888 results on '"Anoxèmia"'
Search Results
2. Predictive Value of the Oxygen Desaturation Induced by the 30-second Sit-to-stand-test combined with COPD Patient Self-assessment Test in Exercise-induced Hypoxemia and Its Clinical Application
- Author
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YANG Tianyi, SITU Xuanming, QUMU Shiwei, WANG Siyuan, JIANG Shan, YANG Ting
- Subjects
pulmonary disease, chronic obstructive ,sit-to-stand-test ,anoxemia ,exercise induced hypoxia ,home-based rehabilitation ,forecasting ,Medicine - Abstract
Background Chronic obstructive pulmonary disease (COPD) is one of the most common respiratory diseases in elderly patients, and a decrease in oxygen saturation during activity is a common phenomenon correlated with the prognosis. Current assessment of exercise-induced hypoxia (EID) has yielded controversial results. Objective To explore methods suitable for inducing EID in community and home-based COPD patients. Methods This was a retrospective study involving 76 patients with stable COPD admitted to China-Japan Friendship Hospital from January 2021 to August 2023. Resting oxygen saturation and the lowest oxygen saturation during exercise (ΔSpO2) in the six-minute walk test 6MWT) were recorded. Based on the criterion of ΔSpO2 ≥4% for the diagnosis of EID, patients were assigned into non-EID group and EID group. Pulmonary function indicators, ΔSpO2 during 30-second sit-to-stand-test (30s STST), and COPD Assessment Test (CAT) were compared between the two groups. The correlation of EID with ΔSpO2 of 30s STST and CAT scores was identified. The predictive value of ΔSpO2 of 30s STST, CAT score, andΔSpO2 of 30s STST combined with CAT score in predicting EID was analyzed using the receiver operating characteristic (ROC) curves. Results There were significant differences in the ΔSpO2 of 30s STST and CAT score between non-EID group and EID group. The cut-off value of ΔSpO2 of 30s STST in predicting EID was 2%, with the sensitivity, specificity and area under the curve (AUC) of 59.6%, 82.8%, 0.730 (95%CI=0.614-0.846, P
- Published
- 2024
- Full Text
- View/download PDF
3. Significance of Duration of Respiratory Events in Nocturnal Hypoxemia in Adults with Obstructive Sleep Apnea
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WANG Jianying, REN Shouan
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sleep apnea, obstructive ,anoxemia ,duration of respiratory event ,apnea-hypopnea index ,polysomnograph ,Medicine - Abstract
Background The prevalence of obstructive sleep apnea (OSA) has been increasing year by year, but the current diagnostic criteria of apnea-hypopnea index (AHI) >5 times/h commonly used for OSA has gradually revealed drawbacks in the diagnosis, severity evaluation, treatment effect and long-term complications prediction of the disease. This study proposed that there is a need for more information about the duration of apnea-hypopnea for assessing OSA in addition to AHI. Objective To investigate the significance of duration of respiratory events in nocturnal hypoxemia in adults with OSA. Methods A total of 296 patients with suspected OSA who were admitted to the sleep monitoring room of the First Hospital of Shanxi Medical University from October 2021 to March 2022 were selected as the study subjects. Before PSG, the subjects underwent a physical examination in terms of height, body mass, neck circumference, and were asked about their sleep history, as well as history of hypertension and diabetes. The subjects were divided into three groups according to AHI of 5 times/h≤AHI0.05) ; TAD, AHT%, and AHI were all negatively correlated with MSpO2 and positively correlated with T90 in the long event group (P
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- 2024
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4. Clinical implications of opioid-induced ventilatory impairment
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Pattullo, Gavin G
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- 2022
5. Efficacy and Safety of Intermittent Hypoxic Training in the Prevention of Acute Hypoxic Injury
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HUANG Dan, ZHANG Qihan, SONG Ge, WANG Qing, LI Yu, JI Xunming, WANG Yuan
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altitude sickness ,acute high altitude sickness ,anoxemia ,intermittent hypoxic training ,efficacy ,safety ,Medicine - Abstract
Background Acute hypoxic injury caused by acute altitude exposure is manifested by different degrees of clinical symptoms, some of which may develop into acute mountain sickness (AMS). However, the current prevention and treatment methods are limited and there is a lack of safe and effective methods to prevent and reduce the severity. Objective To investigate the efficacy and safety of intermittent hypoxic (IH) training in preventing acute hypoxic injury by simulating hypoxic environment at an altitude of 4 400 meters. Methods A total of 40 subjects were recruited by public recruitment in Beijing Xiaotangshan Hospital from 2022-08-01 to 10-31 and randomly divided into the IH group (experimental group, n=20) and sham training group (control group, n=20). The experimental group received the IH exposure intervention with the total duration of 55 min twice a day for 5 d, including 10 min of low oxygen (oxygen concentration of 13%, simulated altitude of 3 800 m), 5 min of normoxia (oxygen concentration of 21%). The control group received the simultaneous long normoxia intervention. On the first day after the IH intervention training, the subjects entered into the simulated high-altitude hypoxia environment for 6 h, and the oxygen concentration was set at 12% (equivalent to the altitude of 4 400 m). The Lake Louise Scale (LLS) was used to assess the severity of AMS. Peripheral oxygen saturation (SpO2), cerebral oxygen saturation (ScO2) and intracranial pressure (ICP) were collected at baseline, before and 6 h after the simulated high-altitude hypoxia environment. Results After 6 h of acute high-altitude hypoxia environment simulation, the incidence of AMS and LLS in the experimental group were significantly lower than those in the control group (P
- Published
- 2023
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6. Investigating the role of hypoxia in the pathophysiology of aortic valve stenosis
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Lewis, Christopher Thomas Andrew, Nixon, Graeme, and Wilson, Heather Marion
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Anoxemia ,Aortic valve - Abstract
Aortic valve stenosis (AVS) is the progressive calcification and loss-of-function of the aortic valve (AV). Left untreated this leads to left-ventricular failure and ultimately death. To date, no medical treatment for AVS exists with only invasive surgery as a treatment option. Central to the limited progress made towards developing novel treatments is our lack of understanding as to how AVS initiates and the environmental changes which occur within the AV. The aim of this study was to investigate hypoxia as a key contributing factor towards the progression of AVS. My hypothesis was that hypoxia would act as a stimulus of angiogenesis in the human aortic valve tissue and stimulate AVS progression. I performed in vitro techniques upon primary human aortic valve interstitial cells (VICs) cultured from valves obtained from patients undergoing valve replacement surgery. Immunohistochemistry was performed on formalin- fixed paraffin embedded human AV tissue which was eitherstenotic (diseased) and non-stenotic (healthy) from patients to to identify morphological and expression changes which occur during the progression of AVS. VICs which were isolated from stenotic aortic valves were placed in a hypoxic environment (1% O2, 5% CO2). These cells demonstrated the ability to proliferate at an increased rate compared to their normoxic control. This result occurred alongside a reduction in cAMP signalling in hypoxic stenotic VIC. Hypertrophy of the AV is central to the progression of AVS. These data may delineate the cause of AV hypertrophy and highlight hypoxia as a key process in the initiation of AVS. The neovascularisation of the AV is also critical to the progression of end-stage AVS. As hypoxia is a canonical stimulus of angiogenesis, the growth of nascent blood vessels from pre-existing vessels, I investigated the role of hypoxia in this process in the AV. Soluble fms-like tyrosine kinase 1 (sFlt-1) is the soluble isoform of the vascular endothelial growth factor (VEGF) receptor 1. It can bind the canonical driver of angiogenesis, VEGF-A, and sequester signalling, thus is an antiangiogenic mediator. VICs from stenotic valves incubated in hypoxia for 24 hours demonstrated increased expression of VEGF-A. Immunohistochemistry of sFlt1 within aortic valves showed a significant decrease in expression in AVs compared to non-stenotic controls. Incubation within hypoxia also stimulated a decrease inprotein expression of sFlt-1 in stenotic VICs. siRNA knockdown of sFlt-1 in VICs resulted in increased in vitro angiogenesis in a conditioned media assay. Furthermore, the addition of recombinant sFlt-1 to either endothelial cells or ex vivo human aortic valve tissue in Matrigel was able to inhibit tubule formation and sprouting of angiogenesis respectively. Together these data demonstrate the ability of hypoxia to drive angiogenesis in the AV. Furthermore, sFlt-1 is highlighted as a critical factor in the maintenance of AV avascularity and as a potential therapeutic target to inhibit angiogenesis in the AV. G-protein coupled receptors (GPCRs) are the target of ~40% of FDA approved drugs. I performed a microarray, which compared the mRNA expression of 355 GPCRs between non-stenotic VICs and stenotic VICs. This array highlighted interesting receptors, which demonstrated increased expression in stenotic VICs or even are only expressed in stenotic VICs. Their success in being targeted in other diseases make GPCRs an exciting source of targets in the search of a novel treatment for AVS. In conclusion, I demonstrate the potentially important role of hypoxia in the initiation and progression of AV by stimulating VIC proliferation and angiogenesis in the AV. These results demonstrate a unique mechanism of disease progression in the aortic valve, which could potentially be targeted for the treatment of AVS. As we seek the first medical treatments for this disease, it is vital that we continue to enhance our understanding of the biology of the aortic valve and the progression of AVS.
- Published
- 2021
7. Mapping and modelling hypoxia in spinal muscular atrophy
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Hernandez Gerez, Elena, Parson, Simon., and Fleming, Ian N.
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Anoxemia ,Spinal muscular atrophy ,Medical mapping - Abstract
Spinal muscular atrophy (SMA) is a childhood neurodegenerative disease caused by homozygous mutation of the survival motor-neuron 1 gene (SMN1), resulting in decreased levels of survivalmotor-neuron (SMN) protein. Although it is a neurodegenerative disease it also has an extensive systemic pathology, including vascular and cardiac defects, as well as hypoxic spinal cord. This thesis focusses on fully mapping the spread of hypoxia beyond the spinal cord, as well as its effects on tissue and cells with low SMN. Hypoxia was mapped using a Taiwanese SMA mouse model. Labelling of 5-day-old Taiwanese SMA pups with pimonidazole and [18F]-FAZA confirmed hypoxia in spinal cord and revealed hypoxia in neural tissue (brain and eyes), skeletomuscular tissue (forelimb, hindlimb and tail) and various organs (spleen, heart, kidney and liver). It also showed that skin and lungs were not-hypoxic. HIF-1 or HIF-2 expression was measured in the hypoxic tissues, as they are the main proteins responsible for the hypoxia response, but there was no significant increase. [18F]-FDG (glucose) uptake, which normally increases as a result of the hypoxia response, was also measured. Both neural tissue and kidney showed upregulation, while heart showed downregulation. Previous studies indicate that the most significant part of the systemic hypoxia response is angiogenesis. Labelling of PECAM -1, an endothelial cell marker, by western blotting showed that most of the hypoxic tissues (brain, spinal cord, kidney, heart, spleen and hindlimb) had reduced vascular density, suggesting that vessel development may be defective. To test angiogenesis, anendothelial in-vitro model was developed from primary culture of Taiwanese SMA mouse aortas. This model showed defects in endothelial tube formation in normoxic conditions compared to cells cultured form controls. The same experiment done in hypoxia showed no significant difference between control and SMA model. A neural model was developed knocking down SMN in NSC-34 motor-neuron like cells. These cultures were used to test the response to hypoxia of low SMN cells. A Flow cytometry protocol was developed to test SMN levels, which made evident that intrapopulation SMN levels vary greatly both in control and SMN knockdown population, resulting in overlap between them. It also showed cell vulnerability to hypoxia (1% O2) correlates with SMN levels, the lower the SMN, the higher chances of death. A different flow cytometry protocol showed that low SMN populations experience cell cycle alteration in hypoxia, connected to G2 and M phases. The low SMN cells also showed abnormal accumulation of lactate inside hypoxic compared to controls. This thesis showed that hypoxia is a widespread stressor in the Taiwanese mouse model of SMA. It also described several defects in angiogenic processes and cellular hypoxia response correlated to SMN decrease in SMA in-vitro cultures. In summary, it emphasizes the importance of systemic treatments, that would also recover SMN levels in blood vessels, and hypoxia monitoring in SMA therapies.
- Published
- 2020
8. Atomic Force Microscopy and High-Resolution Spectrophotometry for Study of Anoxemia and Normoxemia in Model Experiment In Vitro.
- Author
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Kozlova, Elena, Sherstyukova, Ekaterina, Sergunova, Viktoria, Grechko, Andrey, Kuzovlev, Artem, Lyapunova, Snezhanna, Inozemtsev, Vladimir, Kozlov, Aleksandr, and Chernysh, Aleksandr
- Subjects
- *
HYPOXEMIA , *OXYGEN in the blood , *REACTIVE oxygen species , *OPTICAL spectra , *CURVE fitting - Abstract
The oxygen content in the blood may decrease under the influence of various physicochemical factors and different diseases. The state of hypoxemia is especially dangerous for critically ill patients. In this paper, we describe and analyze the changes in the characteristics of red blood cells (RBCs) with decreasing levels of oxygen in the RBC suspension from normoxemia to hypoxemia/anoxemia in an in vitro model experiment. The RBCs were stored in hypoxemia/anoxemia and normoxemia conditions in closed and open tubes correspondingly. For the quantitative study of RBC parameter changes, we used atomic force microscopy, digital spectrophotometry, and nonlinear curve fitting of the optical spectra. In both closed and open tubes, at the end of the storage period by day 29, only 2% of discocytes remained, and mainly irreversible types, such as microspherocytes and ghosts, were observed. RBC hemolysis occurred at a level of 25–30%. Addition of the storage solution, depending on the concentration, changed the influence of hypoxemia on RBCs. The reversibility of the change in hemoglobin derivatives was checked. Based on the experimental data and model approach, we assume that there is an optimal level of hypoxemia at which the imbalance between the oxidative and antioxidant systems, the rate of formation of reactive oxygen species, and, accordingly, the disturbances in RBCs, will be minimal. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
9. Correlation between hypoxaemia and lung ultrasound score in patients presenting to an emergency department with interstitial syndrome: A prospective physiological study
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Vasseur, Eleonore, Moureau, Gauthier, Fasseaux, Antoine, Peyskens, Laurent, Gendebien, Felix, Thys, Frederic, and Dupriez, Florence
- Published
- 2022
10. Capnography monitoring in the Post Anaesthesia Care Unit (PACU)
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Wilks, Casandra and Foran, Paula
- Published
- 2021
11. Surviving Hypoxia : Mechanisms of Control and Adaptation
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Peter W. Hochachka, Peter L. Lutz, Thomas J. Sick, Myron Rosenthal, Peter W. Hochachka, Peter L. Lutz, Thomas J. Sick, and Myron Rosenthal
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- Anoxemia, Energy metabolism, Respiration, Adaptation, Physiological--physiology, Anoxia--physiopathology
- Abstract
Surviving Hypoxia: Mechanisms of Control and Adaptation is a synthesis of findings and thoughts concerning hypoxia. The thermodynamics of hypoxia are discussed in detail, including acid-base balance and self-pollution resulting from the accumulation of anaerobic end-products. The book focuses on descriptions and discussions of common facets, contrasting solutions in a variety of physiological hypoxia defense strategies, including those shown by plants, invertebrates, and vertebrates. Special treatment is given to the distinctive problems that hypoxia presents to vulnerable organs such as the kidney, liver, and brain. It also addresses pathological events in addition to protective mechanisms. Clinical implications of basic research are examined in the book, which provides new insights into underlying pathological processes occuring in hypoxic-induced organ failure and indicates new paths for successful clinical intervention. Surviving Hypoxia: Mechanisms of Control and Adaptation is an excellent reference for all researchers interested in the physiological effects of hypoxia, underlying pathological events, and protective mechanisms.
- Published
- 2022
12. Imaging hypoxia in colorectal cancer and gastroesophageal cancer with positron emission tomography
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Almulhim, Zayed
- Subjects
616.99 ,Anoxemia ,Tomography ,Emission ,Colon (Anatomy) ,Rectum ,Gastrointestinal system ,Esophagus - Abstract
Purpose: Hypoxia in colorectal cancer (CRC) and gastroesophageal cancer (GEC) decreases tumour responsiveness to radio and chemotherapy leading to cancer progression and poor prognosis. This is the first study to utilise [18F]FAZA hypoxia radiotracer in patients with CRC and GEC. Methods: Six patients (mean age 68±8 years, 2 males and 4 females) with CRC and 4 patients diagnosed with GEC (mean age 65 years, 3 males and 1 female) were included in the study. [18F]FAZA was synthesised at the John Mallard Scottish PET Centre. After injection with 370 MBq of [18F]FAZA, PET/CT images with 60 min dynamic scan were acquired. In addition, 15 min static scans 2 hr post injection were performed. 3D PET images were reconstructed iteratively using an ordered subset expectation maximization (OSEM) method and fused to the corresponding low-dose CT images. [18F]FAZA uptake parameters including maximum standard uptake value (SUVmax), tumour-to-muscle ratio (T/M), tumour-to-bowel ratio (T/B) and volume of interest (VOI) were measured. Results: 4 out 6 patients with CRC (66%) showed clear uptake of [18F]FAZA in the primary tumour. The mean tumour SUVmax was 2.2±0.91 (range 1.12 - 3.71). The tumour SUVmax was significantly higher compared with muscle and bowel (t(5) =3.11, P=0.03), (t(5) =3.08, P=0.03), respectively. However, tumour SUVmean didn't differ significantly compared with muscle and bowel (t(5) =2.41 , P=0.06), (t(5) =2.46 , P=0.06) respectively. The mean tumour to muscle ratio (T/M) ratio was 1.89±0.64 (range 1.10 - 2.87), while the mean tumour to normal bowel (T/B) was 1.92±0.64 (range 1.08 - 2.74). However, [18F]FAZA did not accumulate in any of the tumours found in patients with GEC. Conclusions: [18F]FAZA PET/CT imaging is suitable and feasible for detecting CRC hypoxic tumour regions with image quality that can be used in clinical practice.
- Published
- 2017
13. Atomic Force Microscopy and High-Resolution Spectrophotometry for Study of Anoxemia and Normoxemia in Model Experiment In Vitro
- Author
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Elena Kozlova, Ekaterina Sherstyukova, Viktoria Sergunova, Andrey Grechko, Artem Kuzovlev, Snezhanna Lyapunova, Vladimir Inozemtsev, Aleksandr Kozlov, and Aleksandr Chernysh
- Subjects
RBCs ,hypoxemia ,anoxemia ,atomic force microscopy ,spectrophotometry ,hemoglobin derivatives ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The oxygen content in the blood may decrease under the influence of various physicochemical factors and different diseases. The state of hypoxemia is especially dangerous for critically ill patients. In this paper, we describe and analyze the changes in the characteristics of red blood cells (RBCs) with decreasing levels of oxygen in the RBC suspension from normoxemia to hypoxemia/anoxemia in an in vitro model experiment. The RBCs were stored in hypoxemia/anoxemia and normoxemia conditions in closed and open tubes correspondingly. For the quantitative study of RBC parameter changes, we used atomic force microscopy, digital spectrophotometry, and nonlinear curve fitting of the optical spectra. In both closed and open tubes, at the end of the storage period by day 29, only 2% of discocytes remained, and mainly irreversible types, such as microspherocytes and ghosts, were observed. RBC hemolysis occurred at a level of 25–30%. Addition of the storage solution, depending on the concentration, changed the influence of hypoxemia on RBCs. The reversibility of the change in hemoglobin derivatives was checked. Based on the experimental data and model approach, we assume that there is an optimal level of hypoxemia at which the imbalance between the oxidative and antioxidant systems, the rate of formation of reactive oxygen species, and, accordingly, the disturbances in RBCs, will be minimal.
- Published
- 2023
- Full Text
- View/download PDF
14. Oxygen : Creating a New Paradigm
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Paul Marino and Paul Marino
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- Anoxemia, Oxygen therapy, Oxidation-reduction reaction
- Abstract
This unique work from acclaimed author Dr. Paul Marino (Marino's The ICU Book, The Little ICU Book) challenges the traditional notion that the human body thrives on oxygen, and that promoting tissue oxygenation is necessary for promoting life. This concept fails to recognize that oxygen is a destructive molecule that also damages the human body. Instead of welcoming oxygen, the human body limits exposure of the tissues to oxygen, and employs an army of chemical antioxidants to combat the damaging effects of oxygen. This “oxygen protective” human design represents a new paradigm for the relationship between oxygen and human survival, and it has important implications for the excessive and unregulated use of oxygen in clinical practice.
- Published
- 2021
15. Development and use of [18F]FDR as a new powerful radiolabelling agent for Positron Emission Tomography (PET) imaging of hypoxia
- Author
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Musolino, Manuele
- Subjects
616.2 ,Anoxemia ,Positron-Emission Tomography ,Radioactive tracers - Abstract
In recent years tumour hypoxia has been extensively investigated, mainly because it is a source of resistance to the common radio and chemo therapies. In fact, the low levels and heterogeneous distribution of oxygen in hypoxic microenvironment render ionizing radiation ineffective in treating cell proliferation. Furthermore, a low oxygen concentration promotes the activation of HIF-1 transcription factor, which favours the development of a more malignant and resistant cancer cell phenotype often associated with poor prognosis. Positron Emission Tomography (PET) imaging is a valuable diagnostic tool for investigating hypoxia in vivo by means of radiotracers, which incorporates both a radioisotope and a hypoxia-sensitive function. The aim of this multidisciplinary project was to develop small libraries of radiolabelled compounds starting from the biological and chemical features of the two gold standard hypoxia PET tracers [18F]FMISO and [18F]FAZA as well as those of the promising new tracer [18F]HX4. These new radiocompounds display the following peculiar structural characteristics: a 2-nitroimidazole hypoxia-sensitive moiety, different spacers to modulate steric constraint, lipophilicity and metabolic stability and a fluorinated aldopentose sugar as prosthetic group (e.g. [18F]FDR). Two series of compounds were designed and developed based on the conjugation method used to introduce the prosthetic group, namely the oxime bond formation and the thiazolidine ring closure. Six radiotracers belonging to the oxime-derivatives series were tested in vitro on MCF7 breast cancer cell lines in hypoxic conditions and a lead radiocompound incorporating a cyclopropyl group was identified. This new hypoxia tracer showed a better kinetic profile than both [18F]FMISO and [18F]FAZA in MCF7 cancer cell lines and comparable uptake values on a panel of different cancer cell lines, up to 120 min post administration at 1% of O2. These promising results will pave the way for futures in vivo studies.
- Published
- 2016
16. Clinical characteristics of patients with pseudo-subarachnoid haemorrhage who were successfully resuscitated from out-of-hospital cardiopulmonary arrest
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Ahn, JH, Choi, SC, Jung, YS, and Min, YG
- Published
- 2012
17. Hypoxia and Cancer Metastasis
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Daniele M. Gilkes and Daniele M. Gilkes
- Subjects
- Oxygen in the body, Metastasis, Cancer, Anoxemia
- Abstract
The present book is an attempt to provide a detailed review of studies that clarify our current understanding of the role of hypoxia in the progression of primary cancer to metastatic disease. It will enable researchers to discover the critical cellular changes that occur under hypoxic conditions and play a role in metastatic dissemination, from the activation of hypoxia-inducible factors, HIF-1 and HIF-2, to the transcriptional profile changes that occur in cancer cells and promote cancer cell survival under detrimental conditions. Readers will discover the methods and challenges involved in imaging and quantifying the degree of hypoxia in a primary tumor. We will provide an understanding of the hypoxia-induced phenotypes that influence heterogeneity, alter the secretome and tumor microenvironment, modify cellular metabolism, and promote immune suppression and resistance to chemotherapy. Finally, we will uncover the therapeutic strategies that are being devised to target the hypoxic microenvironment in the hopes of preventing metastasis and improving the efficacy of standard-of-care cancer treatments. This work is an up to date source of information on the challenges and complexity of the hypoxic tumor microenvironment. Basic and translational scientists, post-doctoral fellows, graduate students, and those interested in how tumors metastasize will find this book a reference that details how hypoxia influences metastatic disease.
- Published
- 2019
18. Změny nálad při tréninku v hypoxii
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Pernica, Jan, Harsa, Pavel, Suchý, Jiří, Pernica, Jan, Harsa, Pavel, and Suchý, Jiří
- Subjects
- Mood (Psychology), Runners (Sports)--Training of, Running--Training, Anoxemia
- Abstract
Sportovní příprava v přirozeném hypoxickém prostředí je velmi diskutovanou problematikou. Přes četné výzkumy však i nadále existují oblasti, jejichž zkoumání může zefektivnit tréninkový proces nejen ve vyšší nadmořské výšce – například změny emočních stavů sportovce jako reakce na trénink v hypoxii, kterými se zabývá tato monografie. Teoretická část práce pojednává o sportovním tréninku v hypoxii i normoxii, popisuje možné nástroje kontroly trénovanosti a analyzuje změny nálad, ke kterým při tréninku dochází. Praktickou část monografie tvoří výsledky výzkumu zaměřeného na změny nálad u vrcholových vytrvalostních běžců, který byl realizován v reálném prostředí tréninkových kempů v hypoxii. Součástí práce jsou rovněž kazuistiky, v nichž byla využita analýza tréninkové dokumentace sportovců, měření srdeční frekvence a rozbor biochemického vyšetření krve. K měření nálad byl využit dotazník POMS a výsledky výzkumu ukazují statisticky významné změny u některých faktorů tohoto dotazníku.
- Published
- 2019
19. Prevention of hypoxia in helicopter aircrew : acceptable compromises
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Hodkinson, Peter David
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610 ,Anoxemia ,Flight crews--Health and hygiene - Published
- 2015
20. Management of High Altitude Pathophysiology
- Author
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Kshipra Misra, Priyanka Sharma, Anuja Bhardwaj, Kshipra Misra, Priyanka Sharma, and Anuja Bhardwaj
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- Altitude, Influence of, Anoxemia, Oxygen in the body
- Abstract
Management of High Altitude Pathophysiology presents a comprehensive overview on the various therapeutic practices and ongoing research relating to the development of more potent and novel formulations for managing high altitude pathophysiology. It provides a detailed application of both herbal and non-herbal therapeutic agents, including their nanoformulations. This important reference provides benefits to the medical and herbal scientific communities, doctors treating patients with high altitude complications, individuals travelling to high altitudes for recreation or work, and scientists working on future drug development. - Provides the recent advances and potential therapeutic agents for ameliorating the high-altitude complications - Includes herbal remedies for the prophylaxis and treatment of the high-altitude maladies - Elucidates the significance of Yogic practices and ergonomics in managing stress at high altitude
- Published
- 2018
21. Civil aviation and respiratory disease
- Author
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Buick, JBrian
- Published
- 2006
22. Regulation of granulocyte apoptosis by hypoxia and glucocorticoids
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Porter, Linsey
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610 ,Granulocytes ,Apoptosis ,Anoxemia ,Glucocorticoids - Published
- 2014
23. The vortex approach to airway management
- Author
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Chrimes, Nicholas
- Published
- 2019
24. Effects of Inhaled Nitric Oxide in the Treatment of Acute Hypoxemic Respiratory Failure (AHRF) in Pediatrics
- Published
- 2016
25. Hypoxia : Translation in Progress
- Author
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Robert C. Roach, Peter H. Hackett, Peter D. Wagner, Robert C. Roach, Peter H. Hackett, and Peter D. Wagner
- Subjects
- Anoxemia
- Abstract
The latest in a series of books from the International Hypoxia Symposia, this volume spans reviews on key topics in hypoxia, and abstracts from poster and oral presentations. The biannual International Hypoxia Symposia are dedicated to hosting the best basic scientific and clinical minds to focus on the integrative and translational biology of hypoxia. Long before ‘translational medicine'was a catchphrase, the founders of the International Hypoxia Symposia brought together basic scientists, clinicians and physiologists to live, eat, ski, innovate and collaborate in the Canadian Rockies.This collection of reviews and abstracts is divided into six sections, each covering new and important work relevant to a broad range of researchers interested in how humans adjust to hypoxia, whether on the top of Mt. Everest or in the pulmonary or cardiology clinic at low altitude. The sections include:Epigenetic Variations in HypoxiaHigh Altitude AdaptationHypoxia and SleepHypoxia and the BrainMolecular Oxygen SensingPhysiological Responses to Hypoxia
- Published
- 2016
26. Life-threatening bronchiolitis related to electronic cigarette use in a Canadian youth
- Author
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Landman, Simon T., Dhaliwal, Inderdeep, Mackenzie, Constance A., Martinu, Tereza, Steele, Andrew, and Bosma, Karen J.
- Subjects
United States. Centers for Disease Control and Prevention ,Smoking cessation products ,Tiotropium ,Youth ,Tazobactam ,Electronic cigarettes ,Epidemiology ,Flavorings ,Bronchiolitis ,Medical examination ,Lung diseases ,Tomography ,Respiratory tract diseases ,Pulmonary function tests ,Corticosteroid drugs ,Hypercapnia ,Cannabidiol ,Hospital admission and discharge ,Chronic obstructive lung disease ,Smoking cessation ,Cigarettes ,Respiratory insufficiency ,Anoxemia ,Marketing ,Tachycardia ,Workers ,Novels ,Health - Abstract
BACKGROUND: Although electronic cigarettes (e-cigarettes) were initially marketed as a potential smoking-cessation aid and a safer alternative to smoking, the long-term health effect of e-cigarette use ('vaping') is unknown. Vaping e-liquids expose the user to several potentially harmful chemicals, including diacetyl, a flavouring compound known to cause bronchiolitis obliterans with inhalational exposure ('popcorn worker's lung'). CASE DESCRIPTION: We report the case of a 17-year-old male who presented with intractable cough, progressive dyspnea and malaise after vaping flavoured e-liquids and tetrahydrocannabinol intensively. Initial physical examination showed fever, tachycardia, hypoxemia, and bibasilar inspiratory crackles on lung auscultation. Computed tomography of the chest showed diffuse centrilobular 'tree-inbud' nodularity, consistent with acute bronchiolitis. Multiple cultures, including from 2 bronchoalveolar lavage samples, and biopsy stains, were negative for infection. He required intubation, invasive mechanical ventilation and venovenous extracorporeal membrane oxygenation (ECMO) for refractory hypercapnia. The patient's condition improved with high-dose corticosteroids. He was weaned off ECMO and mechanical ventilation, and discharged home after 47 days in hospital. Several months after hospital discharge, his exercise tolerance remained limited and pulmonary function tests showed persistent, fixed airflow obstruction with gas trapping. The patient's clinical picture was suggestive of possible bronchiolitis obliterans, thought to be secondary to inhalation of flavouring agents in the e-liquids, although the exact mechanism of injury and causative agent are unknown. INTERPRETATION: This case of severe acute bronchiolitis, causing near-fatal hypercapnic respiratory failure and chronic airflow obstruction in a previously healthy Canadian youth, may represent vaping-associated bronchiolitis obliterans. This novel pattern of pulmonary disease associated with vaping appears distinct from the type of alveolar injury predominantly reported in the recent outbreak of cases of vaping-associated pulmonary illness in the United States, underscoring the need for further research into all potentially toxic components of e-liquids and tighter regulation of e-cigarettes., Electronic cigarettes (e-cigarettes) are the most commonly used nicotine products among Canadian youth; a 2017 study estimated that 272 000 Canadians aged 15 to 24 years had used e-cigarettes in [...]
- Published
- 2019
- Full Text
- View/download PDF
27. Oxigenoterapia posquirurgica de alto flujo aplicada mediante canula nasal bilateral en dos caninos sometidos a procedimientos de torax: un reporte de caso
- Author
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Salcedo, Jefferson Jaimes, Uribe Rendón, Alejandra, Alzate Velásquez, David, Vergara Saldarriaga, Luis Adolfo, and Correa-Valencia, Nathalia María
- Published
- 2019
- Full Text
- View/download PDF
28. Effect of nitrogen source and oxygen deficiency on carbon metabolism and antioxidant system of rubber tree plants (Hevea spp.)
- Author
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Domiciano, Debora and Guimaraes, Rubens Jose
- Published
- 2018
29. The effects of hypoxia on neutrophil biology
- Author
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Mc Govern, Naomi Nuala
- Subjects
610 ,Anoxemia ,Neutrophils - Published
- 2010
30. Redox regulation of vascular NO bioavailability during hypoxia : implications for oxygen transport and exercise performance
- Author
-
Woodside, John and Bailey, Damian
- Subjects
612.2 ,Respiration ,Anoxemia - Abstract
The reduction in O2peak at altitude is well documented. Maximal exercise in hypoxia is accelerated through a reduction in O2 supply with contributions from central and peripheral origins of fatigue. Changes in cerebral and muscle oxygenation have not been well characterised during incremental exercise in hypoxia. It is possible attainment of O2peak is driven by the oxygenation profile of these tissues whilst changes in molecular biomarkers of endothelial function could provide some insight into the mechanisms driving systemic and regional O2 delivery and vascular hypoxic sensing capabilities. The first study of this thesis examined the impact of acute hypoxia (FIO2 = 0.12) on the cerebral and muscle oxygenation response to incremental cycling exercise using NIRS (n = 14; age: 23 ± 5yr; height: 1.80 ± 0.07m; weight: 84 ± 8kg). The profiles were characterised at equivalent relative and absolute exercise intensities and molecular blood-borne markers of O2 sensing and function were measured before and immediately after maximal exercise for changes in oxidative stress (A• and 3-NT), NO metabolites (NOx, NO3•, NO2• and RSNO) and cell adhesion molecules (sICAM-1 and sVCAM-1). The key observations from this study were: 1) O2peak decreased by 22% and the magnitude of cerebral and muscle deoxygenation (↓O2Hb and ↑HHb) was greater in hypoxia, 2) the slope for the relative HHb response was similar between conditions whereas there was an accelerated slope across the absolute workloads in hypoxia implying cycling performance was driven by a premature attainment of maximal O2 extraction capacity of the muscle, 3) there was no evidence suggesting cerebral O2 metabolism was impaired in hypoxia however since SaO2 was 78 ± 4% at PPO it is possible the reduction in systemic O2 delivery could have influenced central fatigue, 4) there was a tendency for a rightward shift in the cerebral THb profile in hypoxia and although muscle THb peaked at 80% PPO in both trials, the response also tended to be lower in hypoxia, 5) there was no change in oxidative stress markers and NOx after exercise, 6) RSNO increased and NO2• decreased after maximal exercise. The decline in NO2• was attenuated in hypoxia possibly due to a blunted NO2•-HHb-NO pathway and may explain the systemic hypoperfusion response, 7) The increase in sICAM-1 and sVCAM-1 after exercise was augmented in normoxia, 8) Only when normoxia and hypoxia data was pooled was there a correlation between sVCAM-1 pre-post exercise and O2peak. Intermittent hypoxia (IH) may be used to improve the efficiency of exercise training and as a pre-acclimatisation strategy prior to high altitude ascent. The purpose of the second study was to evaluate the efficacy of a 10 day IH regime consisting of 9x 5 min daily exposures of 9.5% O2 breathing followed by equal periods of normoxia on submaximal and maximal cardiorespiratory responses to exercise in hypoxia. Additionally, cerebral and muscle oxygenation was monitored throughout incremental cycling to exhaustion and changes in NO metabolites (NO3•, NO2• and RSNO) and CAMs (sICAM-1 and sVCAM-1) were measured before and immediately after maximal exercise. The key observations from this study were: 1) a tendency for IH to reduce submaximal O2 and increase O2peak in hypoxia, 2) IH increased the muscle THb response to exercise due an increased intercept for both the muscle O2Hb and HHb in the absence of any change in slope, 4) cerebral oxygenation increased (↑O2Hb) at rest and during exercise, 4) the reduction in nitrite was attenuated in the IH group whilst resting sICAM-1 decreased and the pre-post maximal exercise increase in sICAM-1 was augmented after IH. It is concluded that exercise performance in acute hypoxia is driven by the magnitude of hypoxaemia and an accelerated rate of cerebral and muscle deoxygenation. Molecular biomarkers of endothelial function in particular, NO2• and CAMs, are also influenced by hypoxia and may contribute to the reduction in O2peak. IH may be used to improve exercise economy and O2peak in hypoxia by improving cerebral and muscle oxygenation in the absence of any change in central O2 delivery. It is possible a recalibration of mechanisms that affect NO bioactivation could have enhanced vascular hypoxic sensitivity, O2 delivery and adaptation within brain and muscle tissue which ultimately translated to an improved hypoxic exercise performance. These results give motivation for athletes and mountaineers to incorporate an IH strategy prior to athletic performance at altitude.
- Published
- 2010
31. Oxygen-regulated gene expression and cardiopulmonary physiology
- Author
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Smith, Thomas Gregory, Robbins, Peter A., and Dorrington, Keith L.
- Subjects
616.1 ,Gene expression ,Genetic regulation ,Cardiopulmonary system--Physiology ,Anoxemia - Published
- 2007
32. High Altitude : Human Adaptation to Hypoxia
- Author
-
Erik R. Swenson, Peter Bärtsch, Erik R. Swenson, and Peter Bärtsch
- Subjects
- Altitudes, Anoxemia, Adaptation (Physiology), Altitude, Influence of
- Abstract
Over the last decade the science and medicine of high altitude and hypoxia adaptation has seen great advances. High Altitude: Human Adaptation to Hypoxia addresses the challenges in dealing with the changes in human physiology and the particular medical conditions that arise from exposure to high altitude. In-depth and comprehensive chapters cover both the basic science and the clinical consequences of exposure to high altitude. Genetic, cellular, organ and whole body system responses to high altitudes are covered and chapters discuss these effects on a wide range of diseases. Expert authors provide insight into the care of patients with pre-existing medical conditions that fail in some cases to adapt as well as offer insights into how high altitude research can help critically ill patients. High Altitude: Human Adaptation to Hypoxia is an important new volume that offers a window into greater understanding and more successful treatment of hypoxic human diseases.
- Published
- 2014
33. Hypoxia and Cancer : Biological Implications and Therapeutic Opportunities
- Author
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Giovanni Melillo and Giovanni Melillo
- Subjects
- Cancer--Molecular aspects, Toxicology, Anoxemia, Cancer cells
- Abstract
The imbalance between rapidly proliferating tumor cells and inadequate and inefficient tumor vasculature leads to a decrease in oxygen levels (hypoxia and/or anoxia) in tumor tissues. Intra-tumor hypoxia profoundly affects the biological behavior of cancer cells, which become resistant to conventional therapies and acquire a more invasive and metastatic phenotype. Hypoxia is a hallmark of the malignant phenotype and a key feature of the tumor microenvironment. Hypoxia Inducible Factor 1 (HIF-1) is a master regulator of the transcriptional response to oxygen deprivation. HIF triggers the expression of genes whose products induce angiogenesis, decrease oxygen consumption, switch metabolism to glycolysis, maintain a stem cell phenotype and select for more invasive and metastatic cells. Therapeutic approaches targeting HIF, directly or downstream mediators of its transcriptional activity, are being developed. Intra-tumor hypoxia is a topic has been gaining scientific interest over the last few years for its wide involvement in many physiological and pathological processes. This volume will cover the latest research and translational aspects associated with intra-tumor hypoxia, along with opportunities for drug development offered by this unique feature of the tumor microenvironment. The ongoing efforts to translate our understanding of the biology underlying intra-tumor hypoxia in viable therapeutic options face many challenges, but this book will provide an opportunity for an in-depth analysis of the fundamental mechanisms implicated in the adaption to low oxygen levels and will scrutinize the potential for opportunities that are being pursued in both research and the drug development industry.
- Published
- 2014
34. Peripheral venoarterial extracorporeal membrane oxygenation for severe hyperlactataemia after cardiac surgery: A pilot study
- Author
-
Biesenbach, Peter, Ghanpur, Rashmi, Martensson, Johan, Crisman, Marco, Lindstrom, Steven, Hilton, Andrew, Matalanis, George, and Bellomo, Rinaldo
- Published
- 2017
35. Atomic Force Microscopy and High-Resolution Spectrophotometry for Study of Anoxemia and Normoxemia in Model Experiment In Vitro
- Author
-
Chernysh, Elena Kozlova, Ekaterina Sherstyukova, Viktoria Sergunova, Andrey Grechko, Artem Kuzovlev, Snezhanna Lyapunova, Vladimir Inozemtsev, Aleksandr Kozlov, and Aleksandr
- Subjects
RBCs ,hypoxemia ,anoxemia ,atomic force microscopy ,spectrophotometry ,hemoglobin derivatives ,hemolysis level ,optimal hypoxemia level - Abstract
The oxygen content in the blood may decrease under the influence of various physicochemical factors and different diseases. The state of hypoxemia is especially dangerous for critically ill patients. In this paper, we describe and analyze the changes in the characteristics of red blood cells (RBCs) with decreasing levels of oxygen in the RBC suspension from normoxemia to hypoxemia/anoxemia in an in vitro model experiment. The RBCs were stored in hypoxemia/anoxemia and normoxemia conditions in closed and open tubes correspondingly. For the quantitative study of RBC parameter changes, we used atomic force microscopy, digital spectrophotometry, and nonlinear curve fitting of the optical spectra. In both closed and open tubes, at the end of the storage period by day 29, only 2% of discocytes remained, and mainly irreversible types, such as microspherocytes and ghosts, were observed. RBC hemolysis occurred at a level of 25–30%. Addition of the storage solution, depending on the concentration, changed the influence of hypoxemia on RBCs. The reversibility of the change in hemoglobin derivatives was checked. Based on the experimental data and model approach, we assume that there is an optimal level of hypoxemia at which the imbalance between the oxidative and antioxidant systems, the rate of formation of reactive oxygen species, and, accordingly, the disturbances in RBCs, will be minimal.
- Published
- 2023
- Full Text
- View/download PDF
36. New Zealand should introduce nationwide pulse oximetry screening for the detection of critical congenital heart disease and other hypoxaemic conditions in the newborn
- Author
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Cloete, Elza
- Published
- 2020
37. Oxygen delivery in the home setting: Supplemental oxygen can be delivered safely to patients in their home. Here experts discuss the indications for oxygentherapy, the amount needed, and the interface for delivery
- Author
-
Kaviany, Parisa and Collaco, Joseph M.
- Subjects
Diseases -- Care and treatment -- Maryland ,Cardiac patients -- Care and treatment ,Genetic disorders ,Respiratory system agents ,Cardiovascular diseases ,Lung diseases ,Bronchopulmonary dysplasia ,Anoxemia ,Dysplasia ,Respiratory tract diseases ,Health ,Health care industry - Abstract
There are a number of respiratory conditions in infants and children that can lead to hypoxemia, requiring supplemental oxygen (with or without ventilation) in the home setting. Some of the [...]
- Published
- 2019
38. Implementation of a Screening Questionnaire for OSA in the EMR: The ESS is a validated questionnaire that can ensure easy and accurate assessment of daytime sleepiness
- Author
-
Johnson, Shawna
- Subjects
Electronic records -- Surveys -- Reports ,Traffic accidents -- Surveys -- Reports ,Sleep apnea -- Diagnosis -- Surveys -- Reports ,Accidents ,Cardiovascular diseases ,Sleep disorders ,Anoxemia ,Apnea ,Health - Abstract
Obstructive sleep apnea (OSA) is the most common sleep disorder affecting Americans; approximately 80% of patients who report poor sleep have undiagnosed OSA. (1) Sleep apnea is consistently described as [...]
- Published
- 2019
39. Bio-Energia: Trabajo muscular y respiracion en la cornea
- Author
-
del Castillo, Luis F., Ramírez-Calderón, Juanibeth G., Caicedo, Carolina, Ávila-Torres, Yenny, Caicedo-Cano, Diego F., and Compañ, Vicente
- Published
- 2018
- Full Text
- View/download PDF
40. Hypoxia: Causes, Types and Management
- Author
-
Vordermark, Dirk and Vordermark, Dirk
- Subjects
- Anoxemia, Anoxemia--Treatment
- Abstract
Low oxygenation levels are a hallmark of numerous pathologic conditions. Hypoxia occurs in chronic diseases of brain, kidneys and liver. Malignant tumors grow rapidly with insufficient vasculature, thereby producing areas of chronic hypoxia. This book contains contributions from an international group of authors covering a wide range of situations in benign as well as malignant diseases, in which understanding the role of hypoxia may lead to novel diagnostic and therapeutic strategies. These include modulation of tissue oxygenation as well as treatment concepts directed specifically at hypoxic cells.
- Published
- 2013
41. High Altitude Medicine and Physiology 5E
- Author
-
John West, Robert Schoene, Andrew Luks, James Milledge, John West, Robert Schoene, Andrew Luks, and James Milledge
- Subjects
- Anoxemia, Altitudes, Adaptation (Physiology), Mountain sickness, Altitude, Influence of, Acclimatization
- Abstract
A comprehensive update to this preeminent and accessible text, this fifth edition of a bestseller was developed as a response to man's attempts to climb unaided to higher altitudes and to spend more time in these conditions for both work and recreation. It describes the ever-expanding challenges that doctors face in dealing with the changes in huma
- Published
- 2013
42. Hypoxie : Beiträge aus den Jahren 1932 – 1972
- Author
-
Franz Büchner, E. Grundmann, Franz Büchner, and E. Grundmann
- Subjects
- Anoxemia, Diseases--Causes and theories of causation, Abnormalities--Etiology, Anoxia, Heart diseases
- Published
- 2013
43. Home oxygen therapy assessment for COPD patients discharged from hospital: Respiratory NP Model of Care
- Author
-
Hall, Toni
- Published
- 2016
44. Intravenous lipid emulsion for levobupivacaine intoxication in acidotic and hypoxaemic pigs
- Author
-
Heinonen, JA, Skrifvars, MB, Haasio, J, Backman, JT, Rosenberg, PH, and Litonius, E
- Published
- 2016
45. The role of an ambient pressure oxygen source during one lung ventilation for thoracoscopic surgery
- Author
-
Pfitzner, J
- Published
- 2016
46. Intermittent Hypoxia and Human Diseases
- Author
-
Lei Xi, Tatiana V. Serebrovskaya, Lei Xi, and Tatiana V. Serebrovskaya
- Subjects
- Oxygen in the body, Anoxemia
- Abstract
Intermittent hypoxia can cause significant structural and functional impact on the systemic, organic, cellular and molecular processes of human physiology and pathophysiology. This book focuses on the most updated scientific understanding of the adaptive (beneficial) and maladaptive (detrimental) responses to intermittent hypoxia and their potential pathogenetic or prophylactic roles in the development and progression of major human diseases. This is a comprehensive monograph for clinicians, research scientists, academic faculty, postgraduate and medical students, and allied health professionals who are interested in enhancing their up-to-date knowledge of intermittent hypoxia research and its translational applications in preventing and treating major human diseases.
- Published
- 2012
47. The Aymara : Strategies in Human Adaptation to a Rigorous Environment
- Author
-
W.J. Schull, F. Rothhammer, W.J. Schull, and F. Rothhammer
- Subjects
- Aymara Indians--Anthropometry, Aymara Indians--Health and hygiene, Altitude, Influence of, Anoxemia
- Abstract
South America's Andean highlands have seen the rise and decline of several impressive, indigenous civilizations. Separated somewhat in time and place, each developed its distinctive socio-cultural accouterments but all shared a need to adjust to the individual, societal and environmental limitations imposed by life at high altitude. Partial oxygen pressure, temperature and humidity fall systematically as altitude rises, but there are other changes as well. Darwin, Forbes, von Humboldt, von Tschudi and other naturalists of the eighteenth and nineteenth centuries who weaved their way through South America commented repeatedly on the tolerance or apparent indifference of the indigenes to the rigors of life at altitudes above 3000 meters but its impact upon lowlanders. Von Tschudi (1847), for example, observed'in the cordillera the effect of the diminished atmospheric pressure on the human frame shows itself in intolerable symptoms of weariness and an extreme difficulty of breathing.... The first symptoms are usually felt at the elevation of 12,600 feet (3800 m) above the sea. These symptoms are vertigo, dimness of sight and hearing, pains in the head and nausea.... Inhabitants of the coast and Europeans, who for the first time visit the lofty regions of the cordillera, are usually attacked with this disorder.'But von Tschudi's description of acute mountain sickness was hardly the first; his Spanish predecessors had known and commented upon it too.
- Published
- 2012
48. Nitrogen metabolism in the roots of rubber tree ('Hevea brasiliensis') plants supplied with nitrate or ammonium as nitrogen source during hypoxia
- Author
-
de Carvalho, Pollyanna Aparecida, de Oliveira, Luiz Edson Mota, Sodek, Ladaslav, and de Carvalho, Jullyanna Nair
- Published
- 2015
49. The effects of exercise on the chemical control of breathing in man
- Author
-
Pandit, Jaideep Jagdeesh and Robbins, Peter A.
- Subjects
612.2 ,Anoxemia ,Human physiology ,Respiratory organs ,Physiology - Abstract
This thesis is concerned with the chemical control of breathing during exercise in humans. Chapter 1 reviews some of the relevant studies in animals and humans. Chapter 2 describes the experimental apparatus and the technique of dynamic end-tidal forcing performed using a computer-controlled gas-mixing system. Chapter 3 describes a study of the effects of sustained hypoxia on ventilation during steady exercise. The acute ventilatory response to hypoxia (AHR) was increased during exercise as compared with rest, but the magnitude of the subsequent decline in ventilation (HVD), expressed as a fraction of the AHR, was reduced. A simple model of the hypoxic peripheral chemoreflex is proposed, in which the mechanisms underlying AHR and HVD are functionally separate and can be independently modulated by external factors. Chapter 4 assesses changes in peripheral chemoreflex sensitivity to hypoxia in terms of the degree of decline in AHR measured in the resting periods shortly after prior conditioning periods of hypoxia and/or exercise. At rest, a second AHR measured 6 min after a period of sustained hypoxia had declined by 30% as compared with the initial AHR. In contrast, the AHR measured in the resting period after a period of sustained hypoxic exercise was only 11% smaller in magnitude than the AHR measured after a period of euoxic exercise. The results suggest that the degree to which hypoxic sensitivity declines during sustained hypoxia is genuinely attenuated, rather than masked, by exercise. Chapter 5 describes the changes in respiration during prolonged exercise breathing air with and without added CO
2 . During prolonged poikilocapnic exercise, ventilation remained constant, but metabolic CO2 production, respiratory quotient and end-tidal PCO2 declined; a result which suggests that in man, ventilation can be dissociated from the CO2 flux. During hypercapnic exercise, ventilation progressively increased; this was interpreted as being due to a correction by end-tidal forcing of the natural tendency for end-tidal CO2 to decline, together with an independent effect of CO2 per se on the ventilation. Chapter 6. Electrical muscle stimulation was used as means of inducing non-volitional exercise. Electrically-induced exercise increased the AHR as compared with rest, and with voluntary exercise at matched external work rate. The AHRs during electrical stimulation and voluntary exercise matched to the internal work rate were similar. Chapter 7. Electrical muscle stimulation was used in paraplegic subjects in whom there would be no neural control of exercise. Electrically-induced exercise increased the AHR as compared with rest. When compared with the data from Chapter 6, the results suggest that the observed increase in AHR during normal voluntary exercise can be wholly accounted for by the increase in metabolic CO2 production, or closely related factors. Chapter 8 presents a brief summary of the findings in this thesis.- Published
- 1993
50. Mecanismos de resistencia a terapias dirigidas contra BRAF(V600E) y estudio de nuevas combinaciones de fármacos en cáncer de colon
- Author
-
Ramírez Corpas, Lorena, García Palmer, Héctor, and Universitat de Barcelona. Facultat de Farmàcia i Ciències de l'Alimentació
- Subjects
Anoxemia ,Oncologia ,Oncology ,Càncer colorectal ,Drug resistance ,Anoxèmia ,Metilació ,Colorectal cancer ,Methylation ,Resistència als medicaments - Abstract
[spa] Alrededor del 10% de los pacientes con cáncer colorrectal metastático (mCRC) presentan la mutación BRAF(V600E), mutación que está asociada a una peor respuesta al tratamiento estándar con agentes quimioterapéuticos y a una menor supervivencia. Recientemente se ha aprobado el uso de la combinación encorafenib + cetuximab para el tratamiento del mCRC BRAF(V600E). Desafortunadamente, sólo un pequeño porcentaje de los pacientes responden a este tratamiento y una importante fracción de éstos recaen al poco tiempo, lo que hace que sea muy importante identificar los mecanismos asociados a la adquisición de resistencia a los inhibidores de BRAF (BRAFi) y la identificación de nuevas vulnerabilidades. En este proyecto, hemos descrito que en respuesta a terapias combinadas con BRAFi en CRC se da una inducción del programa hipóxico y angiogénico, la activación de los fibroblastos asociados al cáncer (CAFs) y una transición a un fenotipo extremadamente mucinoso. Donde, la calidad de la ramificación de la estructura de las mucinas es necesaria para la adquisición de resistencia a las terapias BRAFi. Además, hemos observado un aumento de la expresión de MMP7, el cual promueve y mejora la liberación y accesibilidad de VEGFA bioactivo, lo que induce la angiogénesis tras el tratamiento en modelos preclínicos PDX y líneas celulares tratados con encorafenib + cetuximab + binimetinib. Estos acontecimientos generan una vulnerabilidad que nos dio la oportunidad de diseñar nuevas combinaciones racionales y efectivas añadiendo un inhibidor de VEGFA (VEGFAi) al tratamiento. Esta nueva combinación con el anticuerpo anti-angiogénico bevacizumab retrasó el tiempo de progresión de las terapias BRAFi y nos ha permitido establecer un ensayo clínico nuevo para validar este nuevo régimen terapéutico en pacientes de CRC con tumores BRAF(V600E). Paralelamente, hemos descrito que en pacientes de CRC la hipermetilación del promotor del gen BRCA1 puede reprimir su expresión, liderando así una deficiencia en la reparación por recombinación homóloga (HRD) y una sensibilidad a los inhibidores de PARP (PARPi). Además, hemos descrito de forma detallada un caso de CRC en el que el tratamiento y la progresión a los BRAFi da lugar a la selección de clones con una reparación homóloga funcional (HRP), los cuales provenían de una enfermedad que inicialmente presentaba HRD. De este caso, hemos extraído una firma de metilación que nos permitiría identificar casos con HRD de diferentes tipos tumorales. Esto es especialmente evidente en tumores donde la HRD es una alteración frecuente, como es el caso del adenocarcinoma de pulmón o el cáncer de ovario. Los datos obtenidos de este paciente apoyan el concepto de tratar a pacientes de CRC con PARPi mientras presenten una HRD. Son necesarios más estudios para refinar y validar el potencial de nuestra firma epigenética como marcador de selección de pacientes HRD sensibles a PARPi., [eng] Around 10% of patients with metastatic colorectal cancer (mCRC) present a BRAF(V600E) mutation, which is associated with a poor response to standard chemotherapy and shorter overall survival. The combination encorafenib + cetuximab has been recently approved for the treatment of mCRC BRAF(V600E). Unfortunately, only a small percentage of them respond to this treatment and a large fraction of patients relapse shortly, so it has become very important to identify the mechanisms associated to the acquired resistance to BRAF inhibitors (BRAFi) and the identification of new vulnerabilities. In this project, we described a hypoxic and angiogenic program induction, the activation of tumour associated fibroblasts (CAFs) and the transition to an extreme mucinous differentiation phenotype as a response to BRAFi- combined therapies in CRC. This drastic tumour tissue remodelling leads to a non-genetic drug resistance. In particular the quality of the branched structure in mucins is required for the acquisition of resistance to BRAFi therapies. Furthermore, we observed an increase in MMP7 expression that promoted an enhanced release of bioactive VEGFA accessible to induce angiogenesis upon treatment of preclinical PDX and cell line models with encorafenib + cetuximab + binimetinib. These events became a vulnerability that gave us the opportunity to design new rational and effective combinations adding a VEGFA inhibitor (VEGFAi) to the treatment. This new combination with the anti- angiogenic antibody bevacizumab delayed the time to progression to BRAFi therapy and led us to set a new clinical trial to validate such therapeutic regime in CRC patients with BRAF(V600E) tumours. In parallel, we describe that in CRC patients the hypermethylation of BRCA1 gene promoter can repress its expression leading to Homologous Repair Deficiency (HRD) and sensitivity to PARP inhibitors (PARPi). Here we also report in detail a CRC case in which treatment and progression to BRAF(V600E) inhibitory therapy selected Homologous Repair Proficient (HRP) clones from an initial disease presenting HRD. From this case, we extracted a methylation signature that could identify HRD cases suffering of different tumour types. This is particularly evident in tumours where HRD has been described as a frequent alteration, such as lung adenocarcinomas or ovarian cancer. Our real patient data supports the concept of treating CRC patients with PARP inhibitors as far as they present HRD. Future studies will be required to refine and validate the potential of our epigenetic signature as biomarker for selecting HRD patients sensitive to PARP inhibitors
- Published
- 2023
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