vivo pharmacokinetics. ME and MME formulations containing RHT were developed by water titration method. Characterization of ME and MME was done for various physicochemical parameters, nasal spray pattern, and in vivo pharmacokinetics quantitatively and qualitatively (gamma scintigraphy studies). The developed ME and MME were transparent having globule size approximately in the range of 53-55 nm. Pharmacokinetic studies showed higher values for C max and DTP for intranasal RHT: CH-ME over RHT-ME, thus indicating the effect of chitosan in modulating tight junctions, thereby enhanced paracellular transport of RHT. Gamma scintigraphy and in vivo pharmacokinetic study suggested enhanced RHT concentration, upon intranasal administration of RHT:CH-ME, compare with other groups administered formulations intranasally. These findings suggested the potential of non-invasive intranasal route for brain delivery, especially for therapeutics, facing challenges in oral administration.

Pulmonary permeability assessed by fluorescent-labeled dextran instilled intranasally into mice with LPS-induced acute lung injury.

Directory of Open Access Journals (Sweden)

Honglei Chen

Full Text Available Several different methods have been used to assess pulmonary permeability in response to acute lung injury (ALI. However, these methods often involve complicated procedures and algorithms that are difficult to precisely control. The purpose of the current study is to establish a feasible method to evaluate alterations in lung permeability by instilling fluorescently labeled dextran (FITC-Dextran intranasally.For the mouse model of direct ALI, lipopolysaccharide (LPS was administered intranasally. FITC-Dextran was instilled intranasally one hour before the mice were euthanized. Plasma fluorescence intensities from the LPS group were significantly higher than in the control group. To determine the reliability and reproducibility of the procedure, we also measured the lung wet-to-dry weight ratio, the protein concentration of the bronchoalveolar lavage fluid, tight and adherens junction markers and pathological changes. Consistent results were observed when the LPS group was compared with the control group. Simultaneously, we found that the concentration of plasma FITC-Dextran was LPS dose-dependent. The concentration of plasma FITC-Dextran also increased with initial intranasal FITC-Dextran doses. Furthermore, increased fluorescence intensity of plasma FITC-Dextran was found in the intraperitoneally LPS-induced ALI model.In conclusion, the measurement of FITC-Dextran in plasma after intranasal instillation is a simple, reliable, and reproducible method to evaluate lung permeability alterations in vivo. The concentration of FITC-Dextran in the plasma may be useful as a potential peripheral biomarker of ALI in experimental clinical studies.

Pulmonary permeability assessed by fluorescent-labeled dextran instilled intranasally into mice with LPS-induced acute lung injury.

Science.gov (United States)

Chen, Honglei; Wu, Shaoping; Lu, Rong; Zhang, Yong-guo; Zheng, Yuanyuan; Sun, Jun

2014-01-01

Several different methods have been used to assess pulmonary permeability in response to acute lung injury (ALI). However, these methods often involve complicated procedures and algorithms that are difficult to precisely control. The purpose of the current study is to establish a feasible method to evaluate alterations in lung permeability by instilling fluorescently labeled dextran (FITC-Dextran) intranasally. For the mouse model of direct ALI, lipopolysaccharide (LPS) was administered intranasally. FITC-Dextran was instilled intranasally one hour before the mice were euthanized. Plasma fluorescence intensities from the LPS group were significantly higher than in the control group. To determine the reliability and reproducibility of the procedure, we also measured the lung wet-to-dry weight ratio, the protein concentration of the bronchoalveolar lavage fluid, tight and adherens junction markers and pathological changes. Consistent results were observed when the LPS group was compared with the control group. Simultaneously, we found that the concentration of plasma FITC-Dextran was LPS dose-dependent. The concentration of plasma FITC-Dextran also increased with initial intranasal FITC-Dextran doses. Furthermore, increased fluorescence intensity of plasma FITC-Dextran was found in the intraperitoneally LPS-induced ALI model. In conclusion, the measurement of FITC-Dextran in plasma after intranasal instillation is a simple, reliable, and reproducible method to evaluate lung permeability alterations in vivo. The concentration of FITC-Dextran in the plasma may be useful as a potential peripheral biomarker of ALI in experimental clinical studies.

Classifying Multiple Types of Hand Motions Using Electrocorticography During Intraoperative Awake Craniotomy & Seizure Monitoring Processes - Case Studies

Directory of Open Access Journals (Sweden)

Tao eXie

2015-10-01

Full Text Available In this work, some case studies were conducted toclassify several kinds of hand motions from electrocorticography(ECoG signals during intraoperative awake craniotomy &extraoperative seizure monitoring processes. Four subjects (P1,P2 with intractable epilepsy during seizure monitoring and P3,P4 with brain tumor during awake craniotomy participatedin the experiments. Subjects performed three types of handmotions (Grasp, Thumb-finger motion and Index-finger motioncontralateral to the motor cortex covered with ECoG electrodes.Two methods were used for signal processing. Method I:autoregressive (AR model with burg method was applied toextract features, and additional waveform length (WL featurehas been considered, finally the linear discriminative analysis(LDA was used as the classifier. Method II: stationary subspaceanalysis (SSA was applied for data preprocessing, and thecommon spatial pattern (CSP was used for feature extractionbefore LDA decoding process. Applying method I, the threeclassaccuracy of P1□P4 were 90.17%, 96.00%, 91.77% and92.95% respectively. For method II, the three-class accuracy ofP1□P4 were 72.00%, 93.17%, 95.22% and 90.36% respectively.This study verified the possibility of decoding multiple handmotion types during an awake craniotomy, which is the firststep towards dexterous neuroprosthetic control during surgicalimplantation, in order to verify the optimal placement of electrodes.The accuracy during awake craniotomy was comparableto results during seizure monitoring. This study also indicatedthat ECoG was a promising approach for precise identificationof eloquent cortex during awake craniotomy, and might forma promising BCI system that could benefit both patients andneurosurgeons.

Intranasal haloperidol-loaded miniemulsions for brain targeting: Evaluation of locomotor suppression and in-vivo biodistribution.

Science.gov (United States)

El-Setouhy, Doaa Ahmed; Ibrahim, A B; Amin, Maha M; Khowessah, Omneya M; Elzanfaly, Eman S

2016-09-20

Haloperidol is a commonly prescribed antipsychotic drug currently administered as oral and injectable preparations. This study aimed to prepare haloperidol intranasal miniemulsion helpful for psychiatric emergencies and exhibiting lower systemic exposure and side effects associated with non-target site delivery. Haloperidol miniemulsions were successfully prepared by spontaneous emulsification adopting 2(3) factorial design. The effect of three independent variables at two levels each namely; oil type (Capmul®-Capryol™90), lipophilic emulsifier type (Span 20-Span 80) and HLB value (12-14) on globule size, PDI and percent locomotor activity inhibition in mice was evaluated. The optimized formula (F4, Capmul®, Tween 80/Span 20, HLB 14) showed globule size of 209.5±0.98nm, PDI of 0.402±0.03 and locomotor inhibition of 83.89±9.15% with desirability of 0.907. Biodistribution study following intranasal and intravenous administration of the radiolabeled (99m)Tc mucoadhesive F4 revealed that intranasal administration achieved 1.72-fold higher and 6 times faster peak brain levels compared with intravenous administration. Drug targeting efficiency percent and brain/blood exposure ratios remained above 100% and 1 respectively after intranasal instillation compared to a maximum brain/blood exposure ratio of 0.8 post intravenous route. Results suggested the CNS delivery of major fraction of haloperidol via direct transnasal to brain pathway that can be a promising alternative to oral and parenteral routes in chronic and acute situations. Haloperidol concentration of 275.6ng/g brain 8h post intranasal instillation, higher than therapeutic concentration range of haloperidol (0.8 to 5.15ng/ml), suggests possible sustained delivery of the drug through nasal route. Copyright © 2016 Elsevier B.V. All rights reserved.

Chronic orbital inflammatory disease and optic neuropathy associated with long-term intranasal cocaine abuse: 2 cases and literature review

NARCIS (Netherlands)

Siemerink, Martin J.; Freling, Nicole J. M.; Saeed, Peerooz

2017-01-01

Orbital inflammatory disease and secondary optic neuropathy is a rare but devastating complication of long-term intranasal cocaine abuse. We describe 2 patients with a history of intranasal cocaine consumption who presented with subacute onset of unilateral vision loss from optic neuropathy and

Surgical benefits of combined awake craniotomy and intraoperative magnetic resonance imaging for gliomas associated with eloquent areas.

Science.gov (United States)

Motomura, Kazuya; Natsume, Atsushi; Iijima, Kentaro; Kuramitsu, Shunichiro; Fujii, Masazumi; Yamamoto, Takashi; Maesawa, Satoshi; Sugiura, Junko; Wakabayashi, Toshihiko

2017-10-01

OBJECTIVE Maximum extent of resection (EOR) for lower-grade and high-grade gliomas can increase survival rates of patients. However, these infiltrative gliomas are often observed near or within eloquent regions of the brain. Awake surgery is of known benefit for the treatment of gliomas associated with eloquent regions in that brain function can be preserved. On the other hand, intraoperative MRI (iMRI) has been successfully used to maximize the resection of tumors, which can detect small amounts of residual tumors. Therefore, the authors assessed the value of combining awake craniotomy and iMRI for the resection of brain tumors in eloquent areas of the brain. METHODS The authors retrospectively reviewed the records of 33 consecutive patients with glial tumors in the eloquent brain areas who underwent awake surgery using iMRI. Volumetric analysis of MRI studies was performed. The pre-, intra-, and postoperative tumor volumes were measured in all cases using MRI studies obtained before, during, and after tumor resection. RESULTS Intraoperative MRI was performed to check for the presence of residual tumor during awake surgery in a total of 25 patients. Initial iMRI confirmed no further tumor resection in 9 patients (36%) because all observable tumors had already been removed. In contrast, intraoperative confirmation of residual tumor during awake surgery led to further tumor resection in 16 cases (64%) and eventually an EOR of more than 90% in 8 of 16 cases (50%). Furthermore, EOR benefiting from iMRI by more than 15% was found in 7 of 16 cases (43.8%). Interestingly, the increase in EOR as a result of iMRI for tumors associated mainly with the insular lobe was significantly greater, at 15.1%, than it was for the other tumors, which was 8.0% (p = 0.001). CONCLUSIONS This study revealed that combining awake surgery with iMRI was associated with a favorable surgical outcome for intrinsic brain tumors associated with eloquent areas. In particular, these benefits were

Stay Awake Behind the Wheel (A Minute of Health with CDC)

Centers for Disease Control (CDC) Podcasts

2016-11-10

Being a safe driver requires complete focus on the road and the cars around you. This podcast discusses the importance of staying awake while driving.  Created: 11/10/2016 by MMWR.   Date Released: 11/10/2016.

The effect of intranasal oxytocin on perceiving and understanding emotion on the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT).

Science.gov (United States)

Cardoso, Christopher; Ellenbogen, Mark A; Linnen, Anne-Marie

2014-02-01

Evidence suggests that intranasal oxytocin enhances the perception of emotion in facial expressions during standard emotion identification tasks. However, it is not clear whether this effect is desirable in people who do not show deficits in emotion perception. That is, a heightened perception of emotion in faces could lead to "oversensitivity" to the emotions of others in nonclinical participants. The goal of this study was to assess the effects of intranasal oxytocin on emotion perception using ecologically valid social and nonsocial visual tasks. Eighty-two participants (42 women) self-administered a 24 IU dose of intranasal oxytocin or a placebo in a double-blind, randomized experiment and then completed the perceiving and understanding emotion components of the Mayer-Salovey-Caruso Emotional Intelligence Test. In this test, emotion identification accuracy is based on agreement with a normative sample. As expected, participants administered intranasal oxytocin rated emotion in facial stimuli as expressing greater emotional intensity than those given a placebo. Consequently, accurate identification of emotion in faces, based on agreement with a normative sample, was impaired in the oxytocin group relative to placebo. No such effect was observed for tests using nonsocial stimuli. The results are consistent with the hypothesis that intranasal oxytocin enhances the salience of social stimuli in the environment, but not nonsocial stimuli. The present findings support a growing literature showing that the effects of intranasal oxytocin on social cognition can be negative under certain circumstances, in this case promoting "oversensitivity" to emotion in faces in healthy people. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Sedation and physiologic response to manual restraint after intranasal administration of midazolam in Hispaniolan Amazon parrots (Amazona ventralis).

Science.gov (United States)

Mans, Christoph; Guzman, David Sanchez-Migallon; Lahner, Lesanna L; Paul-Murphy, Joanne; Sladky, Kurt K

2012-09-01

Administration of intranasal midazolam (2 mg/kg) was evaluated for sedation and effects on cloacal temperature, respiratory rate, and heart rate in manually restrained Hispaniolan Amazon parrots (Amazona ventralis). Adult parrots (n=9) were administered either midazolam (2 mg/kg) or an equal volume of saline solution intranasally before a 15-minute manual restraint in a complete crossover study. Respiratory rate and sedation scores were recorded before and during capture and during and after 15 minutes of manual restraint. Heart rate and cloacal temperature were recorded during manual restraint. After restraint, the parrots received intranasal flumazenil (0.05 mg/kg) or an equal volume of saline solution, and the recovery time was recorded. In those birds that received midazolam, sedation was observed within 3 minutes of administration, and vocalization, flight, and defense responses were significantly reduced during capture. During manual restraint, the mean rate of cloacal temperature increase was significantly slower and remained significantly lower in birds that received midazolam compared with controls. Mean respiratory rates were significantly lower for up to 12 minutes in parrots that received midazolam compared with those receiving saline solution. Flumazenil antagonized the effects of midazolam within 10 minutes. No overt clinical adverse effects to intranasal midazolam and flumazenil administration were observed. Further studies on the safety of intranasal midazolam and flumazenil in this species are warranted.

Effects of Intranasal Oxytocin on the Interpretation and Expression of Emotions in Anorexia Nervosa.

Science.gov (United States)

Leppanen, J; Cardi, V; Ng, K W; Paloyelis, Y; Stein, D; Tchanturia, K; Treasure, J

2017-03-01

Altered social-emotional functioning is considered to play an important role in the development and maintenance of anorexia nervosa (AN). Recently, there has been increasing interest in investigating the role of intranasal oxytocin in social-emotional processing. The present study aimed to investigate the effects of intranasal oxytocin on the interpretation and expression of emotions among people with AN. Thirty women with AN and 29 age-matched healthy women took part in the present study, which used a double-blind, placebo-controlled, cross-over design. The participants received a single dose of 40 IU of intranasal oxytocin in one session and a placebo spray in the other. Fifteen minutes after administration, the participants completed the Reading the Mind in the Eyes Test to assess the interpretation of complex emotions and mental states followed by a video task, which assessed expressions of facial affect when they were viewing humorous and sad film clips. The intranasal oxytocin did not significantly influence the expression or interpretation of emotions in the AN or healthy comparison groups. The AN group expressed significantly less positive emotion, spent more time looking away and reported experiencing a significantly more negative affect in response to the film clips. The finding that intranasal oxytocin had little to no effect on the interpretation or expression of emotions in either group supports the notion that the effects of oxytocin on social-emotional processing are not straightforward and may depend on individual and environmental differences, as well as the emotion being processed. Replication of these findings is necessary to explore the effect of timing on the effects of oxytocin before firm conclusions can be drawn. Nonetheless, these findings add to the steady accumulation of evidence that people with AN have reduced emotional expression and avoidance of emotionally provoking stimuli. © 2017 The Authors. Journal of Neuroendocrinology

Effect of terfenadine on nasal, eustachian tube, and pulmonary function after provocative intranasal histamine challenge.

Science.gov (United States)

Skoner, D P; Doyle, W J; Boehm, S; Fireman, P

1991-12-01

Previous studies have documented that intranasal histamine challenge results in nasal and eustachian tube obstruction (ETO) in human volunteers. The purpose of the present study was to assess the effect of pretreatment with terfenadine, a nonsedating antihistamine on the pathophysiologic consequences of intranasal histamine challenge. Fifteen subjects with allergic rhinitis were challenged intranasally with saline and increasing histamine doses (0.01, 0.1, 0.5, 1.0, 5.0, and 10.0 mg) before pretreatment (baseline) and after 1 week of pretreatment with terfenadine, 60 mg b.i.d., terfenadine, 120 mg b.i.d., and placebo. Nasal conductance as measured by posterior rhinomanometry showed a dose-dependent, monotonic decrease following sequential administration of the histamine solutions, but there were no apparent differences in the average responses among the four challenge sessions. The frequency of ETO after histamine challenge was decreased by pretreatment with both doses of terfenadine, although this was not significant. Histamine-induced sneezing and rhinorrhea, but not congestion, were significantly reduced by terfenadine pretreatment. There was no evidence of extension of the histamine effects to the lower airway. The results of the present study suggest that terfenadine, a nonsedating antihistamine, had a favorable effect on sneezing and rhinorrhea after provocative intranasal histamine challenge, but did not significantly attenuate the subjective or objective nasal and ET obstructive responses.

Cross-sectional study of anxiety symptoms and self-report of awake and sleep bruxism in female TMD patients.

Science.gov (United States)

Tavares, Luisa Maria Faria; da Silva Parente Macedo, Leonora Cristina; Duarte, Cristina Maria Rabelais; de Goffredo Filho, Gilberto Senechal; de Souza Tesch, Ricardo

2016-11-01

The aim of this study was to assess the relationship between levels of anxiety symptoms and prevalence of self-report of awake and sleep bruxism in patients with temporomandibular disorders (TMD). One hundred and eighty-one female patients, aged 19-77 years, were consecutively evaluated. The patients were selected from among those who sought treatment at the TMD and Orofacial Pain Outpatient Clinic of the Petrópolis School of Medicine. All patients completed the questionnaire and underwent clinical examination, both components of the RDC/TMD, in addition to answering questions pertaining to the assessment of levels of anxiety symptoms, taken from the Symptom Check List 90 self-report instrument. The subjects were classified according to the presence of self-reported only awake bruxism, only sleep bruxism, both, or none. A logistic regression procedure was performed to evaluate the possible association through odds ratio between anxiety symptoms and self-reported awake or sleep bruxism. The cofactors for each outcome were age, self-reported bruxism during the circadian period other than the one being evaluated, and the use of selective serotonin reuptake inhibitors. It was possible to demonstrate the presence of a positive and statistically significant relationship between anxiety levels and self-reported awake bruxism. This finding was not observed in those subjects who reported sleep bruxism. A positive relationship was found between self-reported awake bruxism and levels of anxiety symptoms, but not between sleep bruxism and anxiety.

Intranasal inoculation of white-tailed deer (Odocoileus virginianus with lyophilized chronic wasting disease prion particulate complexed to montmorillonite clay.

Directory of Open Access Journals (Sweden)

Tracy A Nichols

Full Text Available Chronic wasting disease (CWD, the only known prion disease endemic in wildlife, is a persistent problem in both wild and captive North American cervid populations. This disease continues to spread and cases are found in new areas each year. Indirect transmission can occur via the environment and is thought to occur by the oral and/or intranasal route. Oral transmission has been experimentally demonstrated and although intranasal transmission has been postulated, it has not been tested in a natural host until recently. Prions have been shown to adsorb strongly to clay particles and upon oral inoculation the prion/clay combination exhibits increased infectivity in rodent models. Deer and elk undoubtedly and chronically inhale dust particles routinely while living in the landscape while foraging and rutting. We therefore hypothesized that dust represents a viable vehicle for intranasal CWD prion exposure. To test this hypothesis, CWD-positive brain homogenate was mixed with montmorillonite clay (Mte, lyophilized, pulverized and inoculated intranasally into white-tailed deer once a week for 6 weeks. Deer were euthanized at 95, 105, 120 and 175 days post final inoculation and tissues examined for CWD-associated prion proteins by immunohistochemistry. Our results demonstrate that CWD can be efficiently transmitted utilizing Mte particles as a prion carrier and intranasal exposure.

Distinct BOLD activation profiles following central and peripheral oxytocin administration in awake rats

Directory of Open Access Journals (Sweden)

Craig F Ferris

2015-09-01

Full Text Available A growing body of literature has suggested that intranasal oxytocin (OT or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood-brain-barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level dependent (BOLD signal intensity in response to peripheral OT injections (0.1, 0.5 or 2.5 mg/kg during functional magnetic resonance (fMRI in awake rats imaged at 7.0 tesla. These data were compared to OT (1ug/5 µl given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose-response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity.

Distinct BOLD Activation Profiles Following Central and Peripheral Oxytocin Administration in Awake Rats.

Science.gov (United States)

Ferris, Craig F; Yee, Jason R; Kenkel, William M; Dumais, Kelly Marie; Moore, Kelsey; Veenema, Alexa H; Kulkarni, Praveen; Perkybile, Allison M; Carter, C Sue

2015-01-01

A growing body of literature has suggested that intranasal oxytocin (OT) or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood-brain barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level-dependent (BOLD) signal intensity in response to peripheral OT injections (0.1, 0.5, or 2.5 mg/kg) during functional magnetic resonance imaging (fMRI) in awake rats imaged at 7.0 T. These data were compared to OT (1 μg/5 μl) given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis, we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors, e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose-response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity.

Meta-analysis of the effects of intranasal oxytocin on interpretation and expression of emotions.

Science.gov (United States)

Leppanen, Jenni; Ng, Kah Wee; Tchanturia, Kate; Treasure, Janet

2017-07-01

Accurate interpretation and appropriate expression of emotions are key aspects of social-cognition. Several mental disorders are characterised by transdiagnostic difficulties in these areas and, recently, there has been increasing interest in exploring the effects of oxytocin on social-emotional functioning. This review consists of 33 studies. Fifteen of the studies included people with autism spectrum disorder, schizophrenia, borderline personality disorder, frontotemporal dementia, anorexia nervosa, bulimia nervosa, post-traumatic stress disorder, depression, and opioid and alcohol dependence. We conducted ten meta-analyses examining the effects of intranasal oxytocin on expression of emotions, emotional theory of mind, sensitivity to recognise basic emotions, and recognition of basic emotions. A single dose of intranasal oxytocin significantly improved the recognition of basic emotions, particularly fear, and increased the expression of positive emotions among the healthy individuals. Oxytocin did not significantly influence theory of mind or the expression of negative emotions among the healthy individuals. Finally, intranasal oxytocin did not significantly influence interpretation or expression of emotions among the clinical populations. Copyright © 2017. Published by Elsevier Ltd.

Safety of Intranasal Fentanyl in the Out-of-Hospital Setting

DEFF Research Database (Denmark)

Karlsen, Anders P H; Pedersen, Danny M B; Trautner, Sven

2014-01-01

: In this prospective observational study, we administered intranasal fentanyl in the out-of-hospital setting to adults and children older than 8 years with severe pain resulting from orthopedic conditions, abdominal pain, or acute coronary syndrome refractory to nitroglycerin spray. Patients received 1 to 3 doses...

Study of embryotoxic effects of intranasally administred desloratadine on laboratory animals

Directory of Open Access Journals (Sweden)

Alekhina Т.А.

2017-04-01

Full Text Available The study was conducted to detect possible changes in embryogenesis and negative effects of third generation antihistamine – desloratadine – after intranasal administration of 1.3 mg/m3 and 13.0 mg/m3 of the substance to laboratory animals during their prenatal period. In these circumstances, desloratadine does not cause any significant changes of embryogenesis parameters. Macroscopic examination of the fetus and placenta in animals of experimental groups did not reveal any pathology or physiological deviations from the norm. 13.0 mg/m3 concentration of the drug caused a decrease in the weight of embryos in comparison with control group of animals and physiological data, despite a well developed, without visible pathology, placenta. This neces­sitates an in-depth study of possible teratogenic effects of intranasally administred desloratadine to laboratory animals.

Tracheostomy as a bridge to spontaneous breathing and awake-ECMO in non-transplant surgical patients.

Science.gov (United States)

Swol, J; Strauch, J T; Schildhauer, T A

2017-05-01

The tracheostomy is a frequently used procedure for the respiratory weaning of ventilated patients allows sedation free ECLS use in awake patient. The aim of this study is to assess the possibility and highlight the benefits of lowering the impact of sedation in surgical non-transplant patients on ECLS. The specific objective was to investigate the use of tracheostomy as a bridge to spontaneous breathing on ECLS. Of the 95 patients, 65 patients received a tracheostomy, and 5 patients were admitted with a tracheostoma. One patient was cannulated without intubation, one is extubated during ECLS course after 48 hours. 4 patients were extubated after weaning and the removal of ECLS. 19 patients died before the indication to tracheostomy was given. Tracheostomy can bridge to spontaneous breathing and awake-ECMO in non-transplant surgical patients. The "awake ECMO" strategy may avoid complications related to mechanical ventilation, sedation, and immobilization and provide comparable outcomes to other approaches for providing respiratory support. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

The First Awake Clipping of a Brain Aneurysm in Malaysia and in ASEAN: Achieving International Standards.

Science.gov (United States)

Idris, Zamzuri; Kandasamy, Regunath; Neoh, Yee Yik; Abdullah, Jafri Malin; Wan Hassan, Wan Mohd Nazaruddin; Mat Hassan, Mohd Erham

2018-02-01

World-renowned neurosurgeon, Professor Saleem Abdulrauf, has been featured in several medical journals for his successful "Awake Brain Aneurysm Surgery". Regarded as a "world first", this surgery, involves clipping un-ruptured brain aneurysms while patients are awake. Only one or two neurosurgery centres worldwide are capable of this. Performing the surgery while the patient is awake lowers risks of brain ischemia with neurological deficits and ventilator associated morbidities. The technique has been viewed as the start of a new era in brain surgery. Physicians from the Universiti Sains Malaysia (USM) School of Medical Sciences, at the Health Campus in Kelantan, headed by Professor Dr Zamzuri Idris (neurosurgeon) and Dr Wan Mohd Nazaruddin Wan Hassan (neuroanaesthetist), recently performed a similar procedure, the first such surgery in Malaysia and Southeast Asia. The USM team can therefore be considered to be among the first few to have done this brain surgery and achieved successful patient outcomes.

Visually Evoked 3-5 Hz Membrane Potential Oscillations Reduce the Responsiveness of Visual Cortex Neurons in Awake Behaving Mice.

Science.gov (United States)

Einstein, Michael C; Polack, Pierre-Olivier; Tran, Duy T; Golshani, Peyman

2017-05-17

Low-frequency membrane potential ( V m ) oscillations were once thought to only occur in sleeping and anesthetized states. Recently, low-frequency V m oscillations have been described in inactive awake animals, but it is unclear whether they shape sensory processing in neurons and whether they occur during active awake behavioral states. To answer these questions, we performed two-photon guided whole-cell V m recordings from primary visual cortex layer 2/3 excitatory and inhibitory neurons in awake mice during passive visual stimulation and performance of visual and auditory discrimination tasks. We recorded stereotyped 3-5 Hz V m oscillations where the V m baseline hyperpolarized as the V m underwent high amplitude rhythmic fluctuations lasting 1-2 s in duration. When 3-5 Hz V m oscillations coincided with visual cues, excitatory neuron responses to preferred cues were significantly reduced. Despite this disruption to sensory processing, visual cues were critical for evoking 3-5 Hz V m oscillations when animals performed discrimination tasks and passively viewed drifting grating stimuli. Using pupillometry and animal locomotive speed as indicators of arousal, we found that 3-5 Hz oscillations were not restricted to unaroused states and that they occurred equally in aroused and unaroused states. Therefore, low-frequency V m oscillations play a role in shaping sensory processing in visual cortical neurons, even during active wakefulness and decision making. SIGNIFICANCE STATEMENT A neuron's membrane potential ( V m ) strongly shapes how information is processed in sensory cortices of awake animals. Yet, very little is known about how low-frequency V m oscillations influence sensory processing and whether they occur in aroused awake animals. By performing two-photon guided whole-cell recordings from layer 2/3 excitatory and inhibitory neurons in the visual cortex of awake behaving animals, we found visually evoked stereotyped 3-5 Hz V m oscillations that disrupt

Resection of Gliomas with and without Neuropsychological Support during Awake Craniotomy—Effects on Surgery and Clinical Outcome

OpenAIRE

Anna Kelm; Nico Sollmann; Nico Sollmann; Sebastian Ille; Sebastian Ille; Bernhard Meyer; Florian Ringel; Florian Ringel; Sandro M. Krieg; Sandro M. Krieg

2017-01-01

BackgroundDuring awake craniotomy for tumor resection, a neuropsychologist (NP) is regarded as a highly valuable partner for neurosurgeons. However, some centers do not routinely involve an NP, and data to support the high influence of the NP on the perioperative course of patients are mostly lacking.ObjectiveThe aim of this study was to investigate whether there is a difference in clinical outcomes between patients who underwent awake craniotomy with and without the attendance of an NP.Metho...

Diagnostic work up for language testing in patients undergoing awake craniotomy for brain lesions in language areas.

Science.gov (United States)

Bilotta, Federico; Stazi, Elisabetta; Titi, Luca; Lalli, Diana; Delfini, Roberto; Santoro, Antonio; Rosa, Giovanni

2014-06-01

Awake craniotomy is the technique of choice in patients with brain tumours adjacent to primary and accessory language areas (Broca's and Wernicke's areas). Language testing should be aimed to detect preoperative deficits, to promptly identify the occurrence of new intraoperative impairments and to establish the course of postoperative language status. Aim of this case series is to describe our experience with a dedicated language testing work up to evaluate patients with or at risk for language disturbances undergoing awake craniotomy for brain tumour resection. Pre- and intra operative testing was accomplished with 8 tests. Intraoperative evaluation was accomplished when patients were fully cooperative (Ramsey awake craniotomy for brain tumour resection with preoperative language disturbances or at risk for postoperative language deficits. This approach allows a systematic evaluation and recording of language function status and can be accomplished even when a neuropsychologist or speech therapist are not involved in the operation crew.

Awake craniotomy for gliomas in a high-field intraoperative magnetic resonance imaging suite: analysis of 42 cases.

Science.gov (United States)

Maldaun, Marcos V C; Khawja, Shumaila N; Levine, Nicholas B; Rao, Ganesh; Lang, Frederick F; Weinberg, Jeffrey S; Tummala, Sudhakar; Cowles, Charles E; Ferson, David; Nguyen, Anh-Thuy; Sawaya, Raymond; Suki, Dima; Prabhu, Sujit S

2014-10-01

The object of this study was to describe the experience of combining awake craniotomy techniques with high-field (1.5 T) intraoperative MRI (iMRI) for tumors adjacent to eloquent cortex. From a prospective database the authors obtained and evaluated the records of all patients who had undergone awake craniotomy procedures with cortical and subcortical mapping in the iMRI suite. The integration of these two modalities was assessed with respect to safety, operative times, workflow, extent of resection (EOR), and neurological outcome. Between February 2010 and December 2011, 42 awake craniotomy procedures using iMRI were performed in 41 patients for the removal of intraaxial tumors. There were 31 left-sided and 11 right-sided tumors. In half of the cases (21 [50%] of 42), the patient was kept awake for both motor and speech mapping. The mean duration of surgery overall was 7.3 hours (range 4.0-13.9 hours). The median EOR overall was 90%, and gross-total resection (EOR ≥ 95%) was achieved in 17 cases (40.5%). After viewing the first MR images after initial resection, further resection was performed in 17 cases (40.5%); the mean EOR in these cases increased from 56% to 67% after further resection. No deficits were observed preoperatively in 33 cases (78.5%), and worsening neurological deficits were noted immediately after surgery in 11 cases (26.2%). At 1 month after surgery, however, worsened neurological function was observed in only 1 case (2.3%). There was a learning curve with regard to patient positioning and setup times, although it did not adversely affect patient outcomes. Awake craniotomy can be safely performed in a high-field (1.5 T) iMRI suite to maximize tumor resection in eloquent brain areas with an acceptable morbidity profile at 1 month.

Brain delivery of valproic acid via intranasal administration of nanostructured lipid carriers: in vivo pharmacodynamic studies using rat electroshock model

Directory of Open Access Journals (Sweden)

Sharareh Eskandari

2011-02-01

Full Text Available Sharareh Eskandari1, Jaleh Varshosaz1, Mohsen Minaiyan2, Majid Tabbakhian11Department of Pharmaceutics, 2Department of Pharmacology, School of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, IranAbstract: The treatment of brain disorders is one of the greatest challenges in drug delivery because of a variety of main barriers in effective drug transport and maintaining therapeutic concentrations in the brain for a prolonged period. The objective of this study was delivery of valproic acid (VPA to the brain by intranasal route. For this purpose, nanostructured lipid carriers (NLCs were prepared by solvent diffusion method followed by ultrasonication and characterized for size, zeta potential, drug-loading percentage, and release. Six groups of rats each containing six animals received drug-loaded NLCs intraperitoneally (IP or intranasally. Brain responses were then examined by using maximal electroshock (MES. The hind limb tonic extension:flexion inhibition ratio was measured at 15-, 30-, 60-, 90-, and 120-minute intervals. The drug concentration was also measured in plasma and brain at the most protective point using gas chromatography method. The particle size of NLCs was 154 ± 16 nm with drug-loading percentage of 47% ± 0.8% and drug release of 75% ± 1.9% after 21 days. In vivo results showed that there was a significant difference between protective effects of NLCs of VPA and control group 15, 30, 60, and 90 minutes after treatment via intranasal route (P < 0.05. Similar protective effect was observed in rats treated with NLCs of VPA in intranasal route and positive control in IP route (P > 0.05. Results of drug determination in brain and plasma showed that brain:plasma concentration ratio was much higher after intranasal administration of NLCs of VPA than the positive control group (IP route. In conclusion, intranasal administration of NLCs of VPA provided a better protection

Inflammatory profile of awake function-controlled craniotomy and craniotomy under general anesthesia

NARCIS (Netherlands)

M. Klimek (Markus); J.W. Hol (Jaap Willem); S.C.A. Wens (Stephan); C. Heijmans-Antonissen (Claudia); S.P. Niehof (Sjoerd); A.J. Vincent (Arnaud); J. Klein (Jan); F.J. Zijlstra (Freek)

2009-01-01

textabstractBackground. Surgical stress triggers an inflammatory response and releases mediators into human plasma such as interleukins (ILs). Awake craniotomy and craniotomy performed under general anesthesia may be associated with different levels of stress. Our aim was to investigate whether

Is non-awake surgery for supratentorial adult low-grade glioma treatment still feasible?

Science.gov (United States)

Duffau, Hugues

2018-01-01

In this short review, the author performs a database search, summarizes, and discusses studies that provide information on the need to perform awake surgery to preserve quality of life/return to work of adult patients who undergo resection for a supratentorial low-grade glioma (LGG). Based upon the currently available data, the author concludes that in LGG, patients with no or only mild deficits at diagnosis, non-awake surgery can no longer be achieved. Indeed, awake craniotomy with intrasurgical electrical mapping has resulted in an increase of the extent of resection and overall survival in LGG. Furthermore, in order to resume a normal familial, social, and professional life, LGG patients with a prolonged survival expectancy have to benefit not only from language mapping when the tumor involves the left "dominant" hemisphere, but also from intraoperative mapping of sensorimotor, visuospatial, higher cognitive, and emotional functions under local anesthesia, even for gliomas situated within presumed "non-language" areas such as the right "non-dominant" hemisphere. In other words, the ultimate goal is to map the functional connectome for each patient in order to perform the resection up to the eloquent networks and then to optimize the onco-functional balance of LGG surgery. To this end, an objective neuropsychological assessment has to be achieved in a more systematic manner before and after resection. Early postoperative cognitive rehabilitation is also recommended, whenever needed.

CERN AWAKE Facility Readiness for First Beam

CERN Document Server

Bracco, Chiara; Butterworth, Andrew; Damerau, Heiko; Döbert, Steffen; Fedosseev, Valentin; Feldbaumer, Eduard; Gschwendtner, Edda; Höfle, Wolfgang; Pardons, Ans; Shaposhnikova, Elena; Vincke, Helmut

2016-01-01

The AWAKE project at CERN was approved in August 2013 and since then a big effort was made to be able to probe the acceleration of electrons before the "2019-2020 Long Shutdown". The next steps in this challenging schedule will be a dry run of all the beam line systems, at the end of the HW commissioning in June 2016, and the first proton beam sent to the plasma cell one month later. The current status of the project is presented together with an outlook over the foreseen works for operation with electrons in 2018.

Intranasal vaccination promotes detrimental Th17-mediated immunity against influenza infection.

Directory of Open Access Journals (Sweden)

Asher Maroof

2014-01-01

Full Text Available Influenza disease is a global health issue that causes significant morbidity and mortality through seasonal epidemics. Currently, inactivated influenza virus vaccines given intramuscularly or live attenuated influenza virus vaccines administered intranasally are the only approved options for vaccination against influenza virus in humans. We evaluated the efficacy of a synthetic toll-like receptor 4 agonist CRX-601 as an adjuvant for enhancing vaccine-induced protection against influenza infection. Intranasal administration of CRX-601 adjuvant combined with detergent split-influenza antigen (A/Uruguay/716/2007 (H3N2 generated strong local and systemic immunity against co-administered influenza antigens while exhibiting high efficacy against two heterotypic influenza challenges. Intranasal vaccination with CRX-601 adjuvanted vaccines promoted antigen-specific IgG and IgA antibody responses and the generation of polyfunctional antigen-specific Th17 cells (CD4(+IL-17A(+TNFα(+. Following challenge with influenza virus, vaccinated mice transiently exhibited increased weight loss and morbidity during early stages of disease but eventually controlled infection. This disease exacerbation following influenza infection in vaccinated mice was dependent on both the route of vaccination and the addition of the adjuvant. Neutralization of IL-17A confirmed a detrimental role for this cytokine during influenza infection. The expansion of vaccine-primed Th17 cells during influenza infection was also accompanied by an augmented lung neutrophilic response, which was partially responsible for mediating the increased morbidity. This discovery is of significance in the field of vaccinology, as it highlights the importance of both route of vaccination and adjuvant selection in vaccine development.

Oral-Fluid Thiol-Detection Test Identifies Underlying Active Periodontal Disease Not Detected by the Visual Awake Examination.

Science.gov (United States)

Queck, Katherine E; Chapman, Angela; Herzog, Leslie J; Shell-Martin, Tamara; Burgess-Cassler, Anthony; McClure, George David

Periodontal disease in dogs is highly prevalent but can only be accurately diagnosed by performing an anesthetized oral examination with periodontal probing and dental radiography. In this study, 114 dogs had a visual awake examination of the oral cavity and were administered an oral-fluid thiol-detection test prior to undergoing a a full-mouth anesthetized oral examination and digital dental radiographs. The results show the visual awake examination underestimated the presence and severity of active periodontal disease. The thiol-detection test was superior to the visual awake examination at detecting the presence and severity of active periodontal disease and was an indicator of progression toward alveolar bone loss. The thiol-detection test detected active periodontal disease at early stages of development, before any visual cues were present, indicating the need for intervention to prevent periodontal bone loss. Early detection is important because without intervention, dogs with gingivitis (active periodontal disease) progress to irreversible periodontal bone loss (stage 2+). As suggested in the current AAHA guidelines, a thiol-detection test administered in conjunction with the visual awake examination during routine wellness examinations facilitates veterinarian-client communication and mitigates under-diagnosis of periodontal disease and underutilization of dental services. The thiol-detection test can be used to monitor the periodontal health status of the conscious patient during follow-up examinations based on disease severity.

Right Hemisphere Cognitive Functions: From Clinical and Anatomic Bases to Brain Mapping During Awake Craniotomy Part I: Clinical and Functional Anatomy.

Science.gov (United States)

Bernard, Florian; Lemée, Jean-Michel; Ter Minassian, Aram; Menei, Philippe

2018-05-12

The nondominant hemisphere (usually the right) is responsible for primary cognitive functions such as visuospatial and social cognition. Awake surgery using direct electric stimulation for right cerebral tumor removal remains challenging because of the complexity of the functional anatomy and difficulties in adapting standard bedside tasks to awake surgery conditions. An understanding of semiology and anatomic bases, along with an analysis of the available cognitive tasks for visuospatial and social cognition per operative mapping allow neurosurgeons to better appreciate the functional anatomy of the right hemisphere and its relevance to tumor surgery. In this article, the first of a 2-part review, we discuss the anatomic and functional basis of right hemisphere function. Whereas part II of the review focuses primarily on semiology and surgical management of right-sided tumors under awake conditions, this article provides a comprehensive review of knowledge underpinning awake surgery on the right hemisphere. Copyright © 2018 Elsevier Inc. All rights reserved.

Sedative effects of midazolam and xylazine with or without ketamine and detomidine alone following intranasal administration in Ring-necked Parakeets.

Science.gov (United States)

Vesal, Nasser; Eskandari, Mohammad H

2006-02-01

To evaluate the effects of intranasal administration of midazolam and xylazine (with or without ketamine) and detomidine and their specific antagonists in parakeets. Prospective study. 17 healthy adult Ring-necked Parakeets (Psittacula krameri) of both sexes (mean weight, 128.83+/-10.46 g [0.28+/-0.02 lb]). The dose of each drug or ketamine-drug combination administered intranasally that resulted in adequate sedation (ie, unrestrained dorsal recumbency maintained for >or=5 minutes) was determined; the onset of action, duration of dorsal recumbency, and duration of sedation associated with these treatments were evaluated. The efficacy of the reversal agents flumazenil, yohimbine, and atipamezole was also evaluated. In parakeets, intranasal administration of midazolam (7.3 mg/kg [3.32 mg/lb]) or detomidine (12 mg/kg [5.45 mg/lb]) caused adequate sedation within 2.7 and 3.5 minutes, respectively. Combinations of midazolam (3.65 mg/kg [1.66 mg/lb]) and xylazine (10 mg/kg [4.55 mg/lb]) with ketamine (40 to 50 mg/kg [18.2 to 22.7 mg/lb]) also achieved adequate sedation. Compared with detomidine, duration of dorsal recumbency was significantly longer with midazolam. Intranasal administration of flumazenil (0.13 mg/kg [0.06 mg/lb]) significantly decreased midazolam-associated recumbency time. Compared with the xylazineketamine combination, duration of dorsal recumbency was longer after midazolam-ketamine administration. Intranasal administration of flumazenil, yohimbine, or atipamezole significantly decreased the duration of sedation induced by midazolam, xylazine, or detomidine, respectively. Intranasal administration of sedative drugs appears to be an acceptable method of drug delivery in Ring-necked Parakeets. Reversal agents are also effective when administered via this route.

Classifying multiple types of hand motions using electrocorticography during intraoperative awake craniotomy and seizure monitoring processes—case studies

Science.gov (United States)

Xie, Tao; Zhang, Dingguo; Wu, Zehan; Chen, Liang; Zhu, Xiangyang

2015-01-01

In this work, some case studies were conducted to classify several kinds of hand motions from electrocorticography (ECoG) signals during intraoperative awake craniotomy & extraoperative seizure monitoring processes. Four subjects (P1, P2 with intractable epilepsy during seizure monitoring and P3, P4 with brain tumor during awake craniotomy) participated in the experiments. Subjects performed three types of hand motions (Grasp, Thumb-finger motion and Index-finger motion) contralateral to the motor cortex covered with ECoG electrodes. Two methods were used for signal processing. Method I: autoregressive (AR) model with burg method was applied to extract features, and additional waveform length (WL) feature has been considered, finally the linear discriminative analysis (LDA) was used as the classifier. Method II: stationary subspace analysis (SSA) was applied for data preprocessing, and the common spatial pattern (CSP) was used for feature extraction before LDA decoding process. Applying method I, the three-class accuracy of P1~P4 were 90.17, 96.00, 91.77, and 92.95% respectively. For method II, the three-class accuracy of P1~P4 were 72.00, 93.17, 95.22, and 90.36% respectively. This study verified the possibility of decoding multiple hand motion types during an awake craniotomy, which is the first step toward dexterous neuroprosthetic control during surgical implantation, in order to verify the optimal placement of electrodes. The accuracy during awake craniotomy was comparable to results during seizure monitoring. This study also indicated that ECoG was a promising approach for precise identification of eloquent cortex during awake craniotomy, and might form a promising BCI system that could benefit both patients and neurosurgeons. PMID:26483627

Surgical and anesthesiological considerations of awake craniotomy: Cerrahpasa experience.

Science.gov (United States)

Sanus, Galip Zihni; Yuksel, Odhan; Tunali, Yusuf; Ozkara, Cigdem; Yeni, Naz; Ozlen, Fatma; Tanriverdi, Taner; Ozyurt, Emin; Uzan, Mustafa

2015-01-01

Awake craniotomy (AC) with electrical cortical stimulation has become popular during the last ten years although the basic principles were introduced almost 50 years ago. The aim of this paper is to share with the readers our experience in 25 patients who underwent AC with electrical stimulation. Twenty-five patients who underwent AC between 2010 and 2013 are the subjects of this paper. All patients were diagnosed with intraaxial lesions involving the functional area itself or very close to it by preoperative imaging. During surgery, the functional area was demonstrated by cortical electrical stimulation and resection aimed to preserve it in order to avoid an irreversible functional deficit. Total resection was possible in 80% while in 20% subtotal resection had to be performed because of involvement of the functional area itself. The neurological complication rate was found to be 16% (4 patients) and all were transient. No complication regarding anesthesia was noted. Awake craniotomy in selected patients is very effective, safe and practical for supratentorial lesions close to the eloquent area. Complications related to the surgery itself are uncommon and general anesthesia is avoided. The hospital stay including the intensive care unit is short which makes it very economical surgical procedure.

Intranasal oxytocin administration in relationship to social behaviour in domestic pigs

NARCIS (Netherlands)

Camerlink, Irene; Reimert, Inonge; Bolhuis, Liesbeth

2016-01-01

Intranasal administration of oxytocin has been shown to alter positive and negative social behaviour. Positive social behaviour in pigs (Sus scrofa) may be expressed through gentle social nosing, and greater insight in the specific expression hereof might contribute to the current search for

Resting state functional connectivity magnetic resonance imaging integrated with intraoperative neuronavigation for functional mapping after aborted awake craniotomy

Science.gov (United States)

Batra, Prag; Bandt, S. Kathleen; Leuthardt, Eric C.

2016-01-01

Background: Awake craniotomy is currently the gold standard for aggressive tumor resections in eloquent cortex. However, a significant subset of patients is unable to tolerate this procedure, particularly the very young or old or those with psychiatric comorbidities, cardiopulmonary comorbidities, or obesity, among other conditions. In these cases, typical alternative procedures include biopsy alone or subtotal resection, both of which are associated with diminished surgical outcomes. Case Description: Here, we report the successful use of a preoperatively obtained resting state functional connectivity magnetic resonance imaging (MRI) integrated with intraoperative neuronavigation software in order to perform functional cortical mapping in the setting of an aborted awake craniotomy due to loss of airway. Conclusion: Resting state functional connectivity MRI integrated with intraoperative neuronavigation software can provide an alternative option for functional cortical mapping in the setting of an aborted awake craniotomy. PMID:26958419

Intranasal dexmedetomidine for sedation for pediatric computed tomography imaging.

Science.gov (United States)

Mekitarian Filho, Eduardo; Robinson, Fay; de Carvalho, Werther Brunow; Gilio, Alfredo Elias; Mason, Keira P

2015-05-01

This prospective observational pilot study evaluated the aerosolized intranasal route for dexmedetomidine as a safe, effective, and efficient option for infant and pediatric sedation for computed tomography imaging. The mean time to sedation was 13.4 minutes, with excellent image quality, no failed sedations, or significant adverse events. Registered with ClinicalTrials.gov: NCT01900405. Copyright © 2015 Elsevier Inc. All rights reserved.

Characterization of scale-free properties of human electrocorticography in awake and slow wave sleep states

Directory of Open Access Journals (Sweden)

John M Zempel

2012-06-01

Full Text Available Like many complex dynamic systems, the brain exhibits scale-free dynamics that follow power law scaling. Broadband power spectral density (PSD of brain electrical activity exhibits state-dependent power law scaling with a log frequency exponent that varies across frequency ranges. Widely divergent naturally occurring neural states, awake and slow wave sleep (SWS periods, were used evaluate the nature of changes in scale-free indices. We demonstrate two analytic approaches to characterizing electrocorticographic (ECoG data obtained during Awake and SWS states. A data driven approach was used, characterizing all available frequency ranges. Using an Equal Error State Discriminator (EESD, a single frequency range did not best characterize state across data from all six subjects, though the ability to distinguish awake and SWS states in individual subjects was excellent. Multisegment piecewise linear fits were used to characterize scale-free slopes across the entire frequency range (0.2-200 Hz. These scale-free slopes differed between Awake and SWS states across subjects, particularly at frequencies below 10 Hz and showed little difference at frequencies above 70 Hz. A Multivariate Maximum Likelihood Analysis (MMLA method using the multisegment slope indices successfully categorized ECoG data in most subjects, though individual variation was seen. The ECoG spectrum is not well characterized by a single linear fit across a defined set of frequencies, but is best described by a set of discrete linear fits across the full range of available frequencies. With increasing computational tractability, the use of scale-free slope values to characterize EEG data will have practical value in clinical and research EEG studies.

[Comparison of immune response after oral and intranasal immunization with recombinant Lactobacillus casei expressing ETEC F41].

Science.gov (United States)

Liu, Jiankui; Wei, Chunhua; Hou, Xilin; Wang, Guihua; Yu, Liyun

2009-04-01

In order to represent a promising strategy for mucosal vaccination, oral or intranasal immunization of Specific Pathogen Free (SPF) BALB/c mice were performed. The mucosal immunity, systemic immune and protective immune responses were compared after immunization with the recombinant Lactobacillus casei (L. casei) harboring enterotoxigenic Escherichia coli (ETEC) F41. The recombinant fusion proteins were detected by Western blot. Surface localization of the fusion protein was verified by immunofluorescence microscopy and flow cytometry. Six-week-old female SPF BALB/c mice (160 heads) were divided into 4 groups for immunization and control. Oral and intranasal immunization of mice was performed with the recombinant strain L. casei harboring pLA-F41 or pLA. For oral immunization, the mice were inoculated daily on days 0 to 4, 7 to 11, 21 to 25, and 49 to 53. A lighter schedule was used for nasal immunization (days 0 to 2, 7 to 9, 21 and 49). Specific anti-F41 IgG antibody in the serum and specific anti-F41 secret immunoglobulin A (sIgA) antibody in the lung, intestines, vagina fluid and feces of mice were detected by indirect ELISA. The mice orally or intranasally immunized with pLA-F41/L. casei and pLA/IL. casei were challenged with standard-type ETEC F41 (C83919) (2 x 10(3) LD50). Mice immunized with pLA-F41/L. casei could produce remarkable anti-F41 antibody level. More than 90% survived in oral immunization group whereas more than 85% survived in intranasal immunization group after challenged with C83919, all dead in the control group. Ninety percent of the pups survived in oral immunization group whereas 80% survived in intranasal immunization group after challenged with C83919, but only a 5% survival rate for pups that were either immunized with a control pLA vector or unimmunized. Oral or intranasal immunization with recombinant L. casei displaying ETEC F41 antigens on the surface induced effective and similar systemic and mucosal immune responses against the

Brief Report: Oxytocin Enhances Paternal Sensitivity to a Child with Autism--A Double-Blind Within-Subject Experiment with Intranasally Administered Oxytocin

Science.gov (United States)

Naber, Fabienne B. A.; Poslawsky, Irina E.; van Ijzendoorn, Marinus H.; van Engeland, Herman; Bakermans-Kranenburg, Marian J.

2013-01-01

Oxytocin seems associated with parenting style, and experimental work showed positive effects of intranasally administered oxytocin on parenting style of fathers. Here, the first double-blind, placebo-controlled, within-subject experiment with intranasal oxytocin administration to fathers of children with autism spectrum disorder (ASD) is…

Effects of intraperitoneal and intranasal application of Lentinan on cellular response in rats.

Science.gov (United States)

Markova, Nadya; Kussovski, Vesselin; Radoucheva, Tatyana; Dilova, Krasimira; Georgieva, Neli

2002-11-01

Lentinan (Ajinomoto, Japan) was administrated intraperitoneally (i.p.) and intranasally (i.n.) at different doses (1, 5 and 10 mg/kg) to rats. Effectiveness of Lentinan treatment was evaluated by comparative testing of cell activation (establishing the number, glycolytic and acid phosphatase activity, H2O2 production and killing ability against Salmonella enteritidis and Staphylococcus aureus) at two different compartments--peritoneal and broncho-alveolar cavities. The results indicated that Lentinan induced high-grade activation of peritoneal cells (PCs) and especially of broncho-alveolar cells (BACs) with markedly enhanced effector function (killing ability against S. aureus). Generally, Lentinan, known usually with its parenteral routes of application, can be successful to stimulate the host cell response in the respiratory tract by intranasal route of administration.

Comparative analysis of monotherapy versus duotherapy antiseizure drug management for postoperative seizure control in patients undergoing an awake craniotomy.

Science.gov (United States)

Eseonu, Chikezie I; Eguia, Francisco; Garcia, Oscar; Kaplan, Peter W; Quiñones-Hinojosa, Alfredo

2018-06-01

OBJECTIVE Postoperative seizures are a common complication in patients undergoing an awake craniotomy, given the cortical manipulation during tumor resection and the electrical cortical stimulation for brain mapping. However, little evidence exists about the efficacy of postoperative seizure prophylaxis. This study aims to determine the most appropriate antiseizure drug (ASD) management regimen following an awake craniotomy. METHODS The authors performed a retrospective analysis of data pertaining to patients who underwent an awake craniotomy for brain tumor from 2007 to 2015 performed by a single surgeon. Patients were divided into 2 groups, those who received a single ASD (the monotherapy group) and those who received 2 types of ASDs (the duotherapy group). Patient demographics, symptoms, tumor characteristics, hospitalization details, and seizure outcome were evaluated. Multivariable logistic regression was used to evaluate numerous clinical variables associated with postoperative seizures. RESULTS A total of 81 patients underwent an awake craniotomy for tumor resection of an eloquent brain lesion. Preoperative baseline characteristics were comparable between the 2 groups. The postoperative seizure rate was 21.7% in the monotherapy group and 5.7% in the duotherapy group (p = 0.044). Seizure outcome at 6 months' follow-up was assessed with the Engel classification scale. The duotherapy group had a significantly higher proportion of seizure-free (Engel Class I) patients than the monotherapy group (90% vs 60%, p = 0.027). The length of stay was similar, 4.02 days in the monotherapy group and 4.51 days in the duotherapy group (p = 0.193). The 90-day readmission rate was higher for the monotherapy group (26.1% vs 8.5% in the duotherapy group, p = 0.044). Multivariate logistic regression showed that preoperative seizure history was a significant predictor for postoperative seizures following an awake craniotomy (OR 2.08, 95% CI 0.56-0.90, p awake craniotomy and may

Treating respiratory viral diseases with chemically modified, second generation intranasal siRNAs.

Science.gov (United States)

Barik, Sailen

2009-01-01

Chemically synthesized short interfering RNA (siRNA) of pre-determined sequence has ushered a new era in the application of RNA interference (RNAi) against viral genes. We have paid particular attention to respiratory viruses that wreak heavy morbidity and mortality worldwide. The clinically significant ones include respiratory syncytial virus (RSV), parainfluenza virus (PIV) and influenza virus. As the infection by these viruses is clinically restricted to the respiratory tissues, mainly the lungs, the logical route for the application of the siRNA was also the same, i.e., via the nasal route. Following the initial success of intranasal siRNA against RSV, second-generation siRNAs were made against the viral polymerase large subunit (L) that were chemically modified and screened for improved stability, activity and pharmacokinetics. 2'-O-methyl (2'-O-Me) and 2'-deoxy-2'-fluoro (2'-F) substitutions in the ribose ring were incorporated in different positions of the sense and antisense strands and the resultant siRNAs were tested with various transfection reagents intranasally against RSV. Based on these results, we propose the following consensus for designing intranasal antiviral siRNAs: (i) modified 19-27 nt long double-stranded siRNAs are functional in the lung, (ii) excessive 2'-OMe and 2'-F modifications in either or both strands of these siRNAs reduce efficacy, and (iii) limited modifications in the sense strand are beneficial, although their precise efficacy may be position-dependent.

Intranasal Coadministration of the Cry1Ac Protoxin with Amoebal Lysates Increases Protection against Naegleria fowleri Meningoencephalitis

Science.gov (United States)

Rojas-Hernández, Saúl; Rodríguez-Monroy, Marco A.; López-Revilla, Rubén; Reséndiz-Albor, Aldo A.; Moreno-Fierros, Leticia

2004-01-01

Cry1Ac protoxin has potent mucosal and systemic adjuvant effects on antibody responses to proteins or polysaccharides. In this work, we examined whether Cry1Ac increased protective immunity against fatal Naegleria fowleri infection in mice, which resembles human primary amoebic meningoencephalitis. Higher immunoglobulin G (IgG) than IgA anti-N. fowleri responses were elicited in the serum and tracheopulmonary fluids of mice immunized by the intranasal or intraperitoneal route with N. fowleri lysates either alone or with Cry1Ac or cholera toxin. Superior protection against a lethal challenge with 5 × 104 live N. fowleri trophozoites was achieved for immunization by the intranasal route. Intranasal immunization of N. fowleri lysates coadministered with Cry1Ac increased survival to 100%; interestingly, immunization with Cry1Ac alone conferred similar protection to that achieved with amoebal lysates alone (60%). When mice intranasally immunized with Cry1Ac plus lysates were challenged with amoebae, both IgG and IgA mucosal responses were rapidly increased, but only the increased IgG response persisted until day 60 in surviving mice. The brief rise in the level of specific mucosal IgA does not exclude the role that this isotype may play in the early defense against this parasite, since higher IgA responses were detected in nasal fluids of mice intranasally immunized with lysates plus either Cry1Ac or cholera toxin, which, indeed, were the treatments that provided the major protection levels. In contrast, serum antibody responses do not seem to be related to the protection level achieved. Both acquired and innate immune systems seem to play a role in host defense against N. fowleri infection, but further studies are required to elucidate the mechanisms involved in protective effects conferred by Cry1Ac, which may be a valuable tool to improve mucosal vaccines. PMID:15271892

Causality Assessment of Olfactory and Gustatory Dysfunction Associated with Intranasal Fluticasone Propionate: Application of the Bradford Hill Criteria

OpenAIRE

Muganurmath, Chandrashekhar S.; Curry, Amy L.; Schindzielorz, Andrew H.

2018-01-01

Causality assessment is crucial to post-marketing pharmacovigilance and helps optimize safe and appropriate use of medicines by patients in the real world. Self-reported olfactory and gustatory dysfunction are common in the general population as well as in patients with allergic rhinitis and nasal polyposis. Intranasal corticosteroids, including intranasal fluticasone propionate (INFP), are amongst the most effective drugs indicated in the treatment of allergic rhinitis and nasal polyposis. W...

Low dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized 4-way crossover trial with nasal cavity dimension assessment

OpenAIRE

Quintana, Daniel; Westlye, Lars Tjelta; Rustan, Øyvind; Tesli, Natalia; Poppy, Claire; Smevik, Hanne; Tesli, Martin Steen; Røine, Marianne; Mahmoud, Ramy; Smerud, Knut Terje; Djupesland, Per G.; Andreassen, Ole Andreas

2015-01-01

Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel ?Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we ...

Sex-Specific Effects of Stress on Oxytocin Neurons Correspond With Responses to Intranasal Oxytocin.

Science.gov (United States)

Steinman, Michael Q; Duque-Wilckens, Natalia; Greenberg, Gian D; Hao, Rebecca; Campi, Katharine L; Laredo, Sarah A; Laman-Maharg, Abigail; Manning, Claire E; Doig, Ian E; Lopez, Eduardo M; Walch, Keenan; Bales, Karen L; Trainor, Brian C

2016-09-01

Oxytocin (OT) is considered to be a stress-buffering hormone, dampening the physiologic effects of stress. However, OT can also be anxiogenic. We examined acute and long-lasting effects of social defeat on OT neurons in male and female California mice. We used immunohistochemistry for OT and c-fos cells to examine OT neuron activity immediately after defeat (n = 6-9) and 2 weeks (n = 6-9) and 10 weeks (n = 4-5) later. We quantified Oxt messenger RNA with quantitative polymerase chain reaction (n = 5-9). Intranasal OT was administered to naïve and stressed mice tested in social interaction and resident-intruder tests (n = 8-14). Acute exposure to a third episode of defeat increased OT/c-fos colocalizations in the paraventricular nucleus of both sexes. In the medioventral bed nucleus of the stria terminalis, defeat increased Oxt messenger RNA, total OT neurons, and OT/c-fos colocalizations in female mice but not male mice. Intranasal OT failed to reverse stress-induced social withdrawal in female mice and reduced social interaction behavior in female mice naïve to defeat. In contrast, intranasal OT increased social interaction in stressed male mice and reduced freezing in the resident-intruder test. Social defeat induces long-lasting increases in OT production and OT/c-fos cells in the medioventral bed nucleus of the stria terminalis of female mice but not male mice. Intranasal OT largely reversed the effects of stress on behavior in male mice, but effects were mixed in female mice. These results suggest that changes in OT-sensitive networks contribute to sex differences in behavioral responses to stress. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Intranasal oxytocin increases neural responses to social reward in post-traumatic stress disorder.

Science.gov (United States)

Nawijn, Laura; van Zuiden, Mirjam; Koch, Saskia B J; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

2017-02-01

Therapeutic alliance and perceived social support are important predictors of treatment response for post-traumatic stress disorder (PTSD). Intranasal oxytocin administration may enhance treatment response by increasing sensitivity for social reward and thereby therapeutic alliance and perceived social support. As a first step to investigate this therapeutical potential, we investigated whether intranasal oxytocin enhances neural sensitivity to social reward in PTSD patients. Male and female police officers with (n = 35) and without PTSD (n = 37) were included in a double-blind, randomized, placebo-controlled cross-over fMRI study. After intranasal oxytocin (40 IU) and placebo administration, a social incentive delay task was conducted to investigate neural responses during social reward and punishment anticipation and feedback. Under placebo, PTSD patients showed reduced left anterior insula (AI) responses to social rewards (i.e. happy faces) compared with controls. Oxytocin administration increased left AI responses during social reward in PTSD patients, such that PTSD patients no longer differed from controls under placebo. Furthermore, in PTSD patients, oxytocin increased responses to social reward in the right putamen. By normalizing abberant insula responses and increasing putamen responses to social reward, oxytocin administration may enhance sensitivity for social support and therapeutic alliance in PTSD patients. Future studies are needed to investigate clinical effects of oxytocin. © The Author (2016). Published by Oxford University Press.

Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish.

Science.gov (United States)

Opler, Lewis A; Opler, Mark G A; Arnsten, Amy F T

2016-02-01

This article reviews the antidepressant actions of ketamine, an N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, and offers a potential neural mechanism for intranasal ketamine's ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5-40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (eg, Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia.

Intranasal boosting with an adenovirus-vectored vaccine markedly enhances protection by parenteral Mycobacterium bovis BCG immunization against pulmonary tuberculosis.

Science.gov (United States)

Santosuosso, Michael; McCormick, Sarah; Zhang, Xizhong; Zganiacz, Anna; Xing, Zhou

2006-08-01

Parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. We examined a heterologous prime-boost regimen utilizing BCG as a prime vaccine and our recently described adenoviral vector expressing Ag85A (AdAg85A) as a boost vaccine. Since we recently demonstrated that a single intranasal but not intramuscular immunization with AdAg85A was able to induce potent protection from pulmonary Mycobacterium tuberculosis challenge in a mouse model, we compared the protective effects of parenteral and mucosal booster immunizations following subcutaneous BCG priming. Protection by BCG prime immunization was not effectively boosted by subcutaneous BCG or intramuscular AdAg85A. In contrast, protection by BCG priming was remarkably boosted by intranasal AdAg85A. Such enhanced protection by intranasal AdAg85A was correlated to the numbers of gamma interferon-positive CD4 and CD8 T cells residing in the airway lumen of the lung. Our study demonstrates that intranasal administration of AdAg85A represents an effective way to boost immune protection by parenteral BCG vaccination.

Intranasal delivery of E-selectin reduces atherosclerosis in ApoE-/- mice.

Directory of Open Access Journals (Sweden)

Xinhui Li

Full Text Available Mucosal tolerance to E-selectin prevents stroke and protects against ischemic brain damage in experimental models of stroke studying healthy animals or spontaneously hypertensive stroke-prone rats. A reduction in inflammation and neural damage was associated with immunomodulatory or "tolerogenic" responses to E-selectin. The purpose of the current study on ApoE deficient mice is to assess the capacity of this stroke prevention innovation to influence atherosclerosis, a major underlying cause for ischemic strokes; human E-selectin is being translated as a potential clinical prevention strategy for secondary stroke. Female ApoE-/- mice received intranasal delivery of E-selectin prior to (pre-tolerization or simultaneously with initiation of a high-fat diet. After 7 weeks on the high-fat diet, lipid lesions in the aorta, serum triglycerides, and total cholesterol were assessed as markers of atherosclerosis development. We also assessed E-selectin-specific antibodies and cytokine responses, in addition to inflammatory responses that included macrophage infiltration of the aorta and altered gene expression profiles of aortic mRNA. Intranasal delivery of E-selectin prior to initiation of high-fat chow decreased atherosclerosis, serum total cholesterol, and expression of the leucocyte chemoattractant CCL21 that is typically upregulated in atherosclerotic lesions of ApoE-/- mice. This response was associated with the induction of E-selectin specific cells producing the immunomodulatory cytokine IL-10 and immunosuppressive antibody isotypes. Intranasal administration of E-selectin generates E-selectin specific immune responses that are immunosuppressive in nature and can ameliorate atherosclerosis, a major risk factor for ischemic stroke. These results provide additional preclinical support for the potential of induction of mucosal tolerance to E-selectin to prevent stroke.

Efeitos anestésicos da administração intranasal ou intramuscular de cetamina S+ e midazolam em pomba-rola (Streptotelia sp. Anesthetic effects of intranasal or intramuscular administration of S+ Ketamine and Midazolam in ring necked dove (Streptotelia sp.

Directory of Open Access Journals (Sweden)

Suzane L. Beier

2013-04-01

Full Text Available A via intranasal é uma boa alternativa por ser indolor e de fácil aplicação em aves. O objetivo deste estudo foi avaliar os efeitos anestésicos da associação de cetamina S+ e midazolam pela via intranasal (IN em comparação com a via intramuscular (IM em pombos. Foram utilizados 12 pombos alocados em dois grupos com 15 dias de intervalo, os quais receberam: grupo IM: 20 mg/kg de cetamina S+ associada a 3,5 mg/kg de midazolam pela via intramuscular (musculatura do peito; e grupo IN, mesmo protocolo, porém, pela via intranasal. Os parâmetros avaliados foram: período de latência, tempo de duração em decúbito dorsal, tempo total de anestesia, tempo de recuperação e efeitos adversos. Para a análise estatística, empregou-se o teste de Wilcoxon, com as diferenças consideradas significativas quando PThe intranasal route is a good alternative because is painless and easy to perform in birds. The objective of this study was to evaluate the anesthetic effects of S+ ketamine and midazolam administered by intranasal or intramuscular route in pigeons. Twelve animals were used in a randomized and crossover design. Animals received two treatments with 2-weeks interval. IM group: animals received 20mg/kg of S+ ketamine and 3.5mg/kg of midazolam by intramuscular route (pectoral muscles; IN group: animals received the same protocol by intranasal route. Parameters evaluated were: onset of action, time of duration in dorsal recumbency; total time of anesthesia and side effects. Statistical analysis was performed using Wilcoxon test and the differences were considered significant when P<0.05. Onset of action was 30 [30-47.5] and 40 [30-50] seconds for IM and IN respectively. Time of duration in dorsal recumbency was 59 [53.25-65] and 63 [37-71.25] minutes for IM and IN respectively, without significant differences between treatments. Total time of anesthesia was 88 [86.25-94.5] and 68 [53.5-93] minutes for IM and IN, respectively, with significant

Evolving Models of Pavlovian Conditioning: Cerebellar Cortical Dynamics in Awake Behaving Mice

Directory of Open Access Journals (Sweden)

Michiel M. ten Brinke

2015-12-01

Full Text Available Three decades of electrophysiological research on cerebellar cortical activity underlying Pavlovian conditioning have expanded our understanding of motor learning in the brain. Purkinje cell simple spike suppression is considered to be crucial in the expression of conditional blink responses (CRs. However, trial-by-trial quantification of this link in awake behaving animals is lacking, and current hypotheses regarding the underlying plasticity mechanisms have diverged from the classical parallel fiber one to the Purkinje cell synapse LTD hypothesis. Here, we establish that acquired simple spike suppression, acquired conditioned stimulus (CS-related complex spike responses, and molecular layer interneuron (MLI activity predict the expression of CRs on a trial-by-trial basis using awake behaving mice. Additionally, we show that two independent transgenic mouse mutants with impaired MLI function exhibit motor learning deficits. Our findings suggest multiple cerebellar cortical plasticity mechanisms underlying simple spike suppression, and they implicate the broader involvement of the olivocerebellar module within the interstimulus interval.

Behavioral effects of acclimatization to restraint protocol used for awake animal imaging.

Science.gov (United States)

Reed, Michael D; Pira, Ashley S; Febo, Marcelo

2013-07-15

Functional MRI in awake rats involves acclimatization to restraint to minimize motion. We designed a study to examine the effects of an acclimatization protocol (5 days of restraint, 60 min per day) on the emission of 22-kHz ultrasonic vocalizations and performance in a forced swim test (FST). Our results showed that USV calls are reduced significantly by days 3, 4 and 5 of acclimatization. Although the rats showed less climbing activity (and more immobility) in FST on day 5 compared to the 1st day of restraint acclimatization, the difference was not detected once the animals were given a 2-week hiatus. Overall, we showed that animals adapt to the restraint over a five-day period; however, restraint may introduce confounding behavioral outcomes that may hinder the interpretation of results derived from awake rat imaging. The present data warrants further testing of the effects of MRI restraint on behavior. Copyright © 2013 Elsevier B.V. All rights reserved.

Intranasal administration of a proteosome-influenza vaccine is well-tolerated and induces serum and nasal secretion influenza antibodies in healthy human subjects.

Science.gov (United States)

Treanor, John; Nolan, Carrie; O'Brien, Diane; Burt, David; Lowell, George; Linden, Janine; Fries, Louis

2006-01-16

Two randomized, blinded, active comparator-controlled trials of a prototype monovalent A/Beijing/262/95 (H1N1) - proteosome vaccine delivered by intranasal spray were performed in healthy adults. Overall, the intranasal proteosome-adjuvanted vaccine was well-tolerated with only mild stuffy nose and rhinorrhea seen more frequently in recipients of vaccine than in recipients of intranasal saline, and there were no serious adverse events. The intranasal proteosome-adjuvanted vaccine induced serum hemagglutination inhibiting (HAI) and nasal secretory IgA (sIgA) responses specific for the influenza antigen. Serum HAI responses were most influenced by the dosage level, whereas mucosal sIgA responses, although demonstrable with both single-dose and two-dose vaccine regimens, appeared to be greater in response to two-dose regimens (regardless of dose level). Further evaluation of mucosal influenza immunization using the proteosome adjuvant/delivery system is clearly warranted.

Pharmacokinetics and -dynamics of intramuscular and intranasal naloxone: an explorative study in healthy volunteers.

Science.gov (United States)

Skulberg, Arne Kristian; Tylleskar, Ida; Nilsen, Turid; Skarra, Sissel; Salvesen, Øyvind; Sand, Trond; Loftsson, Thorsteinn; Dale, Ola

2018-03-22

This study aimed to develop a model for pharmacodynamic and pharmacokinetic studies of naloxone antagonism under steady-state opioid agonism and to compare a high-concentration/low-volume intranasal naloxone formulation 8 mg/ml to intramuscular 0.8 mg. Two-way crossover in 12 healthy volunteers receiving naloxone while receiving remifentanil by a target-controlled infusion for 102 min. The group were subdivided into three different doses of remifentanil. Blood samples for serum naloxone concentrations, pupillometry and heat pain threshold were measured. The relative bioavailability of intranasal to intramuscular naloxone was 0.75. Pupillometry showed difference in antagonism; the effect was significant in the data set as a whole (p < 0.001) and in all three subgroups (p < 0.02-p < 0.001). Heat pain threshold showed no statistical difference. A target-controlled infusion of remifentanil provides good conditions for studying the pharmacodynamics of naloxone, and pupillometry was a better modality than heat pain threshold. Intranasal naloxone 0.8 mg is inferior for a similar dose intramuscular. Our design may help to bridge the gap between studies in healthy volunteers and the patient population in need of naloxone for opioid overdose. clinicaltrials.gov : NCT02307721.

Mucoadhesive microemulsion of ibuprofen: design and evaluation for brain targeting efficiency through intranasal route

Directory of Open Access Journals (Sweden)

Surjyanarayan Mandal

2015-09-01

Full Text Available This study aimed at designing mucoadhesive microemulsion gel to enhance the brain uptake of Ibuprofen through intranasal route. Ibuprofen loaded mucoadhesive microemulsion (MMEI was developed by incorporating polycarbophil as mucoadhesive polymer into Capmul MCM based optimal microemulsion (MEI and was subjected to characterization, stability, mucoadhesion and naso-ciliotoxicity study. Brain uptake of ibuprofen via nasal route was studied by performing biodistribution study in Swiss albino rats. MEI was found to be transparent, stable and non ciliotoxic with 66.29 ± 4.15 nm, -20.9 ± 3.98 mV and 98.66 ± 1.01% as average globule size, zeta potential and drug content respectively. Transmission Electron Microscopy (TEM study revealed the narrow globule size distribution of MEI. Following single intranasal administration of MMEI and MEI at a dose of 2.86 mg/kg, uptake of ibuprofen in the olfactory bulb was around 3.0 and 1.7 folds compared with intravenous injection of ibuprofen solution (IDS. The ratios of AUC in brain tissues to that in plasma obtained after nasal administration of MMEI were significantly higher than those after intravenous administration of IDS. Findings of the present investigation revealed that the developed mucoadhesive microemulsion gel could be a promising approach for brain targeting of ibuprofen through intranasal route.

Prevalence and potential factors associated with probable sleep or awake bruxism and dentin hypersensitivity in undergraduate students

Directory of Open Access Journals (Sweden)

Neusa Barros DANTAS-NETA

Full Text Available OBJECTIVE: To measure the prevalence of probable sleep or awake bruxism and cervical dentin hypersensitivity of undergraduate students and to determine the symptoms associated with these conditions.METHODOLOGY: This was a cross-sectional study. A diagnosis of probable bruxism was reached when students reported clenching or grinding of the teeth during sleep and/or wakefulness, and when they also presented some of the signs and symptoms of bruxism and masseter muscle pain on palpation. Cervical dentinal hypersensitivity was diagnosed by testing for sensitivity to pain in the cervical region of the teeth. Pain was triggered either by touch (using a #5 probe or by an air jet spray. The sample consisted of 306 university students aged between 19 and 35 years old. The data were stored and analysed using SPSS software, version 15.0 for Windows.RESULT: The prevalence of probable bruxism was 34.3%, with no predominance regarding sex. Probable awake bruxism was more prevalent (61.9%, mostly occurring when the individual reported being in a state of mental concentration (63.1%. There was no association between probable sleep or awake bruxism and dentin hypersensitivity (p = 0.195. Individuals with probable sleep bruxism had increased odds of having muscular pain in the face upon waking (OR = 14.14, 95% CI 5.06-39.55, and those with probable awake bruxism had a increased odds of having facial muscle fatigue when chewing or talking for a long time (OR = 2.88, 95% CI 1.53-5.43 and muscular pain in the face upon waking (OR = 5.31, 95% CI 1.93-14.62.CONCLUSION: The prevalence of probable bruxism was 34.3% and that of HDC was 57.8%, with 22.2% of these subjects also showing probable bruxism. Individuals with probable bruxism tended to have a higher odds of facial pain when they awakened and when chewing or talking for long periods. There were no associations between probable sleep and awake bruxism and cervical dentin hypersensitivity.

Successful Insular Glioma Removal in a Deaf Signer Patient During an Awake Craniotomy Procedure.

Science.gov (United States)

Metellus, Philippe; Boussen, Salah; Guye, Maxime; Trebuchon, Agnes

2017-02-01

Resection of tumors located within the insula of the dominant hemisphere represents a technical challenge because of the complex anatomy, including the surrounding vasculature, and the relationship to functional (motor and language) structures. We report here the case of a successful resection of a left insular glioma in a native deaf signer during an awake craniotomy. The patient, a congenitally deaf right-handed patient who is a native user of sign language, presented with a seizure 1 week before he was referred to our department. Magnetic resonance imaging revealed a left heterogeneous insular tumor enhanced after intravenous gadolinium infusion. Because of its deep and dominant hemisphere location, an awake craniotomy was decided. The patient was evaluated intraoperatively using object naming, text reading, and sign repetition tasks. An isolated inferior frontal gyrus site evoked repeated object naming errors. A transopercular parietal approach was performed and allowed the successful removal of the tumor under direct electric stimulation and electrocorticography. To our knowledge, this is the first report of successful removal of a left insular tumor without any functional sequelae in a native deaf signer using intraoperative direct cerebral stimulation during an awake craniotomy. The methodology used also provides the first evidence of the actual anatomo-functional organization of language in deaf signers. Copyright © 2016 Elsevier Inc. All rights reserved.

Intranasal oxytocin reduces social perception in women: Neural activation and individual variation.

Science.gov (United States)

Hecht, Erin E; Robins, Diana L; Gautam, Pritam; King, Tricia Z

2017-02-15

Most intranasal oxytocin research to date has been carried out in men, but recent studies indicate that females' responses can differ substantially from males'. This randomized, double-blind, placebo-controlled study involved an all-female sample of 28 women not using hormonal contraception. Participants viewed animations of geometric shapes depicting either random movement or social interactions such as playing, chasing, or fighting. Probe questions asked whether any shapes were "friends" or "not friends." Social videos were preceded by cues to attend to either social relationships or physical size changes. All subjects received intranasal placebo spray at scan 1. While the experimenter was not blinded to nasal spray contents at Scan 1, the participants were. Scan 2 followed a randomized, double-blind design. At scan 2, half received a second placebo dose while the other half received 24 IU of intranasal oxytocin. We measured neural responses to these animations at baseline, as well as the change in neural activity induced by oxytocin. Oxytocin reduced activation in early visual cortex and dorsal-stream motion processing regions for the social > size contrast, indicating reduced activity related to social attention. Oxytocin also reduced endorsements that shapes were "friends" or "not friends," and this significantly correlated with reduction in neural activation. Furthermore, participants who perceived fewer social relationships at baseline were more likely to show oxytocin-induced increases in a broad network of regions involved in social perception and social cognition, suggesting that lower social processing at baseline may predict more positive neural responses to oxytocin. Copyright © 2016 Elsevier Inc. All rights reserved.

[Attenuation of inhibitory influence of hormones on adenylyl cyclase systems in the myocardium and brain of rats with obesity and type 2 diabetes mellitus and effect of intranasal insulin on it].

Science.gov (United States)

Kuznetsova, L A; Plesneva, S A; Sharova, T S; Pertseva, M N; Shpakov, A O

2014-01-01

The functional state of the adenylyl cyclase signaling system (ACSS) and its regulation by hormones, the inhibitors of adenylyl cyclase (AC)--somatostatin (SST) in the brain and myocardium and 5-nonyloxytryptamine (5-NOT) in the brain of rats of different ages (5- and 7-month-old) with experimental obesity and a combination of obesity and type 2 diabetes mellitus (DM2), and the effect of long-term treatment of animals with intranasally administered insulin (II) on ACSS were studied. It was shown that the basal AC activity in rats with obesity and DM2 was increased in the myocardium, and to the lesser extent in the brain, the treatment with II reducing this parameter. The AC stimulating effects of forskolin are decreased in the myocardium, but not in the brain, of rats with obesity and DM2. The treatment with II restored the AC action of forskolin in the 7-month-old animals, but has little effect on it in the 5-month-old rats. In obesity the basal AC activity and its stimulation by forskolin varied insignificantly and weakly changed in treatment of animals with II. The AC inhibitory effects of SST and 5-NOT in the investigated pathology are essentially attenuated, the effect of SST to the greatest extent, which we believe to be associated with a reduction in the functional activity of Gi-proteins. The II treatment of animals with obesity and with a combination of obesity and DM2 restored completely or partially the AC inhibiting effects of hormones, to the greatest extent in the brain. Since impaired functioning of ACSS is one of the causes of the metabolic syndrome and DM2, their elimination by treatments with II can be an effective approach to treat these diseases and their CNS and cardiovascular system complications.

Hippocampal insulin microinjection and in vivo microdialysis during spatial memory testing.

Science.gov (United States)

McNay, Ewan C; Sandusky, Leslie A; Pearson-Leary, Jiah

2013-01-11

Glucose metabolism is a useful marker for local neural activity, forming the basis of methods such as 2-deoxyglucose and functional magnetic resonance imaging. However, use of such methods in animal models requires anesthesia and hence both alters the brain state and prevents behavioral measures. An alternative method is the use of in vivo microdialysis to take continuous measurement of brain extracellular fluid concentrations of glucose, lactate, and related metabolites in awake, unrestrained animals. This technique is especially useful when combined with tasks designed to rely on specific brain regions and/or acute pharmacological manipulation; for example, hippocampal measurements during a spatial working memory task (spontaneous alternation) show a dip in extracellular glucose and rise in lactate that are suggestive of enhanced glycolysis, and intrahippocampal insulin administration both improves memory and increases hippocampal glycolysis. Substances such as insulin can be delivered to the hippocampus via the same microdialysis probe used to measure metabolites. The use of spontaneous alternation as a measure of hippocampal function is designed to avoid any confound from stressful motivators (e.g. footshock), restraint, or rewards (e.g. food), all of which can alter both task performance and metabolism; this task also provides a measure of motor activity that permits control for nonspecific effects of treatment. Combined, these methods permit direct measurement of the neurochemical and metabolic variables regulating behavior.

High-Flow Nasal Oxygen in Patient With Obstructive Sleep Apnea Undergoing Awake Craniotomy: A Case Report.

Science.gov (United States)

Wong, Jaclyn W M; Kong, Amy H S; Lam, Sau Yee; Woo, Peter Y M

2017-12-15

Patients with obstructive sleep apnea are frequently considered unsuitable candidates for awake craniotomy due to anticipated problems with oxygenation, ventilation, and a potentially difficult airway. At present, only a handful of such accounts exist in the literature. Our report describes the novel use of high-flow nasal oxygen therapy for a patient with moderate obstructive sleep apnea who underwent an awake craniotomy under deep sedation. The intraoperative application of high-flow nasal oxygen therapy achieved satisfactory oxygenation, maintained the partial carbon dioxide pressure within a reasonable range even during periods of deep sedation, permitted responsive patient monitoring during mapping, and provided excellent patient and surgeon satisfaction.

Default-mode-like network activation in awake rodents.

Directory of Open Access Journals (Sweden)

Jaymin Upadhyay

Full Text Available During wakefulness and in absence of performing tasks or sensory processing, the default-mode network (DMN, an intrinsic central nervous system (CNS network, is in an active state. Non-human primate and human CNS imaging studies have identified the DMN in these two species. Clinical imaging studies have shown that the pattern of activity within the DMN is often modulated in various disease states (e.g., Alzheimer's, schizophrenia or chronic pain. However, whether the DMN exists in awake rodents has not been characterized. The current data provides evidence that awake rodents also possess 'DMN-like' functional connectivity, but only subsequent to habituation to what is initially a novel magnetic resonance imaging (MRI environment as well as physical restraint. Specifically, the habituation process spanned across four separate scanning sessions (Day 2, 4, 6 and 8. At Day 8, significant (p<0.05 functional connectivity was observed amongst structures such as the anterior cingulate (seed region, retrosplenial, parietal, and hippocampal cortices. Prior to habituation (Day 2, functional connectivity was only detected (p<0.05 amongst CNS structures known to mediate anxiety (i.e., anterior cingulate (seed region, posterior hypothalamic area, amygdala and parabracial nucleus. In relating functional connectivity between cingulate-default-mode and cingulate-anxiety structures across Days 2-8, a significant inverse relationship (r = -0.65, p = 0.0004 was observed between these two functional interactions such that increased cingulate-DMN connectivity corresponded to decreased cingulate anxiety network connectivity. This investigation demonstrates that the cingulate is an important component of both the rodent DMN-like and anxiety networks.

Awake craniotomy for cortical language mapping and resection of an arteriovenous malformation adjacent to eloquent areas under general anesthesia — A hybrid approach

Directory of Open Access Journals (Sweden)

Pree Nimmannitya

2015-12-01

Full Text Available Surgery of arteriovenous malformation (AVM is sometimes challenging and carries a high risk of morbidity, especially when the AVM is located in an eloquent area of the brain. Unlike gliomas, awake craniotomy has not been widely used for resection of AVM. The authors present a case of an AVM in the left frontal lobe which was successfully removed with the aid of awake craniotomy with cortical language mapping. In conclusion, awake craniotomy for functional cortical mapping is beneficial for AVM resection, especially when the lesion is located in or adjacent to eloquent areas of the brain. A hybrid approach with functional mapping in the awake condition and AVM resection under general anesthesia may be useful in selected cases. Furthermore, en bloc resection with the nidus embedded in the brain parenchyma may be a useful means of removal to reduce operation time and intraoperative blood loss if there is no apparent functional cortex surrounding the AVM, as in the present case.

AMELIORATING TREATMENT-REFRACTORY DEPRESSION WITH INTRANASAL KETAMINE: POTENTIAL NMDA RECEPTOR ACTIONS IN THE PAIN CIRCUITRY REPRESENTING MENTAL ANGUISH

Science.gov (United States)

Opler, Lewis A.; Opler, Mark G.; Arnsten, Amy F.T.

2014-01-01

This paper reviews the anti-depressant actions of the N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, ketamine, and offers a potential neural mechanism for intranasal ketamine’s ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5–40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (e.g. Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia. PMID:25619798

Repeated intranasal TLR7 stimulation reduces allergen responsiveness in allergic rhinitis

Directory of Open Access Journals (Sweden)

Greiff Lennart

2012-06-01

Full Text Available Abstract Background Interactions between Th1 and Th2 immune responses are of importance to the onset and development of allergic disorders. A Toll-like receptor 7 agonist such as AZD8848 may have potential as a treatment for allergic airway disease by skewing the immune system away from a Th2 profile. Objective To evaluate the efficacy and safety of intranasal AZD8848. Methods In a placebo-controlled single ascending dose study, AZD8848 (0.3-600 μg was given intranasally to 48 healthy subjects and 12 patients with allergic rhinitis (NCT00688779. In a placebo-controlled repeat challenge/treatment study, AZD8848 (30 and 60 μg was given once weekly for five weeks to 74 patients with allergic rhinitis out of season: starting 24 hours after the final dose, daily allergen challenges were given for seven days (NCT00770003. Safety, tolerability, pharmacokinetics, and biomarkers were monitored. During the allergen challenge series, nasal symptoms and lavage fluid levels of tryptase and α2-macroglobulin, reflecting mast cell activity and plasma exudation, were monitored. Results AZD8848 produced reversible blood lymphocyte reductions and dose-dependent flu-like symptoms: 30–100 μg produced consistent yet tolerable effects. Plasma interleukin-1 receptor antagonist was elevated after administration of AZD8848, reflecting interferon production secondary to TLR7 stimulation. At repeat challenge/treatment, AZD8848 reduced nasal symptoms recorded ten minutes after allergen challenge up to eight days after the final dose. Tryptase and α2-macroglobulin were also reduced by AZD8848. Conclusions Repeated intranasal stimulation of Toll-like receptor 7 by AZD8848 was safe and produced a sustained reduction in the responsiveness to allergen in allergic rhinitis. Trial registration NCT00688779 and NCT00770003 as indicated above.

Chronic orbital inflammatory disease and optic neuropathy associated with long-term intranasal cocaine abuse: 2 cases and literature review.

Science.gov (United States)

Siemerink, Martin J; Freling, Nicole J M; Saeed, Peerooz

2017-10-01

Orbital inflammatory disease and secondary optic neuropathy is a rare but devastating complication of long-term intranasal cocaine abuse. We describe 2 patients with a history of intranasal cocaine consumption who presented with subacute onset of unilateral vision loss from optic neuropathy and limitation of abduction in the affected eye. Magnetic resonance imaging findings included an orbital mass in combination with absent nasal septum and partial destruction of the paranasal sinuses. Biopsies and histopathologic examination of the nasal cavity and the orbital mass revealed chronic inflammation. Both patients were treated with oral corticosteroids, ocular movements completely normalized but no improvement of visual acuity was noted. Intranasal cocaine abuse can cause orbital complications from chronic sinonasal inflammatory disease and these patients are at risk to develop optic neuropathy. Optic neuropathy may be caused by compression, infiltration, or ischaemia.

Specificities of Awake Craniotomy and Brain Mapping in Children for Resection of Supratentorial Tumors in the Language Area.

Science.gov (United States)

Delion, Matthieu; Terminassian, Aram; Lehousse, Thierry; Aubin, Ghislaine; Malka, Jean; N'Guyen, Sylvie; Mercier, Philippe; Menei, Philippe

2015-12-01

In the pediatric population, awake craniotomy began to be used for the resection of brain tumor located close to eloquent areas. Some specificities must be taken into account to adapt this method to children. The aim of this clinical study is to not only confirm the feasibility of awake craniotomy and language brain mapping in the pediatric population but also identify the specificities and necessary adaptations of the procedure. Six children aged 11 to 16 were operated on while awake under local anesthesia with language brain mapping for supratentorial brain lesions (tumor and cavernoma). The preoperative planning comprised functional magnetic resonance imaging (MRI) and neuropsychologic and psychologic assessment. The specific preoperative preparation is clearly explained including hypnosis conditioning and psychiatric evaluation. The success of the procedure was based on the ability to perform the language brain mapping and the tumor removal without putting the patient to sleep. We investigated the pediatric specificities, psychological experience, and neuropsychologic follow-up. The children experienced little anxiety, probably in large part due to the use of hypnosis. We succeeded in doing the cortical-subcortical mapping and removing the tumor without putting the patient to sleep in all cases. The psychological experience was good, and the neuropsychologic follow-up showed a favorable evolution. Preoperative preparation and hypnosis in children seemed important for performing awake craniotomy and contributing language brain mapping with the best possible psychological experience. The pediatrics specificities are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Use of Intranasal Naloxone by Basic Life Support Providers.

Science.gov (United States)

Weiner, Scott G; Mitchell, Patricia M; Temin, Elizabeth S; Langlois, Breanne K; Dyer, K Sophia

2017-01-01

Intranasal delivery of naloxone to reverse the effects of opioid overdose by Advanced Life Support (ALS) providers has been studied in several prehospital settings. In 2006, in response to the increase in opioid-related overdoses, a special waiver from the state allowed administration of intranasal naloxone by Basic Life Support (BLS) providers in our city. This study aimed to determine: 1) if patients who received a 2-mg dose of nasal naloxone administered by BLS required repeat dosing while in the emergency department (ED), and 2) the disposition of these patients. This was a retrospective review of patients transported by an inner-city municipal ambulance service to one of three academic medical centers. We included patients aged 18 and older that were transported by ambulance between 1/1/2006 and 12/12/2012 and who received intranasal naloxone by BLS providers as per a state approved protocol. Site investigators matched EMS run data to patients from each hospital's EMR and performed a chart review to confirm that the patient was correctly identified and to record the outcomes of interest. Descriptive statistics were then generated. A total of 793 patients received nasal naloxone by BLS and were transported to three hospitals. ALS intervened and transported 116 (14.6%) patients, and 11 (1.4%) were intubated in the field. There were 724 (91.3%) patients successfully matched to an ED chart. Hospital A received 336 (46.4%) patients, Hospital B received 210 (29.0%) patients, and Hospital C received 178 (24.6%) patients. Mean age was 36.2 (SD 10.5) years and 522 (72.1%) were male; 702 (97.1%) were reported to have abused heroin while 21 (2.9%) used other opioids. Nasal naloxone had an effect per the prehospital record in 689 (95.2%) patients. An additional naloxone dose was given in the ED to 64 (8.8%) patients. ED dispositions were: 507 (70.0%) discharged, 105 (14.5%) admitted, and 112 (15.5%) other (e.g., left against medical advice, left without being seen, or

Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives

Directory of Open Access Journals (Sweden)

Yingying Xu

2014-07-01

Full Text Available Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissues (NALT. Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manufacture in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents.

Intranasal delivery of influenza subunit vaccine formulated with GEM particles as an adjuvant

NARCIS (Netherlands)

Saluja, Vinay; Amorij, Jean P; van Roosmalen, Maarten L; Leenhouts, Kees; Huckriede, Anke; Hinrichs, Wouter L J; Frijlink, Henderik W

Nasal administration of influenza vaccine has the potential to facilitate influenza control and prevention. However, when administered intranasally (i.n.), commercially available inactivated vaccines only generate systemic and mucosal immune responses if strong adjuvants are used, which are often

Concentrated insulins: the new basal insulins

Directory of Open Access Journals (Sweden)

Lamos EM

2016-03-01

Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

Serotonin Decreases the Gain of Visual Responses in Awake Macaque V1.

Science.gov (United States)

Seillier, Lenka; Lorenz, Corinna; Kawaguchi, Katsuhisa; Ott, Torben; Nieder, Andreas; Pourriahi, Paria; Nienborg, Hendrikje

2017-11-22

Serotonin, an important neuromodulator in the brain, is implicated in affective and cognitive functions. However, its role even for basic cortical processes is controversial. For example, in the mammalian primary visual cortex (V1), heterogenous serotonergic modulation has been observed in anesthetized animals. Here, we combined extracellular single-unit recordings with iontophoresis in awake animals. We examined the role of serotonin on well-defined tuning properties (orientation, spatial frequency, contrast, and size) in V1 of two male macaque monkeys. We find that in the awake macaque the modulatory effect of serotonin is surprisingly uniform: it causes a mainly multiplicative decrease of the visual responses and a slight increase in the stimulus-selective response latency. Moreover, serotonin neither systematically changes the selectivity or variability of the response, nor the interneuronal correlation unexplained by the stimulus ("noise-correlation"). The modulation by serotonin has qualitative similarities with that for a decrease in stimulus contrast, but differs quantitatively from decreasing contrast. It can be captured by a simple additive change to a threshold-linear spiking nonlinearity. Together, our results show that serotonin is well suited to control the response gain of neurons in V1 depending on the animal's behavioral or motivational context, complementing other known state-dependent gain-control mechanisms. SIGNIFICANCE STATEMENT Serotonin is an important neuromodulator in the brain and a major target for drugs used to treat psychiatric disorders. Nonetheless, surprisingly little is known about how it shapes information processing in sensory areas. Here we examined the serotonergic modulation of visual processing in the primary visual cortex of awake behaving macaque monkeys. We found that serotonin mainly decreased the gain of the visual responses, without systematically changing their selectivity, variability, or covariability. This

arXiv Simulation Study of an LWFA-based Electron Injector for AWAKE Run 2

CERN Document Server

Williamson, B.; Doebert, S.; Karsch, S.; Muggli, P.

The AWAKE experiment aims to demonstrate preservation of injected electron beam quality during acceleration in proton-driven plasma waves. The short bunch duration required to correctly load the wakefield is challenging to meet with the current electron injector system, given the space available to the beamline. An LWFA readily provides short-duration electron beams with sufficient charge from a compact design, and provides a scalable option for future electron acceleration experiments at AWAKE. Simulations of a shock-front injected LWFA demonstrate a 43 TW laser system would be sufficient to produce the required charge over a range of energies beyond 100 MeV. LWFA beams typically have high peak current and large divergence on exiting their native plasmas, and optimisation of bunch parameters before injection into the proton-driven wakefields is required. Compact beam transport solutions are discussed.

Benefits of awake uniportal pulmonary resection in a patient with a previous contralateral lobectomy.

Science.gov (United States)

Galvez, Carlos; Navarro-Martinez, Jose; Bolufer, Sergio; Lirio, Francisco; Mafe, Juan Jose; Rivera, Maria Jesus; Roca, Joaquin; Baschwitz, Benno

2014-09-01

Surgical resection of a contralateral recurrence of non-small cell lung cancer (NSCLC) is indicated in patients without evidence of disseminated disease and considered functionally operable. General anesthesia and double-lumen intubation involves one lobe ventilation in a patient treated with a previous lobectomy, thus increasing the risks of ventilator-induced injuries and the morbidity. Awake procedures facilitate the surgery decreasing the anesthetic and surgical times, keeping the diaphragm motion and diminishing the ventilator-induced injuries into the remaining contralateral lobe. We present a 43-year-old woman with a previous left-lower lobectomy for a 3.1-cm mucinous adenocarcinoma 15 months before without nodal involvement, who presents a right-lower lobe 8-mm cavitated nodule, with evident radiological growth and fine-needle aspiration concordant with mucinous adenocarcinoma. We suggest an awake procedure with locoregional epidural anesthesia.

Imaging circulating tumor cells in freely moving awake small animals using a miniaturized intravital microscope.

Directory of Open Access Journals (Sweden)

Laura Sarah Sasportas

Full Text Available Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process involving the invasion of circulating tumor cells (CTCs into blood vessels. These cells have potential prognostic value as biomarkers for early metastatic risk. But their rarity and the lack of specificity and sensitivity in measuring them render their interrogation by current techniques very challenging. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. In order to provide an insight into this "black box" using non-invasive imaging, we developed a novel miniature intravital microscopy (mIVM strategy capable of real-time long-term monitoring of CTCs in awake small animals. We established an experimental 4T1-GL mouse model of metastatic breast cancer, in which tumor cells express both fluorescent and bioluminescent reporter genes to enable both single cell and whole body tumor imaging. Using mIVM, we monitored blood vessels of different diameters in awake mice in an experimental model of metastasis. Using an in-house software algorithm we developed, we demonstrated in vivo CTC enumeration and computation of CTC trajectory and speed. These data represent the first reported use we know of for a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals.

Imaging circulating tumor cells in freely moving awake small animals using a miniaturized intravital microscope.

Science.gov (United States)

Sasportas, Laura Sarah; Gambhir, Sanjiv Sam

2014-01-01

Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process involving the invasion of circulating tumor cells (CTCs) into blood vessels. These cells have potential prognostic value as biomarkers for early metastatic risk. But their rarity and the lack of specificity and sensitivity in measuring them render their interrogation by current techniques very challenging. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. In order to provide an insight into this "black box" using non-invasive imaging, we developed a novel miniature intravital microscopy (mIVM) strategy capable of real-time long-term monitoring of CTCs in awake small animals. We established an experimental 4T1-GL mouse model of metastatic breast cancer, in which tumor cells express both fluorescent and bioluminescent reporter genes to enable both single cell and whole body tumor imaging. Using mIVM, we monitored blood vessels of different diameters in awake mice in an experimental model of metastasis. Using an in-house software algorithm we developed, we demonstrated in vivo CTC enumeration and computation of CTC trajectory and speed. These data represent the first reported use we know of for a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals.

Auditory ERPs to stimulus deviance in an awake chimpanzee (Pan troglodytes: towards hominid cognitive neurosciences.

Directory of Open Access Journals (Sweden)

Ari Ueno

Full Text Available BACKGROUND: For decades, the chimpanzee, phylogenetically closest to humans, has been analyzed intensively in comparative cognitive studies. Other than the accumulation of behavioral data, the neural basis for cognitive processing in the chimpanzee remains to be clarified. To increase our knowledge on the evolutionary and neural basis of human cognition, comparative neurophysiological studies exploring endogenous neural activities in the awake state are needed. However, to date, such studies have rarely been reported in non-human hominid species, due to the practical difficulties in conducting non-invasive measurements on awake individuals. METHODOLOGY/PRINCIPAL FINDINGS: We measured auditory event-related potentials (ERPs of a fully awake chimpanzee, with reference to a well-documented component of human studies, namely mismatch negativity (MMN. In response to infrequent, deviant tones that were delivered in a uniform sound stream, a comparable ERP component could be detected as negative deflections in early latencies. CONCLUSIONS/SIGNIFICANCE: The present study reports the MMN-like component in a chimpanzee for the first time. In human studies, various ERP components, including MMN, are well-documented indicators of cognitive and neural processing. The results of the present study validate the use of non-invasive ERP measurements for studies on cognitive and neural processing in chimpanzees, and open the way for future studies comparing endogenous neural activities between humans and chimpanzees. This signifies an essential step in hominid cognitive neurosciences.

Efecto del adyuvante vacunal AFCo1 intranasal sobre la concentración plasmática de teofilina en ratas Effect of intranasal vaccine adjuvant AFCo1 on plasma concentration of theophylline in rats

Directory of Open Access Journals (Sweden)

Alexander Batista Duharte

2012-08-01

Full Text Available En este estudio se evaluó el efecto del adyuvante Finlay cocleato 1 (AFCo1, aplicado 4 veces por vía intranasal en 2 niveles de dosis (50 µg y 100 µg sobre la concentración plasmática de teofilina, administrada a las 24 horas de la última aplicación (5 mg/kg, por vía intraperitoneal en ratas Sprague-Dawley. Se empleó como control positivo de inflamación la aplicación de 2 dosis por vía subcutánea de adyuvante completo de Freund (ACF. Las ratas que recibieron AFCo1 no mostraron cambios significativos en la concentración sérica de teofilina; mientras que las tratadas con ACF desarrollaron inflamación local asociadas a signos de toxicidad a la teofilina y elevación de las cifras de inmunoglobulina G específica, de las concentraciones plasmáticas y el tiempo de vida media de teofilina en suero, en comparación con los grupos restantes. Estos resultados indican que la inmunoestimulación inducida por AFCo1 intranasal no incrementa los parámetros farmacocinéticos ni la toxicidad de la teofilina en el modelo empleado.The effect of the adjuvant Finlay cochleate1 (AFCo1, applied intranasally 4 times in 2 dose levels (50 µg and 100 µg on plasma concentration of theophylline administered 24 hours after the last application (5 mg/kg intraperitoneally in Sprague-Dawley rats was evaluated in this study. Application subcutaneously of 2 doses of Freund's complete adjuvant (FCA was used as positive control of inflammation. Rats receiving AFCo1 had no significant changes in serum theophylline concentration, while those treated with FCA developed local inflammation associated with signs of theophylline toxicity and increased specific G immunoglobulin, plasma concentrations and serum theophylline half-life as compared with the remaining groups. These results show that intranasal AFCo1-induced immunostimulation does not increase pharmacokinetic parameters and theophylline toxicity in the model used.

Awake craniotomy to maximize glioma resection: methods and technical nuances over a 27-year period.

Science.gov (United States)

Hervey-Jumper, Shawn L; Li, Jing; Lau, Darryl; Molinaro, Annette M; Perry, David W; Meng, Lingzhong; Berger, Mitchel S

2015-08-01

Awake craniotomy is currently a useful surgical approach to help identify and preserve functional areas during cortical and subcortical tumor resections. Methodologies have evolved over time to maximize patient safety and minimize morbidity using this technique. The goal of this study is to analyze a single surgeon's experience and the evolving methodology of awake language and sensorimotor mapping for glioma surgery. The authors retrospectively studied patients undergoing awake brain tumor surgery between 1986 and 2014. Operations for the initial 248 patients (1986-1997) were completed at the University of Washington, and the subsequent surgeries in 611 patients (1997-2014) were completed at the University of California, San Francisco. Perioperative risk factors and complications were assessed using the latter 611 cases. The median patient age was 42 years (range 13-84 years). Sixty percent of patients had Karnofsky Performance Status (KPS) scores of 90-100, and 40% had KPS scores less than 80. Fifty-five percent of patients underwent surgery for high-grade gliomas, 42% for low-grade gliomas, 1% for metastatic lesions, and 2% for other lesions (cortical dysplasia, encephalitis, necrosis, abscess, and hemangioma). The majority of patients were in American Society of Anesthesiologists (ASA) Class 1 or 2 (mild systemic disease); however, patients with severe systemic disease were not excluded from awake brain tumor surgery and represented 15% of study participants. Laryngeal mask airway was used in 8 patients (1%) and was most commonly used for large vascular tumors with more than 2 cm of mass effect. The most common sedation regimen was propofol plus remifentanil (54%); however, 42% of patients required an adjustment to the initial sedation regimen before skin incision due to patient intolerance. Mannitol was used in 54% of cases. Twelve percent of patients were active smokers at the time of surgery, which did not impact completion of the intraoperative mapping

Preparation of ESAT-6 Nanoparticles and Evaluation of Humoral Immunity after Intranasal Administration

Directory of Open Access Journals (Sweden)

H Najminezhad

2013-01-01

Full Text Available Introduction: Among several tuberculosis vaccine candidates for replacement of BCG, ESAT-6 protein has a special role. Since mycobacterium tuberculosis infection most often attacks the lungs, intranasal rout can be regarded as appropriate methods for tuberculosis vaccines and drug delivery. One of the appropriate systems for intranasal vaccine delivery is using biodegradable nanoparticles. Among biodegradable polymers, chitosan polymer has great features to increase the response of immunity system. This study aimed to investigate the specific humoral immune response of mice model after encapsulation of recombinant ESAT-6 antigen in chitosan nanoparticles. Methods: The chitosan nanoparticles containing ESAT-6 antigen were synthesized by ionic gelation. Nanoparticle properties including morphology, particle size, zeta potential, encapsulation rates, and protein release were measured in vitro. The immunization was performed through the nose for 3 times on days 0 and 14 and 28. 2 weeks after last administration, blood samples were collected and specific IgG titers were measured by indirect ELISA. Results: The nanoparticles synthesized had appropriate properties. The mean size of resulting nanoparticles was 242.8 nm by excellent antigen loading capacity (95.23 %. The vitro release of antigen from nanoparticles after 200 hours was detected as 67.5%. The Level of IgG antibody showed significant increase in the group that had received chitosan nanoparticles containing ESAT-6 compared with other groups. Conclusion: ESAT-6 protein was encapsulated in chitosan nanoparticles successfully. Administration of chitosan nanoparticles can be a suitable method for administration of humoral immunity antigens of Mycobacterium tuberculosis through intranasal rout.

The Cost of Brain Surgery: Awake vs Asleep Craniotomy for Perirolandic Region Tumors.

Science.gov (United States)

Eseonu, Chikezie I; Rincon-Torroella, Jordina; ReFaey, Karim; Quiñones-Hinojosa, Alfredo

2017-08-01

Cost effectiveness has become an important factor in the health care system, requiring surgeons to improve efficacy of procedures while reducing costs. An awake craniotomy (AC) with direct cortical stimulation (DCS) presents one method to resect eloquent region tumors; however, some authors assert that this procedure is an expensive alternative to surgery under general anesthesia (GA) with neuromonitoring. To evaluate the cost effectiveness and clinical outcomes between AC and GA patients. Retrospective analysis of a cohort of 17 patients with perirolandic gliomas who underwent an AC with DCS were case-control matched with 23 patients with perirolandic gliomas who underwent surgery under GA with neuromonitoring (ie, motor-evoked potentials, somatosensory-evoked potentials, phase reversal). Inpatient costs, quality-adjusted life years (QALY), extent of resection, and neurological outcome were compared between the groups. Total inpatient expense per patient was $34 804 in the AC group and $46 798 in the GA group ( P = .046). QALY score for the AC group was 0.97 and 0.47 for the GA group ( P = .041). The incremental cost per QALY for the AC group was $82 720 less than the GA group. Postoperative Karnofsky performance status was 91.8 in the AC group and 81.3 in the GA group (P = .047). Length of hospitalization was 4.12 days in the AC group and 7.61 days in the GA group ( P = .049). The total inpatient costs for awake craniotomies were lower than surgery under GA. This study suggests better cost effectiveness and neurological outcome with awake craniotomies for perirolandic gliomas. Copyright © 2017 by the Congress of Neurological Surgeons

Lung function measurement in awake young children

DEFF Research Database (Denmark)

Bisgaard, H; Klug, B

1995-01-01

) and transcutaneous measurements of oxygen tension (Ptc,O2) were compared with concomitant measurements of specific airway resistance (sRaw) and forced expiratory volume in one second (FEV1) by whole body plethysmography and spirometry, respectively, during methacholine challenge in 21 young children aged 4-6 yrs...... to methacholine in young children aged 4-6 yrs. This implies that ZIOS, Rint and Ptc,O2 provide convenient indices of changes in lung function. Their combined use will be useful for monitoring airway diseases of young children.......The aim of the study was to evaluate methods applicable in a clinical setting for monitoring of changes in lung function in awake young children. Impedance measurements by the impulse oscillation technique (ZIOS), respiratory resistance measurements by the interrupter technique (Rint...

Intranasal Oxytocin Failed to Affect Chimpanzee (Pan troglodytes) Social Behavior

Science.gov (United States)

Calcutt, Sarah E.; Burke, Kimberly; de Waal, Frans B. M.

2017-01-01

Oxytocin has been suggested as a treatment to promote positive social interactions in people with Autism Spectrum Disorders (ASD). However, it is difficult to test this effect outside of the laboratory in realistic social situations. One way to resolve this issue is to study behavioral changes in closely related species with complex social relationships, such as chimpanzees. Here, we use captive, socially housed chimpanzees to evaluate the effects of oxytocin in a socially complex environment. After administering intranasal oxytocin or a placebo to an individual chimpanzee (total n = 8), she was returned to her social group. An experimenter blind to the condition measured the subject's social behavior. We failed to find a behavioral difference between conditions. As one of the goals for oxytocin administration as a treatment for ASD is increasing prosocial behaviors during ‘real world’ encounters, it is problematic that we failed to detect behavioral changes in our closest living relatives. However, our null findings may be related to methodological challenges such as determining an effective dose of oxytocin for chimpanzees and how long oxytocin takes to cross the blood-brain barrier. Thus, more research on intranasal oxytocin dosing and uptake are needed to continue exploring whether oxytocin changes social behavior in naturalistic settings and as a treatment for ASD. PMID:28845444

A Case Report of Onyx Pulmonary Arterial Embolism Contributing to Hypoxemia During Awake Craniotomy for Arteriovenous Malformation Resection.

Science.gov (United States)

Tolly, Brian T; Kosky, Jenna L; Koht, Antoun; Hemmer, Laura B

2017-02-15

A healthy 26-year-old man with cerebral arteriovenous malformation underwent staged endovascular embolization with Onyx followed by awake craniotomy for resection. The perioperative course was complicated by tachycardia and severe intraoperative hypoxemia requiring significant oxygen supplementation. Postoperative chest computed tomography (CT) revealed hyperattenuating Onyx embolization material within the pulmonary vasculature, and an electrocardiogram indicated possible right heart strain, supporting clinically significant embolism. With awake arteriovenous malformation resection following adjunctive Onyx embolization becoming increasingly employed for lesions involving the eloquent cortex, anesthesiologists need to be aware of pulmonary migration of Onyx material as a potential contributor to significant perioperative hypoxemia.

Oral steroids alone or followed by intranasal steroids versus watchful waiting in the management of otitis media with effusion.

Science.gov (United States)

Hussein, A; Fathy, H; Amin, S M; Elsisy, N

2017-10-01

To evaluate the effects of oral steroids alone or followed by intranasal steroids versus watchful waiting on the resolution of otitis media with effusion in children aged 2-11 years. A total of 290 children with bilateral otitis media with effusion were assigned to 3 groups: group A was treated with oral steroids followed by intranasal steroids, group B was treated with oral steroids alone and group C was managed with watchful waiting. Patients were evaluated with audiometry and tympanometry. The complete resolution rates of otitis media with effusion were higher in groups A and B than in group C at six weeks. There were no significant differences in otitis media with effusion resolution rates between the groups at three, six and nine months. Oral steroids lead only to a quick resolution of otitis media with effusion, with no long-term benefits. There was no benefit of using intranasal steroids in the management of otitis media with effusion.

Fast and Accurate Rat Head Motion Tracking With Point Sources for Awake Brain PET.

Science.gov (United States)

Miranda, Alan; Staelens, Steven; Stroobants, Sigrid; Verhaeghe, Jeroen

2017-07-01

To avoid the confounding effects of anesthesia and immobilization stress in rat brain positron emission tomography (PET), motion tracking-based unrestrained awake rat brain imaging is being developed. In this paper, we propose a fast and accurate rat headmotion tracking method based on small PET point sources. PET point sources (3-4) attached to the rat's head are tracked in image space using 15-32-ms time frames. Our point source tracking (PST) method was validated using a manually moved microDerenzo phantom that was simultaneously tracked with an optical tracker (OT) for comparison. The PST method was further validated in three awake [ 18 F]FDG rat brain scans. Compared with the OT, the PST-based correction at the same frame rate (31.2 Hz) reduced the reconstructed FWHM by 0.39-0.66 mm for the different tested rod sizes of the microDerenzo phantom. The FWHM could be further reduced by another 0.07-0.13 mm when increasing the PST frame rate (66.7 Hz). Regional brain [ 18 F]FDG uptake in the motion corrected scan was strongly correlated ( ) with that of the anesthetized reference scan for all three cases ( ). The proposed PST method allowed excellent and reproducible motion correction in awake in vivo experiments. In addition, there is no need of specialized tracking equipment or additional calibrations to be performed, the point sources are practically imperceptible to the rat, and PST is ideally suitable for small bore scanners, where optical tracking might be challenging.

Effect of intranasal manganese administration on neurotransmission and spatial learning in rats

Energy Technology Data Exchange (ETDEWEB)

Blecharz-Klin, Kamilla; Piechal, Agnieszka; Joniec-Maciejak, Ilona; Pyrzanowska, Justyna; Widy-Tyszkiewicz, Ewa, E-mail: etyszkiewicz@wum.edu.pl

2012-11-15

The effect of intranasal manganese chloride (MnCl{sub 2}·4H{sub 2}O) exposure on spatial learning, memory and motor activity was estimated in Morris water maze task in adult rats. Three-month-old male Wistar rats received for 2 weeks MnCl{sub 2}·4H{sub 2}O at two doses the following: 0.2 mg/kg b.w. (Mn0.2) or 0.8 mg/kg b.w. (Mn0.8) per day. Control (Con) and manganese-exposed groups were observed for behavioral performance and learning in water maze. ANOVA for repeated measurements did not show any significant differences in acquisition in the water maze between the groups. However, the results of the probe trial on day 5, exhibited spatial memory deficits following manganese treatment. After completion of the behavioral experiment, the regional brain concentrations of neurotransmitters and their metabolites were determined via HPLC in selected brain regions, i.e. prefrontal cortex, hippocampus and striatum. ANOVA demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the controls. Negative correlations between platform crossings on the previous platform position in Southeast (SE) quadrant during the probe trial and neurotransmitter turnover suggest that impairment of spatial memory and cognitive performance after manganese (Mn) treatment is associated with modulation of the serotonergic, noradrenergic and dopaminergic neurotransmission in the brain. These findings show that intranasally applied Mn can impair spatial memory with significant changes in the tissue level and metabolism of monoamines in several brain regions. -- Highlights: ► Intranasal exposure to manganese in rats impairs spatial memory in the water maze. ► Regional changes in levels of neurotransmitters in the brain have been identified. ► Cognitive disorder correlates with modulation of 5-HT, NA and DA neurotransmission.

Effect of intranasal manganese administration on neurotransmission and spatial learning in rats

International Nuclear Information System (INIS)

Blecharz-Klin, Kamilla; Piechal, Agnieszka; Joniec-Maciejak, Ilona; Pyrzanowska, Justyna; Widy-Tyszkiewicz, Ewa

2012-01-01

The effect of intranasal manganese chloride (MnCl 2 ·4H 2 O) exposure on spatial learning, memory and motor activity was estimated in Morris water maze task in adult rats. Three-month-old male Wistar rats received for 2 weeks MnCl 2 ·4H 2 O at two doses the following: 0.2 mg/kg b.w. (Mn0.2) or 0.8 mg/kg b.w. (Mn0.8) per day. Control (Con) and manganese-exposed groups were observed for behavioral performance and learning in water maze. ANOVA for repeated measurements did not show any significant differences in acquisition in the water maze between the groups. However, the results of the probe trial on day 5, exhibited spatial memory deficits following manganese treatment. After completion of the behavioral experiment, the regional brain concentrations of neurotransmitters and their metabolites were determined via HPLC in selected brain regions, i.e. prefrontal cortex, hippocampus and striatum. ANOVA demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the controls. Negative correlations between platform crossings on the previous platform position in Southeast (SE) quadrant during the probe trial and neurotransmitter turnover suggest that impairment of spatial memory and cognitive performance after manganese (Mn) treatment is associated with modulation of the serotonergic, noradrenergic and dopaminergic neurotransmission in the brain. These findings show that intranasally applied Mn can impair spatial memory with significant changes in the tissue level and metabolism of monoamines in several brain regions. -- Highlights: ► Intranasal exposure to manganese in rats impairs spatial memory in the water maze. ► Regional changes in levels of neurotransmitters in the brain have been identified. ► Cognitive disorder correlates with modulation of 5-HT, NA and DA neurotransmission.

Intranasal delivery of hypoxia-preconditioned bone marrow-derived mesenchymal stem cells enhanced regenerative effects after intracerebral hemorrhagic stroke in mice.

Science.gov (United States)

Sun, Jinmei; Wei, Zheng Zachory; Gu, Xiaohuan; Zhang, James Ya; Zhang, Yongbo; Li, Jimei; Wei, Ling

2015-10-01

Intracerebral hemorrhagic stroke (ICH) causes high mortality and morbidity with very limited treatment options. Cell-based therapy has emerged as a novel approach to replace damaged brain tissues and promote regenerative processes. In this study we tested the hypothesis that intranasally delivered hypoxia-preconditioned BMSCs could reach the brain, promote tissue repair and improve functional recovery after ICH. Hemorrhagic stroke was induced in adult C57/B6 mice by injection of collagenase IV into the striatum. Animals were randomly divided into three groups: sham group, intranasal BMSC treatment group, and vehicle treatment group. BMSCs were pre-treated with hypoxic preconditioning (HP) and pre-labeled with Hoechst before transplantation. Behavior tests, including the mNSS score, rotarod test, adhesive removal test, and locomotor function evaluation were performed at varying days, up to 21days, after ICH to evaluate the therapeutic effects of BMSC transplantation. Western blots and immunohistochemistry were performed to analyze the neurotrophic effects. Intranasally delivered HP-BMSCs were identified in peri-injury regions. NeuN+/BrdU+ co-labeled cells were markedly increased around the hematoma region, and growth factors, including BDNF, GDNF, and VEGF were significantly upregulated in the ICH brain after BMSC treatment. The BMSC treatment group showed significant improvement in behavioral performance compared with the vehicle group. Our data also showed that intranasally delivered HP-BMSCs migrated to peri-injury regions and provided growth factors to increase neurogenesis after ICH. We conclude that intranasal administration of BMSC is an effective treatment for ICH, and that it enhanced neuroregenerative effects and promoted neurological functional recovery after ICH. Overall, the investigation supports the potential therapeutic strategy for BMSC transplantation therapy against hemorrhagic stroke. Copyright © 2015 Elsevier Inc. All rights reserved.

Prolonged protection against Intranasal challenge with influenza virus following systemic immunization or combinations of mucosal and systemic immunizations with a heat-labile toxin mutant.

Science.gov (United States)

Zhou, Fengmin; Goodsell, Amanda; Uematsu, Yasushi; Vajdy, Michael

2009-04-01

Seasonal influenza virus infections cause considerable morbidity and mortality in the world, and there is a serious threat of a pandemic influenza with the potential to cause millions of deaths. Therefore, practical influenza vaccines and vaccination strategies that can confer protection against intranasal infection with influenza viruses are needed. In this study, we demonstrate that using LTK63, a nontoxic mutant of the heat-labile toxin from Escherichia coli, as an adjuvant for both mucosal and systemic immunizations, systemic (intramuscular) immunization or combinations of mucosal (intranasal) and intramuscular immunizations protected mice against intranasal challenge with a lethal dose of live influenza virus at 3.5 months after the second immunization.

Intranasal Immunization Using Mannatide as a Novel Adjuvant for an Inactivated Influenza Vaccine and Its Adjuvant Effect Compared with MF59.

Directory of Open Access Journals (Sweden)

Shu-Ting Ren

Full Text Available Intranasal vaccination is more potent than parenteral injection for the prevention of influenza. However, because the poor efficiency of antigen uptake across the nasal mucosa is a key issue, immunostimulatory adjuvants are essential for intranasal vaccines. The immunomodulator mannatide or polyactin (PA has been used for the clinical treatment of impaired immunity in China, but its adjuvant effect on an inactivated trivalent influenza vaccine (ITIV via intranasal vaccination is unclear. To explore the adjuvant effect of PA, an inactivated trivalent influenza virus with or without PA or MF59 was instilled intranasally once a week in BALB/c mice. Humoral immunity was assessed by both the ELISA and hemagglutination inhibition (HI methods using antigen-specific antibodies. Splenic lymphocyte proliferation and the IFN-γ level were measured to evaluate cell-mediated immunity. The post-vaccination serum HI antibody geometric mean titers (GMTs for the H1N1 and H3N2 strains, antigen-specific serum IgG and IgA GMTs, mucosal SIgA GMT, splenic lymphocyte proliferation, and IFN-γ were significantly increased in the high-dose PA-adjuvanted vaccine group. The seroconversion rate and the mucosal response for the H3N2 strain were significantly elevated after high-dose PA administration. These adjuvant effects of high-dose PA for the influenza vaccine were comparable with those of the MF59 adjuvant, and abnormal signs or pathological changes were not found in the evaluated organs. In conclusion, PA is a novel mucosal adjuvant for intranasal vaccination with the ITIV that has safe and effective mucosal adjuvanticity in mice and successfully induces both serum and mucosal antibody responses and a cell-mediated response.

Kandungan Vitamin pada Bahan Dasar MP-ASI Tepung Campuran Pisang Awak dengan Tepung Beras serta Sumbangannya Terhadap Angka Kecukupan Gizi Bayi

OpenAIRE

Harahap, Yunita

2015-01-01

The complementary feeding given to babies older than 6 months. The complementary feeding different types of materials adapted to the manufacture of the local food supply. Awak banana has one of Indonesian eminent local food that used as complementary feeding. This descriptive research aimed to know the vitamins content from mixed flour of awak banana and rice flour and the contribution of vitamins (RDA). In this research, analyzed the content of fat soluble vitamins by Ultra Performance Li...

Curdlan sulfate-O-linked quaternized chitosan nanoparticles: potential adjuvants to improve the immunogenicity of exogenous antigens via intranasal vaccination.

Science.gov (United States)

Zhang, Shu; Huang, Shengshi; Lu, Lu; Song, Xinlei; Li, Pingli; Wang, Fengshan

2018-01-01

The development of ideal vaccine adjuvants for intranasal vaccination can provide convenience for many vaccinations. As an ideal intranasal vaccine adjuvant, it should have the properties of assisting soluble antigens to pass the mucosal barrier and potentiating both systemic and mucosal immunity via nasal administration. By using the advantages of polysaccharides, which can promote both T-helper 1 and 2 responses, curdlan sulfate (CS)- O -(2-hydroxyl)propyl-3-trimethyl ammonium chitosan chloride ( O -HTCC) nanoparticles were prepared by interacting CS with O -HTCC, and the adjuvancy of the nanoparticles was investigated. The results showed that the polysaccharide-based nanoparticles induced the proliferation and activation of antigen-presenting cells. High protein-loading efficiency was obtained by testing with the model antigen ovalbumin (Ova), and the Ova adsorbed onto the cationic CS/ O -HTCC complexes was taken up easily by the epithelium. To evaluate the capacity of the Ova/CS/ O -HTCC nanoparticles for immune enhancement in vivo, we collected and analyzed immunocytes, serum, and mucosal lavage fluid from intranasally vaccinated mice. The results showed that Ova/CS/ O -HTCC nanoparticles induced activation and maturation of antigen-presenting cells and provoked the proliferation and differentiation of lymphocytes more significantly compared to the immunization of Ova mixed with aluminum hydroxide gel. Furthermore, CS/ O -HTCC evoked a significantly higher level of Ova-specific antibodies. Therefore, these results suggest that CS/ O -HTCC nanoparticles are ideal vaccine adjuvants for soluble antigens used in intranasal or mucosal vaccination.

Intact skull chronic windows for mesoscopic wide-field imaging in awake mice

Science.gov (United States)

Silasi, Gergely; Xiao, Dongsheng; Vanni, Matthieu P.; Chen, Andrew C. N.; Murphy, Timothy H.

2016-01-01

Background Craniotomy-based window implants are commonly used for microscopic imaging, in head-fixed rodents, however their field of view is typically small and incompatible with mesoscopic functional mapping of cortex. New Method We describe a reproducible and simple procedure for chronic through-bone wide-field imaging in awake head-fixed mice providing stable optical access for chronic imaging over large areas of the cortex for months. Results The preparation is produced by applying clear-drying dental cement to the intact mouse skull, followed by a glass coverslip to create a partially transparent imaging surface. Surgery time takes about 30 minutes. A single set-screw provides a stable means of attachment for mesoscale assessment without obscuring the cortical field of view. Comparison with Existing Methods We demonstrate the utility of this method by showing seed-pixel functional connectivity maps generated from spontaneous cortical activity of GCAMP6 signals in both awake and anesthetized mice. Conclusions We propose that the intact skull preparation described here may be used for most longitudinal studies that do not require micron scale resolution and where cortical neural or vascular signals are recorded with intrinsic sensors. PMID:27102043

Anesthesia for awake craniotomy: a how-to guide for the occasional practitioner.

Science.gov (United States)

Meng, Lingzhong; McDonagh, David L; Berger, Mitchel S; Gelb, Adrian W

2017-05-01

Awake craniotomy (AC), defined as the performance of at least part of an open cranial procedure with the patient awake, has been tied to beneficial outcomes compared with similar surgery under general anesthesia. Improved anesthetic techniques have made a major contribution to the increasing popularity of AC. However, the heterogeneity of practice among institutions doing large numbers of ACs raises questions (often among those who only occasionally perform AC - i.e., practitioners in low-volume AC institutions) as to the ideal anesthetic technique for AC. The procedure presents a variety of decision-making dilemmas, the origins of which are the varying institutional preferences, lack of quality evidence, and several practice controversies. Evidence-based data that support a single anesthetic algorithm for AC are sparse. In this narrative review, the technical nuances of 13 aspects of anesthetic care for AC are discussed based on institutional preferences and available evidence, and the various controversies and research priorities are discussed. The skills, experience, and commitment of both the surgeon and the anesthesiologist are large variables that are likely more important than what the literature suggests about "best" techniques for AC. Optimizing patient outcome is the fundamental goal of the anesthesiologist.

a-Band Oscillations in Intracellular Membrane Potentials of Dentate Gyrus Neurons in Awake Rodents

Science.gov (United States)

Anderson, Ross W.; Strowbridge, Ben W.

2014-01-01

The hippocampus and dentate gyrus play critical roles in processing declarative memories and spatial information. Dentate granule cells, the first relay in the trisynaptic circuit through the hippocampus, exhibit low spontaneous firing rates even during locomotion. Using intracellular recordings from dentate neurons in awake mice operating a…

A common oxytocin receptor gene (OXTR) polymorphism modulates intranasal oxytocin effects on the neural response to social cooperation in humans.

Science.gov (United States)

Feng, C; Lori, A; Waldman, I D; Binder, E B; Haroon, E; Rilling, J K

2015-09-01

Intranasal oxytocin (OT) can modulate social-emotional functioning and related brain activity in humans. Consequently, OT has been discussed as a potential treatment for psychiatric disorders involving social behavioral deficits. However, OT effects are often heterogeneous across individuals. Here we explore individual differences in OT effects on the neural response to social cooperation as a function of the rs53576 polymorphism of the oxytocin receptor gene (OXTR). Previously, we conducted a double-blind, placebo-controlled study in which healthy men and women were randomized to treatment with intranasal OT or placebo. Afterwards, they were imaged with functional magnetic resonance imaging while playing an iterated Prisoner's Dilemma Game with same-sex partners. Within the left ventral caudate nucleus, intranasal OT treatment increased activation to reciprocated cooperation in men, but tended to decrease activation in women. Here, we show that these sex differences in OT effects are specific to individuals with the rs53576 GG genotype, and are not found for other genotypes (rs53576 AA/AG). Thus, OT may increase the reward or salience of positive social interactions for male GG homozygotes, while decreasing those processes for female GG homozygotes. These results suggest that rs53576 genotype is an important variable to consider in future investigations of the clinical efficacy of intranasal OT treatment. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Electrocorticographic Frequency Alteration Mapping of Speech Cortex during an Awake Craniotomy: Case Report

Science.gov (United States)

Breshears, J.; Sharma, M.; Anderson, N.R.; Rashid, S.; Leuthardt, E.C.

2010-01-01

Objective Traditional electrocortical stimulation (ECS) mapping is limited by the lengthy serial investigation (one location at a time) and the risk of afterdischarges in localizing eloquent cortex. Electrocorticographic frequency alteration mapping (EFAM) allows the parallel investigation of many cortical sites in much less time and with no risk of afterdischarges because of its passive nature. We examined its use with ECS in the context of language mapping during an awake craniotomy for a tumor resection. Clinical Presentation The patient was a 61-year-old right-handed Caucasian male who presented with headache and mild aphasia. Imaging demonstrated a 3-cm cystic mass in the posterior temporal-parietal lobe. The patient underwent an awake craniotomy for the mapping of his speech cortex and resection of the mass. Intervention Using a 32-contact electrode array, electrocorticographic signals were recorded from the exposed cortex as the patient participated in a 3-min screening task involving active (patient naming visually presented words) and rest (patient silent) conditions. A spectral comparison of the 2 conditions revealed specific cortical locations associated with activation during speech. The patient was then widely mapped using ECS. Three of 4 sites identified by ECS were also identified passively and in parallel by EFAM, 2 with statistical significance and the third by qualitative inspection. Conclusion EFAM was technically achieved in an awake craniotomy patient and had good concordance with ECS mapping. Because it poses no risk of afterdischarges and offers substantial time savings, EFAM holds promise for future development as an adjunct intraoperative mapping tool. Additionally, the cortical signals obtained by this modality can be utilized for localization in the presence of a tumor adjacent to the eloquent regions. PMID:19940544

[Incidence and causes of early end in awake surgery for language mapping not directly related to eloquence].

Science.gov (United States)

Villalba, Gloria; Pacreu, Susana; Fernández-Candil, Juan Luis; León, Alba; Serrano, Laura; Conesa, Gerardo

2016-01-01

The incidence and causes that may lead to an early end (unfinished cortical/subcortical mapping) of awake surgery for language mapping are little known. A study was conducted on 41 patients with brain glioma located in the language area that had awake surgery under conscious sedation. Surgery was ended early in 6 patients. The causes were: tonic-clonic seizure (1), lack of cooperation due to fatigue/sleep (4), whether or not word articulation was involved, a decreased level of consciousness for ammonia encephalopathy that required endotracheal intubation (1). There are causes that could be expected and in some cases avoided. Tumour size, preoperative aphasia, valproate treatment, and type of anaesthesia used are variables to consider to avoid failure in awake surgery for language mapping. With these results, the following measures are proposed: l) If the tumour is large, perform surgery in two times to avoid fatigue, 2) if patient has a preoperative aphasia, do not use sedation during surgery to ensure that sleepiness does not cause worse word articulation, 3) if the patient is on valproate treatment, it is necessary to rule out the pre-operative symptoms that are not due to ammonia encephalopathy. Copyright © 2015 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

Insulin and insulin signaling play a critical role in fat induction of insulin resistance in mouse

Science.gov (United States)

Ning, Jie; Hong, Tao; Yang, Xuefeng; Mei, Shuang; Liu, Zhenqi; Liu, Hui-Yu

2011-01-01

The primary player that induces insulin resistance has not been established. Here, we studied whether or not fat can cause insulin resistance in the presence of insulin deficiency. Our results showed that high-fat diet (HFD) induced insulin resistance in C57BL/6 (B6) mice. The HFD-induced insulin resistance was prevented largely by the streptozotocin (STZ)-induced moderate insulin deficiency. The STZ-induced insulin deficiency prevented the HFD-induced ectopic fat accumulation and oxidative stress in liver and gastrocnemius. The STZ-induced insulin deficiency prevented the HFD- or insulin-induced increase in hepatic expression of long-chain acyl-CoA synthetases (ACSL), which are necessary for fatty acid activation. HFD increased mitochondrial contents of long-chain acyl-CoAs, whereas it decreased mitochondrial ADP/ATP ratio, and these HFD-induced changes were prevented by the STZ-induced insulin deficiency. In cultured hepatocytes, we observed that expressions of ACSL1 and -5 were stimulated by insulin signaling. Results in cultured cells also showed that blunting insulin signaling by the PI3K inhibitor LY-294002 prevented fat accumulation, oxidative stress, and insulin resistance induced by the prolonged exposure to either insulin or oleate plus sera that normally contain insulin. Finally, knockdown of the insulin receptor prevented the oxidative stress and insulin resistance induced by the prolonged exposure to insulin or oleate plus sera. Together, our results show that insulin and insulin signaling are required for fat induction of insulin resistance in mice and cultured mouse hepatocytes. PMID:21586696

Resection of Gliomas with and without Neuropsychological Support during Awake Craniotomy—Effects on Surgery and Clinical Outcome

Directory of Open Access Journals (Sweden)

Anna Kelm

2017-08-01

Full Text Available BackgroundDuring awake craniotomy for tumor resection, a neuropsychologist (NP is regarded as a highly valuable partner for neurosurgeons. However, some centers do not routinely involve an NP, and data to support the high influence of the NP on the perioperative course of patients are mostly lacking.ObjectiveThe aim of this study was to investigate whether there is a difference in clinical outcomes between patients who underwent awake craniotomy with and without the attendance of an NP.MethodsOur analysis included 61 patients, all operated on for resection of a presumably language-eloquent glioma during an awake procedure. Of these 61 cases, 47 surgeries were done with neuropsychological support (NP group, whereas 14 surgeries were performed without an NP (non-NP group due to a language barrier between the NP and the patient. For these patients, neuropsychological assessment was provided by a bilingual resident.ResultsBoth groups were highly comparable regarding age, gender, preoperative language function, and tumor grades (glioma WHO grades 1–4. Gross total resection (GTR was achieved more frequently in the NP group (NP vs. non-NP: 61.7 vs. 28.6%, P = 0.04, which also had shorter durations of surgery (NP vs. non-NP: 240.7 ± 45.7 vs. 286.6 ± 54.8 min, P < 0.01. Furthermore, the rate of unexpected tumor residuals (estimation of the intraoperative extent of resection vs. postoperative imaging was lower in the NP group (NP vs. non-NP: 19.1 vs. 42.9%, P = 0.09, but no difference was observed in terms of permanent surgery-related language deterioration (NP vs. non-NP: 6.4 vs. 14.3%, P = 0.48.ConclusionWe need professional neuropsychological evaluation during awake craniotomies for removal of presumably language-eloquent gliomas. Although these procedures are routinely carried out with an NP, this is one of the first studies to provide data supporting the NP’s crucial role. Despite the small group size, our study shows

Studies on insulin secretion and insulin resistance in non-insulin-dependent diabetes in young Indians

International Nuclear Information System (INIS)

Naidoo, C.

1986-01-01

Patients with Non-insulin-dependent diabetes mellitus (NIDDM) have defects in insulin secretion and insulin action. In the discrete genetic syndrome of NIDDY (non-insulin-dependent diabetes in the young), the situation is less clear and these aspects is the subject of this thesis. This study included Indian pasients with three generation transmission of NIDDM via one parent. The insulin and C-peptide responses to oral and intravenous glucose in patients with NIDDY were studied. The insulin and glucose responses to non-glucose secretogogues glucagon, tolbutamide and arginine, in NIDDY were also investigated. The following aspects with regard to insulin resistance in NIDDY were examined: glucose and free fatty acid response to intravenous insulin administration, insulin binding to circulating erythrocytes and monocytes, 125 I-insulin binding to the solubilized erythrocyte membrane receptor and 125 I-insulin binding to fibroblasts in culture

Studies on insulin secretion and insulin resistance in non-insulin-dependent diabetes in young Indians

Energy Technology Data Exchange (ETDEWEB)

Naidoo, C

1986-01-01

Patients with Non-insulin-dependent diabetes mellitus (NIDDM) have defects in insulin secretion and insulin action. In the discrete genetic syndrome of NIDDY (non-insulin-dependent diabetes in the young), the situation is less clear and these aspects is the subject of this thesis. This study included Indian pasients with three generation transmission of NIDDM via one parent. The insulin and C-peptide responses to oral and intravenous glucose in patients with NIDDY were studied. The insulin and glucose responses to non-glucose secretogogues glucagon, tolbutamide and arginine, in NIDDY were also investigated. The following aspects with regard to insulin resistance in NIDDY were examined: glucose and free fatty acid response to intravenous insulin administration, insulin binding to circulating erythrocytes and monocytes, /sup 125/I-insulin binding to the solubilized erythrocyte membrane receptor and /sup 125/I-insulin binding to fibroblasts in culture.

Cognitive outcome after awake surgery for left and right hemisphere tumours

Directory of Open Access Journals (Sweden)

Elke De Witte

2015-04-01

Full Text Available INTRODUCTION: Awake surgery in eloquent brain regions is performed to preserve language and other cognitive functions. Although in general, no major permanent cognitive deficits are found after awake brain surgery, clinically relevant impairments are detected and cognitive recovery takes longer than generally assumed (3 months (Santini et al., 2012; Satoer et al., 2014; Talacchi et al., 2012. However, as there is a lack of extensive cognitive follow-up data it is unknown when recovery takes place. In addition, the influence of critical language sites identified by direct electrical stimulation (DES and tumour variables (e.g. left/right tumour location, tumour grade on long-term cognitive findings remains unclear. METHODS: In this longitudinal study the short-term and long-term effects of awake surgery on cognition were investigated in 40 patients (29 patients with left and 11 with right hemisphere tumours. Language, memory, attentional, executive and visuospatial functions were assessed in the preoperative phase, at short-term follow-up (6 weeks postsurgery and at long-term follow-up (6 months postsurgery with a neuropsychological protocol. In addition, the effect of intraoperative critical language sites, left/right tumour location, hemispheric language dominance, extent of resection and adjuvant treatment on cognitive change was studied. RESULTS: Both pre- and postoperatively, the mean performance of the patients was worse (impairment = z-score below -2 than the performance of the normal population in the language domain, the memory domain, the attentional and executive domain (p .05. Awake surgery negatively affected language, attentional and executive functions but not memory and visuospatial functions. At 6 weeks postsurgery, performance on all language, attentional and executive tasks deteriorated (object/action naming, semantic/phonological fluency from DuLIP, Token test; Trail Making Test A & B, Stroop I, II, & III. At 6 months

Radiographic findings in cats with intranasal neoplasia or chronic rhinitis: 29 cases (1982-1988)

International Nuclear Information System (INIS)

O'Brien, R.T.; Evans, S.M.; Wortman, J.A.; Hendrick, M.J.

1996-01-01

Objective: To compare radiographic findings and determine useful criteria to differentiate between intranasal neoplasia and chronic rhinitis in cats. Design: Retrospective study. Animals: Cats with chronic nasal disease caused by neoplasia (n = 18) or by chronic rhinitis (n = 11). Procedure: Radiographs were reviewed by 3 radiologists, followed by group review. Diagnosis was determined by intranasal biopsy or necropsy, and specimens were reviewed by a pathologist to confirm cause and histologic diagnosis. Results: Lymphosarcoma was the most common (n = 5) of the 6 histopathologic types in the neoplasia group. Cats in the neoplasia and chronic rhinitis groups had a high prevalence of aggressive radiographic lesions. Prevalence of a facial mass in cats with neoplasia (8/18) versus in those with chronic rhinitis (4/11) and of deviation (9/18 vs 6/11, respectively) or lysis (12/18 vs 7/11) of the nasal septum was similar. However, significantly (P = 0.02) more cats with neoplasia than with chronic rhinitis (13/16 vs 3/7, respectively) had unilateral turbinate destruction/lysis. Additionally, unilateral lateral bone erosion and loss of teeth associated with adjacent intranasal disease were more prevalent in cats with neoplasia (7/8 and 5/18, respectively) than in cats with chronic rhinitis (1/3 and 0/11, respectively). Clinical Implications: Features that may assist in radiographic diagnosis of neoplasia include the appearance of unilateral aggressive lesions, such as lysis of lateral bones, nasal turbinate destruction, and loss of teeth. Bilaterally symmetric lesions are more suggestive of chronic rhinitis than of neoplasia

Suicide and sleep: Is it a bad thing to be awake when reason sleeps?

Science.gov (United States)

Perlis, Michael L.; Grandner, Michael A.; Chakravorty, Subhajit; Bernert, Rebecca A.; Brown, Gregory K.; Thase, Michael E.

2016-01-01

Suicide is the second leading cause of death, worldwide, for those between the ages of 24 and 44 y old. In 2013, more than 41,000 suicides occurred in the United States. These statistics underscore the need to 1) understand why people die by suicide and 2) identify risk factors that are potentially modifiable. While it has been posited that sleep disturbance may represent one such factor, systematic research in this arena did not begin until the 2000s. Since that time, sleep disturbance has been reliably identified as a risk factor for suicidal ideation, suicide attempts, and suicide. While insomnia, nightmares, and other sleep disorders have each been found to contribute to the risk for suicidal ideation and behavior, it is also possible that these factors share some common variance. One possibility is that sleep disturbance results in being awake at night, and being awake at night also confers risk. The hypothesis proffered here is that being awake when one is not biologically prepared to be so results in “hypofrontality” and diminished executive function, and that this represents a common pathway to suicidal ideation and behavior. Such a proposition is highly testable under a variety of possible protocols. The current review summarizes the extant literature on suicide rates by time-of-day, and discusses circadian, psychosocial, and neuro-cognitive explanations of risk. Such a focus promises to enhance our understanding of how sleep disturbance may confer risk, allows for the identification of future lines of research, and further justifies the need for interventions that promote good sleep continuity among at-risk individuals. PMID:26706755

Awake craniotomy for glioma resection: Technical aspects and initial results in a single institution.

Science.gov (United States)

Trimble, Gillian; McStravick, Clodagh; Farling, Peter; Megaw, Katie; McKinstry, Steven; Smyth, Graham; Law, Gillian; Courtney, Heather; Quigley, Gavin; Flannery, Thomas

2015-01-01

Although variations in the technique of awake craniotomy (AC) have been widely reported, a key member of this interdisciplinary procedure is the healthcare professional performing assessments of neurological function during resection. The expertise of the latter will depend on the neurological function to be tested and on available resources of the institution. This report details our initial experience of an AC service utilizing the expertise of a speech and language therapist (SLT) and an experienced neuro-physiotherapist (NP) to monitor patient function during glioma resection. Forty-five patients underwent 50 AC procedures for eloquently located gliomas over a 3-year period. Patients with a glioma involving speech or sensorimotor areas were assessed preoperatively by the SLT/NP respectively. The same therapist monitored the patient's neurological function intraoperatively and executed a rehabilitation program tailored to the needs of the patient in the postoperative period. Three patients underwent biopsy only, due to intraoperative seizures precluding intraoperative mapping (2 cases) or speech arrest on stimulation of a small recurrent tumor. The remaining 47 cases were suitable for repetitive neurological assessment "awake" during tumor debulking. One patient with a large sensorimotor tumor developed intraoperative hemiparesis due to outward brain herniation (which recovered postoperatively). Ten patients developed a new or worsened neurological deficit in the initial postoperative period (6 were detected intraoperatively), of which 5 eventually had resolution and returned to baseline function within 2 weeks. In our initial experience based anecdotally on a previous similar "non-awake" caseload, we have found AC with the input of the SLT/NP to be a key component in ensuring optimal functional outcomes for patients with gliomas in eloquently located areas.

Suicide and sleep: Is it a bad thing to be awake when reason sleeps?

Science.gov (United States)

Perlis, Michael L; Grandner, Michael A; Chakravorty, Subhajit; Bernert, Rebecca A; Brown, Gregory K; Thase, Michael E

2016-10-01

Suicide is the second leading cause of death, worldwide, for those between the ages of 24 and 44 y old. In 2013, more than 41,000 suicides occurred in the United States. These statistics underscore the need to 1) understand why people die by suicide and 2) identify risk factors that are potentially modifiable. While it has been posited that sleep disturbance may represent one such factor, systematic research in this arena did not begin until the 2000s. Since that time, sleep disturbance has been reliably identified as a risk factor for suicidal ideation, suicide attempts, and suicide. While insomnia, nightmares, and other sleep disorders have each been found to contribute to the risk for suicidal ideation and behavior, it is also possible that these factors share some common variance. One possibility is that sleep disturbance results in being awake at night, and being awake at night also confers risk. The hypothesis proffered here is that being awake when one is not biologically prepared to be so results in "hypofrontality" and diminished executive function, and that this represents a common pathway to suicidal ideation and behavior. Such a proposition is highly testable under a variety of possible protocols. The current review summarizes the extant literature on suicide rates by time-of-day, and discusses circadian, psychosocial, and neurocognitive explanations of risk. Such a focus promises to enhance our understanding of how sleep disturbance may confer risk, allows for the identification of future lines of research, and further justifies the need for interventions that promote good sleep continuity among at-risk individuals. Copyright © 2015 Elsevier Ltd. All rights reserved.

In Vivo Tumour Mapping Using Electrocorticography Alterations During Awake Brain Surgery: A Pilot Study.

Science.gov (United States)

Boussen, Salah; Velly, Lionel; Benar, Christian; Metellus, Philippe; Bruder, Nicolas; Trébuchon, Agnès

2016-09-01

During awake brain surgery for tumour resection, in situ EEG recording (ECoG) is used to identify eloquent areas surrounding the tumour. We used the ECoG setup to record the electrical activity of cortical and subcortical tumours and then performed frequency and connectivity analyses in order to identify ECoG impairments and map tumours. We selected 16 patients with cortical (8) and subcortical (8) tumours undergoing awake brain surgery. For each patient, we computed the spectral content of tumoural and healthy areas in each frequency band. We computed connectivity of each electrode using connectivity markers (linear and non-linear correlations, phase-locking and coherence). We performed comparisons between healthy and tumour electrodes. The ECoG alterations were used to implement automated classification of the electrodes using clustering or neural network algorithms. ECoG alterations were used to image cortical tumours.Cortical tumours were found to profoundly alter all frequency contents (normalized and absolute power), with an increase in the δ activity and a decreases for the other bands (P < 0.05). Cortical tumour electrodes showed high level of connectivity compared to surrounding electrodes (all markers, P < 0.05). For subcortical tumours, a relative decrease in the γ1 band and in the alpha band in absolute amplitude (P < 0.05) were the only abnormalities. The neural network algorithm classification had a good performance: 93.6 % of the electrodes were classified adequately on a test subject. We found significant spectral and connectivity ECoG changes for cortical tumours, which allowed tumour recognition. Artificial neural algorithm pattern recognition seems promising for electrode classification in awake tumour surgery.

Intranasal desmopressin versus blood transfusion in cirrhotic patients with coagulopathy undergoing dental extraction: a randomized controlled trial.

Science.gov (United States)

Stanca, Carmen M; Montazem, Andre H; Lawal, Adeyemi; Zhang, Jin X; Schiano, Thomas D

2010-01-01

Cirrhotic patients waiting for liver transplantation who need dental extractions are given fresh frozen plasma and/or platelets to correct coagulopathy. This is costly and may be associated with transfusion reactions and fluid overload. We evaluated the efficacy of intranasal desmopressin as an alternative to transfusion to correct the coagulopathy of cirrhotic patients undergoing dental extraction. Cirrhotic patients with platelet counts of 30,000 to 50,000/microL and/or international normalized ratio (INR) 2.0 to 3.0 were enrolled in a prospective, controlled, randomized clinical trial. Blood transfusion (fresh frozen plasma 10 mL/kg and/or 1 unit of single donor platelets, respectively) or intranasal desmopressin (300 microg) were given before dental extraction. A standard oral and maxillofacial surgical treatment protocol was performed by the same surgeon. Patients were followed for postextraction bleeding and side-effects over the next 24 to 48 hours. No significant differences were noted between the 2 groups in gender, age, INR, platelet count, creatinine, total bilirubin, ALT, albumin, MELD score, or number of teeth removed (median 3 vs 4). The number of teeth removed ranged between 1 and 31 in the desmopressin group and 1 and 22 in the transfusion group. No patients in desmopressin group required rescue blood transfusion after extraction. One patient in the transfusion group had bleeding after the procedure and required an additional transfusion. Another patient experienced an allergic reaction at the end of transfusion, which was effectively treated with diphenhydramine. Treatment associated average costs were lower for desmopressin ($700/patient) compared with transfusion ($1,173/patient). Intranasal desmopressin was as effective as blood transfusion in achieving hemostasis in cirrhotic patients with moderate coagulopathy undergoing dental extraction. Intranasal desmopressin was much more convenient, less expensive, and well tolerated.

Degludec insulin: A novel basal insulin

OpenAIRE

Kalra, Sanjay; Unnikrishnan, Ambika Gopalakrishnan; Baruah, Manash; Kalra, Bharti

2011-01-01

This paper reviews a novel insulin analogue, degludec, which has the potential to emerge as an ideal basal insulin. It reviews the limitations of existing basal insulin and analogues, and highlights the need for a newer molecule. The paper discusses the potential advantages of degludec, while reviewing its pharmacologic and clinical studies done so far. The paper assesses the potential role of insulin degludec and degludec plus in clinical diabetes practice.

Efficacy of Intranasal Scopolamine Gel for Motion Sickness Treatment in Aviation Candidates

Science.gov (United States)

2009-04-13

Baseline 15 25 80 115 145 190 M ea n B lo o d P re ss u re (m m H g ) 0 20 40 60 80 100 120 140 Systolic BP P Systolic BPIN Diastolic BPP Diastolic...scopolamine when compared to placebo, p < .05. BPP = Blood Pressure, Placebo, BPIN = Blood Pressure, Intranasal Scopolamine 31 Time (min) Baseline 15 25 80

Beam Transfer Line Design for a Plasma Wakefield Acceleration Experiment (AWAKE) at the CERN SPS

CERN Document Server

Bracco, C; Brethoux, D; Clerc, V; Goddard, B; Gschwendtner, E; Jensen, L K; Kosmicki, A; Le Godec, G; Meddahi, M; Muggli, P; Mutin, C; Osborne, O; Papastergiou, K; Pardons, A; Velotti, F M; Vincke, H

2013-01-01

The world’s first proton driven plasma wakefield acceleration experiment (AWAKE) is presently being studied at CERN. The experimentwill use a high energy proton beam extracted from the SPS as driver. Two possible locations for installing the AWAKE facility were considered: the West Area and the CNGS beam line. The previous transfer line from the SPS to the West Area was completely dismantled in 2005 and would need to be fully re-designed and re-built. For this option, geometric constraints for radiation protection reasons would limit the maximum proton beam energy to 300 GeV. The existing CNGS line could be used by applying only minor changes to the lattice for the final focusing and the interface between the proton beam and the laser, required for plasma ionisation and bunch-modulation seeding. The beam line design studies performed for the two options are presented.

Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes

DEFF Research Database (Denmark)

Mortensen, Rasmus; Christensen, Dennis; Hansen, Lasse Bøllehuus

2017-01-01

Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future...... vaccine against GAS, it is therefore important to investigate how protective immunity is related to the route of vaccine administration. To explore this, we examined whether a parenterally administered anti-GAS vaccine could protect against an intranasal GAS infection or if this would require locally...... primed immunity. We foundd that a parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently protected against an intraperitoneal GAS infection. However, the same vaccine administered via...

In vivo Brain Delivery of v-myc Overproduced Human Neural Stem Cells via the Intranasal Pathway: Tumor Characteristics in the Lung of a Nude Mouse

Directory of Open Access Journals (Sweden)

Eun Seong Lee

2015-01-01

Full Text Available We aimed to monitor the successful brain delivery of stem cells via the intranasal route and to observe the long-term consequence of the immortalized human neural stem cells in the lungs of a nude mouse model. Stably immortalized HB1.F3 human neural stem cells with firefly luciferase gene (F3-effluc were intranasally delivered to BALB/c nude mice. Bioluminescence images were serially acquired until 41 days in vivo and at 4 hours and 41 days ex vivo after intranasal delivery. Lungs were evaluated by histopathology. After intranasal delivery of F3-effluc cells, the intense in vivo signals were detected in the nasal area, migrated toward the brain areas at 4 hours (4 of 13, 30.8%, and gradually decreased for 2 days. The brain signals were confirmed by ex vivo imaging (2 of 4, 50%. In the mice with initial lung signals (4 of 9, 44.4%, the lung signals disappeared for 5 days but reappeared 2 weeks later. The intense lung signals were confirmed to originate from the tumors in the lungs formed by F3-effluc cells by ex vivo imaging and histopathology. We propose that intranasal delivery of immortalized stem cells should be monitored for their successful delivery to the brain and their tumorigenicity longitudinally.

Clinical outcomes from maximum-safe resection of primary and metastatic brain tumors using awake craniotomy.

Science.gov (United States)

Groshev, Anastasia; Padalia, Devang; Patel, Sephalie; Garcia-Getting, Rosemarie; Sahebjam, Solmaz; Forsyth, Peter A; Vrionis, Frank D; Etame, Arnold B

2017-06-01

To retrospectively analyze outcomes in patients undergoing awake craniotomies for tumor resection at our institution in terms of extent of resection, functional preservation and length of hospital stay. All cases of adults undergoing awake-craniotomy from September 2012-February 2015 were retrospectively reviewed based on an IRB approved protocol. Information regarding patient age, sex, cancer type, procedure type, location, hospital stay, extent of resection, and postoperative complications was extracted. 76 patient charts were analyzed. Resected cancer types included metastasis to the brain (41%), glioblastoma (34%), WHO grade III anaplastic astrocytoma (18%), WHO grade II glioma (4%), WHO grade I glioma (1%), and meningioma (1%). Over a half of procedures were performed in the frontal lobes, followed by temporal, and occipital locations. The most common indication was for motor cortex and primary somatosensory area lesions followed by speech. Extent of resection was gross total for 59% patients, near-gross total for 34%, and subtotal for 7%. Average hospital stay for the cohort was 1.7days with 75% of patients staying at the hospital for only 24h or less post surgery. In the postoperative period, 67% of patients experienced improvement in neurological status, 21% of patients experienced no change, 7% experienced transient neurological deficits, which resolved within two months post op, 1% experienced transient speech deficit, and 3% experienced permanent weakness. In a consecutive series of 76 patients undergoing maximum-safe resection for primary and metastatic brain tumors, awake-craniotomy was associated with a short hospital stay and low postoperative complications rate. Copyright © 2017 Elsevier B.V. All rights reserved.

Rapid intranasal delivery of chloramphenicol acetyltransferase in the active form to different brain regions as a model for enzyme therapy in the CNS.

Science.gov (United States)

Appu, Abhilash P; Arun, Peethambaran; Krishnan, Jishnu K S; Moffett, John R; Namboodiri, Aryan M A

2016-02-01

The blood brain barrier (BBB) is critical for maintaining central nervous system (CNS) homeostasis by restricting entry of potentially toxic substances. However, the BBB is a major obstacle in the treatment of neurotoxicity and neurological disorders due to the restrictive nature of the barrier to many medications. Intranasal delivery of active enzymes to the brain has therapeutic potential for the treatment of numerous CNS enzyme deficiency disorders and CNS toxicity caused by chemical threat agents. The aim of this work is to provide a sensitive model system for analyzing the rapid delivery of active enzymes into various regions of the brain with therapeutic bioavailability. We tested intranasal delivery of chloramphenicol acetyltransferase (CAT), a relatively large (75kD) enzyme, in its active form into different regions of the brain. CAT was delivered intranasally to anaesthetized rats and enzyme activity was measured in different regions using a highly specific High Performance Thin Layer Chromatography (HP-TLC)-radiometry coupled assay. Active enzyme reached all examined areas of the brain within 15min (the earliest time point tested). In addition, the yield of enzyme activity in the brain was almost doubled in the brains of rats pre-treated with matrix metalloproteinase-9 (MMP-9). Intranasal administration of active enzymes in conjunction with MMP-9 to the CNS is both rapid and effective. The present results suggest that intranasal enzyme therapy is a promising method for counteracting CNS chemical threat poisoning, as well as for treating CNS enzyme deficiency disorders. Published by Elsevier B.V.

Insulin secretion and insulin action in non-insulin-dependent diabetes mellitus: which defect is primary?

Science.gov (United States)

Reaven, G M

1984-01-01

Defects in both insulin secretion and insulin action exist in patients with non-insulin-dependent diabetes mellitus (NIDDM). The loss of the acute plasma insulin response to intravenous glucose is seen in patients with relatively mild degrees of fasting hyperglycemia, but patients with severe fasting hyperglycemia also demonstrate absolute hypoinsulinemia in response to an oral glucose challenge. In contrast, day-long circulating insulin levels are within normal limits even in severely hyperglycemic patients with NIDDM. The relationship between NIDDM and insulin action in NIDDM is less complex, and is a characteristic feature of the syndrome. This metabolic defect is independent of obesity, and the severity of the resistance to insulin-stimulated glucose uptake increases with magnitude of hyperglycemia. Control of hyperglycemia with exogenous insulin ameliorates the degree of insulin resistance, and reduction of insulin resistance with weight loss in obese patients with NIDDM leads to an enhanced insulin response. Since neither therapeutic intervention is capable of restoring all metabolic abnormalities to normal, these observations do not tell us which of these two defects is primarily responsible for the development of NIDDM. Similarly, the observation that most patients with impaired glucose tolerance are hyperinsulinemic and insulin resistant does not prove that insulin resistance is the primary defect in NIDDM. In conclusion, reduction in both insulin secretion and action is seen in patients with NIDDM, and the relationship between these two metabolic abnormalities is very complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Sex differences in the neural and behavioral response to intranasal oxytocin and vasopressin during human social interaction.

Science.gov (United States)

Rilling, James K; Demarco, Ashley C; Hackett, Patrick D; Chen, Xu; Gautam, Pritam; Stair, Sabrina; Haroon, Ebrahim; Thompson, Richmond; Ditzen, Beate; Patel, Rajan; Pagnoni, Giuseppe

2014-01-01

Both oxytocin (OT) and vasopressin (AVP) are known to modulate social behavior, and dysfunction in both systems has been postulated as a potential cause of certain psychiatric disorders that involve social behavioral deficits. In particular, there is growing interest in intranasal OT as a potential treatment for certain psychiatric disorders, and preliminary pre-clinical and clinical studies suggest efficacy in alleviating some of the associated symptoms. However, the vast majority of research participants in these studies have been male, and there is evidence for sexually differentiated effects of nonapeptides in both humans and non-human animals. To date, no study has investigated the effect of intranasal OT on brain function in human males and females within the same paradigm. Previously, in a randomized, placebo-controlled, double-blind fMRI study, we reported effects of intranasal OT and AVP on behavior and brain activity of human males as they played an interactive social game known as the Prisoner's Dilemma Game. Here, we present findings from an identical study in human females, and compare these with our findings from males. Overall, we find that both behavioral and neural responses to intranasal OT and AVP are highly sexually differentiated. In women, AVP increased conciliatory behavior, and both OT and AVP caused women to treat computer partners more like humans. In men, AVP increased reciprocation of cooperation from both human and computer partners. However, no specific drug effects on behavior were shared between men and women. During cooperative interactions, both OT and AVP increased brain activity in men within areas rich in OT and AVP receptors and in areas playing a key role in reward, social bonding, arousal and memory (e.g., the striatum, basal forebrain, insula, amygdala and hippocampus), whereas OT and AVP either had no effect or in some cases actually decreased brain activity in these regions in women. OT treatment rendered neural responses

Awake craniotomy for brain lesions within and near the primary motor area: A retrospective analysis of factors associated with worsened paresis in 102 consecutive patients

Science.gov (United States)

Shinoura, Nobusada; Midorikawa, Akira; Yamada, Ryoji; Hana, Taijun; Saito, Akira; Hiromitsu, Kentaro; Itoi, Chisato; Saito, Syoko; Yagi, Kazuo

2013-01-01

Background: We analyzed factors associated with worsened paresis in a large series of patients with brain lesions located within or near the primary motor area (M1) to establish protocols for safe, awake craniotomy of eloquent lesions. Methods: We studied patients with brain lesions involving M1, the premotor area (PMA) and the primary sensory area (S1), who underwent awake craniotomy (n = 102). In addition to evaluating paresis before, during, and one month after surgery, the following parameters were analyzed: Intraoperative complications; success or failure of awake surgery; tumor type (A or B), tumor location, tumor histology, tumor size, and completeness of resection. Results: Worsened paresis at one month of follow-up was significantly associated with failure of awake surgery, intraoperative complications and worsened paresis immediately after surgery, which in turn was significantly associated with intraoperative worsening of paresis. Intraoperative worsening of paresis was significantly related to preoperative paresis, type A tumor (motor tract running in close proximity to and compressed by the tumor), tumor location within or including M1 and partial removal (PR) of the tumor. Conclusions: Successful awake surgery and prevention of deterioration of paresis immediately after surgery without intraoperative complications may help prevent worsening of paresis at one month. Factors associated with intraoperative worsening of paresis were preoperative motor deficit, type A and tumor location in M1, possibly leading to PR of the tumor. PMID:24381792

Restraint training for awake functional brain scanning of rodents can cause long-lasting changes in pain and stress responses.

Science.gov (United States)

Low, Lucie A; Bauer, Lucy C; Pitcher, Mark H; Bushnell, M Catherine

2016-08-01

With the increased interest in longitudinal brain imaging of awake rodents, it is important to understand both the short-term and long-term effects of restraint on sensory and emotional processing in the brain. To understand the effects of repeated restraint on pain behaviors and stress responses, we modeled a restraint protocol similar to those used to habituate rodents for magnetic resonance imaging scanning, and studied sensory sensitivity and stress hormone responses over 5 days. To uncover lasting effects of training, we also looked at responses to the formalin pain test 2 weeks later. We found that while restraint causes acute increases in the stress hormone corticosterone, it can also cause lasting reductions in nociceptive behavior in the formalin test, coupled with heightened corticosterone levels and increased activation of the "nociceptive" central nucleus of the amygdala, as seen by Fos protein expression. These results suggest that short-term repeated restraint, similar to that used to habituate rats for awake functional brain scanning, could potentially cause long-lasting changes in physiological and brain responses to pain stimuli that are stress-related, and therefore could potentially confound the functional activation patterns seen in awake rodents in response to pain stimuli.

Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes

DEFF Research Database (Denmark)

Zinman, Bernard; Philis-Tsimikas, Athena; Cariou, Bertrand

2012-01-01

To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs).......To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs)....

"Awake" ECCO2R superseded intubation in a near-fatal asthma attack.

Science.gov (United States)

Schneider, Thomas-Michael; Bence, Tibor; Brettner, Franz

2017-01-01

Near-fatal asthma attacks are life threatening events that often require mechanical ventilation. Extracorporeal carbon dioxide removal (ECCO 2 R) is, beside extracorporeal membrane oxygenation (ECMO), a well-established rescue option whenever ventilation gets to its limits. But there seems to be very rare experience with those techniques in avoiding mechanical ventilation in severe asthma attacks. A 67-year-old man with a near-fatal asthma attack deteriorated under non-invasive ventilation conditions. Beside pharmacological treatment, the intensivists decided to use an extracorporeal carbon dioxide removal system (ECCO 2 R) to avoid sedation and intubation. Within only a few hours, there was a breakthrough and the patient's status improved continuously. One and a half days later, weaning from ECCO 2 R was already completed. The discussion deals with several advantages of extracorporeal lung support in acute asthma, the potential of avoiding intubation and sedation, as well as the benefits of a conscious and spontaneously breathing patient. Extracorporeal membrane oxygenation (ECMO) in general and ECCO 2 R in particular is a highly effective method for the treatment of an acute near-fatal asthma attack. Pathophysiological aspects favor the "awake" approach, without sedation, intubation, and mechanical ventilation. Therefore, experienced clinicians might consider "awake" ECCO 2 R in similar cases.

The Role of Insulin, Insulin Growth Factor, and Insulin-Degrading Enzyme in Brain Aging and Alzheimer's Disease

OpenAIRE

Messier, Claude; Teutenberg, Kevin

2005-01-01

Most brain insulin comes from the pancreas and is taken up by the brain by what appears to be a receptor-based carrier. Type 2 diabetes animal models associated with insulin resistance show reduced insulin brain uptake and content. Recent data point to changes in the insulin receptor cascade in obesity-related insulin resistance, suggesting that brain insulin receptors also become less sensitive to insulin, which could reduce synaptic plasticity. Insulin transport to the brain is reduced in a...

Status of the proton and electron transfer lines for the AWAKE Experiment at CERN

Energy Technology Data Exchange (ETDEWEB)

Schmidt, J.S., E-mail: janet.schmidt@cern.ch [CERN, Geneva (Switzerland); Bauche, J. [CERN, Geneva (Switzerland); Biskup, B. [CERN, Geneva (Switzerland); Czech Technical University, Prague (Czech Republic); Bracco, C.; Doebert, S.; Goddard, B.; Gschwendtner, E.; Jensen, L.K.; Jones, O.R.; Mazzoni, S.; Meddahi, M.; Pepitone, K.; Petrenko, A.; Velotti, F.M.; Vorozhtsov, A. [CERN, Geneva (Switzerland)

2016-09-01

The AWAKE project at CERN is planned to study proton driven plasma wakefield acceleration with an externally injected electron beam. Therefore two transfer lines are being designed in order to provide the proton beam from the SPS and the electron beam from an RF gun to the plasma cell. The commissioning of the proton line will take place in 2016 for the first phase of the experiment, which is focused on the self-modulation of a 12 cm long proton bunch in the plasma. The electron line will be added for the second phase of AWAKE in 2017, when the wakefield will be probed with an electron beam of 10–20 MeV/c. The challenge for these transfer lines lies in the parallel operation of the proton, electron and laser beam used to ionize the plasma and seed the self-modulation. These beams, of different characteristics, need to be synchronized and positioned for optimized injection conditions into the wakefield. This task requires great flexibility in the transfer line optics. The status of these designs will be presented in this paper.

Invasive aspergillosis in severely neutropenic patients over 18 years: impact of intranasal amphotericin B and HEPA filtration.

Science.gov (United States)

Withington, S; Chambers, S T; Beard, M E; Inder, A; Allen, J R; Ikram, R B; Schousboe, M I; Heaton, D C; Spearing, R I; Hart, D N

1998-01-01

The impact of intranasal amphotericin B and high-efficiency particulate air (HEPA) filtration on the incidence of invasive aspergillosis was reviewed in patients from 1977 to 1994 undergoing intensive chemotherapy. Overall, the incidence of proven invasive aspergillosis was reduced from 24.4% (1977-1984) to 7.1% (1985-1991) (P < 0.001) following the introduction of intranasal prophylaxis, but when probable cases of aspergillosis were included and lymphoma cases excluded, there was no change in incidence. Following the introduction of HEPA filtration, patient exposure to aspergillus spores as measured by air sampling was markedly reduced and there were no new cases of invasive aspergillosis. HEPA filtration proved effective in reducing invasive aspergillosis and has allowed increasingly aggressive treatment regimens to be introduced.

Effects of intranasal corticosteroids on radiated nasal mucosa of guinea pig

International Nuclear Information System (INIS)

Zhu Xinhua; Liu Yuehui

2009-01-01

Objective: To investigate a mechanism protected radiation-induce injure for radiated guinea pigs'nasal mucosa treated with intranasal corticosteroids(fluticasone nasal cavity spray). Methods: 50 health guinea pigs were divided into 2 groups randomly: the irradiated group (control group) with 25 guinea pigs and the administration group after irradiation (test group)with 25 guinea pigs. The nasal part of all guinea pigs were performed irradiation by the 6 MV X-ray with single 5 Gy, one time each week for three weeks. The guinea pigs of test group received intranasal corticosteroids with one time every day and one spray each side nasal cavity on the second day after three weeks irradiation. Five guinea pigs in each group were sacrificed randomly at 1 week, 1 month, 2 months, 3 months and 4 months after irradiation, and the histopathologic changes were observed under optical microscope and electron microscope. At the same time, blood were drawn from the heart and the concentration of IL-1, IL-6 and TNF-α in serum were measured by ELISA. Results: The early nasal mucosa inflammatory reaction of the test group was less than the control group. The coverage rate of cilia of the test group was much than that of the control group (72.9% vs 50.2%) at four months after irradiation. The atrophy of submucosal glandular organ was lessened and they displayed some extent secretory function. The concentration of IL-1 in serum was increased very much in the test group compared with the control group after irradiation and kept higher level in the first two months. After two months, it began to decrease; on four months, it still kept equivalency level with the control group. The concentration of IL-6 and TNF-α in serum were reduced all the while. Conclusions: The intranasal corticosteroids with fluticasone nasal cavity spray can reduce radiation- induced injury of guinea pigs' nasal mucosa. The concentration change of IL-1, IL-6 and TNF-α in serum may be one of mechanism protected

Critical evaluation of colon submucosal microdialysis in awake, mobile rats.

Directory of Open Access Journals (Sweden)

Norbert Cibicek

Full Text Available Sensors able to record large bowel physiology and biochemistry in situ in awake rodents are lacking. Microdialysis is a mini-invasive technique that may be utilized to continuously deliver or recover low-molecular substances from various tissues. In this experiment we evaluated the feasibility of in vivo microdialysis to monitor extracellular fluid chemistry in the descending colon submucosa of conscious, freely moving rodents. Following surgical implantation of a microdialysis probe, male Wistar rats were housed in metabolic cages where they were analgized and clinically followed for four days with free access to standard diet and water. To assess local microcirculation and probe function, glucose, lactate, glucose-to-lactate ratio and urea clearance were determined in the dialysates from the three postoperative days with focus on the final 24-h period. In an attempt to mitigate the expected tissue inflammatory response, one group of animals had the catheters perfused with 5-aminosalicylic acid-enriched medium with final concentration 1 μmol/L. For verification of probe position and the assessment of the surrounding foreign body reaction, standard histological and immunohistochemical methods were employed. Microdialysis of rat gut is associated with considerable technical challenges that may lead to the loss of probe function and high drop-out rate. In this setting, limited data did not allow to draw any firm conclusion regarding local anti-inflammatory effectiveness of 5-aminosalicylic acid perfusion. Although intestinal microdialysis may be suitable for larger anesthetized animals, low reproducibility of the presented method compromises its routine experimental use in awake and freely moving small-sized rodents.

Effect of a Combination of Intranasal Ketorolac and Nitrous Oxide on the Success of the Inferior Alveolar Nerve Block in Patients with Symptomatic Irreversible Pulpitis: A Prospective, Randomized, Double-blind Study.

Science.gov (United States)

Stentz, Daniel; Drum, Melissa; Reader, Al; Nusstein, John; Fowler, Sara; Beck, Mike

2018-01-01

Previous studies in patients with irreversible pulpitis have reported increased success of the inferior alveolar nerve block (IANB) using premedication with ketorolac. Preemptive nitrous oxide administration has also shown an increase in the success of the IANB. Recently, ketorolac has been made available for intranasal delivery. Perhaps combining ketorolac and nitrous oxide would increase success. Therefore, the purpose of this prospective, randomized, double-blind study was to determine the effect of a combination of intranasal ketorolac and nitrous oxide/oxygen on the anesthetic success of the IANB in patients presenting with symptomatic irreversible pulpitis. One hundred two patients experiencing spontaneous moderate to severe pain with symptomatic irreversible pulpitis in a mandibular posterior tooth participated. Patients were randomly divided into 2 groups and received either 31.5 mg intranasal ketorolac or intranasal saline placebo 20 minutes before the administration of nitrous oxide/oxygen. Ten minutes after the administration of nitrous oxide/oxygen, the IANB was given. After profound lip numbness, endodontic treatment was performed. Success was defined as the ability to perform endodontic access and instrumentation with no pain or mild pain. The odds of success for the IANB was 1.631 in the intranasal saline/nitrous oxide group versus the intranasal ketorolac/nitrous oxide group with no significant difference between the groups (P = .2523). Premedication with intranasal ketorolac did not significantly increase the odds of success for the IANB over the use of nitrous oxide/oxygen alone. Supplemental anesthesia will still be needed to achieve adequate anesthesia. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Continuous physical examination during subcortical resection in awake craniotomy patients: Its usefulness and surgical outcome.

Science.gov (United States)

Bunyaratavej, Krishnapundha; Sangtongjaraskul, Sunisa; Lerdsirisopon, Surunchana; Tuchinda, Lawan

2016-08-01

To evaluate the value of physical examination as a monitoring tool during subcortical resection in awake craniotomy patients and surgical outcomes. Authors reviewed medical records of patients underwent awake craniotomy with continuous physical examination for pathology adjacent to the eloquent area. Between January 2006 and August 2015, there were 37 patients underwent awake craniotomy with continuous physical examination. Pathology was located in the left cerebral hemisphere in 28 patients (75.7%). Thirty patients (81.1%) had neuroepithelial tumors. Degree of resections were defined as total, subtotal, and partial in 16 (43.2%), 11 (29.7%) and 10 (27.0%) patients, respectively. Median follow up duration was 14 months. The reasons for termination of subcortical resection were divided into 3 groups as follows: 1) by anatomical landmark with the aid of neuronavigation in 20 patients (54%), 2) by reaching subcortical stimulation threshold in 8 patients (21.6%), and 3) by abnormal physical examination in 9 patients (24.3%). Among these 3 groups, there were statistically significant differences in the intraoperative (p=0.002) and early postoperative neurological deficit (p=0.005) with the lowest deficit in neuronavigation group. However, there were no differences in neurological outcome at later follow up (3-months p=0.103; 6-months p=0.285). There were no differences in the degree of resection among the groups. Continuous physical examination has shown to be of value as an additional layer of monitoring of subcortical white matter during resection and combining several methods may help increase the efficacy of mapping and monitoring of subcortical functions. Copyright © 2016 Elsevier B.V. All rights reserved.

Membrane Potential Dynamics of Spontaneous and Visually Evoked Gamma Activity in V1 of Awake Mice

NARCIS (Netherlands)

Perrenoud, Q.; Pennartz, C.M.A.; Gentet, L.J.

2016-01-01

Cortical gamma activity (30-80 Hz) is believed to play important functions in neural computation and arises from the interplay of parvalbumin-expressing interneurons (PV) and pyramidal cells (PYRs). However, the subthreshold dynamics underlying its emergence in the cortex of awake animals remain

Case Report: Emergency awake craniotomy for cerebral abscess in a patient with unrepaired cyanotic congenital heart disease [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Corinne D’Antico

2016-10-01

Full Text Available We report the case of a 39-year-old male with complex cyanotic congenital heart disease undergoing emergency craniotomy for a cerebral abscess. Maintenance of intraoperative hemodynamic stability and adequate tissue oxygenation during anesthesia may be challenging in patients with cyanotic congenital heart disease. In this case, we decided to perform the surgery as an awake craniotomy after interdisciplinary consensus. We discuss general aspects of anesthetic management during awake craniotomy and specific concerns in the perioperative care of patients with congenital heart disease.

Case Report: Emergency awake craniotomy for cerebral abscess in a patient with unrepaired cyanotic congenital heart disease [version 2; referees: 2 approved

Directory of Open Access Journals (Sweden)

Corinne D’Antico

2017-02-01

Full Text Available We report the case of a 39-year-old male with complex cyanotic congenital heart disease undergoing emergency craniotomy for a cerebral abscess. Maintenance of intraoperative hemodynamic stability and adequate tissue oxygenation during anesthesia may be challenging in patients with cyanotic congenital heart disease. In this case, we decided to perform the surgery as an awake craniotomy after interdisciplinary consensus. We discuss general aspects of anesthetic management during awake craniotomy and specific concerns in the perioperative care of patients with congenital heart disease.

Simultaneous intramammary and intranasal inoculation of lactating cows with bovine herpesvirus 4 induce subclinical mastitis

NARCIS (Netherlands)

Wellenberg, G.J.; Bruschke, C.J.M.; Wisselink, H.J.; Barkema, H.W.; Oirschot, van J.T.

2002-01-01

In this study, we examined whether an experimental bovine herpesvirus 4 (BHV4) infection can induce bovine mastitis, or can enhance bovine mastitis induced by Streptococcus uberis (S. uberis). Four lactating cows were inoculated intramammarily and intranasally with BHV4, and four lactating control

Pathogenesis of infection with 2009 pandemic H1N1 influenza virus in isogenic guinea pigs after intranasal or intratracheal inoculation.

Science.gov (United States)

Wiersma, Lidewij C M; Vogelzang-van Trierum, Stella E; van Amerongen, Geert; van Run, Peter; Nieuwkoop, Nella J; Ladwig, Mechtild; Banneke, Stefanie; Schaefer, Hubert; Kuiken, Thijs; Fouchier, Ron A M; Osterhaus, Albert D M E; Rimmelzwaan, Guus F

2015-03-01

To elucidate the pathogenesis and transmission of influenza virus, the ferret model is typically used. To investigate protective immune responses, the use of inbred mouse strains has proven invaluable. Here, we describe a study with isogenic guinea pigs, which would uniquely combine the advantages of the mouse and ferret models for influenza virus infection. Strain 2 isogenic guinea pigs were inoculated with H1N1pdm09 influenza virus A/Netherlands/602/09 by the intranasal or intratracheal route. Viral replication kinetics were assessed by determining virus titers in nasal swabs and respiratory tissues, which were also used to assess histopathologic changes and the number of infected cells. In all guinea pigs, virus titers peaked in nasal secretions at day 2 after inoculation. Intranasal inoculation resulted in higher virus excretion via the nose and higher virus titers in the nasal turbinates than intratracheal inoculation. After intranasal inoculation, infectious virus was recovered only from nasal epithelium; after intratracheal inoculation, it was recovered also from trachea, lung, and cerebrum. Histopathologic changes corresponded with virus antigen distribution, being largely limited to nasal epithelium for intranasally infected guinea pigs and more widespread in the respiratory tract for intratracheally infected guinea pigs. In summary, isogenic guinea pigs show promise as a model to investigate the role of humoral and cell-mediated immunities to influenza and their effect on virus transmission. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Mucosal vaccination by the intranasal route. Nose-associated lymphoid tissue (NALT)-Structure, function and species differences.

Science.gov (United States)

Pabst, Reinhard

2015-08-26

The advantage of mucosal vaccination in viral and bacterial infections in different age groups is of enormous clinical relevance. The advantages and potential hazards of intranasal vaccination have always to be considered. The intranasal route for vaccination is very successful for some antigens. Specific adjuvants are necessary. In the nose of rodents there is a structured lymphoid tissue (nose-associated lymphoid tissue (NALT)). This abbreviation should not be used for nasopharynx-associated lymphoid tissue, as this includes parts of the tonsils. In children lymphoid tissue is more dispersed in the nose and not concentrated at the bottom of the dorsal nose ducts as in rodents. There are no data on organized lymphoid tissue in the nose of adults. In NALT of rodents there is a unique structure of adhesion molecule expression; the postnatal development and the different composition of T and B lymphocytes in comparison with Peyer's patches document the uniqueness of this lymphoid organ. There is also a mucosa in the nose with antigen-presenting dendritic cells. Thus, it is often unclear whether intranasal vaccination is initiated via NALT or the diffuse nasal mucosa. There are still many open questions e. g., which adjuvant is necessary for a specific virus, bacterium or other allergen, how many doses are critical for an effective nasal vaccination. Species differences are of major importance when extrapolating results from rodents to humans. Copyright © 2015 Elsevier Ltd. All rights reserved.

Carcinoma basocelular simulando tumor intranasal: tratamento com cirurgia micrográfica pelo método de Munique Basal cell carcinoma mimicking intranasal tumor: treatment by Munich method of micrographic surgery

Directory of Open Access Journals (Sweden)

Luis Fernando Figueiredo Kopke

2007-12-01

Full Text Available Relata-se caso incomum de carcinoma basocelular que simulava tumor intranasal de crescimento expansivo, na cavidade da narina esquerda. Operado com cirurgia micrográfica pelo método de Munique, foi possível demonstrar que o tumor se originava da pele aparentemente normal e suprajacente do nariz. Por ser tridimensional, esse método de cirurgia micrográfica permite estudo mais preciso da peça cirúrgica. Discutem-se também aspectos peculiares da cirurgia micrográfica pelo método de Munique, o que contribui para a ampliação do conceito das cirurgias microscopicamente controladas.A rare case of basal cell carcinoma mimicking an expansive intranasal tumor in the left nostril is reported. Through the Munich micrographic surgery method, it was possible to demonstrate that the tumor originated from the apparently normal nose skin. Since this micrographic surgery is a tri-dimensional method, it enables a more accurate study of the specimen. Some peculiar aspects of the micrographic surgery using the Munich method are discussed, thus contributing to further understanding about the concept of microscopically controlled surgeries.

Using Gelatin Nanoparticle Mediated Intranasal Delivery of Neuropeptide Substance P to Enhance Neuro-Recovery in Hemiparkinsonian Rats.

Directory of Open Access Journals (Sweden)

Ying-Zheng Zhao

Full Text Available Intranasal administration of phospholipid-based gelatin nanoparticles (GNP was prepared to investigate the neuro-recovery effects of neuropeptide Substance P (SP on hemiparkinsonian rats.The SP-loaded gelatin nanoparticles (SP-GNP were prepared by a water-in-water emulsion method and possessed high stability, encapsulating efficiency and loading capacity. PC-12 cells were used to examine the growth enhancement of SP-GNP in vitro by MTT assays and flow cytometry (FCM. The therapeutic effects of SP-GNP on 6-hydroxydopamine (6-OHDA induced hemiparkinsonian rats were assessed by quantifying rotational behavior and the levels of tyrosine hydroxylase (TH, phosphorylated c-Jun protein (p-c-Jun and Caspase-3 (Cas-3 expressed in substantia nigra (SN region of hemiparkinsonian rats.PC-12 cells under SP-GNP treatment showed better cell viability and lower degree of apoptosis than those under SP solution treatment. Hemiparkinsonian rats under intranasal SP-GNP administration demonstrated better behavioral improvement, higher level of TH in SN along with much lower extent of p-c-Jun and Cas-3 than those under intranasal SP solution administration and intravenous SP-GNP administration.With the advantages of GNP and nose-to-brain pathway, SP can be effectively delivered into the damaged SN region and exhibit its neuro-recovery function through the inhibition on JNK pathway and dopaminergic neuron apoptosis.

Effect of long-term intranasal oxytocin on sexual dysfunction in premenopausal and postmenopausal women: a randomized trial.

Science.gov (United States)

Muin, Dana A; Wolzt, Michael; Marculescu, Rodrig; Sheikh Rezaei, Safoura; Salama, Mohamed; Fuchs, Carola; Luger, Anton; Bragagna, Elia; Litschauer, Brigitte; Bayerle-Eder, Michaela

2015-09-01

To assess the effect of on-demand intranasal oxytocin administration on female sexual function and activity. Randomized, prospective, double-blind, placebo-controlled, crossover trial with duration of 22 weeks. Academic medical center. Thirty pre-and postmenopausal women with sexual dysfunction. Over 8 weeks, intranasal oxytocin (32 IU) or placebo self-administered by women within 50 minutes before sexual intercourse; after a washout period of 2 weeks, crossover with patients switched to the alternate group for another 8 weeks. Primary outcome parameter: Female Sexual Function Index (FSFI); secondary outcome parameters: Female Sexual Distress Scale (FSDS), Sexual Quality of Life-Female (SQOL-F), Sexual Interest and Desire Inventory-Female (SIDI-F), and Hamilton depression scale (HDS). After oxytocin and placebo, the FSFI score increased by 26% and 31%, SQOL-F score by 144% and 125%, and SIDI-F score by 29% and 23%, respectively (repeated measures analysis of variance between groups). After oxytocin and placebo, the FSDS score decreased by 36% and 45%, respectively (repeated measures analysis of variance between groups). There was no statistically significant treatment, sequence (placebo first/second), or interaction effect. Long-term intranasal oxytocin and placebo administration both improved sexual function and symptoms of depression in women over time with no treatment, sequence (placebo first/second), or interaction effect. NCT02229721. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

“Awake” intraoperative functional MRI (ai-fMRI) for mapping the eloquent cortex: Is it possible in awake craniotomy?☆

Science.gov (United States)

Lu, Jun-Feng; Zhang, Han; Wu, Jin-Song; Yao, Cheng-Jun; Zhuang, Dong-Xiao; Qiu, Tian-Ming; Jia, Wen-Bin; Mao, Ying; Zhou, Liang-Fu

2012-01-01

As a promising noninvasive imaging technique, functional MRI (fMRI) has been extensively adopted as a functional localization procedure for surgical planning. However, the information provided by preoperative fMRI (pre-fMRI) is hampered by the brain deformation that is secondary to surgical procedures. Therefore, intraoperative fMRI (i-fMRI) becomes a potential alternative that can compensate for brain shifts by updating the functional localization information during craniotomy. However, previous i-fMRI studies required that patients be under general anesthesia, preventing the wider application of such a technique as the patients cannot perform tasks unless they are awake. In this study, we propose a new technique that combines awake surgery and i-fMRI, named “awake” i-fMRI (ai-fMRI). We introduced ai-fMRI to the real-time localization of sensorimotor areas during awake craniotomy in seven patients. The results showed that ai-fMRI could successfully detect activations in the bilateral primary sensorimotor areas and supplementary motor areas for all patients, indicating the feasibility of this technique in eloquent area localization. The reliability of ai-fMRI was further validated using intraoperative stimulation mapping (ISM) in two of the seven patients. Comparisons between the pre-fMRI-derived localization result and the ai-fMRI derived result showed that the former was subject to a heavy brain shift and led to incorrect localization, while the latter solved that problem. Additionally, the approaches for the acquisition and processing of the ai-fMRI data were fully illustrated and described. Some practical issues on employing ai-fMRI in awake craniotomy were systemically discussed, and guidelines were provided. PMID:24179766

Qualitative assessment of awake nasopharyngoscopy for prediction of oral appliance treatment response in obstructive sleep apnoea.

Science.gov (United States)

Sutherland, Kate; Chan, Andrew S L; Ngiam, Joachim; Darendeliler, M Ali; Cistulli, Peter A

2018-01-23

Clinical methods to identify responders to oral appliance (OA) therapy for obstructive sleep apnoea (OSA) are needed. Awake nasopharyngoscopy during mandibular advancement, with image capture and subsequent processing and analysis, may predict treatment response. A qualitative assessment of awake nasopharyngoscopy would be simpler for clinical practice. We aimed to determine if a qualitative classification system of nasopharyngoscopic observations reflects treatment response. OSA patients were recruited for treatment with a customised two-piece OA. A custom scoring sheet was used to record observations of the pharyngeal airway (velopharynx, oropharynx, hypopharynx) during supine nasopharyngoscopy in response to mandibular advancement and performance of the Müller manoeuvre. Qualitative scores for degree ( 75%), collapse pattern (concentric, anteroposterior, lateral) and diameter change (uniform, anteroposterior, lateral) were recorded. Treatment outcome was confirmed by polysomnography after a titration period of 14.6 ± 9.8 weeks. Treatment response was defined as (1) Treatment AHI  50% AHI reduction and (3) > 50% AHI reduction. Eighty OSA patients (53.8% male) underwent nasopharyngoscopy. The most common naspharyngoscopic observation with mandibular advancement was a small ( 75% velopharyngeal collapse on performance of the Müller manoeuvre. Mandibular advancement reduced the observed level of pharyngeal collapse at all three pharyngeal regions (p < 0.001). None of the nasopharyngoscopic qualitative scores differed between responder and non-responder groups. Qualitative assessment of awake nasopharyngoscopy appears useful for assessing the effect of mandibular advancement on upper airway collapsibility. However, it is not sensitive enough to predict oral appliance treatment outcome.

Technical Note: On The Usage and Development of the AWAKE Web Server and Web Applications

CERN Document Server

Berger, Dillon Tanner

2017-01-01

The purpose of this technical note is to give a brief explanation of the AWAKE Web Server, the current web applications it serves, and how to edit, maintain, and update the source code. The majority of this paper is dedicated to the development of the server and its web applications.

Formulation and optimization of mucoadhesive microemulsion containing mirtazapine for intranasal delivery

Directory of Open Access Journals (Sweden)

Hetal P Thakkar

2014-01-01

Full Text Available Background: Mirtazapine, an antidepressant drug, has absolute bioavailability of only 50% due to high first pass metabolism. Aim: The purpose of this study was to develop and optimize mucoadhesive microemulsion containing mirtazapine for intranasal delivery. Materials and Methods: Based on solubility study, Capmul Medium chain Monoglyceride, Tween 80 and polyethylene glycol (PEG 400 were selected as oil, surfactant and co surfactant respectively. Microemulsions were prepared using water titration method. 3:1% w/w ratio (Tween 80: PEG 400 was selected for formulation development. The prepared microemulsions were optimized for globule size, zeta potential, % transmittance and polydispersity index. The optimized batch was further characterized for % drug content, conductivity and transmission electron microscopy. Results and Conclusion: All the parameters showed the suitability of microemulsion of mirtazapine for intranasal delivery. Chitosan (0.5% w/w was used as a polymer for the preparation of mucoadhesive microemulsion to enhance the retention time in the nasal mucosa. Results of nasal toxicity study using excised sheep nasal mucosa showed comparatively no damage to epithelium and so formulation was considered safe for nasal administration. mirtazapine mucoadhesive microemulsion showed the highest percentage of diffusion (57.11 ± 0.710% after 210 min during in-vitro drug diffusion study through sheep nasal mucosa, followed by mirtazapine microemulsion (46.08 ± 0.674% and finally by mirtazapine solution (17.63 ± 0.612%.

Acute and repeated intranasal oxytocin administration exerts anti-aggressive and pro-affiliative effects in male rats

NARCIS (Netherlands)

Calcagnoli, Federica; Kreutzmann, Judith C.; de Boer, Sietse F.; Althaus, Monika; Koolhaas, Jaap M.

Socio-emotional deficits and impulsive/aggressive outbursts are prevalent symptoms of many neuropsychiatric disorders, and intranasal administration of oxytocin (OXT) is emerging as a putative novel therapeutic approach to curb these problems. Recently, we demonstrated potent anti-aggressive and

Insulin receptors

International Nuclear Information System (INIS)

Kahn, C.R.; Harrison, L.C.

1988-01-01

This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial

Directory of Open Access Journals (Sweden)

Anagnostou Evdokia

2012-12-01

Full Text Available Abstract Background There are no effective medications for the treatment of social cognition/function deficits in autism spectrum disorder (ASD, and adult intervention literature in this area is sparse. Emerging data from animal models and genetic association studies as well as early, single-dose intervention studies suggest that the oxytocin system may be a potential therapeutic target for social cognition/function deficits in ASD. The primary aim of this study was to examine the safety/therapeutic effects of intranasal oxytocin versus placebo in adults with ASD, with respect to the two core symptom domains of social cognition/functioning and repetitive behaviors. Methods This was a pilot, randomized, double-blind, placebo-controlled, parallel design trial of intranasal oxytocin versus placebo in 19 adults with ASD (16 males; 33.20 ± 13.29 years. Subjects were randomized to 24 IU intranasal oxytocin or placebo in the morning and afternoon for 6 weeks. Measures of social function/cognition (the Diagnostic Analysis of Nonverbal Accuracy and repetitive behaviors (Repetitive Behavior Scale Revised were administered. Secondary measures included the Social Responsiveness Scale, Reading-the-Mind-in-the-Eyes Test and the Yale Brown Obsessive Compulsive Scale – compulsion subscale and quality of life (World Health Organization Quality of Life Questionnaire – emotional/social subscales. Full-information maximum-likelihood parameter estimates were obtained and tested using mixed-effects regression analyses. Results Although no significant changes were detected in the primary outcome measures after correcting for baseline differences, results suggested improvements after 6 weeks in measures of social cognition (Reading-the-Mind-in-the-Eyes Test, p = 0.002, d = 1.2, and quality of life (World Health Organization Quality of Life Questionnaire – emotion, p = 0.031, d = 0.84, both secondary measures. Oxytocin was well tolerated and no serious adverse

Feasibility and safety of inducing modest hypothermia in awake patients with acute stroke through surface cooling

DEFF Research Database (Denmark)

Kammersgaard, L P; Rasmussen, B H; Jørgensen, Henrik Stig

2000-01-01

Hypothermia reduces neuronal damage in animal stroke models. Whether hypothermia is neuroprotective in patients with acute stroke remains to be clarified. In this case-control study, we evaluated the feasibility and safety of inducing modest hypothermia by a surface cooling method in awake patients...

Training anesthesiology residents in providing anesthesia for awake craniotomy: learning curves and estimate of needed case load.

Science.gov (United States)

Bilotta, Federico; Titi, Luca; Lanni, Fabiana; Stazi, Elisabetta; Rosa, Giovanni

2013-08-01

To measure the learning curves of residents in anesthesiology in providing anesthesia for awake craniotomy, and to estimate the case load needed to achieve a "good-excellent" level of competence. Prospective study. Operating room of a university hospital. 7 volunteer residents in anesthesiology. Residents underwent a dedicated training program of clinical characteristics of anesthesia for awake craniotomy. The program was divided into three tasks: local anesthesia, sedation-analgesia, and intraoperative hemodynamic management. The learning curve for each resident for each task was recorded over 10 procedures. Quantitative assessment of the individual's ability was based on the resident's self-assessment score and the attending anesthesiologist's judgment, and rated by modified 12 mm Likert scale, reported ability score visual analog scale (VAS). This ability VAS score ranged from 1 to 12 (ie, very poor, mild, moderate, sufficient, good, excellent). The number of requests for advice also was recorded (ie, resident requests for practical help and theoretical notions to accomplish the procedures). Each task had a specific learning rate; the number of procedures necessary to achieve "good-excellent" ability with confidence, as determined by the recorded results, were 10 procedures for local anesthesia, 15 to 25 procedures for sedation-analgesia, and 20 to 30 procedures for intraoperative hemodynamic management. Awake craniotomy is an approach used increasingly in neuroanesthesia. A dedicated training program based on learning specific tasks and building confidence with essential features provides "good-excellent" ability. © 2013 Elsevier Inc. All rights reserved.

A novel intranasal breath-powered delivery system for sumatriptan: a review of technology and clinical application of the investigational product AVP-825 in the treatment of migraine.

Science.gov (United States)

Cady, Roger

2015-01-01

AVP-825, formerly 'OptiNose Sumatriptan,' is an investigational Breath-Powered(TM) Bi-Directional(TM) intranasal delivery system containing low-dose sumatriptan (22 mg intranasal powder) that avoids limitations of other types of intranasal administration by taking advantage of unique features of nasal anatomy and physiology. This review summarizes intranasal drug delivery for migraine, how the breath-powered technology works, and AVP-825 pharmacokinetic, efficacy and safety/tolerability findings. To identify AVP-825 clinical studies, a PubMed/MEDLINE database search was conducted with the terms AVP-825, OptiNose, OptiNose Sumatriptan, Breath-Powered Nasal Delivery or sumatriptan powder. Of 20 articles, 5 clinical studies were identified, including the head-to-head comparative COMPASS trial (AVP-825 vs oral sumatriptan) and two placebo-controlled studies. AVP-825 has faster sumatriptan absorption versus oral tablets or traditional liquid nasal spray. In Phase II/III randomized, double-blind, placebo-controlled trials, AVP-825 produced early and sustained efficacy with minimal triptan-related adverse effects. In COMPASS, AVP-825 produced earlier reduction of migraine pain intensity and migraine-associated symptoms than 100 mg oral sumatriptan, and higher early rates of pain relief and pain freedom, similar sustained efficacy, and fewer atypical sensations. AVP-825 has the potential to provide migraine patients with improved intranasal administration of sumatriptan that may enhance efficacy and tolerability.

Improved Intranasal Retentivity and Transnasal Absorption Enhancement by PEGylated Poly-l-ornithine

Directory of Open Access Journals (Sweden)

Yusuke Kamiya

2018-01-01

Full Text Available We reported that the introduction of polyethylene glycol (PEG to poly-l-ornithine (PLO, which is an homopolymeric basic amino acid having absorption-enhancement ability, prolonged retention time in an in vitro inclined plate test, probably due to an increase in viscosity caused by PEGylation. The aim of the present study is to investigate whether the introduction of PEG chains to PLO improves intranasal retention and transnasal absorption in vivo. We performed intranasal administration experiments using PLO and PEG-PLO with a model drug, fluorescein isothiocyanate dextran (FD-4, in rats under closed and open systems. In the open system, transition of plasma FD-4 concentration after co-administration with unmodified PLO was low, and the area under the plasma concentration-time curve (AUC decreased to about 60% of that in the closed system. In contrast, the AUC after co-administration with PEG-PLO in the open system was about 90% of that in the closed system, and the transition of plasma FD-4 concentration and FD-4 absorption profile were similar to those of the closed system. These findings indicate that introducing PEG chains to homopolymeric basic amino acids (HPBAAs is a very useful method for developing a functional absorption enhancer that can exhibit an efficient in vivo absorption-enhancing effect.

Oculomotor Behavior Metrics Change According to Circadian Phase and Time Awake

Science.gov (United States)

Flynn-Evans, Erin E.; Tyson, Terence L.; Cravalho, Patrick; Feick, Nathan; Stone, Leland S.

2017-01-01

There is a need for non-invasive, objective measures to forecast performance impairment arising from sleep loss and circadian misalignment, particularly in safety-sensitive occupations. Eye-tracking devices have been used in some operational scenarios, but such devices typically focus on eyelid closures and slow rolling eye movements and are susceptible to the intrusion of head movement artifacts. We hypothesized that an expanded suite of oculomotor behavior metrics, collected during a visual tracking task, would change according to circadian phase and time awake, and could be used as a marker of performance impairment.

Improved insulin sensitivity after exercise: focus on insulin signaling

DEFF Research Database (Denmark)

Frøsig, Christian; Richter, Erik

2009-01-01

After a single bout of exercise, the ability of insulin to stimulate glucose uptake is markedly improved locally in the previously active muscles. This makes exercise a potent stimulus counteracting insulin resistance characterizing type 2 diabetes (T2D). It is believed that at least part...... of the mechanism relates to an improved ability of insulin to stimulate translocation of glucose transporters (GLUT4) to the muscle membrane after exercise. How this is accomplished is still unclear; however, an obvious possibility is that exercise interacts with the insulin signaling pathway to GLUT4...... translocation allowing for a more potent insulin response. Parallel to unraveling of the insulin signaling cascade, this has been investigated within the past 25 years. Reviewing existing studies clearly indicates that improved insulin action can occur independent of interactions with proximal insulin signaling...

One should avoid retro-orbital pharmacokinetic sample collections for intranasal dosing in rats: Illustration of spurious pharmacokinetics generated for anti-migraine drugs zolmitriptan and eletriptan.

Science.gov (United States)

Patel, Harilal; Patel, Prakash; Modi, Nirav; Shah, Shaival; Ghoghari, Ashok; Variya, Bhavesh; Laddha, Ritu; Baradia, Dipesh; Dobaria, Nitin; Mehta, Pavak; Srinivas, Nuggehally R

2017-08-30

Because of the avoidance of first pass metabolic effects due to direct and rapid absorption with improved permeability, intranasal route represents a good alternative for extravascular drug administration. The aim of the study was to investigate the intranasal pharmacokinetics of two anti-migraine drugs (zolmitriptan and eletriptan), using retro-orbital sinus and jugular vein sites sampling. In a parallel study design, healthy male Sprague-Dawley (SD) rats aged between 8 and 12weeks were divided into groups (n=4 or 5/group). The animals of individual groups were dosed intranasal (~1.0mg/kg) and oral doses of 2.1mg/kg of either zolmitriptan or eletriptan. Serial blood sampling was performed from jugular vein or retro-orbital site and plasma samples were analyzed for drug concentrations using LC-MS/MS assay. Standard pharmacokinetics parameters such as T max , C max , AUC last , AUC 0-inf and T 1/2 were calculated and statistics of derived parameters was performed using unpaired t-test. After intranasal dosing, the mean pharmacokinetic parameters C max and AUC inf of zolmitriptan/eletriptan showed about 17-fold and 3-5-fold higher values for retro-orbital sampling as compared to the jugular vein sampling site. Whereas after oral administration such parameters derived for both drugs were largely comparable between the two sampling sites and statistically non-significant. In conclusion, the assessment of plasma levels after intranasal administration with retro-orbital sampling would result in spurious and misleading pharmacokinetics. Copyright © 2017 Elsevier B.V. All rights reserved.

A novel tablet computer platform for advanced language mapping during awake craniotomy procedures.

Science.gov (United States)

Morrison, Melanie A; Tam, Fred; Garavaglia, Marco M; Golestanirad, Laleh; Hare, Gregory M T; Cusimano, Michael D; Schweizer, Tom A; Das, Sunit; Graham, Simon J

2016-04-01

A computerized platform has been developed to enhance behavioral testing during intraoperative language mapping in awake craniotomy procedures. The system is uniquely compatible with the environmental demands of both the operating room and preoperative functional MRI (fMRI), thus providing standardized testing toward improving spatial agreement between the 2 brain mapping techniques. Details of the platform architecture, its advantages over traditional testing methods, and its use for language mapping are described. Four illustrative cases demonstrate the efficacy of using the testing platform to administer sophisticated language paradigms, and the spatial agreement between intraoperative mapping and preoperative fMRI results. The testing platform substantially improved the ability of the surgeon to detect and characterize language deficits. Use of a written word generation task to assess language production helped confirm areas of speech apraxia and speech arrest that were inadequately characterized or missed with the use of traditional paradigms, respectively. Preoperative fMRI of the analogous writing task was also assistive, displaying excellent spatial agreement with intraoperative mapping in all 4 cases. Sole use of traditional testing paradigms can be limiting during awake craniotomy procedures. Comprehensive assessment of language function will require additional use of more sophisticated and ecologically valid testing paradigms. The platform presented here provides a means to do so.

Awake fi beroptic intubation of a patient with amyotrophic lateral sclerosis: case report

Directory of Open Access Journals (Sweden)

Elif Bakı

2012-12-01

Full Text Available Amyotrophic Lateral Sclerosis is a rapidly progressive disease from the fi fth to sixth decades of life causing degeneration and death of the upper and lower motor neurons and no effective treatment. The diagnosis isdependent on the clinical presentation and consistent electrodiagnostic studies. Progressive denervation affects the muscles, causing muscular weakness and atrophy, when the ventilation muscles are affected deathdue to respiratory failure occurs within a few years. We present the case of a 54 years old, 180 cm height and 94 kg weight male patient with amyotrophic lateral sclerosis who underwent surgical treatment of thyroidcancer. Fiberoptic intubation was orally performed providing spontaneus breathing. Propofol was applied after passing vocal cords. Anesthesia was maintained with sevofl orane (%2 and a mixture of oxygen and airunder volume controlled ventilation. Rocuronium was used 20 mg at the beginning of the surgery. At the end of surgery, he wasn’t extubated and transferred to anesthesia intensive care unit. He was extubated after tenhours and he was awaked perfectly. The patient was discharged from intensive care unit after 24 hours and from hospital after ten days. We reported that amyotrophic lateral sclerosis patient with limited mouth opening who underwent thyroid surgery, using awake intubation.

Disrupting neural activity related to awake-state sharp wave-ripple complexes prevents hippocampal learning.

Science.gov (United States)

Nokia, Miriam S; Mikkonen, Jarno E; Penttonen, Markku; Wikgren, Jan

2012-01-01

Oscillations in hippocampal local-field potentials (LFPs) reflect the crucial involvement of the hippocampus in memory trace formation: theta (4-8 Hz) oscillations and ripples (~200 Hz) occurring during sharp waves are thought to mediate encoding and consolidation, respectively. During sharp wave-ripple complexes (SPW-Rs), hippocampal cell firing closely follows the pattern that took place during the initial experience, most likely reflecting replay of that event. Disrupting hippocampal ripples using electrical stimulation either during training in awake animals or during sleep after training retards spatial learning. Here, adult rabbits were trained in trace eyeblink conditioning, a hippocampus-dependent associative learning task. A bright light was presented to the animals during the inter-trial interval (ITI), when awake, either during SPW-Rs or irrespective of their neural state. Learning was particularly poor when the light was presented following SPW-Rs. While the light did not disrupt the ripple itself, it elicited a theta-band oscillation, a state that does not usually coincide with SPW-Rs. Thus, it seems that consolidation depends on neuronal activity within and beyond the hippocampus taking place immediately after, but by no means limited to, hippocampal SPW-Rs.

The effects of intranasal oxytocin on reward circuitry responses in children with autism spectrum disorder.

Science.gov (United States)

Greene, R K; Spanos, M; Alderman, C; Walsh, E; Bizzell, J; Mosner, M G; Kinard, J L; Stuber, G D; Chandrasekhar, T; Politte, L C; Sikich, L; Dichter, G S

2018-03-27

Intranasal oxytocin (OT) has been shown to improve social communication functioning of individuals with autism spectrum disorder (ASD) and, thus, has received considerable interest as a potential ASD therapeutic agent. Although preclinical research indicates that OT modulates the functional output of the mesocorticolimbic dopamine system that processes rewards, no clinical brain imaging study to date has examined the effects of OT on this system using a reward processing paradigm. To address this, we used an incentive delay task to examine the effects of a single dose of intranasal OT, versus placebo (PLC), on neural responses to social and nonsocial rewards in children with ASD. In this placebo-controlled double-blind study, 28 children and adolescents with ASD (age: M = 13.43 years, SD = 2.36) completed two fMRI scans, one after intranasal OT administration and one after PLC administration. During both scanning sessions, participants completed social and nonsocial incentive delay tasks. Task-based neural activation and connectivity were examined to assess the impact of OT relative to PLC on mesocorticolimbic brain responses to social and nonsocial reward anticipation and outcomes. Central analyses compared the OT and PLC conditions. During nonsocial reward anticipation, there was greater activation in the right nucleus accumbens (NAcc), left anterior cingulate cortex (ACC), bilateral orbital frontal cortex (OFC), left superior frontal cortex, and right frontal pole (FP) during the OT condition relative to PLC. Alternatively, during social reward anticipation and outcomes, there were no significant increases in brain activation during the OT condition relative to PLC. A Treatment Group × Reward Condition interaction revealed relatively greater activation in the right NAcc, right caudate nucleus, left ACC, and right OFC during nonsocial relative to social reward anticipation during the OT condition relative to PLC. Additionally, these analyses revealed

Safety and Immunogenicity Testing of an Intranasal Group B Meningococcal Native Outer Membrane Vesicle Vaccine in Healthy Volunteers

National Research Council Canada - National Science Library

Drabick, Joseph

1998-01-01

An intranasal vaccine composed of native outer membrane vesicles (NOMV) not exposed to detergent or denaturing agents was prepared from the group B meningococcal strain and tested in 32 healthy adult volunteers...

Intranasal Nerve Growth Factor administration improves cerebral functions in a child with severe traumatic brain injury: A case report.

Science.gov (United States)

Chiaretti, Antonio; Conti, Giorgio; Falsini, Benedetto; Buonsenso, Danilo; Crasti, Matteo; Manni, Luigi; Soligo, Marzia; Fantacci, Claudia; Genovese, Orazio; Calcagni, Maria Lucia; Di Giuda, Daniela; Mattoli, Maria Vittoria; Cocciolillo, Fabrizio; Ferrara, Pietro; Ruggiero, Antonio; Staccioli, Susanna; Colafati, Giovanna Stefania; Riccardi, Riccardo

2017-01-01

Nerve growth factor (NGF) promotes neural recovery after experimental traumatic brain injury (TBI) supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated protein Doublecortin (DCX). Only a few studies reported NGF administration in paediatric patients with severe TBI. A four-year-old boy in a persistent unresponsive wakefulness syndrome (UWS) was treated with intranasal murine NGF administration 6 months after severe TBI. The patient received four cycles of intranasal NGF (0.1 mg/kg, twice a day for 10 consecutive days). NGF administration improved functional [Positron Emission Tomography/Computed Tomography (PET/CT); Single photon emission/Computed Tomography (SPECT/CT) and Magnetic Resonance Imaging (MRI)] assessment, electrophysiological [Electroencephalogram (EEG) and Visual Evoked Potential (VEP)] studies and clinical conditions. He showed improvements in voluntary movements, facial mimicry, phonation, attention and verbal comprehension, ability to cry, cough reflex, oral motility, feeding capacity, and bowel and urinary functions. After NGF administration, raised levels of both NGF and DCX were found in the cerebrospinal fluid of the patient. No side effects were reported. Although further studies are needed for better understanding the neuroprotective role of this neurotrophin, intranasal NGF administration appears to be a promising and safe rescuing strategy treatment in children with neurological impairment after TBI.

Awake craniotomy versus craniotomy under general anesthesia for the surgical treatment of insular glioma: choices and outcomes

NARCIS (Netherlands)

Gravesteijn, B.Y. (B. Y.); Keizer, M.E. (M. E.); A. Vincent (Audrey); J.W. Schouten (Joost); R.J. Stolker (Robert); M. Klimek (Markus)

2017-01-01

textabstractObjective: To investigate differences in outcomes in patients who underwent surgery for insular glioma using an awake craniotomy (AC) vs. a craniotomy under general anesthesia (GA). Methods: Data from patients treated at our hospital between 2005 and 2015 were analyzed retrospectively.

[THE CHANGES OF NOCICEPTIVE THRESHOLD AND ACTIVITY OF THE ADENYLYL CYCLASE SYSTEM IN THE SKELETAL MUSCLES OF RATS WITH ACUTE AND MILD TYPE 1 DIABETES MELLITUS ].

Science.gov (United States)

Shipilov, V N; Trost, A M; Chistyakova, O V; Derkach, K V; Shpakov, A O

2016-02-01

Diabetic peripheral neuropathy (DPN) is one of the most common complications of the type 1 diabetes mellitus (DM1). The aim of the work was to study the dynamics of a painful DPN and functional state of the hormone-sensitive ACSS in the skeletal muscles of rats with the models of acute and mild DM1, as well as the study of impact on them of insulin therapy with different ways of hormone delivery - intranasal and peripheral. In both models of DM1, the level of nociceptive threshold in rats decreased and the stimulatory effects of guanine nucleotides (GppNHp) and adrenergic agonists (isoproterenol, BRL-37344) on adenylyl cyclase (AC) activity were attenuated. The AC stimulating effect of relaxin decreased in animals with acute DM1, but in mild DM1, the decrease was insignificant. Peripheral administration of insulin in rats with acute DM1 increased the nociceptive threshold and partially restored the AC effect of ß 3-agonist BRL-37344. Intranasal administration of insulin in rats with DM1 also increased the nociceptive threshold and partially restored the basal and BRL-37344-stimulated AC activity in the skeletal muscles of diabetic animals. Thus, in the skeletal muscles of rats with acute and mild DM1 the nociceptive sensitivity and the functions of ACSS were disturbed, and they were partially restored by the treatment with peripheral (acute DM1) or intranasal (mild DM1) insulin.

Use of movable high-field-strength intraoperative magnetic resonance imaging with awake craniotomies for resection of gliomas: preliminary experience.

LENUS (Irish Health Repository)

Leuthardt, Eric C

2011-07-01

Awake craniotomy with electrocortical mapping and intraoperative magnetic resonance imaging (iMRI) are established techniques for maximizing tumor resection and preserving function, but there has been little experience combining these methodologies.

Biofeedback for treatment of awake and sleep bruxism in adults: systematic review protocol

OpenAIRE

Ilovar, Sasa; Zolger, Danaja; Castrillon, Eduardo; Car, Josip; Huckvale, Kit

2014-01-01

Background Bruxism is a disorder of jaw-muscle activity characterised by repetitive clenching or grinding of the teeth which results in discomfort and damage to dentition. The two clinical manifestations of the condition (sleep and awake bruxism) are thought to have unrelated aetiologies but are palliated using similar techniques. The lack of a definitive treatment has prompted renewed interest in biofeedback, a behaviour change method that uses electronic detection to provide a stimulus when...

Unraveling Alzheimer?s: Making Sense of the Relationship between Diabetes and Alzheimer?s Disease 1

OpenAIRE

Schilling, Melissa A.

2016-01-01

Numerous studies have documented a strong association between diabetes and Alzheimer?s disease (AD). The nature of the relationship, however, has remained a puzzle, in part because of seemingly incongruent findings. For example, some studies have concluded that insulin deficiency is primarily at fault, suggesting that intranasal insulin or inhibiting the insulin-degrading enzyme (IDE) could be beneficial. Other research has concluded that hyperinsulinemia is to blame, which implies that intra...

Intranasal ketamine for the management of incidental pain during wound dressing in cancer patients: A pilot study

Directory of Open Access Journals (Sweden)

Nivedita Page

2018-01-01

Full Text Available Introduction: Cancer wounds need regular dressing; else they develop infection, foul odor, and in extreme cases, maggots. Patients resist dressing due to the severe incidental pain during dressing. Intranasal ketamine was tried as an analgesic to reduce this incidental pain. Materials and Methods: Twenty patients with wounds requiring regular dressing were selected; these patients had a basal pain score of 4/10 and incidental pain score of 7/10 during four consecutive dressings. Ketamine 0.5 mg/kg was administered transmucosally 10 min before dressing, and pain scores, hemodynamic parameters, and sedation were recorded for up to 2 h in six consecutive dressings. Results: Ketamine produced a significant reduction in incidental pain without any hemodynamic changes or sedation. Conclusion: Ketamine appears to be a safe and effective analgesic when used intranasally for incidental pain.

[Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy].

Science.gov (United States)

Pesić, Milica; Zivić, Sasa; Radenković, Sasa; Velojić, Milena; Dimić, Dragan; Antić, Slobodan

2007-04-01

Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin) for basal insulin supply in patients with type 1 diabetes. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IT) were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15); 2. NPH insulin twice daily (n = 15); 3. insulin glargine once daily (n = 18). Meal time insulin aspart was continued in all groups. Fasting blood glucose (FBG) was lower in the glargine group (7.30+/-0.98 mmol/1) than in the twice daily NPH group (7.47+/-1.06 mmol/1), but without significant difference. FBG was significantly higher in the once daily NPH group (8.44+/-0.85 mmol/l; p < 0.05). HbAlc after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72+/-0.86% to 6.87+/-0.50%), as well as in the twice daily NPH group (from 7.80+/-0.83% to 7.01+/-0.63%). Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56+/-2.09) than in both NPH groups (9.0+/-1.65 in twice daily NPH group and 8.13+/-1.30 in other NPH group) (episodes/patients-month, p < 0.05). Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbAlc and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

Wide Awake Hand Surgery.

Science.gov (United States)

Lied, Line; Borchgrevink, Grethe E; Finsen, Vilhjalmur

2017-09-01

"Wide awake hand surgery", where surgery is performed in local anaesthesia with adrenaline, without sedation or a tourniquet, has become widespread in some countries. It has a number of potential advantages and we wished to evaluate it among our patients. All 122 patients treated by this method during one year were evaluated by the surgeons and the patients on a numerical scale from 0 (best/least) to 10 (worst/most). Theatre time was compared to that recorded for a year when regional or general anaesthesia had been used. The patients' mean score for the general care they had received was 0.1 (SD 0.6), for pain during lidocaine injection 2.4 (SD 2.2), for pain during surgery 0.9 (SD 1.5), and for other discomfort during surgery 0.5 (SD 1.4). Eight reported that they would want general anaesthesia if they were to be operated again. The surgeons' mean evaluation of bleeding during surgery was 1.6 (SD 1.8), oedema during surgery 0.4 (SD 1.1), general disadvantages with the method 1.0 (SD 1.6) and general advantages 6.5 (SD 4.3). The estimation of advantages was 9.9 (DS 0.5) for tendon suture. 28 patients needed intra-operative additional anaesthesia. The proportion was lower among trained hand surgeons and fell significantly during the study period. Non-surgical theatre time was 46 (SD 15) minutes during the study period and 55 (SD 22) minutes during the regional/general period (p theatre.

Intranasal glukagon til behandling af hypoglykaemi. En fremtidig behandlingsmulighed

DEFF Research Database (Denmark)

Carstens, S; Andersen, I; Gustafsson, Ida

1994-01-01

Nearly 10% of IDDM patients receiving conventional insulin treatment and about three times as many in intensive insulin therapy yearly experience severe hypoglycaemia (requiring external assistance) The conventional treatment of severe hypoglycaemia is glucagon given intramuscularly by a relative...

Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice

DEFF Research Database (Denmark)

Funda, David; Fundova, Petra; Hansen, Axel Kornerup

2014-01-01

gluten-free diets prevent T1D in animal models. Herewith we investigated whether intranasal (i.n.) administration of gliadin or gluten may arrest the diabetogenic process. I.n. administration of gliadin to 4-week-old NOD mice significantly reduced the diabetes incidence. Similarly, the insulitis...

Subcutaneous insulin absorption explained by insulin's physicochemical properties. Evidence from absorption studies of soluble human insulin and insulin analogues in humans.

Science.gov (United States)

Kang, S; Brange, J; Burch, A; Vølund, A; Owens, D R

1991-11-01

To study the influence of molecular aggregation on rates of subcutaneous insulin absorption and to attempt to elucidate the mechanism of absorption of conventional soluble human insulin in humans. Seven healthy male volunteers aged 22-43 yr and not receiving any drugs comprised the study. This study consisted of a single-blind randomized comparison of equimolar dosages of 125I-labeled forms of soluble hexameric 2 Zn2+ human insulin and human insulin analogues with differing association states at pharmaceutical concentrations (AspB10, dimeric; AspB28, mixture of monomers and dimers; AspB9, GluB27, monomeric). After an overnight fast and a basal period of 1 h, 0.6 nmol/kg of either 125I-labeled human soluble insulin (Actrapid HM U-100) or 125I-labeled analogue was injected subcutaneously on 4 separate days 1 wk apart. Absorption was assessed by measurement of residual radioactivity at the injection site by external gamma-counting. The mean +/- SE initial fractional disappearance rates for the four preparations were 20.7 +/- 1.9 (hexameric soluble human insulin), 44.4 +/- 2.5 (dimeric analogue AspB10), 50.6 +/- 3.9 (analogue AspB28), and 67.4 +/- 7.4%/h (monomeric analogue AspB9, GluB27). Absorption of the dimeric analogue was significantly faster than that of hexameric human insulin (P less than 0.001); absorption of monomeric insulin analogue AspB9, GluB27 was significantly faster than that of dimeric analogue AspB10 (P less than 0.01). There was an inverse linear correlation between association state and the initial fractional disappearance rates (r = -0.98, P less than 0.02). Analysis of the disappearance data on a log linear scale showed that only the monomeric analogue had a monoexponential course throughout. Two phases in the rates of absorption were identified for the dimer and three for hexameric human insulin. The fractional disappearance rates (%/h) calculated by log linear regression analysis were monomer 73.3 +/- 6.8; dimer 44.4 +/- 2.5 from 0 to 2 h and

Insulin receptor internalization defect in an insulin-resistant mouse melanoma cell line

International Nuclear Information System (INIS)

Androlewicz, M.J.; Straus, D.S.; Brandenburg, D.F.

1989-01-01

Previous studies from this laboratory demonstrated that the PG19 mouse melanoma cell line does not exhibit a biological response to insulin, whereas melanoma x mouse embryo fibroblast hybrids do respond to insulin. To investigate the molecular basis of the insulin resistance of the PG19 melanoma cells, insulin receptors from the insulin-resistant melanoma cells and insulin-sensitive fibroblast x melanoma hybrid cells were analyzed by the technique of photoaffinity labeling using the photoprobe 125 I-NAPA-DP-insulin. Photolabeled insulin receptors from the two cell types have identical molecular weights as determined by SDS gel electrophoresis under reducing and nonreducing conditions, indicating that the receptors on the two cell lines are structurally similar. Insulin receptor internalization studies revealed that the hybrid cells internalize receptors to a high degree at 37 degree C, whereas the melanoma cells internalize receptors to a very low degree or not at all. The correlation between ability to internalize insulin receptors and sensitivity to insulin action in this system suggests that uptake of the insulin-receptor complex may be required for insulin action in these cells. Insulin receptors from the two cell lines autophosphorylate in a similar insulin-dependent manner both in vitro and in intact cells, indicating that insulin receptors on the melanoma and hybrid cells have functional tyrosine protein kinase activity. Therefore, the block in insulin action in the PG19 melanoma cells appears to reside at a step beyond insulin-stimulated receptor autophosphorylation

Brain Targeting of a Water Insoluble Antipsychotic Drug Haloperidol via the Intranasal Route Using PAMAM Dendrimer.

Science.gov (United States)

Katare, Yogesh K; Daya, Ritesh P; Sookram Gray, Christal; Luckham, Roger E; Bhandari, Jayant; Chauhan, Abhay S; Mishra, Ram K

2015-09-08

Delivery of therapeutics to the brain is challenging because many organic molecules have inadequate aqueous solubility and limited bioavailability. We investigated the efficiency of a dendrimer-based formulation of a poorly aqueous soluble drug, haloperidol, in targeting the brain via intranasal and intraperitoneal administration. Aqueous solubility of haloperidol was increased by more than 100-fold in the developed formulation. Formulation was assessed via different routes of administration for behavioral (cataleptic and locomotor) responses, and for haloperidol distribution in plasma and brain tissues. Dendrimer-based formulation showed significantly higher distribution of haloperidol in the brain and plasma compared to a control formulation of haloperidol administered via intraperitoneal injection. Additionally, 6.7 times lower doses of the dendrimer-haloperidol formulation administered via the intranasal route produced behavioral responses that were comparable to those induced by haloperidol formulations administered via intraperitoneal injection. This study demonstrates the potential of dendrimer in improving the delivery of water insoluble drugs to brain.

Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan

Directory of Open Access Journals (Sweden)

Nicole M. Templeman

2017-07-01

Full Text Available The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1 signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/− mice to Ins2+/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/− mice. Halving Ins2 lowered circulating insulin by 25%–34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan.

Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan.

Science.gov (United States)

Templeman, Nicole M; Flibotte, Stephane; Chik, Jenny H L; Sinha, Sunita; Lim, Gareth E; Foster, Leonard J; Nislow, Corey; Johnson, James D

2017-07-11

The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2 +/- mice to Ins2 +/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2 +/- mice. Halving Ins2 lowered circulating insulin by 25%-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog

Directory of Open Access Journals (Sweden)

Chih-Ting Su

2016-11-01

Full Text Available Insulin antibodies (IA associated with exogenous insulin administration seldom caused hypoglycemia and had different characteristics from insulin autoantibodies (IAA found in insulin autoimmune syndrome (IAS, which was first described by Dr Hirata in 1970. The characteristic of IAS is the presence of insulin-binding autoantibodies and related fasting or late postprandial hypoglycemia. Here, we report a patient with type 1 diabetes mellitus under insulin glargine and insulin aspart treatment who developed recurrent spontaneous post-absorptive hyperinsulinemic hypoglycemia with the cause probably being insulin antibodies induced by exogenous injected insulin. Examinations of serial sera disclosed a high titre of insulin antibodies (33%, normal <5%, high insulin concentration (111.9 IU/mL and undetectable C-peptide when hypoglycemia occurred. An oral glucose tolerance test revealed persistent high serum levels of total insulin and undetectable C-peptide. Image studies of the pancreas were unremarkable, which excluded the diagnosis of insulinoma. The patient does not take any of the medications containing sulfhydryl compounds, which had been reported to cause IAS. After administering oral prednisolone for 3 weeks, hypoglycemic episodes markedly improved, and he was discharged smoothly.

Unraveling Alzheimer's: Making Sense of the Relationship between Diabetes and Alzheimer's Disease1.

Science.gov (United States)

Schilling, Melissa A

2016-01-01

Numerous studies have documented a strong association between diabetes and Alzheimer's disease (AD). The nature of the relationship, however, has remained a puzzle, in part because of seemingly incongruent findings. For example, some studies have concluded that insulin deficiency is primarily at fault, suggesting that intranasal insulin or inhibiting the insulin-degrading enzyme (IDE) could be beneficial. Other research has concluded that hyperinsulinemia is to blame, which implies that intranasal insulin or the inhibition of IDE would exacerbate the disease. Such antithetical conclusions pose a serious obstacle to making progress on treatments. However, careful integration of multiple strands of research, with attention to the methods used in different studies, makes it possible to disentangle the research on AD. This integration suggests that there is an important relationship between insulin, IDE, and AD that yields multiple pathways to AD depending on the where deficiency or excess in the cycle occurs. I review evidence for each of these pathways here. The results suggest that avoiding excess insulin, and supporting robust IDE levels, could be important ways of preventing and lessening the impact of AD. I also describe what further tests need to be conducted to verify the arguments made in the paper, and their implications for treating AD.

Intranasal bevacizumab in the treatment of HHT -related epistaxis: a systematic review.

Science.gov (United States)

Stokes, P; Rimmer, J

2018-03-01

Hereditary haemorrhagic telangiectasia (HHT) remains a difficult disease for the ENT specialist to manage. Affected patients often report recurrent epistaxis as the most debilitating symptom. The pathogenesis of the disease is due to genetic mutations affecting angiogenesis. For this reason, the anti-angiogenic therapy bevacizumab has gained popularity in the local treatment of epistaxis in patients with HHT. A systematic review of the efficacy of bevacizumab in local treatment of epistaxis in patients with HHT based on epistaxis duration, frequency, severity and impact on quality of life. A systematic search was performed using the PubMed, MEDLINE and EMBASE databases. The Preferred Items for Systematic Reviews and Meta-Analyses guidelines were followed. Studies that measured the efficacy of intranasal bevacizumab treatment of epistaxis in patients with HHT were included for qualitative analysis. Thirteen studies (four randomised controlled trials, three prospective studies, three retrospective studies, one case series and two case reports) with a total of 357 patients were included. Local administration (either by submucosal injection or topically) did not have a significant impact on epistaxis duration, frequency, severity or quality of life compared to placebo or other local treatments. The available evidence suggests that intranasal bevacizumab treatment does not have a significant effect on epistaxis in patients with HHT. There are several limitations that require further investigation to confidently rule out local bevacizumab as an effective therapy in HHT related epistaxis.

Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy

Directory of Open Access Journals (Sweden)

Pešić Milica

2007-01-01

Full Text Available Background/Aim. Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin for basal insulin supply in patients with type 1 diabetes. Methods. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IIT were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15; 2. NPH insulin twice daily (n = 15; 3. insulin glargine once daily (n = 18. Meal time insulin aspart was continued in all groups. Results. Fasting blood glucose (FBG was lower in the glargine group (7.30±0.98 mmol/l than in the twice daily NPH group (7.47±1.06 mmol/l, but without significant difference. FBG was significantly higher in the once daily NPH group (8.44±0.85 mmol/l; p < 0.05. HbA1c after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72±0.86% to 6.87±0.50%, as well as in the twice daily NPH group (from 7.80±0.83% to 7.01±0.63%. Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56±2.09 than in both NPH groups (9.0±1.65 in twice daily NPH group and 8.13±1.30 in other NPH group (episodes/patients-month, p < 0.05. Conclusion. Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbA1c and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

Awake craniotomy in a patient with ejection fraction of 10%: considerations of cerebrovascular and cardiovascular physiology.

Science.gov (United States)

Meng, Lingzhong; Weston, Stephen D; Chang, Edward F; Gelb, Adrian W

2015-05-01

A 37-year-old man with nonischemic 4-chamber dilated cardiomyopathy and low-output cardiac failure (estimated ejection fraction of 10%) underwent awake craniotomy for a low-grade oligodendroglioma resection under monitored anesthesia care. The cerebrovascular and cardiovascular physiologic challenges and our management of this patient are discussed. Published by Elsevier Inc.

A model of insulin fibrils derived from the x-ray crystal structure of a monomeric insulin (despentapeptide insulin).

Science.gov (United States)

Brange, J; Dodson, G G; Edwards, D J; Holden, P H; Whittingham, J L

1997-04-01

The crystal structure of despentapeptide insulin, a monomeric insulin, has been refined at 1.3 A spacing and subsequently used to predict and model the organization in the insulin fibril. The model makes use of the contacts in the densely packed despentapeptide insulin crystal, and takes into account other experimental evidence, including binding studies with Congo red. The dimensions of this model fibril correspond well with those measured experimentally, and the monomer-monomer contacts within the fibril are in accordance with the known physical chemistry of insulin fibrils. Using this model, it may be possible to predict mutations in insulin that might alleviate problems associated with fibril formation during insulin therapy.

Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons.

Science.gov (United States)

Rodriguez-Rodriguez, Patricia; Sandebring-Matton, Anna; Merino-Serrais, Paula; Parrado-Fernandez, Cristina; Rabano, Alberto; Winblad, Bengt; Ávila, Jesús; Ferrer, Isidre; Cedazo-Minguez, Angel

2017-12-01

Insulin signalling deficiencies and insulin resistance have been directly linked to the progression of neurodegenerative disorders like Alzheimer's disease. However, to date little is known about the underlying molecular mechanisms or insulin state and distribution in the brain under pathological conditions. Here, we report that insulin is accumulated and retained as oligomers in hyperphosphorylated tau-bearing neurons in Alzheimer's disease and in several of the most prevalent human tauopathies. The intraneuronal accumulation of insulin is directly dependent on tau hyperphosphorylation, and follows the tauopathy progression. Furthermore, cells accumulating insulin show signs of insulin resistance and decreased insulin receptor levels. These results suggest that insulin retention in hyperphosphorylated tau-bearing neurons is a causative factor for the insulin resistance observed in tauopathies, and describe a novel neuropathological concept with important therapeutic implications. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Development and implementation of intranasal naloxone opioid overdose response protocol at a homeless health clinic.

Science.gov (United States)

Dahlem, Chin Hwa Y; Horstman, Molly J; Williams, Brent C

2016-01-01

To describe the development, implementation, and preliminary evaluation of Opioid Overdose Response Protocol using intranasal (IN) naloxone in a homeless shelter. Opioid Overdose Response Protocol and training curriculum were developed using the Massachusetts Department of Public Health Opioid Overdose Education and Naloxone Distribution (OEND) flow chart, the American Heart Association (AHA) simplified adult basic life support algorithm, and resources through Harms Reduction Coalition. Intranasal naloxone offers a safe and effective method for opioid reversal. To combat the rising incidence of opioid overdose, IN naloxone should be made available at homeless shelters and other facilities with high frequency of opioid overdose, including the training of appropriate staff. This project has demonstrated the effective training and implementation of an Opioid Overdose Response Protocol, based on feedback received from cardiopulmonary resuscitation (CPR) trained nonhealthcare staff. Nurse practitioners (NPs), with our focus on patient care, prevention, and education, are well suited to the deployment of this life-saving protocol. NPs are in critical positions to integrate opioid overdose prevention education and provide naloxone rescue kits in clinical practices. ©2015 American Association of Nurse Practitioners.

Neurotoxicity of low-dose repeatedly intranasal instillation of nano- and submicron-sized ferric oxide particles in mice

Energy Technology Data Exchange (ETDEWEB)

Wang Bing; Feng Weiyue, E-mail: fengwy@mail.ihep.ac.cn; Zhu Motao; Wang Yun; Wang Meng [Chinese Academy of Sciences, Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics (China); Gu Yiqun [Maternity Hospital of Haidian District (China); Ouyang Hong; Wang Huajian; Li Ming; Zhao Yuliang, E-mail: zhaoyuliang@mail.ihep.ac.cn; Chai Zhifang [Chinese Academy of Sciences, Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics (China); Wang Haifang [Peking University, College of Chemistry and Molecular Engineering (China)

2009-01-15

Olfactory tract has been demonstrated to be an important portal for inhaled solid nanoparticle transportation into the central nervous system (CNS). We have previously demonstrated that intranasally instilled Fe{sub 2}O{sub 3} nanoparticles could transport into the CNS via olfactory pathway. In this study, we investigated the neurotoxicity and size effect of repeatedly low-dose (130 {mu}g) intranasal exposure of nano- and submicron-sized Fe{sub 2}O{sub 3} particles (21 nm and 280 nm) to mice. The biomarkers of oxidative stress, activity of nitric oxide synthases and release of monoamine neurotransmitter in the brain were studied. Our results showed that significant oxidative stress was induced by the two sizes of Fe{sub 2}O{sub 3} particles. The activities of GSH-Px, Cu,Zn-SOD, and cNOS significantly elevated and the total GSH and GSH/GSSG ratio significantly decreased in the olfactory bulb and hippocampus after the nano- and submicron-sized Fe{sub 2}O{sub 3} particle treatment (p < 0.05). The nano-sized Fe{sub 2}O{sub 3} generally induced greater alteration and more significant dose-effect response than the submicron-sized particle did. Some slight perturbation of monoamine neurotransmitters were found in the hippocampus after exposure to the two sizes of Fe{sub 2}O{sub 3} particle. The TEM image showed that some ultrastructural alterations in nerve cells, including neurodendron degeneration, membranous structure disruption and lysosome increase in the olfactory bulb, slight dilation in the rough endoplasmic reticulum and lysosome increase in the hippocampus were induced by the nano-sized Fe{sub 2}O{sub 3} treatment. In contrast, in the submicron-sized Fe{sub 2}O{sub 3} treated mice, slightly swollen mitochondria and some vacuoles were observed in the olfactory bulb and hippocampus, respectively. These results indicate that intranasal exposure of Fe{sub 2}O{sub 3} nanoparticles could induce more severe oxidative stress and nerve cell damage in the brain than the

Enhanced Brain Delivery of 2-(Phosphonomethyl)pentanedioic Acid Following Intranasal Administration of Its gamma-Substituted Ester Prodrugs

Czech Academy of Sciences Publication Activity Database

Nedelcovych, M.; Dash, R. P.; Tenora, Lukáš; Zimmermann, S. C.; Gadiano, A. J.; Garrett, C.; Alt, J.; Hollinger, K. R.; Pommier, E.; Jančařík, Andrej; Rojas, C.; Thomas, A. G.; Wu, Y.; Wozniak, K.; Majer, Pavel; Slusher, B. S.; Rais, R.

2017-01-01

Roč. 14, č. 10 (2017), s. 3248-3257 ISSN 1543-8384 Institutional support: RVO:61388963 Keywords : 2-PMPA * glutamate carboxypeptidase II * neurological disease * intranasal * pharmacokinetics * prodrugs Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 4.440, year: 2016

Intranasal delivery of nanoparticle encapsulated tarenflurbil: A potential brain targeting strategy for Alzheimer's disease.

Science.gov (United States)

Muntimadugu, Eameema; Dhommati, Raju; Jain, Anjali; Challa, Venu Gopala Swami; Shaheen, M; Khan, Wahid

2016-09-20

Poor brain penetration of tarenflurbil (TFB) was one of the major reasons for its failure in phase III clinical trials conducted on Alzheimer's patients. Thus there is a tremendous need of developing efficient delivery systems for TFB. This study was designed with the aim of improving drug delivery to brain through intranasally delivered nanocarriers. TFB was loaded into two different nanocarriers i.e., poly (lactide-co-glycolide) nanoparticles (TFB-NPs) and solid lipid nanoparticles (TFB-SLNs). Particle size of both the nanocarriers (targeting site. Pharmacokinetics suggested improved circulation behavior of nanoparticles and the absolute bioavailabilities followed this order: TFB-NPs (i.n.)>TFB-SLNs (i.n.)>TFB solution (i.n.)>TFB suspension (oral). Brain targeting efficiency was determined in terms of %drug targeting efficiency (%DTE) and drug transport percentage (DTP). The higher %DTE (287.24) and DTP (65.18) were observed for TFB-NPs followed by TFB-SLNs (%DTE: 183.15 and DTP: 45.41) among all other tested groups. These encouraging results proved that therapeutic concentrations of TFB could be transported directly to brain via olfactory pathway after intranasal administration of polymeric and lipidic nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.

Anti-insulin antibody test

Science.gov (United States)

Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... Normally, there are no antibodies against insulin in your blood. ... different laboratories. Some labs use different measurements or ...

Cerebral insulin, insulin signaling pathway, and brain angiogenesis.

Science.gov (United States)

Zeng, Yi; Zhang, Le; Hu, Zhiping

2016-01-01

Insulin performs unique non-metabolic functions within the brain. Broadly speaking, two major areas of these functions are those related to brain endothelial cells and the blood-brain barrier (BBB) function, and those related to behavioral effects, like cognition in disease states (Alzheimer's disease, AD) and in health. Recent studies showed that both these functions are associated with brain angiogenesis. These findings raise interesting questions such as how they are linked to each other and whether modifying brain angiogenesis by targeting certain insulin signaling pathways could be an effective strategy to treat dementia as in AD, or even to help secure healthy longevity. The two canonical downstream pathways involved in mediating the insulin signaling pathway, the phosphoinositide-3 kinase (PI3K), and mitogen-activated protein kinase (MAPK) cascades, in the brain are supposed to be similar to those in the periphery. PI3K and MAPK pathways play important roles in angiogenesis. Both are involved in stimulating hypoxia inducible factor (HIF) in angiogenesis and could be activated by the insulin signaling pathway. This suggests that PI3K and MAPK pathways might act as cross-talk between the insulin signaling pathway and the angiogenesis pathway in brain. But the cerebral insulin, insulin signaling pathway, and the detailed mechanism in the connection of insulin signaling pathway, brain angiogenesis pathway, and healthy aging or dementias are still mostly not clear and need further studies.

Insulin resistance in obesity can be reliably identified from fasting plasma insulin.

Science.gov (United States)

ter Horst, K W; Gilijamse, P W; Koopman, K E; de Weijer, B A; Brands, M; Kootte, R S; Romijn, J A; Ackermans, M T; Nieuwdorp, M; Soeters, M R; Serlie, M J

2015-12-01

Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely measured variables. We assembled data from non-obese (n=112) and obese (n=100) men who underwent two-step EHCs using [6,6-(2)H2]glucose as tracer (insulin infusion dose 20 and 60 mU m(-2) min(-1), respectively). Reference ranges for hepatic and peripheral insulin sensitivity were calculated from healthy non-obese men. Based on these reference values, obese men with preserved insulin sensitivity or insulin resistance were identified. Cutoff points for insulin-mediated suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disappearance rate (Rd) were 46.5% and 37.3 μmol kg(-)(1) min(-)(1), respectively. Most obese men (78%) had EGP suppression within the reference range, whereas only 12% of obese men had Rd within the reference range. Obese men with Rd obese men in age, body mass index (BMI), body composition, fasting glucose or cholesterol, but did have higher fasting insulin (110±49 vs 63±29 pmol l(-1), Pobese men could be identified with good sensitivity (80%) and specificity (75%) from fasting insulin >74 pmol l(-1). Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l(-1) with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings.

Comparison of dexmedetomidine and sufentanil for conscious sedation in patients undergoing awake fibreoptic nasotracheal intubation: a prospective, randomised and controlled clinical trial.

Science.gov (United States)

Shen, She-Liang; Xie, Yi-hong; Wang, Wen-Yuan; Hu, Shuang-Fei; Zhang, Yun-Long

2014-01-01

Fibreoptic intubation is a valuable technique for difficult airway management in which conscious sedation is paramount. To investigate the efficacy and safety of dexmedetomidine (DEX) and sufentanil (SUF) for conscious sedation during awake nasotracheal intubation under vision by a fibreoptic bronchoscope. Forty patients with anticipated difficult airways of American Society of Anesthesiologists I-II scheduled for awake fibreoptic nasotracheal intubation were randomised into two groups each containing 20 subjects. DEX group received DEX at a dose of 1.0 μg/kg over 10 min followed by a continuous infusion of 0.5 μg/kg per hour, while SUF group received SUF target controlled infusion in which the target plasma concentration was 0.3 ng/mL. The nasotracheal intubation conditions and the tolerance to nasotracheal intubation were observed; the occurrence of adverse events including hypertension, bradycardia and respiratory depression during nasotracheal intubation and post-surgical throat pain and hoarseness, and post-surgical memory score were recorded. Better nasotracheal intubation conditions and higher tolerance to intubation were observed in DEX group than those in SUF group (P memory score for sedation during awake fibreoptic nasotracheal intubation. © 2013 John Wiley & Sons Ltd.

Absence of down-regulation of the insulin receptor by insulin. A possible mechanism of insulin resistance in the rat.

OpenAIRE

Walker, A P; Flint, D J

1983-01-01

Insulin resistance occurs in rat adipocytes during pregnancy and lactation despite increased or normal insulin binding respectively; this suggests that a post-receptor defect exists. The possibility has been examined that, although insulin binding occurs normally, internalization of insulin or its receptor may be impaired in these states. Insulin produced a dose-dependent reduction in the number of insulin receptors on adipocytes from virgin rats maintained in culture medium, probably due to ...

Representation of dynamic interaural phase difference in auditory cortex of awake rhesus macaques.

Science.gov (United States)

Scott, Brian H; Malone, Brian J; Semple, Malcolm N

2009-04-01

Neurons in auditory cortex of awake primates are selective for the spatial location of a sound source, yet the neural representation of the binaural cues that underlie this tuning remains undefined. We examined this representation in 283 single neurons across the low-frequency auditory core in alert macaques, trained to discriminate binaural cues for sound azimuth. In response to binaural beat stimuli, which mimic acoustic motion by modulating the relative phase of a tone at the two ears, these neurons robustly modulate their discharge rate in response to this directional cue. In accordance with prior studies, the preferred interaural phase difference (IPD) of these neurons typically corresponds to azimuthal locations contralateral to the recorded hemisphere. Whereas binaural beats evoke only transient discharges in anesthetized cortex, neurons in awake cortex respond throughout the IPD cycle. In this regard, responses are consistent with observations at earlier stations of the auditory pathway. Discharge rate is a band-pass function of the frequency of IPD modulation in most neurons (73%), but both discharge rate and temporal synchrony are independent of the direction of phase modulation. When subjected to a receiver operator characteristic analysis, the responses of individual neurons are insufficient to account for the perceptual acuity of these macaques in an IPD discrimination task, suggesting the need for neural pooling at the cortical level.

Clinical use of the co-formulation of insulin degludec and insulin aspart

DEFF Research Database (Denmark)

Kumar, A; Awata, T; Bain, S C

2016-01-01

(HbA1c ) to current modern insulins, but with lower risk of nocturnal hypoglycaemia. In prior insulin users, glycaemic control was achieved with lower or equal insulin doses vs. other basal+meal-time or premix insulin regimens. In insulin-naïve patients with T2DM, IDegAsp can be started once or twice...... a simpler insulin regimen than other available basal-bolus or premix-based insulin regimens, with stable daytime basal coverage, a lower rate of hypoglycaemia and some flexibility in injection timing compared with premix insulins....

[Case of awake intubation in semi-sitting position for a patient with myasthenia gravis combined with cervical disc hernia utilizing Pentax-AWS Airwayscope].

Science.gov (United States)

Komasawa, Nobuyasu; Ueki, Ryusuke; Tomita, Yukihiko; Kaminoh, Yoshiroh; Tashiro, Chikara

2011-01-01

We report a case of awake intubation utilizing Pentax-AWS Airwayscope in semi-sitting position. A 74-year-old man with myasthenia gravis and cervical disc hernia was scheduled for distal gastrectomy under general anesthesia. He could not move his head due to severe cervical disc hernia and also could not sufficiently breathe due to the fatigue of respiratory muscles by myasthenia gravis in supine position. With fentanyl bolus administration and lidocaine spray for laryngotracheal anesthesia, we performed awake intubation in semi-sitting position with AWS from cranial side. The patient did not buck during intubation and no hemodynamic change was observed.

Spiking in primary somatosensory cortex during natural whisking in awake head-restrained rats is cell-type specific

NARCIS (Netherlands)

de Kock, C.P.J.; Sakmann, B.

2009-01-01

Sensation involves active movement of sensory organs, but it remains unknown how position or movement of sensory organs is encoded in cortex. In the rat whisker system, each whisker is represented by an individual cortical (barrel) column. Here, we quantified in awake, head-fixed rats the impact of

Measurement of lung function in awake 2-4-year-old asthmatic children during methacholine challenge and acute asthma

DEFF Research Database (Denmark)

Klug, B; Bisgaard, H

1996-01-01

This study evaluated three techniques for testing of lung function in young awake children. We compared measurements by the forced or impulse oscillation technique (IOS), the interrupter technique (IT), and transcutaneous measurements of oxygen (tcPo2) with concomitant measurements of specific ai...

Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance

DEFF Research Database (Denmark)

Højlund, Kurt

2014-01-01

. These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes...... described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance....... Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin...

Generating pulsatility by pump speed modulation with continuous-flow total artificial heart in awake calves.

Science.gov (United States)

Fukamachi, Kiyotaka; Karimov, Jamshid H; Sunagawa, Gengo; Horvath, David J; Byram, Nicole; Kuban, Barry D; Dessoffy, Raymond; Sale, Shiva; Golding, Leonard A R; Moazami, Nader

2017-12-01

The purpose of this study was to evaluate the effects of sinusoidal pump speed modulation of the Cleveland Clinic continuous-flow total artificial heart (CFTAH) on hemodynamics and pump flow in an awake chronic calf model. The sinusoidal pump speed modulations, performed on the day of elective sacrifice, were set at ±15 and ± 25% of mean pump speed at 80 bpm in four awake calves with a CFTAH. The systemic and pulmonary arterial pulse pressures increased to 12.0 and 12.3 mmHg (±15% modulation) and to 15.9 and 15.7 mmHg (±25% modulation), respectively. The pulsatility index and surplus hemodynamic energy significantly increased, respectively, to 1.05 and 1346 ergs/cm at ±15% speed modulation and to 1.51 and 3381 ergs/cm at ±25% speed modulation. This study showed that it is feasible to generate pressure pulsatility with pump speed modulation; the platform is suitable for evaluating the physiologic impact of pulsatility and allows determination of the best speed modulations in terms of magnitude, frequency, and profiles.

The acute effects of intranasal oxytocin administration on endocrine and sexual function in males.

Science.gov (United States)

Burri, Andrea; Heinrichs, Markus; Schedlowski, Manfred; Kruger, Tillmann H C

2008-06-01

The role of the neuropeptide oxytocin (OT) ranges from the modulation of neuroendocrine physiological effects to the establishment of complex social and bonding behaviours. Experimental studies in animals, as well as case reports in humans, suggest that OT affects different aspects of sexual behaviour and has predominantly facilitating properties for sexual appetence and performance. Using a previously established experimental paradigm of sexual arousal and masturbation-induced orgasm, this study investigated the acute effects of intranasal OT application (24I.U.) on endocrine parameters and measures of sexual appetence and function in healthy men (n=10). In a double-blind, placebo-controlled, balanced cross-over design, sexual arousal, and orgasm were induced by an erotic film and masturbation. In addition to the continuous recording of endocrine (OT, cortisol, prolactin, epinephrine, norepinephrine) and cardiovascular data (heart rate), parameters of appetitive, consummatory, and refractory sexual behaviour were assessed using the acute sexual experience scale (ASES). OT plasma levels were significantly elevated after intranasal OT throughout the whole experiment (>60 min). In addition, OT treatment induced significantly higher increases in epinephrine plasma levels during sexual activity without affecting cortisol levels, prolactin levels or heart rate. OT treatment did not alter appetitive, consummatory, and refractory sexual behaviour according to the ASES. However, when subjects were asked about their subjective perception of whether OT or placebo had been applied, eight out of 10 subjects in the OT group answered correctly, thus pointing to an altered perception of arousal. In conclusion, intranasally administered OT leads to a marked increase in OT plasma levels together with increased secretion of catecholamines when subjects are engaged in sexual activity in a laboratory setting. As the effects of OT on sexual behaviour were equivocal, future studies

Awake Craniotomy vs Craniotomy Under General Anesthesia for Perirolandic Gliomas: Evaluating Perioperative Complications and Extent of Resection.

Science.gov (United States)

Eseonu, Chikezie I; Rincon-Torroella, Jordina; ReFaey, Karim; Lee, Young M; Nangiana, Jasvinder; Vivas-Buitrago, Tito; Quiñones-Hinojosa, Alfredo

2017-09-01

A craniotomy with direct cortical/subcortical stimulation either awake or under general anesthesia (GA) present 2 approaches for removing eloquent region tumors. With a reported higher prevalence of intraoperative seizures occurring during awake resections of perirolandic lesions, oftentimes, surgery under GA is chosen for these lesions. To evaluate a single-surgeon's experience with awake craniotomies (AC) vs surgery under GA for resecting perirolandic, eloquent, motor-region gliomas. Between 2005 and 2015, a retrospective analysis of 27 patients with perirolandic, eloquent, motor-area gliomas that underwent an AC were case-control matched with 31 patients who underwent surgery under GA for gliomas in the same location. All patients underwent direct brain stimulation with neuromonitoring and perioperative risk factors, extent of resection, complications, and discharge status were assessed. The postoperative Karnofsky Performance Score (KPS) was significantly lower for the GA patients at 81.1 compared to the AC patients at 93.3 ( P = .040). The extent of resection for GA patients was 79.6% while the AC patients had an 86.3% resection ( P = .136). There were significantly more 100% total resections in the AC patients 25.9% compared to the GA group (6.5%; P = .041). Patients in the GA group had a longer mean length of hospitalization of 7.9 days compared to the AC group at 4.2 days ( P = .049). We show that AC can be performed with more frequent total resections, better postoperative KPS, shorter hospitalizations, as well as similar perioperative complication rates compared to surgery under GA for perirolandic, eloquent motor-region glioma. Copyright © 2017 by the Congress of Neurological Surgeons

Resection of highly language-eloquent brain lesions based purely on rTMS language mapping without awake surgery.

Science.gov (United States)

Ille, Sebastian; Sollmann, Nico; Butenschoen, Vicki M; Meyer, Bernhard; Ringel, Florian; Krieg, Sandro M

2016-12-01

The resection of left-sided perisylvian brain lesions harbours the risk of postoperative language impairment. Therefore the individual patient's language distribution is investigated by intraoperative direct cortical stimulation (DCS) during awake surgery. Yet, not all patients qualify for awake surgery. Non-invasive language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) has frequently shown a high correlation in comparison with the results of DCS language mapping in terms of language-negative brain regions. The present study analyses the extent of resection (EOR) and functional outcome of patients who underwent left-sided perisylvian resection of brain lesions based purely on rTMS language mapping. Four patients with left-sided perisylvian brain lesions (two gliomas WHO III, one glioblastoma, one cavernous angioma) underwent rTMS language mapping prior to surgery. Data from rTMS language mapping and rTMS-based diffusion tensor imaging fibre tracking (DTI-FT) were transferred to the intraoperative neuronavigation system. Preoperatively, 5 days after surgery (POD5), and 3 months after surgery (POM3) clinical follow-up examinations were performed. No patient suffered from a new surgery-related aphasia at POM3. Three patients underwent complete resection immediately, while one patient required a second rTMS-based resection some days later to achieve the final, complete resection. The present study shows for the first time the feasibility of successfully resecting language-eloquent brain lesions based purely on the results of negative language maps provided by rTMS language mapping and rTMS-based DTI-FT. In very select cases, this technique can provide a rescue strategy with an optimal functional outcome and EOR when awake surgery is not feasible.

Intranasal administration of oxytocin modulates behavioral and amygdala responses to infant crying in females with insecure attachment representations.

Science.gov (United States)

Riem, Madelon M E; Bakermans-Kranenburg, Marian J; van IJzendoorn, Marinus H

2016-01-01

The current study examined the effects of oxytocin administration on the response to infant crying in individuals with secure or insecure attachment representations as assessed with the Adult Attachment Interview. We measured feelings of irritation and the use of excessive force as indicated by grip strength using a handgrip dynamometer during exposure to infant crying in 42 women without children who were administered intranasal oxytocin or a placebo. In addition, amygdala responses to infant crying and control sounds were measured with functional magnetic resonance imaging (fMRI). The effects of oxytocin on reactivity to crying were moderated by attachment security. Oxytocin decreased the use of excessive handgrip force and amygdala reactivity in response to crying in individuals with insecure attachment representations. Our findings indicate that insecure individuals, who show emotional, behavioral, and neural hyperreactivity to crying, benefit the most from intranasal oxytocin.

Psychological insulin resistance in type 2 diabetes patients regarding oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin.

Science.gov (United States)

Petrak, Frank; Herpertz, Stephan; Stridde, Elmar; Pfützner, Andreas

2013-08-01

"Psychological insulin resistance" (PIR) is an obstacle to insulin treatment in type 2 diabetes, and patients' expectations regarding alternative ways of insulin delivery are poorly understood. PIR and beliefs regarding treatment alternatives were analyzed in patients with type 2 diabetes (n=532; mean glycated hemoglobin, 68±12 mmol/mol [8.34±1.5%]) comparing oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin. Questionnaires were used to assess barriers to insulin treatment (BIT), generic and diabetes-specific quality of life (Short Form 36 and Problem Areas in Diabetes, German version), diabetes knowledge, locus of control (Questionnaire for the Assessment of Diabetes-Specific Locus of Control, in German), coping styles (Freiburg Questionnaire of Illness Coping, 15-Items Short Form), self-esteem (Rosenberg Self-Esteem Scale, German version), and mental disorders (Patient Health Questionnaire, German version). Patients discussed treatment optimization options with a physician and were asked to make a choice about future diabetes therapy options in a two-step treatment choice scenario. Step 1 included oral antidiabetes drugs or subcutaneous insulin injection (SCI). Step 2 included an additional treatment alternative of inhaled insulin (INH). Subgroups were analyzed according to their treatment choice. Most patients perceived their own diabetes-related behavior as active, problem-focused, internally controlled, and oriented toward their doctors' recommendations, although their diabetes knowledge was limited. In Step 1, rejection of the recommended insulin was 82%, and in Step 2, it was 57%. Fear of hypoglycemia was the most important barrier to insulin treatment. Patients choosing INH (versus SCI) scored higher regarding fear of injection, expected hardship from insulin therapy, and BIT-Sumscore. The acceptance of insulin is very low in type 2 diabetes patients. The option to inhale insulin increases the acceptability for some but