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Sample records for hypoxic respiratory failure

  1. Transient hypoxic respiratory failure in a patient with severe hypophosphatemia.

    Science.gov (United States)

    Oud, Lavi

    2009-03-01

    Respiratory failure in severely hypophosphatemic patients has been attributed to respiratory muscle weakness, leading to ventilatory failure. While frequently documenting hypercarbic respiratory failure, previous reports of hypophosphatemia-related respiratory failure in patients otherwise free of pulmonary or airway disease often did not provide sufficient information on gas exchange and pulmonary function, precluding inference on alternative or additional sources of respiratory dysfunction in this population. We report a case of acute hypoxic respiratory failure in a 26 year-old bulimic woman with severe hypophosphatemia. The patient presented with acute onset of dyspnea, paresthesias, limb shaking, and severe hyperventilation. SpO2 was 74%, requiring administration of 100% O2, with normal chest radiograph. Serum phosphate was <0.3 mmol/liter (1.0 mg/dL). Further evaluation did not support pulmonary, vascular, neurogenic or external exposure-related causes of hypoxic respiratory failure, which rapidly resolved with parenteral correction of hypophosphatemia. To date, hypoxic respiratory failure has not been reported in association with hypophosphatemia. Increased awareness and further investigations can help elucidate the mechanisms of hypophosphatemia-associated hypoxemia.

  2. Acute kidney injury with hypoxic respiratory failure

    OpenAIRE

    Neubert, Zachary; Hoffmann, Paul; Owshalimpur, David

    2014-01-01

    A 27-year-old Caucasian man was transferred from a remote clinic with acute kidney injury for the prior 7–10 days preceded by gastroenteritis. His kidney biopsy showed non-specific mesangiopathic glomerular changes, minimal tubulointerstitial disease without sclerosis, crescents, nor evidence of vasculitis. On his third hospital day, he developed acute hypoxic respiratory failure requiring intubation and mechanical ventilation. Pulmonary renal syndromes ranked highest on his differential diag...

  3. Adult-onset nemaline myopathy presenting as respiratory failure.

    LENUS (Irish Health Repository)

    Kelly, Emer

    2008-11-01

    Nemaline myopathy is a rare congenital myopathy that generally presents in childhood. We report a case of a 44-year-old man who presented with severe hypoxic hypercapnic respiratory failure as the initial manifestation of nemaline myopathy. After starting noninvasive ventilation, his pulmonary function test results improved substantially, and over the 4 years since diagnosis his respiratory function remained stable. There are few reported cases of respiratory failure in patients with adult-onset nemaline myopathy, and the insidious onset in this case is even more unusual. This case highlights the varied presenting features of adult-onset nemaline myopathy and that noninvasive ventilation improves respiratory function.

  4. Treatment of respiratory failure in COPD

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    Stephan Budweiser

    2008-12-01

    Full Text Available Stephan Budweiser1, Rudolf A Jörres2, Michael Pfeifer1,31Center for Pneumology, Hospital Donaustauf, Donaustauf, Germany; 2Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-University, Munich, Germany; 3Department of Internal Medicine II, Division of Respirology, University of Regensburg, Regensburg, GermanyAbstract: Patients with advanced COPD and acute or chronic respiratory failure are at high risk for death. Beyond pharmacological treatment, supplemental oxygen and mechanical ventilation are major treatment options. This review describes the physiological concepts underlying respiratory failure and its therapy, as well as important treatment outcomes. The rationale for the controlled supply of oxygen in acute hypoxic respiratory failure is undisputed. There is also a clear survival benefit from long-term oxygen therapy in patients with chronic hypoxia, while in mild, nocturnal, or exercise-induced hypoxemia such long-term benefits appear questionable. Furthermore, much evidence supports the use of non-invasive positive pressure ventilation in acute hypercapnic respiratory failure. It application reduces intubation and mortality rates, and the duration of intensive care unit or hospital stays, particularly in the presence of mild to moderate respiratory acidosis. COPD with chronic hypercapnic respiratory failure became a major indication for domiciliary mechanical ventilation, based on pathophysiological reasoning and on data regarding symptoms and quality of life. Still, however, its relevance for long-term survival has to be substantiated in prospective controlled studies. Such studies might preferentially recruit patients with repeated hypercapnic decompensation or a high risk for death, while ensuring effective ventilation and the patients’ adherence to therapy.Keywords: respiratory failure, COPD, mechanical ventilation, non-invasive ventilation long-term oxygen therapy, chronic

  5. Oxygen saturation index and severity of hypoxic respiratory failure.

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    Rawat, Munmun; Chandrasekharan, Praveen K; Williams, Ashley; Gugino, Sylvia; Koenigsknecht, Carmon; Swartz, Daniel; Ma, Chang Xing; Mathew, Bobby; Nair, Jayasree; Lakshminrusimha, Satyan

    2015-01-01

    The oxygenation index (OI = mean airway pressure, MAP × FiO2 × 100 : PaO2) is used to assess the severity of hypoxic respiratory failure (HRF) and persistent pulmonary hypertension of the newborn (PPHN). An indwelling arterial line or arterial punctures are necessary to obtain PaO2 for the calculation of OI. Oxygenation can be continuously and noninvasively assessed using pulse oximetry. The use of the oxygen saturation index (OSI = MAP × FiO2 × 100 : SpO2) can be an alternate method of assessing the severity of HRF. To evaluate the correlation between OSI and OI in the following: (1) neonates with HRF and (2) a lamb model of meconium aspiration syndrome. Human neonates: a retrospective chart review of 74 ventilated late preterm/term neonates with indwelling arterial access and SpO2 values in the first 24 h of life was conducted. OSI and OI were calculated and correlated. Lamb model: arterial blood gases were drawn and preductal SpO2 was documented in 40 term newborn lambs with asphyxia and meconium aspiration. OI and OSI were calculated and correlated with pulmonary vascular resistance (PVR). Mean values of OSI and OI showed a correlation coefficient of 0.952 in neonates (mean value of 308 observations in 74 neonates) and 0.948 in lambs (mean value of 743 observations in 40 lambs). In lambs, with increasing PVR, there was a decrease in OI and OSI. OSI correlates significantly with OI in infants with HRF. This noninvasive measure may be used to assess the severity of HRF and PPHN in neonates without arterial access. © 2015 S. Karger AG, Basel

  6. Experience with inhaled nitric oxide therapy in hypoxic respiratory failure of the newborn.

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    Sehgal, Arvind; Callander, Ian; Stack, Jacqueline; Momsen, Tracey; Sterling-Levis, Katy

    2005-01-01

    Respiratory diseases are the commonest cause of morbidity and mortality in newborns. Inhaled nitric oxide (iNO) has been shown to be effective in the management of persistent pulmonory hypertension of newborn (PPHN). To retrospectively analyse data to determine the effectiveness of inhaled nitric oxide (iNO) in the management of newborns with PPHN in terms of survival and changes in oxygenation status. Neo-natal data since inception of iNO therapy at the unit (past six years) was reviewed. Pertinent demographic and clinical information was collected from medical records of newborns that received inhaled nitric oxide therapy during their stay. Details of underlying illnesses, other therapeutic modalities, arterial blood gas, ventilatory and nitric oxide parameters were assessed and analysed to ascertain efficacy of iNO. A total of 36 babies (gestational age ranging from 24-41 weeks) received iNO during this period; two were excluded from final analysis. Overall survival rate was 80 percent. There was a statistically significant increase in systemic oxygenation (PaO2) from 41.1 +/- 2.1 mmHg to 128.5 +/- 13.2 mmHg and a decline in oxygenation index (OI) from 49.4 +/- 5.9 to 17.3 +/- 2.5, when assessed after four hours (P < 0.001). Mean duration of iNO therapy was 63 +/- 7.3 hours and the maximum methaemoglobin levels were noted to be 2.1 percent. Inhaled nitric oxide appears to be an effective rescue therapy for the management of PPHN associated with hypoxic respiratory failure. It is safe and well tolerated with no evidence of clinical or biochemical side effects.

  7. Acute respiratory failure as primary manifestation of antineutrophil cytoplasmic antibodies-associated vasculitis

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    Evdokia Sourla

    2014-07-01

    Full Text Available The systemic vasculitides are multifocal diseases characterized by the presence of blood vessel inflammation in multiple organ systems. Their clinical presentation is variable extending from self-limited illness to critical complications including diffuse alveolar hemorrhage and glomerulonephritis. Alveolar hemorrhage is a lifethreatening manifestation of pulmonary vasculitis that can rapidly progress into acute respiratory failure requiring ventilatory support. We present the case of a 74-year-old patient admitted to the Intensive Care Unit with severe hypoxic respiratory failure and diffuse alveolar infiltrates in chest imaging that was later diagnosed as antineutrophil cytoplasmic antibodies-associated vasculitis. The report highlights the importance of differentiate between alveolar hemorrhage and acute respiratory distress syndrome of other etiology because alveolar hemorrhage is reversible with prompt initiation of treatment.

  8. Insufficiency of Medical Care for Patients with Acute Respiratory Failure

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    A. V. Dats

    2017-01-01

    Full Text Available The purpose of the research: to analyze insufficiency of medical care for patients with acute respiratory failure in the ICU.Materials and methods. It was a retrospective study of 160 patients' medical records (age from 15 to 84 years with acute respiratory failure (ARF hospitalized in the ICUs of 24 regional and municipal hospitals of the Irkutsk Oblast. Medical records were provided by the Territorial Fund of Compulsory Medical Insurance of citizens of Irkutsk region.The results. The basic defects in conducting mechanical ventilation were associated with improper lung function evaluation, microbiological tests of sputum and radiology. ARF was not diagnosed in 32 of 160 ICU patients (20%. In 23% of cases the causes of ARF were not diagnosed. The greatest part of the defects in the treatment of patients with acute respiratory failure was found during the treatment of hypoxemia: no recovery of the respiratory tract patency, no prescription of oxygen for hypoxemia, no mechanical ventilation for persistent hypoxemia on the background of maximum oxygen supply and late switching to mechanical ventilation at the stage of hypoxic cardiac arrest.Conclusions. The use of pulse oximetry alone in the absence of arterial blood gas analysis in 98% of patients with acute respiratory failure and failure to perform the lung X-ray and/or MSCT imaging in 21% of patients were accompanied by a high level of undiagnosed acute respiratory distress syndrome (78%, lung contusion (60%, pulmonary embolism (40%, cardiogenic pulmonary edema (33%, and nosocomial pneumonia (28%. Defects of treatment of patients with ARF in 46% of cases were caused by inadequate management of hypoxemia associated with the recovery of the respiratory tract patency, prescription of oxygen, and mechanical ventilation. 

  9. Respiratory Failure

    Science.gov (United States)

    Respiratory failure happens when not enough oxygen passes from your lungs into your blood. Your body's organs, ... brain, need oxygen-rich blood to work well. Respiratory failure also can happen if your lungs can' ...

  10. [Disturbed respiratory cycle accompanying hypoxic-ischemic encephalopathy].

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    Saito, Yoshiaki; Masuko, Kaori; Kaneko, Kaori; Saito, Kazuyo; Chikumaru, Yuri; Iwamoto, Hiroko; Matsui, Akira; Kimura, Seiji

    2005-09-01

    We report the case of a 2-year-old boy who experienced total asphyxia at 4 months of age, and suffered abnormalities at specific phases of the respiratory cycle. The patient was bedridden due to severe tetraplegia and showed little response to external stimuli. He has been tube-fed since the initial asphyxia and a tracheotomy was performed after recurrent hypoxic episodes as a result of the respiratory dysfunction. Upon examination, his respiratory pattern was characterized by arrest during the inspiratory phase with a possible over-riding secondary inspiration. The respiratory pause at the inspiratory phase was markedly prolonged during an episode of pulmonary infection, resulting in recurrent cyanosis that necessitated artificial ventilation. The "second" inspiration typically occurred during the mid- or late-inspiratory phases, with this pattern often shown to be variable after epileptic seizures. The characteristic breathing of this patient suggested that difficulty in forming a normal respiratory cycle, other than during periods of hypoventilation or apnoea, could be a significant respiratory dysfunction following asphyxiation. Strategies for the management of such patients should be carefully designed after close observation of breathing patterns within the respiratory cycle, and with consideration for the influence of epileptic seizures and other inputs from somatic afferents.

  11. Post-hypoxic recovery of respiratory rhythm generation is gender dependent.

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    Alfredo J Garcia

    Full Text Available The preBötzinger complex (preBötC is a critical neuronal network for the generation of breathing. Lesioning the preBötC abolishes respiration, while when isolated in vitro, the preBötC continues to generate respiratory rhythmic activity. Although several factors influence rhythmogenesis from this network, little is known about how gender may affect preBötC function. This study examines the influence of gender on respiratory activity and in vitro rhythmogenesis from the preBötC. Recordings of respiratory activity from neonatal mice (P10-13 show that sustained post-hypoxic depression occurs with greater frequency in males compared to females. Moreover, extracellular population recordings from the preBötC in neonatal brainstem slices (P10-13 reveal that the time to the first inspiratory burst following reoxygenation (TTFB is significantly delayed in male rhythmogenesis when compared to the female rhythms. Altering activity of ATP sensitive potassium channels (KATP with either the agonist, diazoxide, or the antagonist, tolbutamide, eliminates differences in TTFB. By contrast, glucose supplementation improves post-hypoxic recovery of female but not male rhythmogenesis. We conclude that post-hypoxic recovery of respiration is gender dependent, which is, in part, centrally manifested at the level of the preBötC. Moreover, these findings provide potential insight into the basis of increased male vulnerability in a variety of conditions such as Sudden Infant Death Syndrome (SIDS.

  12. Neurological Respiratory Failure

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    Mohan Rudrappa

    2018-01-01

    Full Text Available West Nile virus infection in humans is mostly asymptomatic. Less than 1% of neuro-invasive cases show a fatality rate of around 10%. Acute flaccid paralysis of respiratory muscles leading to respiratory failure is the most common cause of death. Although the peripheral nervous system can be involved, isolated phrenic nerve palsy leading to respiratory failure is rare and described in only two cases in the English literature. We present another case of neurological respiratory failure due to West Nile virus-induced phrenic nerve palsy. Our case reiterates the rare, but lethal, consequences of West Nile virus infection, and the increase of its awareness among physicians.

  13. Management of Postoperative Respiratory Failure.

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    Mulligan, Michael S; Berfield, Kathleen S; Abbaszadeh, Ryan V

    2015-11-01

    Despite best efforts, postoperative complications such as postoperative respiratory failure may occur and prompt recognition of the process and management is required. Postoperative respiratory failure, such as postoperative pneumonia, postpneumonectomy pulmonary edema, acute respiratory distress-like syndromes, and pulmonary embolism, are associated with high morbidity and mortality. The causes of these complications are multifactorial and depend on preoperative, intraoperative, and postoperative factors, some of which are modifiable. The article identifies some of the risk factors, causes, and treatment strategies for successful management of the patient with postoperative respiratory failure. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Application of non-invasive mechanical ventilation in an asthmatic pregnant woman in respiratory failure: a case report

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    Caner, Hanife; Eryuksel, Emel; Kosar, Filiz

    2013-01-01

    The use of non-invasive mechanical ventilation (NIV) during an asthma attack is controversial. We report a case of a 28-year-old female patient in her 16th week of pregnancy with community-acquired pneumonia who presented during an asthma attack, which led to hypoxic respiratory failure. She was successfully treated using NIV. This case is worth discussing as it includes two clinical conditions in which NIV is often considered contraindicated. PMID:23372957

  15. Application of non-invasive mechanical ventilation in an asthmatic pregnant woman in respiratory failure: a case report

    OpenAIRE

    Dalar, Levent; Caner, Hanife; Eryuksel, Emel; Kosar, Filiz

    2013-01-01

    The use of non-invasive mechanical ventilation (NIV) during an asthma attack is controversial. We report a case of a 28-year-old female patient in her 16th week of pregnancy with community-acquired pneumonia who presented during an asthma attack, which led to hypoxic respiratory failure. She was successfully treated using NIV. This case is worth discussing as it includes two clinical conditions in which NIV is often considered contraindicated.

  16. Acute Liver Impairment in a Young, Healthy Athlete: Hypoxic Hepatitis and Rhabdomyolysis following Heat Stroke

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    Neville Azzopardi

    2012-08-01

    Full Text Available Any process that substantially diminishes arterial blood flow or arterial oxygen content to the liver can result in hypoxic (ischaemic hepatitis. 90% of hypoxic hepatitis occurs in unstable patients in intensive care units with haemodynamic failure secondary to heart failure, respiratory failure and toxic shock. The rate of in-hospital mortality in hypoxic hepatitis is very high with studies recording mortalities of 61.5%. It tends to be very uncommon in healthy, young patients with no underlying medical problems. We report here the case of a young healthy athlete who developed heat stroke associated with rhabdomyolysis and hypoxic hepatitis while he was running the final stages of a marathon. The patient required intensive care admission and inotropic support for a few hours after he was admitted with heat stroke. He underwent a rapid recovery after he was resuscitated with fluids. N-acetyl cysteine was also given during the acute stage of the hepatitis. This case highlights an uncommon case of hypoxic hepatitis in a young, healthy patient secondary to hypotension and heat stroke. Inotropic support might have precipitated the hypoxic hepatitis in this young patient.

  17. Bidirectional Cardio-Respiratory Interactions in Heart Failure

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    Nikola N. Radovanović

    2018-03-01

    Full Text Available We investigated cardio-respiratory coupling in patients with heart failure by quantification of bidirectional interactions between cardiac (RR intervals and respiratory signals with complementary measures of time series analysis. Heart failure patients were divided into three groups of twenty, age and gender matched, subjects: with sinus rhythm (HF-Sin, with sinus rhythm and ventricular extrasystoles (HF-VES, and with permanent atrial fibrillation (HF-AF. We included patients with indication for implantation of implantable cardioverter defibrillator or cardiac resynchronization therapy device. ECG and respiratory signals were simultaneously acquired during 20 min in supine position at spontaneous breathing frequency in 20 healthy control subjects and in patients before device implantation. We used coherence, Granger causality and cross-sample entropy analysis as complementary measures of bidirectional interactions between RR intervals and respiratory rhythm. In heart failure patients with arrhythmias (HF-VES and HF-AF there is no coherence between signals (p < 0.01, while in HF-Sin it is reduced (p < 0.05, compared with control subjects. In all heart failure groups causality between signals is diminished, but with significantly stronger causality of RR signal in respiratory signal in HF-VES. Cross-sample entropy analysis revealed the strongest synchrony between respiratory and RR signal in HF-VES group. Beside respiratory sinus arrhythmia there is another type of cardio-respiratory interaction based on the synchrony between cardiac and respiratory rhythm. Both of them are altered in heart failure patients. Respiratory sinus arrhythmia is reduced in HF-Sin patients and vanished in heart failure patients with arrhythmias. Contrary, in HF-Sin and HF-VES groups, synchrony increased, probably as consequence of some dominant neural compensatory mechanisms. The coupling of cardiac and respiratory rhythm in heart failure patients varies depending on the

  18. Bidirectional Cardio-Respiratory Interactions in Heart Failure.

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    Radovanović, Nikola N; Pavlović, Siniša U; Milašinović, Goran; Kirćanski, Bratislav; Platiša, Mirjana M

    2018-01-01

    We investigated cardio-respiratory coupling in patients with heart failure by quantification of bidirectional interactions between cardiac (RR intervals) and respiratory signals with complementary measures of time series analysis. Heart failure patients were divided into three groups of twenty, age and gender matched, subjects: with sinus rhythm (HF-Sin), with sinus rhythm and ventricular extrasystoles (HF-VES), and with permanent atrial fibrillation (HF-AF). We included patients with indication for implantation of implantable cardioverter defibrillator or cardiac resynchronization therapy device. ECG and respiratory signals were simultaneously acquired during 20 min in supine position at spontaneous breathing frequency in 20 healthy control subjects and in patients before device implantation. We used coherence, Granger causality and cross-sample entropy analysis as complementary measures of bidirectional interactions between RR intervals and respiratory rhythm. In heart failure patients with arrhythmias (HF-VES and HF-AF) there is no coherence between signals ( p respiratory signal in HF-VES. Cross-sample entropy analysis revealed the strongest synchrony between respiratory and RR signal in HF-VES group. Beside respiratory sinus arrhythmia there is another type of cardio-respiratory interaction based on the synchrony between cardiac and respiratory rhythm. Both of them are altered in heart failure patients. Respiratory sinus arrhythmia is reduced in HF-Sin patients and vanished in heart failure patients with arrhythmias. Contrary, in HF-Sin and HF-VES groups, synchrony increased, probably as consequence of some dominant neural compensatory mechanisms. The coupling of cardiac and respiratory rhythm in heart failure patients varies depending on the presence of atrial/ventricular arrhythmias and it could be revealed by complementary methods of time series analysis.

  19. What Can We Apply to Manage Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Acute Respiratory Failure?

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    Kim, Deog Kyeom; Lee, Jungsil; Park, Ju Hee; Yoo, Kwang Ha

    2018-04-01

    Acute exacerbation(s) of chronic obstructive pulmonary disease (AECOPD) tend to be critical and debilitating events leading to poorer outcomes in relation to chronic obstructive pulmonary disease (COPD) treatment modalities, and contribute to a higher and earlier mortality rate in COPD patients. Besides pro-active preventative measures intended to obviate acquisition of AECOPD, early recovery from severe AECOPD is an important issue in determining the long-term prognosis of patients diagnosed with COPD. Updated GOLD guidelines and recently published American Thoracic Society/European Respiratory Society clinical recommendations emphasize the importance of use of pharmacologic treatment including bronchodilators, systemic steroids and/or antibiotics. As a non-pharmacologic strategy to combat the effects of AECOPD, noninvasive ventilation (NIV) is recommended as the treatment of choice as this therapy is thought to be most effective in reducing intubation risk in patients diagnosed with AECOPD with acute respiratory failure. Recently, a few adjunctive modalities, including NIV with helmet and helium-oxygen mixture, have been tried in cases of AECOPD with respiratory failure. As yet, insufficient documentation exists to permit recommendation of this therapy without qualification. Although there are too few findings, as yet, to allow for regular andr routine application of those modalities in AECOPD, there is anecdotal evidence to indicate both mechanical and physiological benefits connected with this therapy. High-flow nasal cannula oxygen therapy is another supportive strategy which serves to improve the symptoms of hypoxic respiratory failure. The therapy also produced improvement in ventilatory variables, and it may be successfully applied in cases of hypercapnic respiratory failure. Extracorporeal carbon dioxide removal has been successfully attempted in cases of adult respiratory distress syndrome, with protective hypercapnic ventilatory strategy. Nowadays, it is

  20. Acute Respiratory Failure in Acute Poisoning by Neutrotropic Substances

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    A. N. Lodyagin

    2008-01-01

    Full Text Available Objective: to evaluate the efficiency of methods for diagnosing and treating critically ill patients with acute respiratory failure (ARF in acute poisoning by neurotropic substances. Subjects and methods. Two hundred and thirty-three patients with acute severe intoxication with neurotropic poisons were examined. All the patients were admitted for toxic-hypoxic coma and ARF; in this connection all the patients underwent artificial ventilation (AV. The patients were divided into 3 groups: 1 those in whom the traditional treatments (AV, detoxifying therapy, and infusional and cardiotropic support could restore the basic parameters of vital functions, as judged from the recovered oxygenation index; these patients had no metabolic shifts; 2 those who had signs of pulmonary hyperhydration, low cardiac output and moderate metabolic disorders, as suggested by elevated lactate levels; 3 seriously ill patients in whom the interval between the time of poisoning to care delivery was more than 20 hours; the patients of this group had the most significant metabolic disorders. Results. Correction of ARF in critically ill patients with acute poisoning should include, in addition to the rational parameters of AV and detoxifying therapy, agents for targeted therapy for sequels of hypoxia and energy deficiency states. For maximally rapid and effective oxygen transport recovery, the addition of perfluorane to the complex therapy cardinally improves the results of treatment and reduces mortality rates. Conclusion. The complexity of the pathogenesis of ARF and its sequels is a ground for diagnosing and correcting not only ventilation disturbances, but also pulmonary microcirculatory disorders and metabolic disturbances. Key words: acute intoxication with neu-rotropic poisons, acute respiratory failure, pulmonary hyperhydration, hypoxia, metabolic disturbances.

  1. [Autonomic regulation at emotional stress under hypoxic conditions in the elderly with physiological and accelerated aging: effect of hypoxic training].

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    Os'mak, E D; Asanov, É O

    2014-01-01

    The effect of hypoxic training on autonomic regulation in psycho-emotional stress conditions in hypoxic conditions in older people with physiological (25 people) and accelerated (28 people) aging respiratory system. It is shown that hypoxic training leads to an increase in vagal activity indicators (HF) and reduced simpatovagal index (LF/HF), have a normalizing effect on the autonomic balance during stress loads in older people with different types of aging respiratory system.

  2. Successful treatment of two cases of urorectal septum malformation sequence with oligohydramnios and severe respiratory failure

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    Sekiguchi K

    2013-03-01

    Full Text Available Kazuhito Sekiguchi, Daijiro Takahashi, Takehiko Hiroma, Tomohiko Nakamura Division of Neonatology, Nagano Children's Hospital, Nagano, Japan Abstract: Urorectal septum malformation sequence can be diagnosed prenatally. We report herein the successful treatment of severe respiratory failure in two patients with urorectal septum malformation sequence and prenatally diagnosed oligohydramnios. The patients showed significant hypoxic deterioration and persistent pulmonary artery hypertension soon after birth. We used high-frequency ventilation (HFO, nitric oxide (NO, and extracorporeal membrane oxygenation (ECMO. The patients were successfully weaned from ECMO and artificial ventilation and discharged to home. Although termination of the pregnancy has often been selected for fetuses with oligohydramnios-related urorectal septum malformation sequence, our results suggest the opportunity for these fetuses to be treated using respiratory supports including HFO, NO, and ECMO after birth. Keywords: urorectal septum malformation sequence, oligohydramnios, pulmonary hypoplasia

  3. Two Cases of Arnold-Chiari Malformation with Respiratory Failure

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    Sinem Iliaz

    2014-03-01

    Full Text Available Arnold–Chiari malformation is defined as downward displacement of the brainstem and cerebellum through the foramen magnum. It has different clinical presentations and four subtypes. It is known that downward migration of posterior fossa components through the foramen magnum and associated lower cranial nerve palsy and brainstem compression can cause respiratory failure. Acute respiratory failure could mark the onset of the disease. Posterior fossa decompression performed to treat primary disease can improve the central sleep abnormalities. As respiratory failure is rarely seen, this paper presents two cases of Arnold–Chiari malformation with respiratory failure.

  4. [Characteristics of the sympathoadrenal system response to psychoemotional stress under hypoxic conditions in aged people with physiological and accelerated aging of the respiratory system].

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    Asanov, E O; Os'mak, Ie D; Kuz'mins'ka, L A

    2013-01-01

    The peculiarities of the response of the sympathoadrenal system to psychoemotional and hypoxic stress in healthy young people and in aged people with physiological and accelerated aging of respiratory system were studied. It was shown that in aging a more pronounced response of the sympathoadrenal system to psychoemotional stress. At the same time, elderly people with different types of aging of the respiratory system did not demonstrate a difference in the response of the sympathoadrenal system to psychoemotional stress. Unlike in young people, in aged people, combination of psychoemotional and hypoxic stresses resulted in further activation of the sympathoadrenal system. The reaction of the sympathoadrenal system was more expressed in elderly people with accelerated ageing of the respiratory system.

  5. [Respiratory hypercapnic-hypoxic training is an effective component of complex therapy of polyneuropathy in children with diabetes type 1].

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    Smirnov, K V; Smirnova, Yu V; Kulikov, V P; Nazarkina, O M

    2018-01-01

    To study the effectiveness of respiratory hypercapnic-hypoxic training in complex treatment of neuropathy due to diabetes type 1. Fifty children, 31 girls and 19 boys, were examined. The inclusion criteria were the presence of polyneuropathy, verified on the basis of clinical data and electromyographic changes. The patients were divided into 2 groups: the main group (n=25, 15 girls and 10 boys, mean age 12.9±1.8 years (M±SD) and the comparison group (n=25, 16 girls and 9 boys, mean age 13.2±2.0 years). Patients of the main group, along with standard therapy received respiratory hypercapnic-hypoxic training. The positive clinical and neurophysiological dynamics was noted in both groups, with more significant changes in children after respiratory training. Hypercapnic exercises significantly contribute to the pathogenetic therapy of diabetes mellitus and polyneuropathy in this disease, have a significant clinical effects reducing serum concentrations of fasting glucose and severity of neurological deficit scores on the NIS-LL, increasing the speed of conduction of excitation through the nerves, reducing the residual latency of EMG activity.

  6. Predictive Factors of Respiratory Failure in Children with Guillain-Barre Syndrome

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    Nemat Bilan

    2015-03-01

    Full Text Available Introduction:Guillain-Barre Syndrome(GBS is the most common cause of acute flaccid paralysis. Respiratory failure is the most serious short-term complication of GBS and invasive mechanical ventilation is required in 30% of patients.moreover,60% of those who are intubated develop major complications including pnemonia,sepsis,GI bleeding and pulmonary embolism. Thus respiratory failure prediction is crucial. the aim of this study was to determine clinical predictors of respiratory failure to avoid respiratory distress and aspiration.Methods and materials: in a cross sectional and analytical study 140 patients with clinically diagnosis of Guillain-Barre Syndrome were enrolled in study,from october 2008 to october 2014. .demographic data,nerologic examination,cranial nerve and autonomic nervous system involvement, and respiratory failure were recorded prospectively.Results:15 out of 140 patients(10,7% developed respiratory failure and underwent mechanical ventilation.the male/female ratio in patients with respiratory failure and patients without respiratory involvement were (53%/(47% and (54%/(46% respectively(p-value:0.4.the mean age in these two groups were 2,7±1,9 and 5,5±3,2(p-value:0,003.cranial nerve involvement (7,9,10 was recorded in patients with respiratory failure and without respiratory failure54% and25% respectively (p-value:0,03.absent upper limb deep tendon reflexes in these two groups were 70% and 44% respectively.(p-value:0,03 and autonomic nervous system involvement 24% vs. 14%(p-value:0,3.conclusion : our study suggests that younger age , cranial nerve involvement and absent upper limb deep tendon reflexes are predictive factors of respiratory failure in patients with Guillain-Barre Syndrome(GBS.

  7. Submersion and acute respiratory failure

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    Yu-Jang Su

    2014-01-01

    Conclusions: Submersion patients who are hypothermic on arrival of emergency department (ED are risky to respiratory failure and older, more hypothermic, longer hospital stay in suicidal submersion patients.

  8. DiapHRaGM: A mnemonic to describe the work of breathing in patients with respiratory failure.

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    Aiman Tulaimat

    Full Text Available The assessment of the work of breathing in the definitions of respiratory failure is vague and variable.Identify a parsimonious set of signs to describe the work of breathing in hypoxemic, acutely ill patients.We examined consecutive medical ICU patients receiving oxygen with a mask, non-invasive ventilation, or T-piece. A physician inspected each patient for 10 seconds, rated the level of respiratory distress, and then examined the patient for vital signs and 17 other physical signs. We used the rating of distress as a surrogate for measuring the work of breathing, constructed three multivariate models to identify the one with the smallest number of signs and largest explained variance, and validated it with bootstrap analysis.We performed 402 observations on 240 patients. Respiratory distress was absent in 78, mild in 157, moderate in 107, and severe in 60. Respiratory rate, hypoxia, heart rate, and frequency of most signs increased as distress increased. Respiratory rate and hypoxia explained 43% of the variance in respiratory distress. Diaphoresis, gasping, and contraction of the sternomastoid explained an additional 28%. Heart rate, blood pressure, alertness, agitation, body posture, nasal flaring, audible breathing, cyanosis, tracheal tug, retractions, paradox, scalene or abdominal muscles contraction did not increase the explained variance in respiratory distress.Most of the variance is respiratory distress can be explained by five signs summarized by the mnemonic DiapHRaGM (diaphoresis, hypoxia, respiratory rate, gasping, accessory muscle. This set of signs may allow for efficient, standardized assessments of the work of breathing of hypoxic patients.

  9. Maternal and neonatal outcomes of respiratory failure during pregnancy

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    Chen-Yiu Hung

    2018-05-01

    Full Text Available Background: Obstetric patients comprise a limited portion of intensive care unit patients, but they often present with unfamiliar conditions and exhibit the potential for catastrophic deterioration. This study evaluated the maternal and neonatal outcomes of respiratory failure during pregnancy. Methods: Information on 71 patients at >25 weeks gestation in the ICU with respiratory failure was recorded between 2009 and 2013. The characteristics and outcomes of mothers and fetuses were determined through a retrospective chart review and evaluated using Student's t test, chi-square test, and Fisher's exact test. Results: The leading causes of respiratory failure were postpartum hemorrhage and severe preeclampsia in the obstetric causes group and pneumonia in the nonobstetric causes group during pregnancy and the peripartum period. The non-obstetric causes group exhibited a higher incidence of acute respiratory distress syndrome and renal replacement therapy as well as requiring more ventilator days. The patients in the obstetric causes group showed significant improvement after delivery in the partial pressure of arterial oxygen to the fraction of inspired oxygen and peak inspiratory pressure decrease. Both groups exhibited high incidences of neonatal respiratory distress syndrome. Neonatal complications resulting from meconium aspiration syndrome (MAS and sepsis were more common in the non-obstetric causes group; however, neurological development impairment was more common in the obstetric causes group. Conclusion: Obstetric cause was associated with longer ventilator free days and fewer episodes of ARDS after delivery. Neonatal complications resulting from different etiologies of respiratory failure were found to differ. Keywords: Acute respiratory distress syndrome, Neonatal, Obstetric, Outcome, Respiratory failure

  10. Noninvasive ventilation in hypoxemic respiratory failure

    Directory of Open Access Journals (Sweden)

    Raja Dhar

    2016-01-01

    Full Text Available Noninvasive ventilation (NIV refers to positive pressure ventilation delivered through a noninvasive interface (nasal mask, facemask, or nasal plugs etc. Over the past decade its use has become more common as its benefits are increasingly recognized. This review will focus on the evidence supporting the use of NIV in various conditions resulting in acute hypoxemic respiratory failure (AHRF, that is, non-hypercapnic patients having acute respiratory failure in the absence of a cardiac origin or underlying chronic pulmonary disease. Outcomes depend on the patient's diagnosis and clinical characteristics. Patients should be monitored closely for signs of noninvasive ventilation failure and promptly intubated before a crisis develops. The application of noninvasive ventilation by a trained and experienced team, with careful patient selection, should optimize patient outcomes.

  11. Hypoxemic Respiratory Failure from Acute Respiratory Distress Syndrome Secondary to Leptospirosis

    Directory of Open Access Journals (Sweden)

    Shannon M. Fernando

    2017-01-01

    Full Text Available Acute respiratory distress syndrome (ARDS, characterized by hypoxemic respiratory failure, is associated with a mortality of 30–50% and is precipitated by both direct and indirect pulmonary insults. Treatment is largely supportive, consisting of lung protective ventilation and thereby necessitating Intensive Care Unit (ICU admission. The most common precipitant is community-acquired bacterial pneumonia, but other putative pathogens include viruses and fungi. On rare occasions, ARDS can be secondary to tropical disease. Accordingly, a history should include travel to endemic regions. Leptospirosis is a zoonotic disease most common in the tropics and typically associated with mild pulmonary complications. We describe a case of a 25-year-old male with undiagnosed leptospirosis, presenting with fever and severe hypoxemic respiratory failure, returning from a Costa Rican holiday. There was no other organ failure. He was intubated and received lung protective ventilation. His condition improved after ampicillin and penicillin G were added empirically. This case illustrates the rare complication of ARDS from leptospirosis, the importance of taking a travel history, and the need for empiric therapy because of diagnostic delay.

  12. Acute respiratory failure following ovarian hyperstimulation syndrome

    Directory of Open Access Journals (Sweden)

    Antonello Nicolini

    2013-03-01

    Full Text Available Ovarian hyperstimulation syndrome is a serious and potentially life-threatening physiological complication that may be encountered in patients who undergo controlled ovarian hyperstimulation cycles. The syndrome is typically associated with regimes of exogenous gonadotropins, but it can be seen, albeit rarely, when clomiphene is administered during the induction phase. Although this syndrome is widely described in scientific literature and is well known by obstetricians, the knowledge of this pathological and potentially life-threatening condition is generally less than satisfactory among physicians. The dramatic increase in therapeutic strategies to treat infertility has pushed this condition into the realm of acute care therapy. The potential complications of this syndrome, including pulmonary involvement, should be considered and identified so as to allow a more appropriate diagnosis and management. We describe a case of a woman with an extremely severe (Stage 6 ovarian hyperstimulation syndrome who presented ascites, bilateral pleural effusion and severe respiratory failure treated with non-invasive ventilation. The patient was admitted to the intensive care unit because of severe respiratory failure, ascites, and bilateral pleural effusion due to ovarian hyperstimulation syndrome. Treatment included non-invasive ventilation and three thoracentesis procedures, plus the administration of albumin, colloid solutions and high-dose furosemid. Severe form of ovarian hyperstimulation syndrome is observed in 0.5-5% of the women treated, and intensive care may be required for management of thromboembolic complications, renal failure and severe respiratory failure. Pulmonary intensive care may involve thoracentesis, oxygen supplementation and, in more severe cases, assisted ventilation. To our knowledge, there have been only two studies in English language medical literature that describe severe respiratory failure treated with non

  13. Relation between lowered colloid osmotic pressure, respiratory failure, and death.

    Science.gov (United States)

    Tonnesen, A S; Gabel, J C; McLeavey, C A

    1977-01-01

    Plasma colloid osmotic pressure was measured each day in 84 intensive care unit patients. Probit analysis demonstrated a direct relationship between colloid osmotic pressure (COP) and survival. The COP associated with a 50% survival rate was 15.0 torr. COP was higher in survivors than in nonsurvivors without respiratory failure and in patients who recovered from respiratory failure. We conclude that lowered COP is associated with an elevated mortality rate. However, the relationship to death is not explained by the relationship to respiratory failure.

  14. Failure of Noninvasive Ventilation for De Novo Acute Hypoxemic Respiratory Failure: Role of Tidal Volume.

    Science.gov (United States)

    Carteaux, Guillaume; Millán-Guilarte, Teresa; De Prost, Nicolas; Razazi, Keyvan; Abid, Shariq; Thille, Arnaud W; Schortgen, Frédérique; Brochard, Laurent; Brun-Buisson, Christian; Mekontso Dessap, Armand

    2016-02-01

    A low or moderate expired tidal volume can be difficult to achieve during noninvasive ventilation for de novo acute hypoxemic respiratory failure (i.e., not due to exacerbation of chronic lung disease or cardiac failure). We assessed expired tidal volume and its association with noninvasive ventilation outcome. Prospective observational study. Twenty-four bed university medical ICU. Consecutive patients receiving noninvasive ventilation for acute hypoxemic respiratory failure between August 2010 and February 2013. Noninvasive ventilation was uniformly delivered using a simple algorithm targeting the expired tidal volume between 6 and 8 mL/kg of predicted body weight. Expired tidal volume was averaged and respiratory and hemodynamic variables were systematically recorded at each noninvasive ventilation session. Sixty-two patients were enrolled, including 47 meeting criteria for acute respiratory distress syndrome, and 32 failed noninvasive ventilation (51%). Pneumonia (n = 51, 82%) was the main etiology of acute hypoxemic respiratory failure. The median (interquartile range) expired tidal volume averaged over all noninvasive ventilation sessions (mean expired tidal volume) was 9.8 mL/kg predicted body weight (8.1-11.1 mL/kg predicted body weight). The mean expired tidal volume was significantly higher in patients who failed noninvasive ventilation as compared with those who succeeded (10.6 mL/kg predicted body weight [9.6-12.0] vs 8.5 mL/kg predicted body weight [7.6-10.2]; p = 0.001), and expired tidal volume was independently associated with noninvasive ventilation failure in multivariate analysis. This effect was mainly driven by patients with PaO2/FIO2 up to 200 mm Hg. In these patients, the expired tidal volume above 9.5 mL/kg predicted body weight predicted noninvasive ventilation failure with a sensitivity of 82% and a specificity of 87%. A low expired tidal volume is almost impossible to achieve in the majority of patients receiving noninvasive ventilation

  15. Maternal and neonatal outcomes of respiratory failure during pregnancy.

    Science.gov (United States)

    Hung, Chen-Yiu; Hu, Han-Chung; Chiu, Li-Chung; Chang, Chih-Hao; Li, Li-Fu; Huang, Chung-Chi; Kao, Chuan-Chi; Cheng, Po-Jen; Kao, Kuo-Chin

    2018-05-01

    Obstetric patients comprise a limited portion of intensive care unit patients, but they often present with unfamiliar conditions and exhibit the potential for catastrophic deterioration. This study evaluated the maternal and neonatal outcomes of respiratory failure during pregnancy. Information on 71 patients at >25 weeks gestation in the ICU with respiratory failure was recorded between 2009 and 2013. The characteristics and outcomes of mothers and fetuses were determined through a retrospective chart review and evaluated using Student's t test, chi-square test, and Fisher's exact test. The leading causes of respiratory failure were postpartum hemorrhage and severe preeclampsia in the obstetric causes group and pneumonia in the nonobstetric causes group during pregnancy and the peripartum period. The non-obstetric causes group exhibited a higher incidence of acute respiratory distress syndrome and renal replacement therapy as well as requiring more ventilator days. The patients in the obstetric causes group showed significant improvement after delivery in the partial pressure of arterial oxygen to the fraction of inspired oxygen and peak inspiratory pressure decrease. Both groups exhibited high incidences of neonatal respiratory distress syndrome. Neonatal complications resulting from meconium aspiration syndrome (MAS) and sepsis were more common in the non-obstetric causes group; however, neurological development impairment was more common in the obstetric causes group. Obstetric cause was associated with longer ventilator free days and fewer episodes of ARDS after delivery. Neonatal complications resulting from different etiologies of respiratory failure were found to differ. Copyright © 2017. Published by Elsevier B.V.

  16. Acute hypoxemic respiratory failure in immunocompromised patients

    DEFF Research Database (Denmark)

    Azoulay, Elie; Pickkers, Peter; Soares, Marcio

    2017-01-01

    BACKGROUND: In immunocompromised patients with acute hypoxemic respiratory failure (ARF), initial management aims primarily to avoid invasive mechanical ventilation (IMV). METHODS: To assess the impact of initial management on IMV and mortality rates, we performed a multinational observational.......54-0.87), day-1 SOFA excluding respiratory score (1.12/point, 1.08-1.16), PaO2/FiO2

  17. Emerging indications for extracorporeal membrane oxygenation in adults with respiratory failure.

    Science.gov (United States)

    Abrams, Darryl; Brodie, Daniel

    2013-08-01

    Recent advances in technology have spurred the increasing use of extracorporeal membrane oxygenation (ECMO) in patients with severe hypoxemic respiratory failure. However, this accounts for only a small percentage of patients with respiratory failure. We envision the application of ECMO in many other forms of respiratory failure in the coming years. Patients with less severe forms of acute respiratory distress syndrome, for instance, may benefit from enhanced lung-protective ventilation with the very low tidal volumes made possible by direct carbon dioxide removal from the blood. For those in whom hypercapnia predominates, extracorporeal support will allow for the elimination of invasive mechanical ventilation in some cases. The potential benefits of ECMO may be further enhanced by improved techniques, which facilitate active mobilization. Although ECMO for these and other expanded applications is under active investigation, it has yet to be proven beneficial in these settings in rigorous controlled trials. Ultimately, with upcoming and future technological advances, there is the promise of true destination therapy, which could lead to a major paradigm shift in the management of respiratory failure.

  18. Physiologic basis for intermittent hypoxic episodes in preterm infants.

    Science.gov (United States)

    Martin, R J; Di Fiore, J M; Macfarlane, P M; Wilson, C G

    2012-01-01

    Intermittent hypoxic episodes are typically a consequence of immature respiratory control and remain a troublesome challenge for the neonatologist. Furthermore, their frequency and magnitude are commonly underestimated by clinically employed pulse oximeter settings. In extremely low birth weight infants the incidence of intermittent hypoxia [IH] progressively increases over the first 4 weeks of postnatal life, with a subsequent plateau followed by a slow decline beginning at weeks six to eight. Over this period of unstable respiratory control, increased oxygen-sensitive peripheral chemoreceptor activity has been associated with a higher incidence of apnea of prematurity. In contrast, infants with bronchopulmonary dysplasia [chronic neonatal lung disease] exhibit decreased peripheral chemosensitivity, although the effect on respiratory stability in this population is unclear. Such episodic hypoxia/reoxygenation in early life has the potential to sustain a proinflammatory cascade with resultant multisystem, including respiratory, morbidity. Therapeutic approaches for intermittent hypoxic episodes comprise careful titration of baseline or supplemental inspired oxygen as well as xanthine therapy to prevent apnea of prematurity. Characterization of the pathophysiologic basis for such intermittent hypoxic episodes and their consequences during early life is necessary to provide an evidence-based approach to their management.

  19. Toluene inducing acute respiratory failure in a spray paint sniffer.

    Science.gov (United States)

    Peralta, Diego P; Chang, Aymara Y

    2012-01-01

    Toluene, formerly known as toluol, is an aromatic hydrocarbon that is widely used as an industrial feedstock and as a solvent. Like other solvents, toluene is sometimes also used as an inhalant drug for its intoxicating properties. It has potential to cause multiple effects in the body including death. I report a case of a 27-year-old male, chronic spray paint sniffer, who presented with severe generalized muscle weakness and developed acute respiratory failure requiring ventilatory support. Toluene toxicity was confirmed with measurement of hippuric acid of 8.0 g/L (normal <5.0 g/L). Acute respiratory failure is a rare complication of chronic toluene exposure that may be lethal if it is not recognized immediately. To our knowledge, this is the second case of acute respiratory failure due to toluene exposure.

  20. Poison hemlock-induced respiratory failure in a toddler.

    Science.gov (United States)

    West, Patrick L; Horowitz, B Zane; Montanaro, Marc T; Lindsay, James N

    2009-11-01

    The ingestion of poison hemlock, or Conium maculatum, is described in a 2-year-old boy. He had the onset of abdominal pain and weakness after being fed C. maculatum picked by his sister from the roadside 2 hours earlier. He had a rapidly progressive muscular weakness and was intubated for respiratory failure. His symptoms completely resolved within 24 hours of the ingestion. Conium maculatum is a common weed that causes toxicity by its primary toxin, coniine, which stimulates nicotinic receptors and causes a syndrome of rapidly progressive muscle weakness and paralysis. We describe the course of a benign-appearing plant ingestion resulting in respiratory failure.

  1. Respiratory failure due to tracheobronchomalacia.

    Science.gov (United States)

    Collard, P.; Freitag, L.; Reynaert, M. S.; Rodenstein, D. O.; Francis, C.

    1996-01-01

    A case is described of tracheobronchomegaly progressing to extensive tracheomalacia, complicated by episodic choking, recurrent pulmonary infections, and irreversible hypercapnic respiratory failure. A Y-shaped tracheobronchial stent was placed endoscopically to splint the trachea open, with excellent clinical and physiological improvement. New stent designs may provide long term palliation in selected cases of diffuse tracheal collapse or stenosis, and offer an alternative to surgical repair. PMID:8711665

  2. Respiratory failure due to tracheobronchomalacia.

    OpenAIRE

    Collard, P.; Freitag, L.; Reynaert, M. S.; Rodenstein, D. O.; Francis, C.

    1996-01-01

    A case is described of tracheobronchomegaly progressing to extensive tracheomalacia, complicated by episodic choking, recurrent pulmonary infections, and irreversible hypercapnic respiratory failure. A Y-shaped tracheobronchial stent was placed endoscopically to splint the trachea open, with excellent clinical and physiological improvement. New stent designs may provide long term palliation in selected cases of diffuse tracheal collapse or stenosis, and offer an alternative to surgical repair.

  3. Non-invasive ventilation in acute respiratory failure in children.

    Science.gov (United States)

    Abadesso, Clara; Nunes, Pedro; Silvestre, Catarina; Matias, Ester; Loureiro, Helena; Almeida, Helena

    2012-04-02

    The aim of this paper is to assess the clinical efficacy of non-invasive ventilation (NIV) in avoiding endotracheal intubation (ETI), to demonstrate clinical and gasometric improvement and to identify predictive risk factors associated with NIV failure. An observational prospective clinical study was carried out. Included Patients with acute respiratory disease (ARD) treated with NIV, from November 2006 to January 2010 in a Pediatric Intensive Care Unit (PICU). NIV was used in 151 patients with acute respiratory failure (ARF). Patients were divided in two groups: NIV success and NIV failure, if ETI was required. Mean age was 7.2±20.3 months (median: 1 min: 0,3 max.: 156). Main diagnoses were bronchiolitis in 102 (67.5%), and pneumonia in 44 (29%) patients. There was a significant improvement in respiratory rate (RR), heart rate (HR), pH, and pCO(2) at 2, 6, 12 and 24 hours after NIV onset (Papneia (P<0.001; odds ratio 15.8; 95% confidence interval: 3.42-71.4) and pneumonia (P<0.001, odds ratio 31.25; 95% confidence interval: 8.33-111.11). There were no major complications related with NIV. In conclusion this study demonstrates the efficacy of NIV as a form of respiratory support for children and infants with ARF, preventing clinical deterioration and avoiding ETI in most of the patients. Risk factors for failure were related with immaturity and severe infection.

  4. Evaluation of radioimmunoassay for renal functions in senile patients with cor pulmonale without respiratory failure

    International Nuclear Information System (INIS)

    Fu Benqi; Chen Mingxi; Zhou Gangyi; Zhang Zhengzhong

    1995-01-01

    The results of RIA about serum β 2 -MG and urine β 2 -MG, Alb, IgG in the senile patients with cor pulmonale are reported. The contents of sβ 2 -MG, uβ 2 -MG, uAlb in non-respiratory failure group are higher than that of the control group. The contents of sβ 2 -MG, uβ 2 -MG, uAlb and uIgG in the respiratory failure group are higher than that of the non-respiratory failure group. The results show that the renal glamorous and renal tubules functions are slightly damaged in non-respiratory failure group, while functions of the respiratory failure group become worse

  5. Three cases of respiratory failure after I-131 radioiodine therapy

    International Nuclear Information System (INIS)

    Watanabe, Ken; Uchiyama, Masayuki; Fukuda, Kunihiko

    2016-01-01

    We report three cases of respiratory failure after I-131 radioiodine therapy. All cases involved relapsed cervical lesions, and two showed edema of the larynx. Emergency tracheostomy was performed to treat the respiratory failure in one case while the others were treated conservatively. All patients showed improvements without after-effects. Patients who undergo I-131 radioiodine therapy, especially those with cervical lesions, should be carefully monitored for this rare complication after treatment. (author)

  6. Acute respiratory failure in Pakistani patients: risk factors associated with mortality

    International Nuclear Information System (INIS)

    Hussain, S.F.; Irfan, M.; Naqi, Y.S.; Islam, M.; Akhtar, W.

    2006-01-01

    Objective: To assess the outcome and risk factors associated with mortality in patients with acute respiratory failure (ARF). Design: Observational study. Place and Duration of Study: The Aga Khan University Hospital, Karachi, between January 1997 and June 2001. Patients and Methods: All adult patients admitted with a medical cause of acute respiratory failure were reviewed. The primary outcome measure was mortality and secondary outcome measures were factors associated with mortality in ARF. Multiple logistic regression analysis was used to identify the independent risk factors for mortality. Results: A total of 270 patients were admitted with ARF. Hypercapnic respiratory failure was seen in 186 (69%) and hypoxemic in 84 (31%) cases. Pneumonia and COPD exacerbation were the most common underlying causes of ARF. Ventilator support was required in 93 (34.4%) patients. Hospital mortality was 28%. Chronic renal failure, malignancy, hypokalemia, severe acidosis (pH <7.25), septicemia and ARDS independently correlated with mortality. Mortality rate increased sharply (84%) with the presence of three or more risk factors. Conclusion: Acute respiratory failure has a high mortality rate (28%). Development of ARDS or septicemia was associated with high mortality. Presence of more than one risk factor significantly increased the mortality rate. (author)

  7. Risk factors for and impact of respiratory failure on mortality in the early phase of acute pancreatitis

    DEFF Research Database (Denmark)

    Dombernowsky, Tilde; Kristensen, Marlene Østermark; Rysgaard, Sisse

    2016-01-01

    : Retrospective cohort study including 359 patients admitted with acute pancreatitis. Information was gathered from electronic patient records. We defined respiratory failure based on the modified Marshall scoring system in the revised Atlanta criteria. Predictors of respiratory failure were evaluated......, or pneumonia may develop respiratory failure, suggests that acute lung injury, possibly associated with systemic inflammation, may be important.......BACKGROUND: The incidence of respiratory failure and other respiratory complications in the early phase of acute pancreatitis (AP) is not well investigated. OBJECTIVE: To evaluate the incidence and risk factors of respiratory failure, and its impact on mortality in the early phase AP. METHODS...

  8. End-of-life decision making in respiratory failure. The therapeutic choices in chronic respiratory failure in a 7-item questionnaire

    Directory of Open Access Journals (Sweden)

    Dagmar Elfriede Rinnenburger

    2012-01-01

    Full Text Available INTRODUCTION: The transition from paternalistic medicine to a healthcare culture centred on the patient's decision making autonomy presents problems of communication and understanding. Chronic respiratory failure challenges patients, their families and caregivers with important choices, such as invasive and non-invasive mechanical ventilation and tracheostomy, which, especially in the case of neuromuscular diseases, can significantly postpone the end of life. MATERIAL AND METHODS: A 7-item questionnaire was administered to 100 patients with advanced COPD, neuromuscular diseases and pulmonary fibrosis, all of them on oxygen therapy and receiving day-hospital treatment for respiratory failure. The objective was to find out whether or not patients, if faced with a deterioration of their health condition, would want to take part in the decision making process and, if so, how and with whom. RESULTS. Results showed that: 90% of patients wanted to be interviewed, 10% preferred not to be interviewed, 82% wanted to be regularly updated on their clinical situation, 75% wanted to be intubated, if necessary, and 56% would also agree to have a tracheostomy. These choices have been confirmed one year later, with 93% of respondents accepting the questionnaire and considering it useful. CONCLUSIONS: It is possible to conclude that a simple questionnaire can be a useful tool contributing to therapeutic decision making in respiratory failure.

  9. Technological advances in extracorporeal membrane oxygenation for respiratory failure.

    Science.gov (United States)

    Rehder, Kyle J; Turner, David A; Bonadonna, Desiree; Walczak, Richard J; Rudder, Robert J; Cheifetz, Ira M

    2012-08-01

    Extracorporeal membrane oxygenation (ECMO) for neonatal and pediatric cardiac and/or respiratory failure is well established, and its use for adult respiratory failure is rapidly increasing. Management strategies developed over the past 30 years coupled with significant recent technological advances have led to improved ECMO survival. These new technologies are expanding the potential applications for ECMO in exciting ways, including new patient populations and the ability to make ECMO mobile for both intra- and inter-hospital transport. In this article, we highlight some of the recent technological advances and their impact on the utilization of ECMO in increasingly diverse patient populations.

  10. Amyotrophic Lateral Sclerosis Presenting Respiratory Failure as the Sole Initial Manifestation

    Directory of Open Access Journals (Sweden)

    Fuyuki Tateno

    2014-08-01

    Full Text Available It is rare that amyotrophic lateral sclerosis (ALS presents with respiratory failure as the sole initial manifestation. A 72-year-old man with mild chronic obstructive pulmonary disease developed exertional dyspnea for 13 months. He then progressed to limb weakness that led to the diagnosis of ALS. Although rare, ALS can present with respiratory failure as the sole initial manifestation more than 1 year prior to limb weakness.

  11. Early predictors of success of non-invasive positive pressure ventilation in hypercapnic respiratory failure.

    Science.gov (United States)

    Bhattacharyya, D; Prasad, Bnbm; Tampi, P S; Ramprasad, R

    2011-10-01

    Non-invasive positive pressure ventilation (NIPPV) has emerged as a significant advancement in the management of acute hypercapnic respiratory failure. Patients with hypercapnic respiratory failure requiring ventilation therapy (respiratory rate [RR] of > 30 breaths per minutes, PaCO2 > 55 mmHg and arterial pH success group and these parameters continued to improve even after four and 24 hours of NIPPV treatment. Out of 24 (24%) patients who failed to respond, 13 (54%) needed endotracheal intubation within one hour. The failure group had higher baseline HR than the success group. Improvement in HR, RR, pH, and PCO2 one hour after putting the patient on NIPPV predicts success of non-invasive positive pressure ventilation in hypercapnic respiratory failure.

  12. Acute respiratory failure in asthma

    OpenAIRE

    Soubra Said; Guntupalli Kalapalatha

    2005-01-01

    Although asthma is a condition that is managed in the outpatient setting in most patients, the poorly controlled and severe cases pose a major challenge to the health-care team. Recognition of the more common insidious and the less common rapid onset "acute asphyxic" asthma are important. The intensivist needs to be familiar with the factors that denote severity of the exacerbation. The management of respiratory failure in asthma, including pharmacologic and mechanical ventilation, are discus...

  13. [Analogies between heart and respiratory muscle failure. Importance to clinical practice].

    Science.gov (United States)

    Köhler, D

    2009-01-01

    Heart failure is an established diagnosis. Respiratory muscle or ventilatory pump failure, however, is less well known. The latter becomes obvious through hypercapnia, caused by hypoventilation. The respiratory centre tunes into hypercapnea in order to prevent the danger of respiratory muscle overload (hypercapnic ventilatory failure). Hypoventilation will consecutively cause hypoxemia but this will not be responsible for performance limitation. One therefore has to distinguish primary hypoxemia evolving from diseases in the lung parenchyma. Here hypoxemia is the key feature and compensatory hyperventilation usually decreases PaCO2 levels. The cardiac as well as the respiratory pump adapt to an inevitable burden caused by chronic disease. In either case organ muscle mass will increase. If the burden exceeds the range of possible physiological adaptation, compensatory mechanisms will set in that are similar in both instances. During periods of overload either muscle system is mainly fueled by muscular glycogen. In the recovery phase (e. g. during sleep) stores are replenished, which can be recognized by down-regulation of the blood pressure in case of the cardiac pumb or by augmentation of hypercapnia through hypoventilation in case of the respiratory pump. The main function of cardiac and respiratory pump is maintenance of oxygen transport. The human body has developed certain compensatory mechanisms to adapt to insufficient oxygen supply especially during periods of overload. These mechanisms include shift of the oxygen binding curve, expression of respiratory chain isoenzymes capable of producing ATP at lower partial pressures of oxygen and the development of polyglobulia. Medically or pharmacologically the cardiac pump can be unloaded with beta blockers, the respiratory pump by application of inspired oxygen. Newer forms of therapy augment the process of recovery. The heart can be supported through bypass surgery or intravascular pump systems, while respiratory

  14. Hypoxic Episodes in Bronchopulmonary Dysplasia.

    Science.gov (United States)

    Martin, Richard J; Di Fiore, Juliann M; Walsh, Michele C

    2015-12-01

    Hypoxic episodes are troublesome components of bronchopulmonary dysplasia (BPD) in preterm infants. Immature respiratory control seems to be the major contributor, superimposed on abnormal respiratory function. Relatively short respiratory pauses may precipitate desaturation and bradycardia. This population is predisposed to pulmonary hypertension; it is likely that pulmonary vasoconstriction also plays a role. The natural history has been well-characterized in the preterm population at risk for BPD; however, the consequences are less clear. Proposed associations of intermittent hypoxia include retinopathy of prematurity, sleep disordered breathing, and neurodevelopmental delay. Future study should address whether these associations are causal relationships. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Determinants of noninvasive ventilation success or failure in morbidly obese patients in acute respiratory failure.

    Science.gov (United States)

    Lemyze, Malcolm; Taufour, Pauline; Duhamel, Alain; Temime, Johanna; Nigeon, Olivier; Vangrunderbeeck, Nicolas; Barrailler, Stéphanie; Gasan, Gaëlle; Pepy, Florent; Thevenin, Didier; Mallat, Jihad

    2014-01-01

    Acute respiratory failure (ARF) is a common life-threatening complication in morbidly obese patients with obesity hypoventilation syndrome (OHS). We aimed to identify the determinants of noninvasive ventilation (NIV) success or failure for this indication. We prospectively included 76 consecutive patients with BMI>40 kg/m2 diagnosed with OHS and treated by NIV for ARF in a 15-bed ICU of a tertiary hospital. NIV failed to reverse ARF in only 13 patients. Factors associated with NIV failure included pneumonia (n = 12/13, 92% vs n = 9/63, 14%; psuccessful response to NIV was idiopathic decompensation of OHS (n = 30, 48% vs n = 0, 0%; p = 0.001). In the NIV success group (n = 63), 33 patients (53%) experienced a delayed response to NIV (with persistent hypercapnic acidosis during the first 6 hours). Multiple organ failure and pneumonia were the main factors associated with NIV failure and death in morbidly obese patients in hypoxemic ARF. On the opposite, NIV was constantly successful and could be safely pushed further in case of severe hypercapnic acute respiratory decompensation of OHS.

  16. Acute Respiratory Failure due to Neuromyelitis Optica Treated Successfully with Plasmapheresis

    Directory of Open Access Journals (Sweden)

    Massa Zantah

    2016-01-01

    Full Text Available Neuromyelitis Optica (NMO is a demyelinating autoimmune disease involving the central nervous system. Acute respiratory failure from cervical myelitis due to NMO is known to occur but is uncommon in monophasic disease and is treated with high dose steroids. We report a case of a patient with NMO who developed acute respiratory failure related to cervical spinal cord involvement, refractory to pulse dose steroid therapy, which resolved with plasmapheresis.

  17. Acute respiratory failure requiring mechanical ventilation in severe chronic obstructive pulmonary disease (COPD).

    Science.gov (United States)

    Gadre, Shruti K; Duggal, Abhijit; Mireles-Cabodevila, Eduardo; Krishnan, Sudhir; Wang, Xiao-Feng; Zell, Katrina; Guzman, Jorge

    2018-04-01

    There are limited data on the epidemiology of acute respiratory failure necessitating mechanical ventilation in patients with severe chronic obstructive pulmonary disease (COPD). The prognosis of acute respiratory failure requiring invasive mechanical ventilation is believed to be grim in this population. The purpose of this study was to illustrate the epidemiologic characteristics and outcomes of patients with underlying severe COPD requiring mechanical ventilation.A retrospective study of patients admitted to a quaternary referral medical intensive care unit (ICU) between January 2008 and December 2012 with a diagnosis of severe COPD and requiring invasive mechanical ventilation for acute respiratory failure.We evaluated 670 patients with an established diagnosis of severe COPD requiring mechanical ventilation for acute respiratory failure of whom 47% were male with a mean age of 63.7 ± 12.4 years and Acute physiology and chronic health evaluation (APACHE) III score of 76.3 ± 27.2. Only seventy-nine (12%) were admitted with a COPD exacerbation, 27(4%) had acute respiratory distress syndrome (ARDS), 78 (12%) had pneumonia, 78 (12%) had sepsis, and 312 (47%) had other causes of respiratory failure, including pulmonary embolism, pneumothorax, etc. Eighteen percent of the patients received a trial of noninvasive positive pressure ventilation. The median duration of mechanical ventilation was 3 days (interquartile range IQR 2-7); the median duration for ICU length of stay (LOS) was 5 (IQR 2-9) days and the median duration of hospital LOS was 12 (IQR 7-22) days. The overall ICU mortality was 25%. Patients with COPD exacerbation had a shorter median duration of mechanical ventilation (2 vs 4 days; P = .04), ICU (3 vs 5 days; P = .01), and hospital stay (10 vs 13 days; P = .01). The ICU mortality (9% vs 27%; P respiratory failure. A 1-unit increase in the APACHE III score was associated with a 1% decrease and having an active cancer was associated

  18. Interhospital transfer of children in respiratory failure: a clinician interview qualitative study.

    Science.gov (United States)

    Odetola, Folafoluwa O; Anspach, Renee R; Han, Yong Y; Clark, Sarah J

    2017-02-01

    To investigate the decision making underlying transfer of children with respiratory failure from level II to level I pediatric intensive care unit care. Interviews with 19 eligible level II pediatric intensive care unit physicians about a hypothetical scenario of a 2-year-old girl in respiratory failure: RESULTS: At baseline, indices critical to management were as follows: OI (53%), partial pressure of oxygen in arterial blood (Pao 2 )/Fio 2 (32%), and inflation pressure (16%). Poor clinical response was signified by high OI, inflation pressure, and Fio 2 , and low Pao 2 /Fio 2 . At EP 1, 18 of 19 respondents would initiate high-frequency oscillatory ventilation, and 1 would transfer. At EP 2, 15 of 18 respondents would maintain high-frequency oscillatory ventilation, 9 of them calling to discuss transfer. All respondents would transfer if escalated therapies failed to reverse the patient's clinical deterioration. Interhospital transfer of children in respiratory failure is triggered by poor response to escalation of locally available care modalities. This finding provides new insight into decision making underlying interhospital transfer of children with respiratory failure. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. CESAR: conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure

    Directory of Open Access Journals (Sweden)

    Mugford Miranda

    2006-12-01

    Full Text Available Abstract Background An estimated 350 adults develop severe, but potentially reversible respiratory failure in the UK annually. Current management uses intermittent positive pressure ventilation, but barotrauma, volutrauma and oxygen toxicity can prevent lung recovery. An alternative treatment, extracorporeal membrane oxygenation, uses cardio-pulmonary bypass technology to temporarily provide gas exchange, allowing ventilator settings to be reduced. While extracorporeal membrane oxygenation is proven to result in improved outcome when compared to conventional ventilation in neonates with severe respiratory failure, there is currently no good evidence from randomised controlled trials to compare these managements for important clinical outcomes in adults, although evidence from case series is promising. Methods/Design The aim of the randomised controlled trial of Conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR is to assess whether, for patients with severe, but potentially reversible, respiratory failure, extracorporeal membrane oxygenation will increase the rate of survival without severe disability ('confined to bed' and 'unable to wash or dress' by six months post-randomisation, and be cost effective from the viewpoints of the NHS and society, compared to conventional ventilatory support. Following assent from a relative, adults (18–65 years with severe, but potentially reversible, respiratory failure (Murray score ≥ 3.0 or hypercapnea with pH Discussion Analysis will be based on intention to treat. A concurrent economic evaluation will also be performed to compare the costs and outcomes of both treatments.

  20. Plasma Orexin-A Levels in COPD Patients with Hypercapnic Respiratory Failure

    Directory of Open Access Journals (Sweden)

    Lin-Yun Zhu

    2011-01-01

    Full Text Available Orexins have previously been shown to promote wakefulness, regulate lipid metabolism and participate in energy homeostasis. The aim of the study was to determine the relationship between plasma orexin-A and body composition in COPD in-patients with hypercapnic respiratory failure. 40 patients with hypercapnic respiratory failure and 22 healthy individuals were enrolled prospectively in this study. Plasma orexin-A levels, BMI, SaO2, PaCO2 and PaO2 were noted for all the patients. Plasma orexin-A levels were higher in the underweight (UW group, normal weight (NW group and overweight (OW group of COPD patients as compared with UW, NW and OW group of the control group (P<.05. Plasma orexin-A in COPD patients were higher in the OW group than in the NW group and the UW group. Plasma orexin-A levels showed significant correlation with body mass index (BMI, independent of PaO2 (r=0.576; P<.05 and %fat (r=0.367; P<.05; a negative correlation was noted between plasma orexin-A levels and PaO2 (r=−0.738; P<.05 and SaO2 (r=−0.616; P<.05. Our results suggest that orexin-A levels are high in COPD patients with hypercapnic respiratory failure, and vary according to BMI and body composition. Orexin-A may be associated with the severity of hypoxemia in COPD patients with hypercapnic respiratory failure.

  1. Metabolic alkalosis contributes to acute hypercapnic respiratory failure in adult cystic fibrosis.

    Science.gov (United States)

    Holland, Anne E; Wilson, John W; Kotsimbos, Thomas C; Naughton, Matthew T

    2003-08-01

    and study objectives: Patients with end-stage cystic fibrosis (CF) develop respiratory failure and hypercapnia. In contrast to COPD patients, altered electrolyte transport and malnutrition in CF patients may predispose them to metabolic alkalosis and, therefore, may contribute to hypercapnia. The aim of this study was to determine the prevalence of metabolic alkalosis in adults with hypercapnic respiratory failure in the setting of acute exacerbations of CF compared with COPD. Levels of arterial blood gases, plasma electrolytes, and serum albumin from 14 consecutive hypercapnic CF patients who had been admitted to the hospital with a respiratory exacerbation were compared with 49 consecutive hypercapnic patients with exacerbations of COPD. Hypercapnia was defined as a PaCO(2) of > or = 45 mm Hg. Despite similar PaCO(2) values, patients in the CF group were significantly more alkalotic than were those in the COPD group (mean [+/- SD] pH, 7.43 +/- 0.03 vs 7.37 +/- 0.05, respectively; p respiratory acidosis and metabolic alkalosis was evident in 71% of CF patients and 22% of COPD patients (p alkalosis contributes to hypercapnic respiratory failure in adults with acute exacerbations of CF. This acid-base disturbance occurs in conjunction with reduced total body salt levels and hypoalbuminemia.

  2. Successful management of acute respiratory failure with noninvasive mechanical ventilation after drowning, in an epileptic-patient

    Directory of Open Access Journals (Sweden)

    Paolo Ruggeri

    2016-01-01

    Full Text Available Sea drowning is a common cause of accidental death worldwide. Respiratory complications such as acute pulmonary oedema, which is often complicated by acute respiratory distress syndrome, is often seen. Noninvasive ventilation is already widely used as a first approach to treat acute respiratory failure resulting from multiple diseases. We report a case of a 45 year old man with a history of epilepsy, motor and mental handicap who developed acute respiratory failure secondary to sea water drowning after an epileptic crisis. We illustrate successful and rapid management of this case with noninvasive ventilation. We emphasize the advantages and limitations of using noninvasive ventilation to treat acute respiratory failure due to sea water drowning syndrome.

  3. Hypoxic-cell sensitizers

    International Nuclear Information System (INIS)

    Dische, S.

    1983-01-01

    There is now 6 years of clinical experience with misonidazole as a hypoxic-cell sensitizer. Neurotoxicity limits the total dose which may be given, and so relatively low concentrations of radiosensitizing drugs are likely to be achieved in hypoxic cells in man as compared with those in animal tumors. It is likely that benefit will only be shown in those situations where radioresistant hypoxic cells strongly dominate as a cause of radiation failure. Many clinical trials are underway, and thus far some show no benefit while in others there is a definite advantage to the patients given the drug. These trials must be continued to their conclusion, but misonidazole must be regarded as the first of a series of radiosensitizers to reach the clinic for trial. There is a promise of more effective drugs becoming available within the next few years. Those showing a lower lipophilicity than misonidazole have been found to have a shorter half-life and a lower uptake in neural tissue in animal studies. One such drug, desmethylmisonidazole, is presently undergoing clinical trial

  4. Phrenic Nerve Conduction Study in the Early Stage of Guillain-Barre Syndrome as a Predictor of Respiratory Failure.

    Science.gov (United States)

    Sen, Barun Kumar; Pandit, Alak

    2018-01-01

    Guillain-Barré syndrome (GBS) has unpredictable clinical course with severe complication of respiratory failure. To identify clinical profiles and electrophysiological study particularly non-invasive Phrenic nerve conduction study in patients of early GBS to predict respiratory failure. 64 adult (age≥18yrs) patients of early GBS (onset ≤ 14 days) during the study period from January 2014 to October 2015 were evaluated by clinical profiles of age, gender, antecedent infection, time to peak disability, single breath counts, cranial nerve involvement, autonomic dysfunction and non-invasive Phrenic nerve conduction study. Patients with predisposition factors of polyneuropathy like diabetes mellitus, hypothyroidism, vitamin deficiency, renal failure were excluded. Among 64 patients abnormal phrenic nerve conduction study was seen in 65.62% cases (42/64) and 45.23% (19/42) of them developed respiratory failure. Phrenic nerve sum latency, amplitude, duration and area were abnormal in those who developed respiratory failure and they had sum of phrenic nerve latency >28 msec, sum of CMAP amplitude 50 msec and sum of area phrenic nerve study developed respiratory failure. It was found that age, gender, preceding infection, autonomic involvement and types of GB syndrome had no influence on development of respiratory failure (p>0.05). Rapid disease progression to peak disability, more severe disease, shorter single breath counts and cranial nerve involvement were seen more often in patients with respiratory failure. Abnormal Phrenic nerve conduction study in the early Guillain-Barré syndrome might be of great value independently in predicting impending respiratory failure.

  5. Phrenic Nerve Conduction Study in the Early Stage of Guillain–Barre Syndrome as a Predictor of Respiratory Failure

    Science.gov (United States)

    Sen, Barun Kumar; Pandit, Alak

    2018-01-01

    Background: Guillain-Barré syndrome (GBS) has unpredictable clinical course with severe complication of respiratory failure. Objective: To identify clinical profiles and electrophysiological study particularly non-invasive Phrenic nerve conduction study in patients of early GBS to predict respiratory failure. Methods: 64 adult (age≥18yrs) patients of early GBS (onset ≤ 14 days) during the study period from January 2014 to October 2015 were evaluated by clinical profiles of age, gender, antecedent infection, time to peak disability, single breath counts, cranial nerve involvement, autonomic dysfunction and non-invasive Phrenic nerve conduction study. Patients with predisposition factors of polyneuropathy like diabetes mellitus, hypothyroidism, vitamin deficiency, renal failure were excluded. Results: Among 64 patients abnormal phrenic nerve conduction study was seen in 65.62% cases (42/64) and 45.23% (19/42) of them developed respiratory failure. Phrenic nerve sum latency, amplitude, duration and area were abnormal in those who developed respiratory failure and they had sum of phrenic nerve latency >28 msec, sum of CMAP amplitude 50 msec and sum of area phrenic nerve study developed respiratory failure. It was found that age, gender, preceding infection, autonomic involvement and types of GB syndrome had no influence on development of respiratory failure (p>0.05). Rapid disease progression to peak disability, more severe disease, shorter single breath counts and cranial nerve involvement were seen more often in patients with respiratory failure. Conclusion: Abnormal Phrenic nerve conduction study in the early Guillain-Barré syndrome might be of great value independently in predicting impending respiratory failure. PMID:29720799

  6. Relationship between respiratory failure and plasma noradrenaline levels in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Yamashita, A; Koike, Y; Takahashi, A; Hirayama, M; Murakami, N; Sobue, G

    1997-08-01

    We evaluated plasma noradrenaline (NA) levels at test and during head-up tilt test in 20 patients with sporadic amyotrophic lateral sclerosis (ALS). Their fasting plasma NA levels ranged from 195 to 4227 pg/ml. The average plasma NA level was 483 pg/ml in five ambulatory patients, 341 in two wheelchair-bound patients, 1264 in 11 bedridden patients, and 208 in two respirator-dependent patients whose disability grading was the worst among the four groups. Arterial carbon dioxide (PCO2) was evaluated as a measure of respiratory function. The coefficient of correlation between PCO2 and plasma NA was r = 0.654 (p respiratory failure or lower motor neuron dysfunction may relate to the elevation of plasma NA levels. In the two bedridden patients, plasma NA levels and heart rate at rest increased significantly as the disease progressed. Cardiovascular responses to head-up tilting were normal. These data suggest that the elevation of plasma NA levels may be related to progression of respiratory failure and lower motor neuron dysfunction. In conclusion, sympathetic hyperactivity in ALS is considered to be not primary, but secondary to somatic motor disabilities and respiratory failure.

  7. pRotective vEntilation with veno-venouS lung assisT in respiratory failure: A protocol for a multicentre randomised controlled trial of extracorporeal carbon dioxide removal in patients with acute hypoxaemic respiratory failure.

    Science.gov (United States)

    McNamee, J J; Gillies, M A; Barrett, N A; Agus, A M; Beale, R; Bentley, A; Bodenham, A; Brett, S J; Brodie, D; Finney, S J; Gordon, A J; Griffiths, M; Harrison, D; Jackson, C; McDowell, C; McNally, C; Perkins, G D; Tunnicliffe, W; Vuylsteke, A; Walsh, T S; Wise, M P; Young, D; McAuley, D F

    2017-05-01

    One of the few interventions to demonstrate improved outcomes for acute hypoxaemic respiratory failure is reducing tidal volumes when using mechanical ventilation, often termed lung protective ventilation. Veno-venous extracorporeal carbon dioxide removal (vv-ECCO 2 R) can facilitate reducing tidal volumes. pRotective vEntilation with veno-venouS lung assisT (REST) is a randomised, allocation concealed, controlled, open, multicentre pragmatic trial to determine the clinical and cost-effectiveness of lower tidal volume mechanical ventilation facilitated by vv-ECCO 2 R in patients with acute hypoxaemic respiratory failure. Patients requiring intubation and mechanical ventilation for acute hypoxaemic respiratory failure will be randomly allocated to receive either vv-ECCO 2 R and lower tidal volume mechanical ventilation or standard care with stratification by recruitment centre. There is a need for a large randomised controlled trial to establish whether vv-ECCO 2 R in acute hypoxaemic respiratory failure can allow the use of a more protective lung ventilation strategy and is associated with improved patient outcomes.

  8. January 2015 Phoenix pulmonary journal club: noninvasive ventilation in acute respiratory failure

    Directory of Open Access Journals (Sweden)

    Mathew M

    2015-01-01

    Full Text Available No abstract available. Article truncated after 150 words. Noninvasive positive pressure ventilation has expanded its role in the treatment of both chronic and acute respiratory failure. Its initial use in conditions such as obstructive sleep apnea, neuromuscular disease and tracheobronchomalacia, have been shown to improve quality of life and reduce mortality. Over the past 20 years studies have looked at using noninvasive ventilation in the management of acute respiratory failure from pulmonary edema, asthma and COPD exacerbations. During this month's journal club we reviewed 3 articles evaluating the efficacy of noninvasive ventilation in acute respiratory failure. Gupta D, Nath A, Agarwal R, Behera D. A prospective randomized controlled trial on the efficacy of noninvasive ventilation in severe acute asthma. Respir Care. 2010;55(5:536-43. [PubMed] This was a small unblinded randomized controlled trial (RCT looking at the efficacy using noninvasive ventilation (NIV in acute asthma. A total of 53 patients were included and divided into 2 groups of 28 patients ...

  9. A comparison of volume control and pressure-regulated volume control ventilation in acute respiratory failure

    OpenAIRE

    Guldager, Henrik; Nielsen, Soeren L; Carl, Peder; Soerensen, Mogens B

    1997-01-01

    Background: The aim of this study was to test the hypothesis that a new mode of ventilation (pressure-regulated volume control; PRVC) is associated with improvements in respiratory mechanics and outcome when compared with conventional volume control (VC) ventilation in patients with acute respiratory failure. We conducted a randomised, prospective, open, cross over trial on 44 patients with acute respiratory failure in the general intensive care unit of a university hospital. After a stabiliz...

  10. Management of hypoxaemic respiratory failure in a Respiratory High-dependency Unit.

    Science.gov (United States)

    Hukins, Craig; Wong, Mimi; Murphy, Michelle; Upham, John

    2017-07-01

    There are limited data on outcomes of hypoxaemic respiratory failure (HRF), especially in non-intensive care unit (ICU) settings. To assess outcomes in HRF (without multi-system disease and not requiring early intubation) of patients directly admitted to a Respiratory High-dependency Unit (R-HDU). This is a retrospective cohort study of HRF compared to hypercapnic respiratory failure (HCRF) in a R-HDU (2007-2011). Patient characteristics (age, gender, pre-morbid status, diagnoses) and outcomes (non-invasive ventilation (NIV) use, survival, ICU admission) were assessed. There were 1207 R-HDU admissions in 2007-2011, 205 (17%) with HRF and 495 (41%) with HCRF. The proportion with HRF increased from 12.2% in 2007 to 20.1% in 2011 (P < 0.05). HRF patients were younger, more often male and had better pre-morbid performance. Compared to HCRF, HRF was more frequently associated with lung consolidation (61% vs 15%, P < 0.001), interstitial lung disease (12% vs 1%, P < 0.001) and pulmonary hypertension (7% vs 0%, P < 0.001) and less frequently with chronic obstructive pulmonary disease (24% vs 65%, P < 0.001) and obstructive sleep apnoea (8% vs 26%, P < 0.001). Fewer patients with HRF were treated with NIV (28% vs 87%, P < 0.001), but NIV was discontinued early more often (28% vs 7%, P < 0.001). A total of 18% with HRF was transferred to ICU compared to 6% with HCRF (P = 0.06). More patients with HRF died (19.5% vs 12.3%, P = 0.02). Interstitial lung disease, consolidation, shock, malignancy and poorer pre-morbid function were associated with increased mortality. Initial R-HDU management is an effective option in selected HRF to reduce ICU demand, although mortality and clinical deterioration despite NIV are more common than in HCRF. © 2017 Royal Australasian College of Physicians.

  11. Repeated Bronchoscopy - Treatment of Severe Respiratory Failure in a Fire Victim

    Directory of Open Access Journals (Sweden)

    Petris Ovidiu Rusalim

    2017-10-01

    Full Text Available A case of respiratory failure in a domestic fire victim presenting with 1-3-degree skin burns on 10% of the total body surface, is reported. Forty-eight hours after admission to hospital, the patient developed severe respiratory failure that did not respond to mechanical ventilation. Severe obstruction of the airway had resulted from secretions and deposits of soot forming bronchial casts. The patient required repeated bronchoscopies to separate and remove the bronchial secretions and soot deposits. An emergency bronchial endoscopic exam was crucial in the patient’s survival and management. The patient was discharged from the hospital after twenty-four days.

  12. Pulmonary hydatid cyst in a pregnant patient causing acute respiratory failure

    Directory of Open Access Journals (Sweden)

    Hijazi Mohammed

    2007-01-01

    Full Text Available A 21-year-old primigravida, at 32 weeks of gestation, presented with acute onset of respiratory failure and circulatory shock. Chest imaging showed findings suggestive of ruptured hydatid cyst, which was confirmed by histology post-thoracotomy. Tissue cultures from the removed cyst grew Mycobacterium tuberculosis also. She was successfully managed in the intensive care unit and was then discharged home on antituberculosis medications in addition to albendazole after prolonged hospitalization and a need for chest tube for bronchopleural fistula. Acute respiratory failure and anaphylactic shock secondary to ruptured pulmonary hydatid cyst and superimposed pulmonary tuberculosis in a pregnant lady should be considered in patients living in endemic areas.

  13. Determinants of noninvasive ventilation success or failure in morbidly obese patients in acute respiratory failure.

    Directory of Open Access Journals (Sweden)

    Malcolm Lemyze

    Full Text Available Acute respiratory failure (ARF is a common life-threatening complication in morbidly obese patients with obesity hypoventilation syndrome (OHS. We aimed to identify the determinants of noninvasive ventilation (NIV success or failure for this indication.We prospectively included 76 consecutive patients with BMI>40 kg/m2 diagnosed with OHS and treated by NIV for ARF in a 15-bed ICU of a tertiary hospital.NIV failed to reverse ARF in only 13 patients. Factors associated with NIV failure included pneumonia (n = 12/13, 92% vs n = 9/63, 14%; p<0.0001, high SOFA (10 vs 5; p<0.0001 and SAPS2 score (63 vs 39; p<0.0001 at admission. These patients often experienced poor outcome despite early resort to endotracheal intubation (in-hospital mortality, 92.3% vs 17.5%; p<0.001. The only factor significantly associated with successful response to NIV was idiopathic decompensation of OHS (n = 30, 48% vs n = 0, 0%; p = 0.001. In the NIV success group (n = 63, 33 patients (53% experienced a delayed response to NIV (with persistent hypercapnic acidosis during the first 6 hours.Multiple organ failure and pneumonia were the main factors associated with NIV failure and death in morbidly obese patients in hypoxemic ARF. On the opposite, NIV was constantly successful and could be safely pushed further in case of severe hypercapnic acute respiratory decompensation of OHS.

  14. Acetazolamide improves oxygenation in patients with respiratory failure and metabolic alkalosis.

    Science.gov (United States)

    Gulsvik, Ragnhild; Skjørten, Ingunn; Undhjem, Kenneth; Holø, Lars; Frostad, Anne; Saure, Eirunn Waatevik; Lejlic, Vasvija; Humerfelt, Sjur; Hansen, Gunnar; Bruun Wyller, Torgeir

    2013-10-01

    Coexistent respiratory failure and metabolic alkalosis is a common finding. Acidotic diuretics cause a fall in pH that may stimulate respiration. The purpose of the study was to evaluate the effectiveness of short-term treatment with acetazolamide for combined respiratory failure and metabolic alkalosis. A randomised, placebo-controlled and double-blind parallel group trial where oral acetazolamide 250 mg three times a day for 5 days were administered to patients hospitalised for respiratory failure because of a pulmonary disease (Pa O2 ≤ 8 kPa and/or Pa CO2 ≥ 7 kPa) who had concurrent metabolic alkalosis [base excess (BE) ≥ 8 mmol/L]. Pa O2 after 5 days was the primary effect variable. Secondary effect variables were Pa CO2 , BE and pH on day 5, and the total number of days in hospital. Of 70 patients enrolled (35 in each group), data from 54 were analysed per protocol, while last observation carried forward was used for the remaining 16. During the 5-day treatment, Pa O2 increased on average 0.81 kPa in the placebo group and 1.41 kPa in the acetazolamide group. After adjustment for baseline skewness, the difference was statistically significant (adjusted mean difference 0.55 kPa, 95% confidence interval 0.03-1.06). Pa CO2 decreased in both groups, but the difference was not statistically significant. As expected, pH and BE decreased markedly in the acetazolamide group. Acetazolamide may constitute a useful adjuvant treatment mainly to be considered in selected patients with respiratory failure combined with prominent metabolic alkalosis or where non-invasive ventilation is insufficient or infeasible. © 2013 John Wiley & Sons Ltd.

  15. New Combined Scoring System for Predicting Respiratory Failure in Iraqi Patients with Guillain-Barré Syndrome

    Directory of Open Access Journals (Sweden)

    Zaki Noah Hasan

    2010-09-01

    Full Text Available The Guillain-Barré syndrome (GBS is an acute post-infective autoimmune polyradiculoneuropathy, it is the commonest peripheral neuropathy causing respiratory failure. The aim of the study is to use the New Combined Scoring System in anticipating respiratory failure in order to perform elective measures without waiting for emergency situations to occur.
    Patients and methods: Fifty patients with GBS were studied. Eight clinical parameters (including progression of patients to maximum weakness, respiratory rate/minute, breath holding
    count (the number of digits the patient can count in holding his breath, presence of facial muscle weakness (unilateral or bilateral, presence of weakness of the bulbar muscle, weakness of the neck flexor muscle, and limbs weakness were assessed for each patient and a certain score was given to
    each parameter, a designed combined score being constructed by taking into consideration all the above mentioned clinical parameters. Results and discussion: Fifteen patients (30% that were enrolled in our study developed respiratory failure. There was a highly significant statistical association between the development of respiratory failure and the lower grades of (bulbar muscle weakness score, breath holding count scores, neck muscle weakness score, lower limbs and upper limbs weakness score , respiratory rate score and the total sum score above 16 out of 30 (p-value=0.000 . No significant statistical difference was found regarding the progression to maximum weakness (p-value=0.675 and facial muscle weakness (p-value=0.482.
    Conclusion: The patients who obtained a combined score (above 16’30 are at great risk of having respiratory failure.

  16. Successful Treatment of Fibrosing Organising Pneumonia Causing Respiratory Failure with Mycophenolic Acid.

    Science.gov (United States)

    Paul, Christina; Lin-Shaw, Ammy; Joseph, Mariamma; Kwan, Keith; Sergiacomi, Gianluigi; Mura, Marco

    2016-01-01

    Organising pneumonia (OP) is usually promptly responsive to corticosteroid treatment. We describe a series of 3 cases of severe, progressive, biopsy-proven fibrosing OP causing respiratory failure. All cases presented with peribronchial and subpleural consolidations, had a fibro-inflammatory infiltrative component in the alveolar septa, and only had a partial and unsatisfactory response to corticosteroids. However, they responded to mycophenolic acid (MPA) treatment with resolution of respiratory failure as well as clinical and functional improvement. MPA as an additional treatment option for aggressive forms of fibrosing OP and interstitial lung disease needs to be further explored. © 2016 S. Karger AG, Basel.

  17. Progressive Diaphragm Atrophy in Pediatric Acute Respiratory Failure.

    Science.gov (United States)

    Glau, Christie L; Conlon, Thomas W; Himebauch, Adam S; Yehya, Nadir; Weiss, Scott L; Berg, Robert A; Nishisaki, Akira

    2018-02-05

    Diaphragm atrophy is associated with delayed weaning from mechanical ventilation and increased mortality in critically ill adults. We sought to test for the presence of diaphragm atrophy in children with acute respiratory failure. Prospective, observational study. Single-center tertiary noncardiac PICU in a children's hospital. Invasively ventilated children with acute respiratory failure. Diaphragm thickness at end-expiration and end-inspiration were serially measured by ultrasound in 56 patients (median age, 17 mo; interquartile range, 5.5-52), first within 36 hours of intubation and last preceding extubation. The median duration of mechanical ventilation was 140 hours (interquartile range, 83-201). At initial measurement, thickness at end-expiration was 2.0 mm (interquartile range, 1.8-2.5) and thickness at end-inspiration was 2.5 mm (interquartile range, 2-2.8). The change in thickness at end-expiration during mechanical ventilation between first and last measurement was -13.8% (interquartile range, -27.4% to 0%), with a -3.4% daily atrophy rate (interquartile range, -5.6 to 0%). Thickening fraction = ([thickness at end-inspiration - thickness at end-expiration]/thickness at end-inspiration) throughout the course of mechanical ventilation was linearly correlated with spontaneous breathing fraction (beta coefficient, 9.4; 95% CI, 4.2-14.7; p = 0.001). For children with a period of spontaneous breathing fraction less than 0.5 during mechanical ventilation, those with exposure to a continuous neuromuscular blockade infusion (n = 15) had a significantly larger decrease in thickness at end-expiration compared with children with low spontaneous breathing fraction who were not exposed to a neuromuscular blockade infusion (n = 18) (-16.4%, [interquartile range, -28.4% to -7.0%] vs -7.3%; [interquartile range, -10.9% to -0%]; p = 0.036). Diaphragm atrophy is present in children on mechanical ventilation for acute respiratory failure. Diaphragm contractility, measured as

  18. CESAR: conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure.

    Science.gov (United States)

    Peek, Giles J; Clemens, Felicity; Elbourne, Diana; Firmin, Richard; Hardy, Pollyanna; Hibbert, Clare; Killer, Hilliary; Mugford, Miranda; Thalanany, Mariamma; Tiruvoipati, Ravin; Truesdale, Ann; Wilson, Andrew

    2006-12-23

    An estimated 350 adults develop severe, but potentially reversible respiratory failure in the UK annually. Current management uses intermittent positive pressure ventilation, but barotrauma, volutrauma and oxygen toxicity can prevent lung recovery. An alternative treatment, extracorporeal membrane oxygenation, uses cardio-pulmonary bypass technology to temporarily provide gas exchange, allowing ventilator settings to be reduced. While extracorporeal membrane oxygenation is proven to result in improved outcome when compared to conventional ventilation in neonates with severe respiratory failure, there is currently no good evidence from randomised controlled trials to compare these managements for important clinical outcomes in adults, although evidence from case series is promising. The aim of the randomised controlled trial of Conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR) is to assess whether, for patients with severe, but potentially reversible, respiratory failure, extracorporeal membrane oxygenation will increase the rate of survival without severe disability ('confined to bed' and 'unable to wash or dress') by six months post-randomisation, and be cost effective from the viewpoints of the NHS and society, compared to conventional ventilatory support. Following assent from a relative, adults (18-65 years) with severe, but potentially reversible, respiratory failure (Murray score >/= 3.0 or hypercapnea with pH service will minimise by type of conventional treatment centre, age, duration of high pressure ventilation, hypoxia/hypercapnea, diagnosis and number of organs failed, to ensure balance in key prognostic variables. Extracorporeal membrane oxygenation will not be available for patients meeting entry criteria outside the trial. 180 patients will be recruited to have 80% power to be able to detect a one third reduction in the primary outcome from 65% at 5% level of statistical significance

  19. Acute respiratory failure in 3 children with juvenile myelomonocytic leukemia

    DEFF Research Database (Denmark)

    Gustafsson, Britt; Hellebostad, Marit; Ifversen, Marianne

    2011-01-01

    Juvenile myelomonocytic leukemia is a rare hematopoietic stem cell disease in children with features of both myelodysplasia and myeloproliferation. Extramedullary involvement has been reported and pulmonary involvement secondary to leukemic infiltration is an initial manifestation, which may resu...... in acute respiratory failure....

  20. Stridor and respiratory failure due to tracheobronchomalacia: case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Ramon Andrade de Mello

    Full Text Available CONTEXT: Tracheobronchomalacia (TBM results from structural and functional abnormalities of the respiratory system. It is characterized by excessive collapse: at least 50% of the cross-sectional area of the trachea and main bronchi. In this paper, we present a rare case of a patient with TBM who first presented with stridor and respiratory failure due to exacerbation of chronic bronchitis. CASE REPORT: An 81-year-old Caucasian man was admitted presenting coughing, purulent sputum, stridor and respiratory failure. He had a medical history of chronic obstructive pulmonary disease (COPD and silicosis and was a former smoker. Axial computed tomography on the chest revealed marked collapse of the trachea in its middle third. Bronchoscopy showed characteristics compatible with TBM. He was treated with noninvasive ventilation, without any good response. Subsequently, a Dumon Y stent was placed by means of rigid bronchoscopy. After the procedure, he was discharged with a clinical improvement. CONCLUSION: TBM is fatal and often underdiagnosed. In COPD patients, stridor and respiratory failure may be helpful signs that should alert physicians to consider TBM as an early diagnosis. Thus, these signs may be important for optimizing the treatment and evolution of such patients.

  1. Using a virtual breakthrough series collaborative to reduce postoperative respiratory failure in 16 Veterans Health Administration hospitals.

    Science.gov (United States)

    Zubkoff, Lisa; Neily, Julia; Mills, Peter D; Borzecki, Ann; Shin, Marlena; Lynn, Marilyn M; Gunnar, William; Rosen, Amy

    2014-01-01

    The Institute for Healthcare Improvement (IHI) Virtual Breakthrough Series (VBTS) process was used in an eight-month (June 2011-January 2012) quality improvement (QI) project to improve care related to reducing postoperative respiratory failure. The VBTS collaborative drew on Patient Safety Indicator 11: Postoperative Respiratory Failure Rate to guide changes in care at the bedside. Sixteen Veterans Health Administration hospitals, each representing a regional Veterans Integrated Service Network, participated in the QI project. During the prework phase (initial two months), hospitals formed multidisciplinary teams, selected measures related to their goals, and collected baseline data. The six-month action phase included group conference calls in which the faculty presented clinical background on the topic, discussed evidence-based processes of care, and/or presented content regarding reducing postoperative respiratory failure. During a final, six-month continuous improvement and spread phase, teams were to continue implementing changes as part of their usual processes. The six most commonly reported interventions to reduce postoperative respiratory failure focused on improving incentive spirometer use, documenting implementation of targeted interventions, oral care, standardized orders, early ambulation, and provider education. A few teams reported reduced ICU readmissions for respiratory failure. The VBTS collaborative helped teams implement process changes to help reduce postoperative respiratory complications. Teams reported initial success at implementing site-specific improvements using real-time data. The VBTS model shows promise for knowledge sharing and efficient multifacility improvement efforts, although long-term sustainability and testing in these and other settings need to be examined.

  2. Mechanism and Clinical Importance of Respiratory Failure Induced by Anticholinesterases

    Directory of Open Access Journals (Sweden)

    Ivosevic Anita

    2017-12-01

    Full Text Available Respiratory failure is the predominant cause of death in humans and animals poisoned with anticholinesterases. Organophosphorus and carbamate anticholinesterases inhibit acetylcholinesterase irreversibly and reversibly, respectively. Some of them contain a quaternary atom that makes them lipophobic, limiting their action at the periphery, i.e. outside the central nervous system. They impair respiratory function primarily by inducing a desensitization block of nicotinic receptors in the neuromuscular synapse. Lipophilic anticholinesterases inhibit the acetylcholinesterase both in the brain and in other tissues, including respiratory muscles. Their doses needed for cessation of central respiratory drive are significantly less than doses needed for paralysis of the neuromuscular transmission. Antagonist of muscarinic receptors atropine blocks both the central and peripheral muscarinic receptors and effectively antagonizes the central respiratory depression produced by anticholinesterases. To manage the peripheral nicotinic receptor hyperstimulation phenomena, oximes as acetylcholinesterase reactivators are used. Addition of diazepam is useful for treatment of seizures, since they are cholinergic only in their initial phase and can contribute to the occurrence of central respiratory depression. Possible involvement of central nicotinic receptors as well as the other neurotransmitter systems – glutamatergic, opioidergic – necessitates further research of additional antidotes.

  3. Variables predictive of outcome in patients with acute hypercapneic respiratory failure treated with noninvasive ventilation

    International Nuclear Information System (INIS)

    Salahuddin, N.; Irfan, M.; Khan, S.; Naeem, M.; Haque, A.S.

    2010-01-01

    To assess results with NIV in acute hypercapneic respiratory failure and to identify outcome predictors. This was a retrospective observational study on consecutive patients presenting with acute type II respiratory failure and meeting criteria for NIV use over a 5 year period. Patients presenting with haemodynamic instability, inability to protect their airway, malignant arrhythmias and recent oesophageal surgery were excluded. Univariate and Multivariate regression analysis was used to determine the impact on survival. A p value of 35 Meq/L (adjusted Odds ratio 0.9; 95% CI 0.83, 0.98, p < 0.015) identified those less at risk for intubation. NIV was found to be both safe and effective in the management of acute hypercapneic respiratory failure. Sepsis and serum HCO/sub 3/ at admission identified patients having poor outcomes (JPMA 60:13; 2010). (author)

  4. Adult venovenous extracorporeal membrane oxygenation for severe respiratory failure: Current status and future perspectives.

    Science.gov (United States)

    Sen, Ayan; Callisen, Hannelisa E; Alwardt, Cory M; Larson, Joel S; Lowell, Amelia A; Libricz, Stacy L; Tarwade, Pritee; Patel, Bhavesh M; Ramakrishna, Harish

    2016-01-01

    Extracorporeal membrane oxygenation (ECMO) for severe acute respiratory failure was proposed more than 40 years ago. Despite the publication of the ARDSNet study and adoption of lung protective ventilation, the mortality for acute respiratory failure due to acute respiratory distress syndrome has continued to remain high. This technology has evolved over the past couple of decades and has been noted to be safe and successful, especially during the worldwide H1N1 influenza pandemic with good survival rates. The primary indications for ECMO in acute respiratory failure include severe refractory hypoxemic and hypercarbic respiratory failure in spite of maximum lung protective ventilatory support. Various triage criteria have been described and published. Contraindications exist when application of ECMO may be futile or technically impossible. Knowledge and appreciation of the circuit, cannulae, and the physiology of gas exchange with ECMO are necessary to ensure lung rest, efficiency of oxygenation, and ventilation as well as troubleshooting problems. Anticoagulation is a major concern with ECMO, and the evidence is evolving with respect to diagnostic testing and use of anticoagulants. Clinical management of the patient includes comprehensive critical care addressing sedation and neurologic issues, ensuring lung recruitment, diuresis, early enteral nutrition, treatment and surveillance of infections, and multisystem organ support. Newer technology that delinks oxygenation and ventilation by extracorporeal carbon dioxide removal may lead to ultra-lung protective ventilation, avoidance of endotracheal intubation in some situations, and ambulatory therapies as a bridge to lung transplantation. Risks, complications, and long-term outcomes and resources need to be considered and weighed in before widespread application. Ethical challenges are a reality and a multidisciplinary approach that should be adopted for every case in consideration.

  5. Hypokalemic muscular paralysis causing acute respiratory failure due to rhabdomyolysis with renal tubular acidosis in a chronic glue sniffer.

    Science.gov (United States)

    Kao, K C; Tsai, Y H; Lin, M C; Huang, C C; Tsao, C Y; Chen, Y C

    2000-01-01

    A 34-year-old male was admitted to the emergency department with the development of quadriparesis and respiratory failure due to hypokalemia after prolonged glue sniffing. The patient was subsequently given mechanical ventilatory support for respiratory failure. He was weaned from the ventilator 4 days later after potassium replacement. Toluene is an aromatic hydrocarbon found in glues, cements, and solvents. It is known to be toxic to the nervous system, hematopoietic system, and causes acid-base and electrolyte disorders. Acute respiratory failure with hypokalemia and rhabdomyolysis with acute renal failure should be considered as potential events in a protracted glue sniffing.

  6. Respiratory failure following anti-lung serum: study on mechanisms associated with surfactant system damage

    International Nuclear Information System (INIS)

    Lachmann, B.; Hallman, M.; Bergmann, K.C.

    1987-01-01

    Within 2 minutes intravenous anti-lung serum (ALS) into guinea pig induces a respiratory failure that is fatal within 30 min. The relationship between surfactant, alveolar-capillary permeability and respiratory failure was studied. Within two minutes ALS induced a leak in the alveolar-capillary barrier. Within 30 minutes 28.3% (controls, given normal rabbit serum: 0.7%) of iv 131 I-albumin, and 0.5% (controls 0.02%) of iv surfactant phospholipid tracer were recovered in bronchoalveolar lavage. Furthermore, 57% (controls 32%) of the endotracheally administered surfactant phospholipid became associated with lung tissue and only less than 0.5% left the lung. The distribution of proteins and phospholipids between the in vivo small volume bronchoalveolar lavages and the ex vivo bronchoalveolar lavages were dissimilar: 84% (controls 20%) of intravenously injected, lavageable 131 I-albumin and 23% (controls 18%) of total lavageable phospholipid were recovered in the in vivo small volume bronchoalveolar lavages. ALS also decreased lavageable surfactant phospholipid by 41%. After ALS the minimum surface tension increased. The supernatant of the lavage increased the minimum surface tension of normal surfactant. In addition, the sediment fraction of the lavage had slow surface adsorption, and a marked reduction in 35,000 and 10,000 MW peptides. Exogenous surfactant ameliorated the ALS-induced respiratory failure. We propose that inhibition, altered intrapulmonary distribution, and dissociation of protein and phospholipid components of surfactant are important in early pathogenesis of acute respiratory failure

  7. Hypercapnic Respiratory Acidosis During An In-Flight Oxygen Assessment.

    Science.gov (United States)

    Spurling, Kristofer J; Moonsie, Ian K; Perks, Joseph L

    2016-02-01

    Patients with respiratory disease are at risk of excessive hypoxemia in the hypobaric commercial aircraft cabin environment, and the consensus is that this is easily corrected with supplementary oxygen. However, despite the risks of hypercapnia with increasing inspired oxygen in some patients being well established, this issue is not currently addressed in medical guidelines for air travel. A 76-yr-old woman with chronic type 2 respiratory failure underwent hypoxic challenge testing (HCT) to assess in-flight oxygen requirements. She is stable on home ventilation, and baseline arterial blood gases showed mild hypoxemia (Pao2 9.12 kPa), normal P(a)co(2) (5.64 kPa) and pH (7.36) with 98% S(p)O(2). HCT was performed delivering 15% FIo(2) via a mask, and the patient desaturated to respiratory acidosis (pH 7.25). The patient was advised against flying due to hypoxemia during HCT and the precipitous drop in pH on oxygen. It is possible to hyperoxygenate patients with type 2 respiratory failure in flight with the minimum level of supplementary oxygen available on many aircraft. In these cases P(a)co(2) and pH should be scrutinized during HCT before recommending in-flight oxygen. No current guidelines discuss the risk of hypercapnia from in-flight oxygen; it is therefore recommended that this be addressed in future revisions of medical air travel guidelines, should further research indicate it.

  8. Adult venovenous extracorporeal membrane oxygenation for severe respiratory failure: Current status and future perspectives

    Directory of Open Access Journals (Sweden)

    Ayan Sen

    2016-01-01

    Full Text Available Extracorporeal membrane oxygenation (ECMO for severe acute respiratory failure was proposed more than 40 years ago. Despite the publication of the ARDSNet study and adoption of lung protective ventilation, the mortality for acute respiratory failure due to acute respiratory distress syndrome has continued to remain high. This technology has evolved over the past couple of decades and has been noted to be safe and successful, especially during the worldwide H1N1 influenza pandemic with good survival rates. The primary indications for ECMO in acute respiratory failure include severe refractory hypoxemic and hypercarbic respiratory failure in spite of maximum lung protective ventilatory support. Various triage criteria have been described and published. Contraindications exist when application of ECMO may be futile or technically impossible. Knowledge and appreciation of the circuit, cannulae, and the physiology of gas exchange with ECMO are necessary to ensure lung rest, efficiency of oxygenation, and ventilation as well as troubleshooting problems. Anticoagulation is a major concern with ECMO, and the evidence is evolving with respect to diagnostic testing and use of anticoagulants. Clinical management of the patient includes comprehensive critical care addressing sedation and neurologic issues, ensuring lung recruitment, diuresis, early enteral nutrition, treatment and surveillance of infections, and multisystem organ support. Newer technology that delinks oxygenation and ventilation by extracorporeal carbon dioxide removal may lead to ultra-lung protective ventilation, avoidance of endotracheal intubation in some situations, and ambulatory therapies as a bridge to lung transplantation. Risks, complications, and long-term outcomes and resources need to be considered and weighed in before widespread application. Ethical challenges are a reality and a multidisciplinary approach that should be adopted for every case in consideration.

  9. Respiratory acidosis

    Science.gov (United States)

    Ventilatory failure; Respiratory failure; Acidosis - respiratory ... Causes of respiratory acidosis include: Diseases of the airways (such as asthma and COPD ) Diseases of the lung tissue (such as ...

  10. [Predictive factors for failure of non-invasive positive pressure ventilation in immunosuppressed patients with acute respiratory failure].

    Science.gov (United States)

    Jia, Xiangli; Yan, Ci; Xu, Sicheng; Gu, Xingli; Wan, Qiufeng; Hu, Xinying; Li, Jingwen; Liu, Guangming; Caikai, Shareli; Guo, Zhijin

    2018-02-01

    To evaluate the predictive factors for failure of non-invasive positive pressure ventilation (NIPPV) in immunosuppressed patients with acute respiratory failure (ARF). The clinical data of 118 immuno-deficient patients treated with NIPPV in the respiratory and intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from January 2012 to August 2017 were retrospectively analyzed. The patients were divided into a non-endotracheal intubation (ETI) group (n = 62) and ETI group (n = 56) according to whether ETI was performed during the hospitalization period or not. Each observed indicator was analyzed by univariate analysis, and factors leading to failure of NIPPV were further analyzed by Logistic regression. Receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of risk factors for failure of NIPPV in immunosuppressed patients with ARF. The non-intubation rate for NIPPV in immunosuppressed patients was 50.8% (60/118). Compared with the non-ETI group, the body temperature, pH value in the ETI group were significantly increased, the partial pressure of arterial carbon dioxide (PaCO 2 ) was significantly decreased, the ratio of oxygenation index (PaO 2 /FiO 2 ) failure of NIPPV. ROC curve analysis showed that the APACHE II score ≥ 20 and PaO 2 /FiO 2 failure of NIPPV, the area under ROC curve (AUC) of the APACHE II score ≥ 20 was 0.787, the sensitivity was 83.93%, the specificity was 69.35%, the positive predict value (PPV) was 71.21%, the negative predict value (NPV) was 82.69%, the positive likelihood ratio (PLR) was 2.74, the negative likelihood ratio (NLR) was 0.23, and Youden index was 0.53; the AUC of PaO 2 /FiO 2 failure of NIPPV in immunocompromised patients.

  11. Immunoadjuvant Therapy and Noninvasive Ventilation for Acute Respiratory Failure in Lung Tuberculosis: A Case Study

    Directory of Open Access Journals (Sweden)

    René Agustín Flores-Franco

    2015-01-01

    Full Text Available Acute respiratory failure caused by pulmonary tuberculosis is a rare event but with a high mortality even while receiving mechanical ventilatory support. We report the case of a young man with severe pulmonary tuberculosis refractory to conventional therapy who successfully overcame the critical period of his condition using noninvasive ventilation and immunoadjuvant therapy that included three doses of etanercept 25 mg subcutaneously. We conclude that the use of etanercept along with antituberculosis treatment appears to be safe and effective in patients with pulmonary tuberculosis presenting with acute respiratory failure.

  12. Severe acute respiratory syndrome (SARS)

    Science.gov (United States)

    SARS; Respiratory failure - SARS ... Complications may include: Respiratory failure Liver failure Heart failure ... 366. McIntosh K, Perlman S. Coronaviruses, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). ...

  13. Health-related quality of life measurement in patients with chronic respiratory failure.

    Science.gov (United States)

    Oga, Toru; Windisch, Wolfram; Handa, Tomohiro; Hirai, Toyohiro; Chin, Kazuo

    2018-05-01

    The improvement of health-related quality of life (HRQL) is an important goal in managing patients with chronic respiratory failure (CRF) receiving long-term oxygen therapy (LTOT) and/or domiciliary noninvasive ventilation (NIV). Two condition-specific HRQL questionnaires have been developed to specifically assess these patients: the Maugeri Respiratory Failure Questionnaire (MRF) and the Severe Respiratory Insufficiency Questionnaire (SRI). The MRF is more advantageous in its ease of completion; conversely, the SRI measures diversified health impairments more multi-dimensionally and discriminatively with greater balance, especially in patients receiving NIV. The SRI is available in many different languages as a result of back-translation and validation processes, and is widely validated for various disorders such as chronic obstructive pulmonary disease, restrictive thoracic disorders, neuromuscular disorders, and obesity hypoventilation syndrome, among others. Dyspnea and psychological status were the main determinants for both questionnaires, while the MRF tended to place more emphasis on activity limitations than SRI. In comparison to existing generic questionnaires such as the Medical Outcomes Study 36-item short form (SF-36) and disease-specific questionnaires such as the St. George's Respiratory Questionnaire (SGRQ) and the Chronic Respiratory Disease Questionnaire (CRQ), both the MRF and the SRI have been shown to be valid and reliable, and have better discriminatory, evaluative, and predictive features than other questionnaires. Thus, in assessing the HRQL of patients with CRF using LTOT and/or NIV, we might consider avoiding the use of the SF-36 or even the SGRQ or CRQ alone and consider using the CRF-specific SRI and MRF in addition to existing generic and/or disease-specific questionnaires. Copyright © 2018 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  14. Creatine and creatine pyruvate reduce hypoxia-induced effects on phrenic nerve activity in the juvenile mouse respiratory system.

    Science.gov (United States)

    Scheer, Monika; Bischoff, Anna M; Kruzliak, Peter; Opatrilova, Radka; Bovell, Douglas; Büsselberg, Dietrich

    2016-08-01

    Adequate concentrations of ATP are required to preserve physiological cell functions and protect tissue from hypoxic damage. Decreased oxygen concentration results in ATP synthesis relying increasingly on the presence of phosphocreatine. The lack of ATP through hypoxic insult to neurons that generate or regulate respiratory function, would lead to the cessation of breathing (apnea). It is not clear whether creatine plays a role in maintaining respiratory phrenic nerve (PN) activity during hypoxic challenge. The aim of the study was to test the effects of exogenously applied creatine or creatine pyruvate in maintaining PN induced respiratory rhythm against the deleterious effects of severe hypoxic insult using Working Heart-Brainstem (WHB) preparations of juvenile Swiss type mice. WHB's were perfused with control perfusate or perfusate containing either creatine [100μM] or creatine pyruvate [100μM] prior to hypoxic challenge and PN activity recorded throughout. Results showed that severe hypoxic challenge resulted in an initial transient increase in PN activity, followed by a reduction in that activity leading to respiratory apnea. The results demonstrated that perfusing the WHB preparation with creatine or creatine pyruvate, significantly reduced the onset of apnea compared to control conditions, with creatine pyruvate being the more effective substance. Overall, creatine and creatine pyruvate each produced time-dependent degrees of protection against severe hypoxic-induced disturbances of PN activity. The underlying protective mechanisms are unknown and need further investigations. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Hypophosphatemia and duration of respiratory failure and mortality in critically ill patients

    DEFF Research Database (Denmark)

    Federspiel, C K; Itenov, T S; Thormar, K

    2018-01-01

    BACKGROUND: Hypophosphatemia has been associated with prolonged duration of respiratory failure and increased mortality in critically ill patients, but there is very limited evidence supporting the negative effects of low phosphate. We examined the association between hypophosphatemia at ICU...

  16. Efficacy of high-flow oxygen by nasal cannula with active humidification in a patient with acute respiratory failure of neuromuscular origin.

    Science.gov (United States)

    Díaz-Lobato, Salvador; Folgado, Miguel Angel; Chapa, Angel; Mayoralas Alises, Sagrario

    2013-12-01

    The treatment of choice for patients with respiratory failure of neuromuscular origin, especially in patients with hypercapnic respiratory acidosis, is noninvasive ventilation (NIV). Endotracheal intubation and invasive ventilation are indicated for patients with severe respiratory compromise or failure of NIV. In recent years, high-flow oxygen therapy and active humidification devices have been introduced, and emerging evidence suggests that high-flow oxygen may be effective in various clinical settings, such as acute respiratory failure, after cardiac surgery, during sedation and analgesia, in acute heart failure, in hypoxemic respiratory distress, in do-not-intubate patients, in patients with chronic cough and copious secretions, pulmonary fibrosis, or cancer, in critical areas and the emergency department. We report on a patient with amyotrophic lateral sclerosis who arrived at the emergency department with acute hypercapnic respiratory failure. She did not tolerate NIV and refused intubation, but was treated successfully with heated, humidified oxygen via high-flow nasal cannula. Arterial blood analysis after an hour on high-flow nasal cannula showed improved pH, P(aCO2), and awareness. The respiratory acidosis was corrected, and she was discharged after 5 days of hospitalization. Her response to high-flow nasal cannula was similar to that expected with NIV. We discuss the mechanisms of action of heated, humidified high-flow oxygen therapy.

  17. Large-area burns with pandrug-resistant Pseudomonas aeruginosa infection and respiratory failure.

    Science.gov (United States)

    Ning, Fang-Gang; Zhao, Xiao-Zhuo; Bian, Jing; Zhang, Guo-An

    2011-02-01

    Infection due to pandrug-resistant Pseudomonas aeruginosa (PDRPA) has become a challenge in clinical practice. The aim of this research was to summarize the treatment of large-area burns (60% - 80%) with PDRPA infection and respiratory failure in our hospital over the last two years, and to explore a feasible treatment protocol for such patients. We retrospectively analyzed the treatment of five patients with large-area burns accompanied by PDRPA infection and respiratory failure transferred to our hospital from burn units in hospitals in other Chinese cities from January 2008 to February 2010. Before PDRPA infection occurred, all five patients had open wounds with large areas of granulation because of the failure of surgery and dissolving of scar tissue; they had also undergone long-term administration of carbapenems. This therapy included ventilatory support, rigorous repair of wounds, and combined antibiotic therapy targeted at drug-resistance mechanisms, including carbapenems, ciprofloxacin, macrolide antibiotics and β-lactamase inhibitors. Four patients recovered from burns and one died after therapy. First, compromised immunity caused by delayed healing of burn wounds in patients with large-area burns and long-term administration of carbapenems may be the important factors in the initiation and progression of PDRPA infection. Second, if targeted at drug-resistance mechanisms, combined antibiotic therapy using carbapenems, ciprofloxacin, macrolide antibiotics and β-lactamase inhibitors could effectively control PDRPA infection. Third, although patients with large-area burns suffered respiratory failure and had high risks from anesthesia and surgery, only aggressive skin grafting with ventilatory support could control the infection and save lives. Patients may not be able to tolerate a long surgical procedure, so the duration of surgery should be minimized, and the frequency of surgery increased.

  18. Noninvasive radiographic assessment of cardiovascular function in acute and chronic respiratory failure

    International Nuclear Information System (INIS)

    Berger, H.J.; Matthay, R.A.

    1981-01-01

    Noninvasive radiographic techniques have provided a means of studying the natural history and pathogenesis of cardiovascular performance in acute and chronic respiratory failure. Chest radiography, radionuclide angiocardiography and thallium-201 imaging, and M mode and cross-sectional echocardiography have been employed. Each of these techniques has specific uses, attributes and limitations. For example, measurement of descending pulmonary arterial diameters on the plain chest radiograph allows determination of the presence or absence of pulmonary arterial hypertension. Right and left ventricular performance can be evaluated at rest and during exercise using radionuclide angiocardiography. The biventricular response to exercise and to therapeutic interventions also can be assessed with this approach. Evaluation of the pulmonary valve echogram and echocardiographic right ventricular dimensions have been shown to reflect right ventricular hemodynamics and size. Each of these noninvasive techniques has been applied to the study of patients with respiratory failure and has provided important physiologic data

  19. Intermittent hypoxic episodes in preterm infants: do they matter?

    Science.gov (United States)

    Martin, Richard J; Wang, Katherine; Köroğlu, Ozge; Di Fiore, Juliann; Kc, Prabha

    2011-01-01

    Intermittent hypoxic episodes are typically a consequence of immature respiratory control and remain a troublesome challenge for the neonatologist. Furthermore, their frequency and magnitude are underestimated by clinically employed pulse oximeter settings. In extremely low birth weight infants the incidence of intermittent hypoxia progressively increases over the first 4 weeks of postnatal life, with a subsequent plateau followed by a slow decline beginning at weeks 6-8. Such episodic hypoxia/reoxygenation has the potential to sustain a proinflammatory cascade with resultant multisystem morbidity. This morbidity includes retinopathy of prematurity and impaired growth, as well as possible longer-term cardiorespiratory instability and poor neurodevelopmental outcome. Therapeutic approaches for intermittent hypoxic episodes comprise determination of optimal baseline saturation and careful titration of supplemental inspired oxygen, as well as xanthine therapy to prevent apnea of prematurity. In conclusion, characterization of the pathophysiologic basis for such intermittent hypoxic episodes and their consequences during early life is necessary to provide an evidence-based approach to their management. Copyright © 2011 S. Karger AG, Basel.

  20. Acute respiratory failure revealing a multilocular thymic cyst in an infant: a case report.

    Science.gov (United States)

    Asma, Bouziri; Ammar, Khaldi; Khaled, Menif; Najoua, Guandoura; Nejla, Ben Jaballah

    2009-11-30

    Multilocular thymic cysts are rare benign lesions of the neck and mediastinum that can occur at any age. In children, multilocular thymic cysts are usually symptomatic after the age of 2 years and produce few symptoms. We present an unusual case of a multilocular thymic cyst diagnosed in a 3-month-old girl and causing severe respiratory failure. A 3 month-old-girl, with a medical history of dyspnea and wheezing since the age of 20 days, presented in our pediatric intensive care unit for acute respiratory failure requiring mechanical ventilation. The chest radiograph showed thoracic distension without any other abnormalities. The diagnosis of severe asthma was initially suspected and the patient was treated by intravenous corticosteroids and continuous perfusion of salbutamol without any improvement. A chest tomography scan was performed and demonstrated an anterior mediastinal multiseptated cystic mass extending from the inferior face of the thyroid gland to the left cardiophrenic angle. Sternotomy and excision biopsy were planned urgently. The cystic mass was excised completely. The histopathological examination confirmed the diagnosis of a multilocular thymic cyst. The particularities of our observation are the occurrence of a multilocular thymic cyst in a young infant and its presentation by a severe acute respiratory failure mimicking asthma.

  1. Long-term effects of oxygen-enriched high-flow nasal cannula treatment in COPD patients with chronic hypoxemic respiratory failure

    Directory of Open Access Journals (Sweden)

    Storgaard LH

    2018-04-01

    Full Text Available Line Hust Storgaard,1 Hans-Ulrich Hockey,2 Birgitte Schantz Laursen,3,4 Ulla Møller Weinreich1,3 1Department of Respiratory Diseases, Aalborg University Hospital, Aalborg, Denmark; 2Biometrics Matters Limited, Hamilton, New Zealand; 3Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 4Clinical Nursing Research Unit, Aalborg University Hospital, Aalborg, Denmark Background: This study investigated the long-term effects of humidified high-flow nasal cannula (HFNC in COPD patients with chronic hypoxemic respiratory failure treated with long-term oxygen therapy (LTOT.Patients and methods: A total of 200 patients were randomized into usual care ± HFNC. At inclusion, acute exacerbation of COPD (AECOPD and hospital admissions 1 year before inclusion, modified Medical Research Council (mMRC score, St George’s Respiratory Questionnaire (SGRQ, forced expiratory volume in 1 second (FEV1, 6-minute walk test (6MWT and arterial carbon dioxide (PaCO2 were recorded. Patients completed phone interviews at 1, 3 and 9 months assessing mMRC score and AECOPD since the last contact. At on-site visits (6 and 12 months, mMRC, number of AECOPD since last contact and SGRQ were registered and FEV1, FEV1%, PaCO2 and, at 12 months, 6MWT were reassessed. Hospital admissions during the study period were obtained from hospital records. Hours of the use of HFNC were retrieved from the high-flow device.Results: The average daily use of HFNC was 6 hours/day. The HFNC group had a lower AECOPD rate (3.12 versus 4.95/patient/year, p<0.001. Modeled hospital admission rates were 0.79 versus 1.39/patient/year for 12- versus 1-month use of HFNC, respectively (p<0.001. The HFNC group had improved mMRC scores from 3 months onward (p<0.001 and improved SGRQ at 6 and 12 months (p=0.002, p=0.033 and PaCO2 (p=0.005 and 6MWT (p=0.005 at 12 months. There was no difference in all-cause mortality.Conclusion: HFNC treatment reduced AECOPD, hospital admissions and

  2. Epigenetic regulation of hypoxic sensing disrupts cardiorespiratory homeostasis.

    Science.gov (United States)

    Nanduri, Jayasri; Makarenko, Vladislav; Reddy, Vaddi Damodara; Yuan, Guoxiang; Pawar, Anita; Wang, Ning; Khan, Shakil A; Zhang, Xin; Kinsman, Brian; Peng, Ying-Jie; Kumar, Ganesh K; Fox, Aaron P; Godley, Lucy A; Semenza, Gregg L; Prabhakar, Nanduri R

    2012-02-14

    Recurrent apnea with intermittent hypoxia is a major clinical problem in preterm infants. Recent studies, although limited, showed that adults who were born preterm exhibit increased incidence of sleep-disordered breathing and hypertension, suggesting that apnea of prematurity predisposes to autonomic dysfunction in adulthood. Here, we demonstrate that adult rats that were exposed to intermittent hypoxia as neonates exhibit exaggerated responses to hypoxia by the carotid body and adrenal chromaffin cells, which regulate cardio-respiratory function, resulting in irregular breathing with apneas and hypertension. The enhanced hypoxic sensitivity was associated with elevated oxidative stress, decreased expression of genes encoding antioxidant enzymes, and increased expression of pro-oxidant enzymes. Decreased expression of the Sod2 gene, which encodes the antioxidant enzyme superoxide dismutase 2, was associated with DNA hypermethylation of a single CpG dinucleotide close to the transcription start site. Treating neonatal rats with decitabine, an inhibitor of DNA methylation, during intermittent hypoxia exposure prevented oxidative stress, enhanced hypoxic sensitivity, and autonomic dysfunction. These findings implicate a hitherto uncharacterized role for DNA methylation in mediating neonatal programming of hypoxic sensitivity and the ensuing autonomic dysfunction in adulthood.

  3. A Case of Biotinidase Deficiency in an Adult with Respiratory Failure in the Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    Zerrin Demirtürk

    2016-10-01

    Full Text Available Background: Biotinidase deficiency (BD is a rare, inherited autosomal recessive disorder that is treatable within childhood. We present a patient with pneumonia and respiratory acidosis who was not diagnosed with any systemic disorders; the patient was finally diagnosed as BD. Case Report: A thirty-year-old woman was admitted to the emergency department with respiratory failure that had persisted for a few days and progressively weakening over the previous six months. Then, the patient was admitted to the intensive care unit with marked respiratory acidosis, respiratory failure and alterations in consciousness. At the follow-up, the patient was not diagnosed with a systematic disorder. Rather, the patient’s historical clinical findings suggested a metabolic disorder. Finally, the patient was diagnosed with biotinidase deficiency. Conclusion: Even though biotinidase deficiency is not frequently seen in the intensive care unit, metabolic syndromes such as biotinidase deficiency should be considered. Patients should be evaluated holistically with attention to medical history, family history and clinical findings.

  4. Effect of Intermittent Hypercapnia on Respiratory Control in Rat Pups

    Science.gov (United States)

    Steggerda, Justin A.; Mayer, Catherine A.; Martin, Richard J.; Wilson, Christopher G.

    2010-01-01

    Preterm infants are subject to fluctuations in blood gas status associated with immature respiratory control. Intermittent hypoxia during early postnatal life has been shown to increase chemoreceptor sensitivity and destabilize the breathing pattern; however, intermittent hypercapnia remains poorly studied. Therefore, to test the hypothesis that intermittent hypercapnia results in altered respiratory control, we examined the effects of daily exposure to intermittent hypercapnia on the ventilatory response to subsequent hypercapnic and hypoxic exposure in neonatal rat pups. Exposure cycles consisted of 5 min of intermittent hypercapnia (5% CO2, 21% O2, balance N2) followed by 10 min of normoxia. Rat pups were exposed to 18 exposure cycles each day for 1 week, from postnatal day 7 to 14. We analyzed diaphragm electromyograms (EMGs) from pups exposed to subsequent acute hypercapnic (5% CO2) and hypoxic (12% O2) challenges. In response to a subsequent hypercapnia challenge, there was no significant difference in the ventilatory response between control and intermittent hypercapnia-exposed groups. In contrast, intermittent hypercapnia-exposed rat pups showed an enhanced ventilatory response to hypoxic challenge with an increase in minute EMG to 118 ± 14% of baseline versus 107 ± 13% for control pups (p < 0.05). We speculate that prior hypercapnic exposure may increase peripheral chemoreceptor response to subsequent hypoxic exposures and result in perturbed neonatal respiratory control. PMID:19752577

  5. Acute hypoxemic respiratory failure in immunocompromised patients : The Efraim multinational prospective cohort study

    NARCIS (Netherlands)

    Azoulay, Elie; Pickkers, Peter; Soares, Marcio; Perner, Anders; Rello, Jordi; Bauer, Philippe R.; van de Louw, Andry; Hemelaar, Pleun; Lemiale, Virginie; Taccone, Fabio Silvio; Loeches, Ignacio Martin; Meyhoff, Tine Sylvest; Salluh, Jorge; Schellongowski, Peter; Rusinova, Katerina; Terzi, Nicolas; Mehta, Sangeeta; Antonelli, Massimo; Kouatchet, Achille; Barratt-Due, Andreas; Valkonen, Miia; Landburg, Precious Pearl; Bruneel, Fabrice; Bukan, Ramin Brandt; Pene, Frederic; Metaxa, Victoria; Moreau, Anne Sophie; Souppart, Virginie; Burghi, Gaston; Girault, Christophe; Silva, Ulysses V. A.; Montini, Luca; Barbier, Francois; Nielsen, Lene B.; Gaborit, Benjamin; Mokart, Djamel; Chevret, Sylvie

    2017-01-01

    Background: In immunocompromised patients with acute hypoxemic respiratory failure (ARF), initial management aims primarily to avoid invasive mechanical ventilation (IMV). Methods: To assess the impact of initial management on IMV and mortality rates, we performed a multinational observational

  6. Acute hypoxemic respiratory failure in immunocompromised patients: the Efraim multinational prospective cohort study

    NARCIS (Netherlands)

    Azoulay, E.; Pickkers, P.; Soares, M.; Perner, A.; Rello, J.; Bauer, P.R.; Louw, A. van de; Hemelaar, P.; Lemiale, V.; Taccone, F.S.; Loeches, I.M.; Meyhoff, T.S.; Salluh, J.; Schellongowski, P.; Rusinova, K.; Terzi, N.; Mehta, S.; Antonelli, M.; Kouatchet, A.; Barratt-Due, A.; Valkonen, M.; Landburg, P.P.; Bruneel, F.; Bukan, R.B.; Pene, F.; Metaxa, V.; Moreau, A.S.; Souppart, V.; Burghi, G.; Girault, C.; Silva, U.V.A.; Montini, L.; Barbier, F.; Nielsen, L.B.; Gaborit, B.; Mokart, D.; Chevret, S.

    2017-01-01

    BACKGROUND: In immunocompromised patients with acute hypoxemic respiratory failure (ARF), initial management aims primarily to avoid invasive mechanical ventilation (IMV). METHODS: To assess the impact of initial management on IMV and mortality rates, we performed a multinational observational

  7. Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure

    NARCIS (Netherlands)

    Kneyber, Martin C. J.; van Heerde, Marc; Twisk, Jos W. R.; Plotz, Frans B.; Markhors, Dick G.

    2009-01-01

    Introduction Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of

  8. Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure

    NARCIS (Netherlands)

    Kneijber, M.C.J.; van Heerde, M.; Twisk, J.W.R.; Plotz, F.; Markhorst, D.G.

    2009-01-01

    Introduction: Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of

  9. Always Consider the Possibility of Opioid Induced Respiratory Depression in Patients Presenting with Hypercapnic Respiratory Failure Who Fail to Improve as Expected with Appropriate Therapy

    Directory of Open Access Journals (Sweden)

    Martin Steynor

    2015-01-01

    Full Text Available Hypercapnic respiratory failure is a frequently encountered medical emergency. Two common causes are acute exacerbations of chronic obstructive pulmonary disease (COPD and as a side effect of opioids. The two causes may coexist leading to diagnostic confusion and consequent delay in optimal management. We report a case of what was initially thought to be an exacerbation of COPD. The patient failed to improve with treatment as expected which led to the empirical administration of naloxone resulting in a dramatic reversal of her respiratory failure. The patient was subsequently discovered to be taking regular dihydrocodeine for chronic back pain.

  10. Intermittent Hypoxic Episodes in Preterm Infants: Do They Matter?

    OpenAIRE

    Martin, Richard J.; Wang, Katherine; Köroğlu, Özge; Di Fiore, Juliann; Kc, Prabha

    2011-01-01

    Intermittent hypoxic episodes are typically a consequence of immature respiratory control and remain a troublesome challenge for the neonatologist. Furthermore, their frequency and magnitude are underestimated by clinically employed pulse oximeter settings. In extremely low birth weight infants the incidence of intermittent hypoxia progressively increases over the first 4 weeks of postnatal life, with a subsequent plateau followed by a slow decline beginning at weeks 6–8. Such episodic hypoxi...

  11. Features of the Early Adaptation Period of Newborns with Hypoxic-Ischemic Encephalopathy Depending on Birth Weight

    Directory of Open Access Journals (Sweden)

    Ye.P. Ortemenka

    2015-04-01

    Full Text Available In the department of neonatal pathology of Chernivtsi regional children’s clinical hospital, 41 full-term newborns with hypoxic-ischemic encephalopathy have been exa­mined in order to study the features of early period of their adaptation depending on birth weight. It was found that the early adaptation period of full-term newborns with hypoxi­­c-ischemic encephalopathy and body weight adequate in terms of gestational age was characterized by: pathological deli­very in one third (32.1 % of cases and the birth of one fourth (25 % of infants with tight nuchal cord that three times more often (22.2 % of neonates led to severe asphyxia, associated with the development of the multiple organ failure (14.3 % of cases and seizures (17.9 % of observations. Full-term children with hypoxic-ischemic encephalopathy and body weight low in terms of gestational age are characterized by: lower gestational age (37–39 weeks at birth (84.6 % of children, which has been associated with young (under 20 years age of mothers in 15.4 % of cases, and twice as likely (61.5 % of children led to respiratory disorders at birth, requiring artificial lung ventilation.

  12. [Recurrent laryngeal papillomatosis complicated by decompensated respiratory failure in two children].

    Science.gov (United States)

    Aurégan, C; Thierry, B; Blanchard, M; Chéron, G

    2015-11-01

    Laryngeal papillomatosis is a rare, potentially severe cause of recurrent laryngeal dyspnea. It should be known as a cause of laryngeal dyspnea resistant to the usual treatments. We report on two pediatric cases of severe laryngeal papillomatosis with respiratory distress and failure. These observations illustrate the importance of early adequate treatment. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  13. The outcomes and prognostic factors of acute respiratory failure in the patients 90 years old and over

    Science.gov (United States)

    Kung, Shu-Chen; Wang, Ching-Min; Lai, Chih-Cheng; Chao, Chien-Ming

    2018-01-01

    This retrospective cohort study investigated the outcomes and prognostic factors in nonagenarians (patients 90 years old or older) with acute respiratory failure. Between 2006 and 2016, all nonagenarians with acute respiratory failure requiring invasive mechanical ventilation (MV) were enrolled. Outcomes including in-hospital mortality and ventilator dependency were measured. A total of 173 nonagenarians with acute respiratory failure were admitted to the intensive care unit (ICU). A total of 56 patients died during the hospital stay and the rate of in-hospital mortality was 32.4%. Patients with higher APACHE (Acute Physiology and Chronic Health Evaluation) II scores (adjusted odds ratio [OR], 5.91; 95 % CI, 1.55-22.45; p = 0.009, APACHE II scores ≥ 25 vs APACHE II scores < 15), use of vasoactive agent (adjust OR, 2.67; 95% CI, 1.12-6.37; p = 0.03) and more organ dysfunction (adjusted OR, 11.13; 95% CI, 3.38-36.36, p < 0.001; ≥ 3 organ dysfunction vs ≤ 1 organ dysfunction) were more likely to die. Among the 117 survivors, 25 (21.4%) patients became dependent on MV. Female gender (adjusted OR, 3.53; 95% CI, 1.16-10.76, p = 0.027) and poor consciousness level (adjusted OR, 4.98; 95% CI, 1.41-17.58, p = 0.013) were associated with MV dependency. In conclusion, the mortality rate of nonagenarians with acute respiratory failure was high, especially for those with higher APACHE II scores or more organ dysfunction. PMID:29467961

  14. The outcomes and prognostic factors of acute respiratory failure in the patients 90 years old and over.

    Science.gov (United States)

    Chen, Wan-Ling; Chen, Chin-Ming; Kung, Shu-Chen; Wang, Ching-Min; Lai, Chih-Cheng; Chao, Chien-Ming

    2018-01-23

    This retrospective cohort study investigated the outcomes and prognostic factors in nonagenarians (patients 90 years old or older) with acute respiratory failure. Between 2006 and 2016, all nonagenarians with acute respiratory failure requiring invasive mechanical ventilation (MV) were enrolled. Outcomes including in-hospital mortality and ventilator dependency were measured. A total of 173 nonagenarians with acute respiratory failure were admitted to the intensive care unit (ICU). A total of 56 patients died during the hospital stay and the rate of in-hospital mortality was 32.4%. Patients with higher APACHE (Acute Physiology and Chronic Health Evaluation) II scores (adjusted odds ratio [OR], 5.91; 95 % CI, 1.55-22.45; p = 0.009, APACHE II scores ≥ 25 vs APACHE II scores < 15), use of vasoactive agent (adjust OR, 2.67; 95% CI, 1.12-6.37; p = 0.03) and more organ dysfunction (adjusted OR, 11.13; 95% CI, 3.38-36.36, p < 0.001; ≥ 3 organ dysfunction vs ≤ 1 organ dysfunction) were more likely to die. Among the 117 survivors, 25 (21.4%) patients became dependent on MV. Female gender (adjusted OR, 3.53; 95% CI, 1.16-10.76, p = 0.027) and poor consciousness level (adjusted OR, 4.98; 95% CI, 1.41-17.58, p = 0.013) were associated with MV dependency. In conclusion, the mortality rate of nonagenarians with acute respiratory failure was high, especially for those with higher APACHE II scores or more organ dysfunction.

  15. Fit for high altitude: are hypoxic challenge tests useful?

    Directory of Open Access Journals (Sweden)

    Matthys Heinrich

    2011-02-01

    Full Text Available Abstract Altitude travel results in acute variations of barometric pressure, which induce different degrees of hypoxia, changing the gas contents in body tissues and cavities. Non ventilated air containing cavities may induce barotraumas of the lung (pneumothorax, sinuses and middle ear, with pain, vertigo and hearing loss. Commercial air planes keep their cabin pressure at an equivalent altitude of about 2,500 m. This leads to an increased respiratory drive which may also result in symptoms of emotional hyperventilation. In patients with preexisting respiratory pathology due to lung, cardiovascular, pleural, thoracic neuromuscular or obesity-related diseases (i.e. obstructive sleep apnea an additional hypoxic stress may induce respiratory pump and/or heart failure. Clinical pre-altitude assessment must be disease-specific and it includes spirometry, pulsoximetry, ECG, pulmonary and systemic hypertension assessment. In patients with abnormal values we need, in addition, measurements of hemoglobin, pH, base excess, PaO2, and PaCO2 to evaluate whether O2- and CO2-transport is sufficient. Instead of the hypoxia altitude simulation test (HAST, which is not without danger for patients with respiratory insufficiency, we prefer primarily a hyperoxic challenge. The supplementation of normobaric O2 gives us information on the acute reversibility of the arterial hypoxemia and the reduction of ventilation and pulmonary hypertension, as well as about the efficiency of the additional O2-flow needed during altitude exposure. For difficult judgements the performance of the test in a hypobaric chamber with and without supplemental O2-breathing remains the gold standard. The increasing numbers of drugs to treat acute pulmonary hypertension due to altitude exposure (acetazolamide, dexamethasone, nifedipine, sildenafil or to other etiologies (anticoagulants, prostanoids, phosphodiesterase-5-inhibitors, endothelin receptor antagonists including mechanical aids to

  16. Fit for high altitude: are hypoxic challenge tests useful?

    Science.gov (United States)

    Matthys, Heinrich

    2011-02-28

    Altitude travel results in acute variations of barometric pressure, which induce different degrees of hypoxia, changing the gas contents in body tissues and cavities. Non ventilated air containing cavities may induce barotraumas of the lung (pneumothorax), sinuses and middle ear, with pain, vertigo and hearing loss. Commercial air planes keep their cabin pressure at an equivalent altitude of about 2,500 m. This leads to an increased respiratory drive which may also result in symptoms of emotional hyperventilation. In patients with preexisting respiratory pathology due to lung, cardiovascular, pleural, thoracic neuromuscular or obesity-related diseases (i.e. obstructive sleep apnea) an additional hypoxic stress may induce respiratory pump and/or heart failure. Clinical pre-altitude assessment must be disease-specific and it includes spirometry, pulsoximetry, ECG, pulmonary and systemic hypertension assessment. In patients with abnormal values we need, in addition, measurements of hemoglobin, pH, base excess, PaO2, and PaCO2 to evaluate whether O2- and CO2-transport is sufficient.Instead of the hypoxia altitude simulation test (HAST), which is not without danger for patients with respiratory insufficiency, we prefer primarily a hyperoxic challenge. The supplementation of normobaric O2 gives us information on the acute reversibility of the arterial hypoxemia and the reduction of ventilation and pulmonary hypertension, as well as about the efficiency of the additional O2-flow needed during altitude exposure. For difficult judgements the performance of the test in a hypobaric chamber with and without supplemental O2-breathing remains the gold standard. The increasing numbers of drugs to treat acute pulmonary hypertension due to altitude exposure (acetazolamide, dexamethasone, nifedipine, sildenafil) or to other etiologies (anticoagulants, prostanoids, phosphodiesterase-5-inhibitors, endothelin receptor antagonists) including mechanical aids to reduce periodical or

  17. A comparison of volume control and pressure-regulated volume control ventilation in acute respiratory failure

    Science.gov (United States)

    Guldager, Henrik; Nielsen, Soeren L; Carl, Peder; Soerensen, Mogens B

    1997-01-01

    Background: The aim of this study was to test the hypothesis that a new mode of ventilation (pressure-regulated volume control; PRVC) is associated with improvements in respiratory mechanics and outcome when compared with conventional volume control (VC) ventilation in patients with acute respiratory failure. We conducted a randomised, prospective, open, cross over trial on 44 patients with acute respiratory failure in the general intensive care unit of a university hospital. After a stabilization period of 8 h, a cross over trial of 2 × 2 h was conducted. Apart from the PRVC/VC mode, ventilator settings were comparable. The following parameters were recorded for each patient: days on ventilator, failure in the assigned mode of ventilation (peak inspiratory pressure > 50 cmH2O) and survival. Results: In the crossover trial, peak inspiratory pressure was significantly lower using PRVC than with VC (20 cmH2O vs 24 cmH2O, P < 0.0001). No other statistically significant differences were found. Conclusions: Peak inspiratory pressure was significantly lower during PRVC ventilation than during VC ventilation, and thus PRVC may be superior to VC in certain patients. However, in this small group of patients, we could not demonstrate that PRVC improved outcome. PMID:11056699

  18. Acute respiratory failure caused by aspiration of high density barium: A case report

    International Nuclear Information System (INIS)

    Park, Ki Soon; Jung, Eun A; Yang, Ik; Lee, Yul; Chung, Soo Young

    1994-01-01

    Accidental aspiration of barium contrast medium during the upper gastrointestinal study can occur in patients with swallowing disorder, especially in the elderly patients. We experienced a case of respiratory failure followed by death within a few hours in 85 year-old patient after barium aspiration

  19. Clinical and high-resolution computed tomographic findings in five patients with pulmonary tuberculosis who developed respiratory failure following chemotherapy

    International Nuclear Information System (INIS)

    Akira, Masanori; Sakatani, Mitsunori

    2001-01-01

    AIM: The purpose of this study was to describe the clinical and high-resolution computed tomographic (HRCT) findings in patients with pulmonary tuberculosis who developed respiratory failure after starting chemotherapy. MATERIALS AND METHODS: The clinical records, chest radiographs, and HRCT findings in five patients with non-miliary pulmonary tuberculosis who developed respiratory failure after starting chemotherapy were reviewed. RESULTS: Chest radiographs taken early in the course of acute respiratory failure showed progression of the original lesions with (n = 4) or without (n = 1) new areas of opacity away from the site of the original lesions. HRCT demonstrated widespread ground-glass attenuation with a reticular pattern as well as segmental or lobar consolidation with cavitation and nodules, consistent with active tuberculous foci in all five cases. Prominent interlobular septal thickening was seen in two cases. Four of the five patients had received corticosteroids. Of these five, two died and three recovered with continued corticosteroid therapy. Transbronchial biopsy in three cases showed evidence of acute alveolar damage. CONCLUSION: In selected patients with tuberculosis who develop respiratory failure following the initiation of antituberculous therapy, HRCT may be a helpful adjunct to clinical evaluation in differentiating hypersensitivity reactions (presumed to be due to the release of mycobacterial antigens) from other pulmonary complications. Akira, M. and Sakatani, M. (2001)

  20. Skull and Posterior Rib Fractures with Respiratory Failure caused by Child Abuse

    Directory of Open Access Journals (Sweden)

    Dzulfikar Djalil Lukmanul Hakim

    2017-03-01

    Full Text Available Background: Presence of multiple fractures suggests child abuse. Skull fractures rarely occurred but posterior rib fractures are commonly found and have high specificity as a radiological finding in child abuse. A respiratory failure can occur as a result of the damage to the osseous structure of the thorax that destabilizes the rib cage and impairs spontaneous breathing mechanism. Methods: A case report of a 6-month-old boy who presented with respiratory failure, multiple bilateral parietal and occipital bone fractures, and also fractures of right rib 5–8. The patient required ventilatory support for 9 days in the Pediatric Intensive Care Unit, Dr.HasanSadikin General Hospital. Results: The patient was on ventilatory support for 9 days, and was given antibiotics for 2 weeks. Next, the patient was referred to the High Care Unit (HCU after the condition was stabilized, and then referred to the ward, for treatment by the Social Pediatric Division. The patient was still having issues about his foster care. Conclusions: Recognition of presence of fractures is important in early diagnosis and treatment of child abuse.

  1. Developing and managing a team to participate in trials involving acute respiratory failure: advice for the inexperienced.

    Science.gov (United States)

    Arabi, Yaseen; Ahmed, Qanta A

    2006-02-01

    Conducting large-scale clinical trials in the field of acute respiratory failure requires substantial collaboration. Teamwork is still in its infancy within the realm of clinical research. This review evaluates the need for and grassroots process of teamwork and considers the challenges facing teamwork in the specific context of conducting acute respiratory failure research today. Acute respiratory failure research demands complex, interdependent tasks, dictating a teamwork approach. The team is comprised of a sponsor, a leader and members. The sponsor provides essential administrative support, the leader performs many of the functions of a traditional manager in addition to adopting three distinct roles of initiator, role model and coach, and members are selected not only on their technical expertise, but also on their problem-solving and interpersonal skills. As large-scale (oftentimes international) multicenter trials are increasingly providing answers to our research questions, greater emphasis must be placed on team building within the clinical research environment. An urgent need for further work in this area is revealed. Critical care fellowships should integrate teamwork skills into the curriculum.

  2. Management of kyphoscoliosis patients with respiratory failure in the intensive care unit and during long term follow up

    Directory of Open Access Journals (Sweden)

    Adıgüzel Nalan

    2012-09-01

    Full Text Available Abstract Background We aimed to evaluate the ICU management and long-term outcomes of kyphoscoliosis patients with respiratory failure. Methods A retrospective observational cohort study was performed in a respiratory ICU and outpatient clinic from 2002–2011. We enrolled all kyphoscoliosis patients admitted to the ICU and followed-up at regular intervals after discharge. Reasons for acute respiratory failure (ARF, ICU data, mortality, length of ICU stay and outpatient clinic data, non-invasive ventilation (NIV device settings, and compliance were recorded. NIV failure in the ICU and the long term effect of NIV on pulmonary performance were analyzed. Results Sixty-two consecutive ICU kyphoscoliosis patients with ARF were enrolled in the study. NIV was initially applied to 55 patients, 11 (20% patients were intubated, and the majority had sepsis and septic shock (p  Conclusions We strongly discourage the use of NIV in the case of septic shock in ICU kyphoscoliosis patients with ARF. Pulmonary performance improved with NIV during long term follow up.

  3. Targeted inactivation of the murine Abca3 gene leads to respiratory failure in newborns with defective lamellar bodies

    International Nuclear Information System (INIS)

    Hammel, Markus; Michel, Geert; Hoefer, Christina; Klaften, Matthias; Mueller-Hoecker, Josef; Angelis, Martin Hrabe de; Holzinger, Andreas

    2007-01-01

    Mutations in the human ABCA3 gene, encoding an ABC-transporter, are associated with respiratory failure in newborns and pediatric interstitial lung disease. In order to study disease mechanisms, a transgenic mouse model with a disrupted Abca3 gene was generated by targeting embryonic stem cells. While heterozygous animals developed normally and were fertile, individuals homozygous for the altered allele (Abca3-/-) died within one hour after birth from respiratory failure, ABCA3 protein being undetectable. Abca3-/- newborns showed atelectasis of the lung in comparison to a normal gas content in unaffected or heterozygous littermates. Electron microscopy demonstrated the absence of normal lamellar bodies in type II pneumocytes. Instead, condensed structures with apparent absence of lipid content were found. We conclude that ABCA3 is required for the formation of lamellar bodies and lung surfactant function. The phenotype of respiratory failure immediately after birth corresponds to the clinical course of severe ABCA3 mutations in human newborns

  4. Mechanical Ventilation during Extracorporeal Membrane Oxygenation in Patients with Acute Severe Respiratory Failure.

    Science.gov (United States)

    Zhang, Zhongheng; Gu, Wan-Jie; Chen, Kun; Ni, Hongying

    2017-01-01

    Conventionally, a substantial number of patients with acute respiratory failure require mechanical ventilation (MV) to avert catastrophe of hypoxemia and hypercapnia. However, mechanical ventilation per se can cause lung injury, accelerating the disease progression. Extracorporeal membrane oxygenation (ECMO) provides an alternative to rescue patients with severe respiratory failure that conventional mechanical ventilation fails to maintain adequate gas exchange. The physiology behind ECMO and its interaction with MV were reviewed. Next, we discussed the timing of ECMO initiation based on the risks and benefits of ECMO. During the running of ECMO, the protective ventilation strategy can be employed without worrying about catastrophic hypoxemia and carbon dioxide retention. There is a large body of evidence showing that protective ventilation with low tidal volume, high positive end-expiratory pressure, and prone positioning can provide benefits on mortality outcome. More recently, there is an increasing popularity on the use of awake and spontaneous breathing for patients undergoing ECMO, which is thought to be beneficial in terms of rehabilitation.

  5. Mechanical Ventilation during Extracorporeal Membrane Oxygenation in Patients with Acute Severe Respiratory Failure

    Directory of Open Access Journals (Sweden)

    Zhongheng Zhang

    2017-01-01

    Full Text Available Conventionally, a substantial number of patients with acute respiratory failure require mechanical ventilation (MV to avert catastrophe of hypoxemia and hypercapnia. However, mechanical ventilation per se can cause lung injury, accelerating the disease progression. Extracorporeal membrane oxygenation (ECMO provides an alternative to rescue patients with severe respiratory failure that conventional mechanical ventilation fails to maintain adequate gas exchange. The physiology behind ECMO and its interaction with MV were reviewed. Next, we discussed the timing of ECMO initiation based on the risks and benefits of ECMO. During the running of ECMO, the protective ventilation strategy can be employed without worrying about catastrophic hypoxemia and carbon dioxide retention. There is a large body of evidence showing that protective ventilation with low tidal volume, high positive end-expiratory pressure, and prone positioning can provide benefits on mortality outcome. More recently, there is an increasing popularity on the use of awake and spontaneous breathing for patients undergoing ECMO, which is thought to be beneficial in terms of rehabilitation.

  6. Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

    Science.gov (United States)

    Pamenter, Matthew E.; Powell, Frank L.

    2016-01-01

    Ventilatory responses to hypoxia vary widely depending on the pattern and length of hypoxic exposure. Acute, prolonged, or intermittent hypoxic episodes can increase or decrease breathing for seconds to years, both during the hypoxic stimulus, and also after its removal. These myriad effects are the result of a complicated web of molecular interactions that underlie plasticity in the respiratory control reflex circuits and ultimately control the physiology of breathing in hypoxia. Since the time domains of the physiological hypoxic ventilatory response (HVR) were identified, considerable research effort has gone toward elucidating the underlying molecular mechanisms that mediate these varied responses. This research has begun to describe complicated and plastic interactions in the relay circuits between the peripheral chemoreceptors and the ventilatory control circuits within the central nervous system. Intriguingly, many of these molecular pathways seem to share key components between the different time domains, suggesting that varied physiological HVRs are the result of specific modifications to overlapping pathways. This review highlights what has been discovered regarding the cell and molecular level control of the time domains of the HVR, and highlights key areas where further research is required. Understanding the molecular control of ventilation in hypoxia has important implications for basic physiology and is emerging as an important component of several clinical fields. PMID:27347896

  7. Tei index in neonatal respiratory distress and perinatal asphyxia

    OpenAIRE

    Ahmed Anwer Attia Khattab

    2015-01-01

    Cardiovascular compromise is a common complication of neonatal respiratory distress and perinatal asphyxia. Tei index is a Doppler-derived index for the assessment of overall left ventricular function that combines systolic and diastolic time intervals. Aim: Assess the role of MPI versus cardiac troponin I as early indicator of hypoxic cardiac damage in neonates with respiratory distress or perinatal asphyxia. The present work was conducted on forty neonates, 15 with neonatal respiratory dist...

  8. Cheyne-Stokes respiration: hypoxia plus a deep breath that interrupts hypoxic drive, initiating cyclic breathing.

    Science.gov (United States)

    Guntheroth, Warren G

    2011-11-01

    In the 19th Century, Cheyne and Stokes independently reported cycles of respiration in patients with heart failure, beginning with apnea, followed by a few breaths. However Cheyne-Stokes respiration (C-SR) can also occur in healthy individuals with sleep, and was demonstrated in 1908 with voluntary hyperventilation, followed by apnea that Haldane blamed on hypoxia, subsequently called post-hyperventilation apnea. Additional theories explaining C-SR did not appear until 1954, based on control theory, specifically a feed-back regulator controlling CO(2). This certainly describes control of normal respiration, but to produce an unstable state such as C-SR requires either a very long transit time (3½ min) or an increase of the controller gain (13 times), physiologically improbable. There is general agreement that apnea initiates C-SR but that has not been well explained except for post-hyperventilation apnea, and that explanation is not compatible with a study by Nielsen and Smith in 1951. They plotted the effects of diminished oxygen on ventilation (V) in relation to CO(2) (Fig. 1). They found that the slope of V/CO(2) (gain) increased with hypoxia, but it flattened at a moderate CO(2) level and had nointercept with zero (apnea). It is also incompatible with our published findings in 1975 that showed that apnea did not occur until an extreme level of hypoxia occurred (the PO(2) fell below 10 mmHg), followed shortly by gasping. Much milder hypoxia underlies most cases of C-SR, when hypoxic drive replaces the normal CO(2)-based respiratory drive, in a failsafe role. I hypothesize that the cause of apnea is a brief interruption of hypoxic drive caused by a pulse of oxygen from a stronger than average breath, such as a sigh. The rapidity of onset of apnea in response to a pulse of oxygen, reflects the large pressure gradient for oxygen from air to lung with each breath, in contrast to CO(2). With apnea, there is a gradual fall in oxygen, resulting in a resumption of

  9. Pancreaticopleural Fistula Causing Massive Right Hydrothorax and Respiratory Failure

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    Esther Ern-Hwei Chan

    2016-01-01

    Full Text Available Hydrothorax secondary to a pancreaticopleural fistula (PPF is a rare complication of acute pancreatitis. In patients with a history of pancreatitis, diagnosis is made by detection of amylase in the pleural exudate. Imaging, particularly magnetic resonance cholangiopancreatography, aids in the detection of pancreatic ductal disruption. Management includes thoracocentesis and pancreatic duct drainage or pancreatic resection procedures. We present a case of massive right hydrothorax secondary to a PPF due to recurrent acute pancreatitis. Due to respiratory failure, urgent thoracocentesis was done. Distal pancreatectomy with splenectomy and cholecystectomy was performed. The patient remains well at one-year follow-up.

  10. Bulbar impairment score predicts noninvasive volume-cycled ventilation failure during an acute lower respiratory tract infection in ALS.

    Science.gov (United States)

    Servera, Emilio; Sancho, Jesús; Bañuls, Pilar; Marín, Julio

    2015-11-15

    Amyotrophic lateral sclerosis (ALS) patients can suffer episodes of lower respiratory tract infections (LRTI) leading to an acute respiratory failure (ARF) requiring noninvasive ventilation (NIV). To determine whether clinical or functional parameters can predict noninvasive management failure during LRTI causing ARF in ALS. A prospective study involving all ALS patients with ARF requiring NIV in a Respiratory Care Unit. NIV was provided with volume-cycled ventilators. 63 ALS patients were included (APACHE II: 14.93±3.56, Norris bulbar subscore (NBS): 18.78±9.68, ALSFRS-R: 19.90±6.98, %FVC: 40.01±18.07%, MIC: 1.62±0.74L, PCF 2.51±1.15L/s, PImax -34.90±19.44cmH2O, PEmax 51.20±28.84cmH2O). In 73.0% of patients NIV was successful in averting death or endotracheal intubation. Differences were found between the success and failure in the NBS (22.08±6.15 vs 8.66±3.39, pNIV failure was the NBS (OR 0.53, 95% CI 0.31-0.92, p 0.002) with a cut-off point of 12 (S 0.93; E 0.97; PPV 0.76; NPV 0.97). NBS can predict noninvasive management failure during LRTI in ALS. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Inclusion Body Myositis: A Case Presenting with Respiratory Failure and Autopsy Findings Leading to the Hypothesis of a Paraneoplastic Cause.

    Science.gov (United States)

    Dardis, Christopher; Antezana, Ariel; Tanji, Kurenai; Maccabee, Paul J

    2017-06-23

    BACKGROUND Sporadic inclusion body myositis (IBM) is the most common acquired myopathy seen in adults aged over 50 years, with a prevalence estimated at between 1 and 70 per million. Weakness of the diaphragm with loss of vital capacity is almost universal in IBM. This is almost always asymptomatic. When respiratory complications occur, they are most often due to aspiration. Respiratory failure due to diaphragmatic weakness is exceptionally rare, particularly as the presenting symptom of the disease. It is not currently considered to be a paraneoplastic syndrome. CASE REPORT Our patient presented with hypercarbic respiratory failure. This is the first such reported case without signs of weakness elsewhere of which we are aware. We suspected IBM based on her history of progressive weakness and findings on electromyography. There was a delay of 5 years in obtaining biopsy for confirmation, during which she presented with recurrent episodes of respiratory failure despite using non-invasive ventilation. An autopsy revealed the presence of papillary thyroid carcinoma with spread to local lymph nodes. On the basis that these co-morbidities are unlikely to have occurred by chance (we estimate 1×10-17), we hypothesize that IBM may be a paraneoplastic condition. We acknowledge that proof would require demonstrating a pathogenic antibody. CONCLUSIONS IBM should be considered in older patients (age >45) presenting with otherwise unexplained respiratory failure. A workup for possible malignancy in this setting appears reasonable.

  12. Caffeine in the milk prevents respiratory disorders caused by in utero caffeine exposure in rats.

    Science.gov (United States)

    Bodineau, Laurence; Saadani-Makki, Fadoua; Jullien, Hugues; Frugière, Alain

    2006-01-25

    Consequences of postnatal caffeine exposure by the milk on ponto-medullary respiratory disturbances observed following an in utero caffeine exposure were analysed. Ponto-medullary-spinal cord preparations from newborn rats exposed to caffeine during gestation but not after the birth display an increase in respiratory frequency and an exaggeration of the hypoxic respiratory depression compared to not treated preparations. These data suggest that tachypneic and apneic episodes encountered in human newborns whose mother consumed caffeine during pregnancy are due in large part to central effect of caffeine at the ponto-medullary level. Both baseline respiratory frequency increase and emphasis of hypoxic respiratory depression are not encountered if rat dams consumed caffeine during nursing. Our hypothesis is that newborn rats exposed to caffeine during gestation but not after the birth would be in withdrawal situation whereas, when caffeine is present in drinking fluid of lactating dams, it goes down the milk and is able to prevent ponto-medullary respiratory disturbances.

  13. Maternal and fetal recovery after severe respiratory failure due to influenza: a case report

    Directory of Open Access Journals (Sweden)

    Madsen Kristine

    2013-02-01

    Full Text Available Abstract Background During pregnancy women are at increased risk of severe complications to influenza infection, including death of mother or fetus, especially if chronic comorbid medical conditions such as diabetes mellitus are present. Case presentation A 36 years old Caucasian pregnant woman with type 1 diabetes underwent mechanical ventilation in gestation week 27 for severe respiratory failure due to influenza and pneumonia. For three weeks during and following her most severe illness, fetal growth could not be detected and the umbilical flows and amniotic fluid volumes were affected too. The possibility of preterm delivery and extracorporeal membrane oxygenation (ECMO treatment were considered, however the patient and her fetus recovered gradually on conservative treatment. Under close surveillance the pregnancy continued until term, with delivery of an infant with appropriate weight for gestational age. Conclusion Preterm delivery and decreased birth weight were reported for women with antepartum pneumonia. Mechanical ventilation and ECMO treatment for severe respiratory failure in pregnancy are life threatening conditions and have been associated with preterm delivery. It remains uncertain if delivery improves the respiratory status of a critically ill woman, and the fetal condition is likely to improve, if the maternal condition is stabilized. Severe respiratory insufficiency requiring mechanical ventilation in a diabetic pregnant woman with influenza was successfully treated conservatively. Despite clear signs of impaired fetal condition in the acute phase, watchful waiting resulted in delivery of a normal weight infant at term.

  14. Impaired Ventilatory and Thermoregulatory Responses to Hypoxic Stress in Newborn Phox2b Heterozygous Knock-Out Mice

    OpenAIRE

    Ramanantsoa, Nelina; Matrot, Boris; Vardon, Guy; Lajard, Anne-Marie; Voituron, Nicolas; Dauger, Stéphane; Denjean, André; Hilaire, Gérard; Gallego, Jorge

    2011-01-01

    The Phox2b genesis necessary for the development of the autonomic nervous system, and especially, of respiratory neuronal circuits. In the present study, we examined the role of Phox2b in ventilatory and thermoregulatory responses to hypoxic stress, which are closely related in the postnatal period. Hypoxic stress was generated by strong thermal stimulus, combined or not with reduced inspired O2. To this end, we exposed 6-day-old Phox2b +/? pups and their wild-type littermates (Phox2b +/+) to...

  15. [A case of Crow-Fukase syndrome with respiratory failure due to bilateral diaphragmatic paralysis].

    Science.gov (United States)

    Namekawa, Michito; Muramatsu, Shin-ichi; Hashimoto, Ritsuo; Kawakami, Tadataka; Fujimoto, Ken-ichi; Nakano, Imaharu

    2002-07-01

    A 62-year-old man with well-controlled diabetes mellitus developed numbness of the bilateral feet and hands, followed by subacutely progressive weakness and amyotrophy of extremities. He became bed-ridden state, and dyspnea also appeared, so he was referred to our hospital. Physical examination revealed a lean man, with dark-reddish skin pigmentation, crabbed fingers, bilateral pretibial pitting edema, and bristles in extremities. Thoracoabdominal paradoxical respiration was observed and pulmonary vesicular sounds was decreased markedly in the both lungs. Laboratory data revealed hypoproteinemia, abnormalities of endocrine system, but M-protein was not detected. Serum vascular endothelial growth factor level was quite high. Chest radiography revealed elevation of the bilateral diaphragm, the % vital capacity (%VC) was 24%, and arterial blood gas analysis showed marked hypoxia with hypercapnia. These findings suggested that his respiratory failure was induced by bilateral diaphragmatic paralysis caused by bilateral phrenic nerve palsy due to Crow-Fukase syndrome. He became somnolent because of hypercapnic narcosis, so non-invasive positive pressure ventilation (NIPPV) was started. We treated him with intravenous immunoglobulin and oral corticosteroids therapies, and after these therapies, his symptoms were remarkably recovered and NIPPV became unnecessary soon. The most frequent causes of respiratory failure in Crow-Fukase syndrome are pleural effusion and pulmonary hypertension, and only two cases of this syndrome with respiratory failure caused by bilateral diaphragmatic paralysis were reported until now. When the patients with Crow-Fukase syndrome complain of dyspnea, we should take the diaphragmatic paralysis into consideration, which may be improved by appropriate therapies.

  16. Reduced hypoxic ventilatory response in newborn mice knocked-out for the progesterone receptor.

    Science.gov (United States)

    Potvin, Catherine; Rossignol, Orlane; Uppari, NagaPraveena; Dallongeville, Arnaud; Bairam, Aida; Joseph, Vincent

    2014-11-01

    Recent studies showed that progesterone stimulates the hypoxic ventilatory response and may reduce apnoea frequency in newborn rats, but so far we still do not know by what mechanisms and whether endogenous progesterone might contribute to respiratory control in neonates. We therefore determined the role of the nuclear progesterone receptor (PR; member of the steroid receptor superfamily) by using wild-type (WT) and PR knock-out (PRKO) mice at postnatal days (P) 1, 4 and 10. We measured the hypoxic ventilatory response (14 and 12% O2, 20 min each) and apnoea frequency in both male and female mice by using whole-body plethysmography. In response to hypoxia, WT male mice had a marked hypoxic ventilatory response at P1 and P10, but not at P4. At P1 and P10, PRKO male mice had a lower hypoxic ventilatory response than WT males. Wild-type female mice had a marked hypoxic ventilatory response at P10, but not at P1 and P4. At P1 and P10, PRKO female mice had a lower hypoxic ventilatory response than WT females. In basal conditions, apnoea frequency was similar in WT and PRKO mice at P1, P4 and P10. During hypoxia, apnoea frequency was higher in WT male mice compared with PRKO male mice and WT female mice at P1. We conclude that PR is a key contributor to the hypoxic ventilatory response in newborn mice, but PR deletion does not increase the frequency of apnoea during normoxia or hypoxia. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  17. Respiratory failure in tetanic patient: maintenance of airway problem in intensive care unit setting

    Science.gov (United States)

    Utami, I. N.; Arifin; Susilo, R. S. B.; Redhono, D.; Sumandjar, T.

    2018-03-01

    Tetanus is a toxin-mediated disease caused by Clostridium tetani resulting in muscular stiffness and painful spasm. The case fatality rates are high (10-80%), and the most frequent cause of mortality is airway problem that results in respiratory failure. A 52-year-old malecame to the hospital with lockjaw, rhesussardonicus, opisthotonus, and seizure for the last 12 hours, diagnosed with tetanus grade II. We placed the patient in an isolation room, gave 3000U tetanus immunoglobulin, 20mg diazepam in 500ml dextrose 5%/8 hours, and 500mg/6hrs metronidazole. On the seventh day, seizure became frequent, respiratory rate increased with crackles found on the auscultation, and the blood gas analysis showed respiratory failure type II (PCO2 53mmHg). The patientwas immediately sent to the ICU, intubated and given ventilator support. The patientwas sedated with continuous injection of midazolam 3 mg/h, morphine 10mcg/kgBW/h and also levofloxacin 750mg/24hours. Bronchoalveolar lavage culture was positive for Acinetobacter baumanii, so we changed the antibiotic to amikacin injection 500 mg/8hrs. After four days, we extubated the ventilator and transferred from HCU three days later. The patient was fully recovered and discharged after eighteen days of hospitalization.

  18. A Prospective One-Year Microbiologic Survey of Combined Pneumonia and Respiratory Failure.

    Science.gov (United States)

    Fisher, Kristen; Trupka, Tracy; Micek, Scott T; Juang, Paul; Kollef, Marin H

    2017-10-01

    Pneumonia and respiratory failure are common problems in the intensive care unit (ICU) setting, often occurring together. The relative prevalence of pneumonia types (community acquired, hospital acquired, ventilator associated) and causative pathogens is not well described in patients with respiratory failure. This was a prospective observational cohort study conducted in the medical ICU (34 beds) of Barnes-Jewish Hospital, an academic referral center of 1,300 beds from January 2016-December 2016. All patients who were prospectively adjudicated to have respiratory failure and pneumonia (RFP) regardless of pneumonia type were classified into one of four microbiologic categories: pathogen negative, antibiotic-susceptible pathogen (according to ceftriaxone susceptibility), antibiotic-resistant pathogen, and viruses. The primary outcomes assessed were the hospital mortality rate and inappropriate initial antibiotic therapy (IIAT) for non-viral pathogens. Among 364 consecutive patients with RFP, 63 (17.3%) had organisms that were antibiotic susceptible, 104 (28.6%) had antibiotic-resistant organisms, 118 (32.4%) were pathogen negative, and 79 (21.7%) had viral infections. For these categories, IIAT occurred in 3.2%, 21.2%, 0.8%, and 0, respectively (p < 0.001). Vasopressor-requiring shock was present in 61.9%, 72.1%, 68.6%, and 67.1%, respectively (p = 0.585), and the hospital mortality rates were 27.0%, 48.1%, 31.4%, and 36.7%, respectively (p = 0.020). Multivariable logistic regression analysis identified IIAT as an independent predictor of in-hospital death (adjusted odds ratio 5.28; 95% confidence interval 2.72-10.22; p = 0.012). Male gender, increasing Acute Physiology and Chronic Health Evaluation (APACHE) II scores, greater age, and the presence of shock also predicted death. Microbiologic categorization of patients with RFP suggests that antibiotic-resistant pathogens and viruses are associated with the highest mortality rates. Vasopressor

  19. Episodic medical home interventions in severe bedridden chronic respiratory failure patients: a 4 year retrospective study.

    Science.gov (United States)

    Barbano, L; Bertella, E; Vitacca, M

    2009-09-01

    Home care for respiratory patients includes a complex array of services delivered in an uncontrolled setting. The role of a respiratory specialist inside the home healthcare team has been scarcely studied up to now. Our aims were to analyse the number and quality of episodic home visits performed by respiratory physicians to severe bedridden Chronic Respiratory Failure (CRF) patients, and also to evaluate the safety of tracheotomy tube substitutions at home. 231 home interventions (59.8/year) in 123 CRF patients (59 males; age 63 +/- 17 y, 24 on oxygen therapy, 35 under non invasive mechanical ventilation, 46 under invasive ventilation, 74 with tracheostomy) located 35 +/- 16 km far from referred hospital, were revised in a period of 4 years (2005-2008). Chronic Obstructive Pulmonary Disease (COPD) (31%) and amyotrophic lateral sclerosis (ALS) (28%) were the more frequent diagnoses. Interventions were: tracheotomy tube substitution (64%) presenting 22% of minor adverse events and 1.4% of major adverse events; change or new oxygen prescription (37%); nocturnal pulsed saturimetric trend prescription (24%); change in mechanical ventilation (MV) setting (4%); new MV adaptation (7%). After medical intervention, new home medical equipment devices (oxygen and MV) were prescribed in 36% of the cases while rehabilitative hospital admission and home respiratory physiotherapy prescription was proposed in 9% and 6% of the cases respectively. Patient/caregiver's satisfaction was reported on average 8.48 +/- 0.79 (1 = the worst; 10 = the higher). The local health care system (HCS) reimbursed 70 euros for each home intervention. Families saved 42 +/- 20 euros per visit for ambulance transportation. Home visits performed by a respiratory physician to bedridden patients with chronic respiratory failure: 1. include predominantly patients affected by COPD and ALS; 2. determine a very good satisfaction to patients/caregivers; 3. allow money saving to caregivers; 4. are predominantly

  20. [Ten-year evolution of mechanical ventilation in acute respiratory failure in the hematogical patient admitted to the intensive care unit].

    Science.gov (United States)

    Belenguer-Muncharaz, A; Albert-Rodrigo, L; Ferrandiz-Sellés, A; Cebrián-Graullera, G

    2013-10-01

    A comparison was made between invasive mechanical ventilation (IMV) and noninvasive positive pressure ventilation (NPPV) in haematological patients with acute respiratory failure. A retrospective observational study was made from 2001 to December 2011. A clinical-surgical intensive care unit (ICU) in a tertiary hospital. Patients with hematological malignancies suffering acute respiratory failure (ARF) and requiring mechanical ventilation in the form of either IMV or NPPV. Analysis of infection and organ failure rates, duration of mechanical ventilation and ICU and hospital stays, as well as ICU, hospital and mortality after 90 days. The same variables were analyzed in the comparison between NPPV success and failure. Forty-one patients were included, of which 35 required IMV and 6 NPPV. ICU mortality was higher in the IMV group (100% vs 37% in NPPV, P=.006). The intubation rate in NPPV was 40%. Compared with successful NPPV, failure in the NPPV group involved more complications, a longer duration of mechanical ventilation and ICU stay, and greater ICU and hospital mortality. Multivariate analysis of mortality in the NPPV group identified NPPV failure (OR 13 [95%CI 1.33-77.96], P=.008) and progression to acute respiratory distress syndrome (OR 10 [95%CI 1.95-89.22], P=.03) as prognostic factors. The use of NPPV reduced mortality compared with IMV. NPPV failure was associated with more complications. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  1. Electrical impedance tomography in the assessment of extravascular lung water in noncardiogenic acute respiratory failure

    NARCIS (Netherlands)

    Kunst, P. W.; Vonk Noordegraaf, A.; Raaijmakers, E.; Bakker, J.; Groeneveld, A. B.; Postmus, P. E.; de Vries, P. M.

    1999-01-01

    STUDY OBJECTIVES: To establish the value of electrical impedance tomography (EIT) in assessing pulmonary edema in noncardiogenic acute respiratory failure (ARF), as compared to the thermal dye double indicator dilution technique (TDD). DESIGN: Prospective clinical study. SETTING: ICU of a general

  2. Therapeutic hypothermia for neonates with hypoxic ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Ming-Chou Chiang

    2017-12-01

    Full Text Available Therapeutic hypothermia (TH is a recommended regimen for newborn infants who are at or near term with evolving moderate-to-severe hypoxic ischemic encephalopathy (HIE. The Task Force of the Taiwan Child Neurology Society and the Taiwan Society of Neonatology held a joint meeting in 2015 to establish recommendations for using TH on newborn patients with HIE. Based on current evidence and experts' experiences, this review article summarizes the key points and recommendations regarding TH for newborns with HIE, including: (1 selection criteria for TH; (2 choices of method and equipment for TH; (3 TH prior to and during transport; (4 methods for temperature maintenance, monitoring, and rewarming; (5 systemic care of patients during TH, including the care of respiratory and cardiovascular systems, management of fluids, electrolytes, and nutrition, as well as sedation and drug metabolism; (6 monitoring and management of seizures; (7 neuroimaging, prognostic factors, and outcomes; and (8 adjuvant therapy for TH. Key Words: hypoxic ischemic encephalopathy, neonate, patient care, perinatal asphyxia, therapeutic hypothermia

  3. Antibiotic treatment failure when consulting patients with respiratory tract infections in general practice

    DEFF Research Database (Denmark)

    Bordado Sköld, Margrethe; Aabenhus, Rune; Guassora, Ann Dorrit

    2017-01-01

    as cases of antibiotic treatment failure (ATF). Objectives: We studied antibiotic treatment failure in patients with acute RTIs from a general practitioner (GP) perspective, aiming to explore (i) GPs’ views of ATF in primary care; (ii) how ATF influences the doctor-patient relationship; and (iii) GPs....... GPs used many communicative tools to maintain trust with patients in cases of ATF, but they did not consider such incidents to affect the doctor-patient relationship adversely. Conclusion: These findings suggest a possible communication gap between doctors and patients, partly due to a narrow medical...... definition of ATF. Studies describing patients’ views are still missing. General practitioners’ experiences and views on antibiotic treatment failure in acute respiratory infections or its effects on the doctor–patient relationship have not been studied previously....

  4. Understanding Hypoxic Drive and the Release of Hypoxic Vasoconstriction.

    Science.gov (United States)

    Inkrott, Jon C

    2016-01-01

    Understanding the hypoxic drive and release of hypoxic vasoconstriction in the chronic obstructive pulmonary disease population can be somewhat confusing and misunderstood. Furthermore, the hypoxic drive theory is one in which there really is no scientific evidence to support and yet continues to prosper in every aspect of care in regard to the chronic lung patient, from prehospital all the way to intensive care unit and home care therapy. This subject review will hopefully enhance some understanding of what exactly goes on with these patients and the importance of providing oxygen when it is desperately needed. Copyright © 2016 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.

  5. Hypoxic radiosensitization: adored and ignored

    DEFF Research Database (Denmark)

    Overgaard, Jens

    2007-01-01

    resistance can be eliminated or modified by normobaric or hyperbaric oxygen or by the use of nitroimidazoles as hypoxic radiation sensitizers. More recently, attention has been given to hypoxic cytotoxins, a group of drugs that selectively or preferably destroys cells in a hypoxic environment. An updated......Since observations from the beginning of the last century, it has become well established that solid tumors may contain oxygen-deficient hypoxic areas and that cells in such areas may cause tumors to become radioresistant. Identifying hypoxic cells in human tumors has improved by the help of new...

  6. Chemical sensitizers for hypoxic cells: a decade of experience in clinical radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Dische, S [Mount Vernon Hospital, Northwood (UK)

    1985-02-01

    The clinical work with chemical agents to restore the radiosensitivity of hypoxic cells began in 1973 with metronidazole, misonidazole was first given in 1974. The results so far recorded of the clinical trials with misonidazole have been generally disappointing. Hypoxic cells must exist in all human tumours presenting for treatment and it is, however, probable that the oxygen effect is an important one at all dose fractionation regimes employed in radiotherapy but, after conventional fractionated radiotherapy, hypoxia may be a reason for failure in only a proportion of cases. The most important factor underlying the failure of misonidazole to acheive useful advantage is undoubtedly the low radiosensitizing concentrations achievable with the permitted dose of this neurotoxic drug. New drugs are under development and some have different dose-limiting toxicity. Those showing promise at this time are the Stanford compound, SR-2508 and the Roche compounds, Ro 03-8799. It is possible that the greatest sensitization with the greatest tolerance will be achieved by a combination of drugs.

  7. Clinical experience in treatment of five H1N1 flu patients with respiratory failure with high-frequency oscillatory mechanical ventilation

    Directory of Open Access Journals (Sweden)

    Zhi-gang ZHANG

    2011-08-01

    Full Text Available Objective To investigate the application and safety of high-frequency oscillation ventilation(HFOV in the treatment of patients suffering from H1N1 influenza with respiratory failure.Methods Self-control study was conducted.The treatment of five H1N1 influenza patients with respiratory failure was switched to HFOV after failure of conventional mechanical ventilation(CMV.Blood gas [partial pressure of oxygen(PaO2,partial pressure of carbon dioxide(PCO2,pH],respiratory mechanics indices [oxygen concentration(FiO2,mean airway pressure(Paw,static response(Cst,oxygenation index(PaO2/FiO2] before and after treatment were observed.Lung biopsy and clinical treatment data were also analyzed.Results Oxygenation was improved in 3 patients 6 to 8 hours after HFOV treatment,and marked improvement was observed after 24-48h.48-72h later,HFOV was replaced by CMV,and the patients weaned from mechanical ventilation successfully at 144h.In two patients symptoms were exacerbated after HFOV for 8 hours and the treatment was switched to CMV.Among them one died at 75h,and another one was treated with extracorporeal membrane oxygenation(ECMO and died at 145h.Conclusions HFOV can significantly improve the outcome of H1N1 flu patients with respiratory failure.The sequential treatment with HFOV followed by CMV can reduce complications and mortality.

  8. Acute respiratory failure caused by organizing pneumonia secondary to antineoplastic therapy for non-Hodgkin's lymphoma

    Science.gov (United States)

    Santana, Adriell Ramalho; Amorim, Fábio Ferreira; Soares, Paulo Henrique Alves; de Moura, Edmilson Bastos; Maia, Marcelo de Oliveira

    2012-01-01

    Interstitial lung diseases belong to a group of diseases that typically exhibit a subacute or chronic progression but that may cause acute respiratory failure. The male patient, who was 37 years of age and undergoing therapy for non-Hodgkin's lymphoma, was admitted with cough, fever, dyspnea and acute hypoxemic respiratory failure. Mechanical ventilation and antibiotic therapy were initiated but were associated with unfavorable progression. Thoracic computed tomography showed bilateral pulmonary "ground glass" opacities. Methylprednisolone pulse therapy was initiated with satisfactory response because the patient had used three drugs related to organizing pneumonia (cyclophosphamide, doxorubicin and rituximab), and the clinical and radiological symptoms were suggestive. Organizing pneumonia may be idiopathic or linked to collagen diseases, drugs and cancer and usually responds to corticosteroid therapy. The diagnosis was anatomopathological, but the patient's clinical condition precluded performing a lung biopsy. Organizing pneumonia should be a differential diagnosis in patients with apparent pneumonia and a progression that is unfavorable to antimicrobial treatment. PMID:23917942

  9. Intermittent hypoxia, respiratory plasticity and sleep apnea in humans: present knowledge and future investigations.

    Science.gov (United States)

    Mateika, Jason H; Syed, Ziauddin

    2013-09-15

    This review examines the role that respiratory plasticity has in the maintenance of breathing stability during sleep in individuals with sleep apnea. The initial portion of the review considers the manner in which repetitive breathing events may be initiated in individuals with sleep apnea. Thereafter, the role that two forms of respiratory plasticity, progressive augmentation of the hypoxic ventilatory response and long-term facilitation of upper airway and respiratory muscle activity, might have in modifying breathing events in humans is examined. In this context, present knowledge regarding the initiation of respiratory plasticity in humans during wakefulness and sleep is addressed. Also, published findings which reveal that exposure to intermittent hypoxia promotes breathing instability, at least in part, because of progressive augmentation of the hypoxic ventilatory response and the absence of long-term facilitation, are considered. Next, future directions are presented and are focused on the manner in which forms of plasticity that stabilize breathing might be promoted while diminishing destabilizing forms, concurrently. These future directions will consider the potential role of circadian rhythms in the promotion of respiratory plasticity and the role of respiratory plasticity in enhancing established treatments for sleep apnea. Published by Elsevier B.V.

  10. Intermittent hypoxia, respiratory plasticity and sleep apnea in humans; present knowledge and future investigations

    Science.gov (United States)

    Mateika, Jason H.; Syed, Ziauddin

    2013-01-01

    This review examines the role that respiratory plasticity has in the maintenance of breathing stability during sleep in individuals with sleep apnea. The initial portion of the review considers the manner in which repetitive breathing events may be initiated in individuals with sleep apnea. Thereafter, the role that two forms of respiratory plasticity, progressive augmentation of the hypoxic ventilatory response and long-term facilitation of upper airway and respiratory muscle activity, might have in modifying breathing events in humans is examined. In this context, present knowledge regarding the initiation of respiratory plasticity in humans during wakefulness and sleep is addressed. Also, published findings which reveal that exposure to intermittent hypoxia promotes breathing instability, at least in part, because of progressive augmentation of the hypoxic ventilatory response and the absence of long-term facilitation, are considered. Next, future directions are presented and are focused on the manner in which forms of plasticity that stabilize breathing might be promoted while diminishing destabilizing forms, concurrently. These future directions will consider the potential role of circadian rhythms in the promotion of respiratory plasticity and the role of respiratory plasticity in enhancing established treatments for sleep apnea. PMID:23587570

  11. Introduction to altitude/hypoxic training symposium.

    Science.gov (United States)

    Wilber, Randall L

    2007-09-01

    Altitude/hypoxic training has traditionally been an intriguing and controversial area of research and sport performance. This controversial aspect was evident recently in the form of scholarly debates in highly regarded professional journals, as well as the World Anti-Doping Agency's (WADA) consideration of placing "artificially-induced hypoxic conditions" on the 2007 Prohibited List of Substances/Methods. In light of the ongoing controversy surrounding altitude/hypoxic training, this symposium was organized with the following objectives in mind: 1) to examine the primary physiological responses and underlying mechanisms associated with altitude/hypoxic training, including the influence of genetic predisposition; 2) to present evidence supporting the effect of altitude/hypoxic acclimatization on both hematological and nonhematological markers, including erythrocyte volume, skeletal muscle-buffering capacity, hypoxic ventilatory response, and physiological efficiency/economy; 3) to evaluate the efficacy of several contemporary simulated altitude modalities and training strategies, including hypoxic tents, nitrogen apartments, and intermittent hypoxic exposure (IHE) or training, and to address the legal and ethical issues associated with the use of simulated altitude; and 4) to describe different altitude/hypoxic training strategies used by elite-level athletes, including Olympians and military special forces. In addressing these objectives, papers will be presented on the topics of: 1) effect of hypoxic "dose" on physiological responses and sea-level performance (Drs. Benjamin Levine and James Stray-Gundersen), 2) nonhematological mechanisms of improved performance after hypoxic exposure (Dr. Christopher Gore), 3) application of altitude/hypoxic training by elite athletes (Dr. Randall Wilber), and 4) military applications of hypoxic training (Dr. Stephen Muza).

  12. SMART phones and the acute respiratory patient.

    LENUS (Irish Health Repository)

    Gleeson, L

    2012-05-01

    Definition of Respiratory Failure using PaO2 alone is confounded when patients are commenced on oxygen therapy prior to arterial blood gas (ABG) measurement. Furthermore, classification of Respiratory Failure as Type 1 or Type 2 using PaCO2 alone can give an inaccurate account of events as both types can co-exist. 100 consecutive presentations of acute respiratory distress were assessed initially using PaO2, and subsequently PaO2\\/FiO2 ratio, to diagnose Respiratory Failure. Respiratory Failure cases were classified as Type 1 or Type 2 initially using PaCO2, and subsequently alveolar-arterial (A-a) gradient. Any resultant change in management was documented. Of 100 presentations, an additional 16 cases were diagnosed as Respiratory Failure using PaO2\\/FiO2 ratio in place of PaO2 alone (p = 0.0338). Of 57 cases of Respiratory Failure, 22 cases classified as Type 2 using PaCO2 alone were reclassified as Type 1 using A-a gradient (p < 0.001). Of these 22 cases, management changed in 18.

  13. Sleep quality under mild hypoxia in men with low hypoxic ventilatory response.

    Science.gov (United States)

    Hoshikawa, Masako; Uchida, Sunao; Ganeko, Masashi; Sumitomo, Junya; Totoki, Masatsugu; Kojima, Takuto; Nakamura, Yukiko; Kawahara, Takashi

    2014-01-01

    The present study evaluated whether slow-wave sleep and whole-night delta power of the non-rapid eye movement (NREM) sleep electroencephalogram (EEG) decrease during sleep at a simulated altitude of 2000 m, and whether such changes related to measures of hypoxic ventilatory response (HVR). This study consisted of two parts; in the first, HVR was measured in 41 subjects and each seven subjects with the lowest or the highest HVR were selected for the subsequent sleep study. In the second part, polysomnogram, arterial oxygen saturation (SpO2) and respiratory events are recorded on the selected subjects under normoxic and hypoxic conditions. Hypoxia decreased SpO2 and increased respiratory disturbances for both groups. The low HVR group, but not the high HVR group, showed decreases in the whole-night delta power of NREM sleep EEG under hypoxia. On the other hand, two subjects in the high HVR group, who showed relatively high apnoea indices, also showed lower SpO2 nadirs and decreases in the whole-night delta power under hypoxia. These results suggest that acute hypoxia equivalent to that at a 2000 m altitude decreases slow-wave sleep in individuals that show low HVR. However, low HVR may not be the only, but one of some factors that decrease the whole-night delta power under hypoxia. Therefore, it was not sufficient to identify individuals likely to be susceptible to deteriorated sleep quality at a simulated altitude of 2000 m only using the HVR test. Other factors, which relate to respiratory instabilities, should be taken into consideration to identify them.

  14. Current application of high flow oxygen nasal cannula in acute hypoxemic respiratory failure in the emergency department

    Directory of Open Access Journals (Sweden)

    Giulia Bottani

    2018-03-01

    Full Text Available High flow oxygen with nasal cannula (HFONC is a relatively new mode of oxygen delivery. Advantages of HFONC versus conventional oxygen therapy (COT encompass carbon dioxide washout, generation of a slight positive end-expiratory pressure and maintenance of humidified gas flow through airways. These features are mostly shared with non-invasive mechanical ventilation (NIMV, although with lack of a clearly comparable efficacy. In the last few years, HFONC has gained interest as a third alternative to COT and NIMV in the management of acute hypoxemic respiratory failure in the critically ill patient, both in intensive care units and emergency departments. The aim of this article is to review indications, effects and existing evidence on HFONC, COT and NIMV in the setting of acute hypoxemic respiratory failure.

  15. Unrecognized hypoxia and respiratory depression in emergency department patients sedated for psychomotor agitation: pilot study.

    Science.gov (United States)

    Deitch, Kenneth; Rowden, Adam; Damiron, Kathia; Lares, Claudia; Oqroshidze, Nino; Aguilera, Elizabeth

    2014-07-01

    The incidence of respiratory depression in patients who are chemically sedated in the emergency department (ED) is not well understood. As the drugs used for chemical restraint are respiratory depressants, improving respiratory monitoring practice in the ED may be warranted. The objective of this study is to describe the incidence of respiratory depression in patients chemically sedated for violent behavior and psychomotor agitation in the ED. Adult patients who met eligibility criteria with psychomotor agitation and violent behavior who were chemically sedated were eligible. SpO2 and ETCO2 (end-tidal CO2) was recorded and saved every 5 seconds. Demographic data, history of drug or alcohol abuse, medical and psychiatric history, HR and BP every 5 minutes, any physician intervention for hypoxia or respiratory depression, or adverse events were also recorded. We defined respiratory depression as an ETCO2 of ≥50 mmHg, a change of 10% above or below baseline, or a loss of waveform for ≥15 seconds. Hypoxia was defined as a SpO2 of ≤93% for ≥15 seconds. We enrolled 59 patients, and excluded 9 because of ≥35% data loss. Twenty-eight (28/50) patients developed respiratory depression at least once during their chemical restraint (56%, 95% CI 42-69%); the median number of events was 2 (range 1-6). Twenty-one (21/50) patients had at least one hypoxic event during their chemical restraint (42%, 95% CI 29-55%); the median number of events was 2 (range 1-5). Nineteen (19/21) (90%, 95% CI 71-97%) of the patients that developed hypoxia had a corresponding ETCO2 change. Fifteen (15/19) (79%, 95% CI 56-91%) patients who became hypoxic met criteria for respiratory depression before the onset of hypoxia. The sensitivity of ETCO2 to predict the onset of a hypoxic event was 90.48% (95% CI: 68-98%) and specificity 69% (95% CI: 49-84%). Five patients received respiratory interventions from the healthcare team to improve respiration [Airway repositioning: (2), Verbal stimulation

  16. Occupational mercury vapour poisoning with a respiratory failure, pneumomediastinum and severe quadriparesis

    Directory of Open Access Journals (Sweden)

    Jakub Smiechowicz

    2017-02-01

    Full Text Available Objectives: Despite restrictions, mercury continues to pose a health concern. Mercury has the ability to deposit in most parts of the body and can cause a wide range of unspecific symptoms leading to diagnostic mistakes. Methods and results: We report the case of severe mercury vapour poisoning after occupational exposure in a chloralkali plant worker that resulted in life-threatening respiratory failure, pneumomediastinum and quadriparesis. Conclusions: Prolonged mechanical ventilation and treatment with penicillamine and spironolactone was used with successful outcome.

  17. Hypokalemic paralysis and respiratory failure due to excessive intake of licorice syrup

    Directory of Open Access Journals (Sweden)

    Mehmet Oguzhan Ay

    2014-04-01

    Full Text Available Licorice is the root of Glycyrrhiza glabra, which has a herbal ingredient, glycyrrhizic acid. Excessive intake of licorice may cause a hypermineralocorticoidism-like syndrome characterized by sodium and water retention, hypokalemia, hypertension, metabolic alkalosis, low-renin activity, and hypoaldosteronism. In this paper, an 34 years old man who admitted to the emergency department with respiratory failure and marked muscle weakness of all extremities that progressed to paralysis after excessive intake of licorice syrup was presented. It was aimed to draw attention to the necessity of questioning whether there is excessive intake of licorice or not in patients who admitted to emergency department with paralysis and dyspnea. Plasma potassium concentration of the patient was 1.4 mmol/L. The patient\\'s respiratory distress and loss of muscle strength recovered completely after potassium replacement. [Cukurova Med J 2014; 39(2.000: 387-391

  18. Can patients with moderate to severe acute respiratory failure from COPD be treated safely with noninvasive mechanical ventilation on the ward?

    Science.gov (United States)

    Yalcinsoy, Murat; Salturk, Cuneyt; Oztas, Selahattin; Gungor, Sinem; Ozmen, Ipek; Kabadayi, Feyyaz; Oztim, Aysem Askim; Aksoy, Emine; Adıguzel, Nalan; Oruc, Ozlem; Karakurt, Zuhal

    2016-01-01

    Noninvasive mechanical ventilation (NIMV) usage outside of intensive care unit is not recommended in patients with COPD for severe acute respiratory failure (ARF). We assessed the factors associated with failure of NIMV in patients with ARF and severe acidosis admitted to the emergency department and followed on respiratory ward. This is a retrospective observational cohort study conducted in a tertiary teaching hospital specialized in chest diseases and thoracic surgery between June 1, 2013 and May 31, 2014. COPD patients who were admitted to our emergency department due to ARF were included. Patients were grouped according to the severity of acidosis into two groups: group 1 (pH=7.20-7.25) and group 2 (pH=7.26-7.30). Group 1 included 59 patients (mean age: 70±10 years, 30.5% female) and group 2 included 171 patients (mean age: 67±11 years, 28.7% female). On multivariable analysis, partial arterial oxygen pressure to the inspired fractionated oxygen (PaO2/FiO2) ratio failure in COPD patients with ARF in the ward. NIMV is effective not only in mild respiratory failure but also with severe forms of COPD patients presenting with severe exacerbation. The determination of the failure criteria of NIMV and the expertise of the team is critical for treatment success.

  19. Treatment Failure and Mortality amongst Children with Severe Acute Malnutrition Presenting with Cough or Respiratory Difficulty and Radiological Pneumonia

    Science.gov (United States)

    Chisti, Mohammod Jobayer; Salam, Mohammed Abdus; Bardhan, Pradip Kumar; Faruque, Abu S. G.; Shahid, Abu S. M. S. B.; Shahunja, K. M.; Das, Sumon Kumar; Hossain, Md Iqbal; Ahmed, Tahmeed

    2015-01-01

    Background Appropriate intervention is critical in reducing deaths among under-five, severe acutely malnourished (SAM) children with danger signs of severe pneumonia; however, there is paucity of data on outcome of World Health Organisation (WHO) recommended interventions of SAM children with severe pneumonia. We sought to evaluate outcome of the interventions in such children. Methods We prospectively enrolled SAM children aged 0–59 months, admitted to the Intensive Care Unit (ICU) or Acute Respiratory Infection (ARI) ward of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), between April 2011 and June 2012 with cough or respiratory difficulty and radiological pneumonia. All the enrolled children were treated with ampicillin and gentamicin, and micronutrients as recommended by the WHO. Comparison was made among pneumonic children with (n = 111) and without WHO defined danger signs of severe pneumonia (n = 296). The outcomes of interest were treatment failure (if a child required changing of antibiotics) and deaths during hospitalization. Further comparison was also made among those who developed treatment failure and who did not and among the survivors and deaths. Results SAM children with danger signs of severe pneumonia more often experienced treatment failure (58% vs. 20%; ppp<0.01). Conclusion and Significance The result suggests that SAM children with cough or respiratory difficulty and radiologic pneumonia who had WHO-defined danger signs of severe pneumonia more often had treatment failure and fatal outcome compared to those without the danger signs. In addition to danger signs of severe pneumonia, other common causes of both treatment failure and deaths were dehydration, hypocalcaemia, and bacteraemia on admission. The result underscores the importance for further research especially a randomized, controlled clinical trial to validate standard WHO therapy in SAM children with pneumonia especially with

  20. Treatment Failure and Mortality amongst Children with Severe Acute Malnutrition Presenting with Cough or Respiratory Difficulty and Radiological Pneumonia.

    Directory of Open Access Journals (Sweden)

    Mohammod Jobayer Chisti

    Full Text Available Appropriate intervention is critical in reducing deaths among under-five, severe acutely malnourished (SAM children with danger signs of severe pneumonia; however, there is paucity of data on outcome of World Health Organisation (WHO recommended interventions of SAM children with severe pneumonia. We sought to evaluate outcome of the interventions in such children.We prospectively enrolled SAM children aged 0-59 months, admitted to the Intensive Care Unit (ICU or Acute Respiratory Infection (ARI ward of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b, between April 2011 and June 2012 with cough or respiratory difficulty and radiological pneumonia. All the enrolled children were treated with ampicillin and gentamicin, and micronutrients as recommended by the WHO. Comparison was made among pneumonic children with (n = 111 and without WHO defined danger signs of severe pneumonia (n = 296. The outcomes of interest were treatment failure (if a child required changing of antibiotics and deaths during hospitalization. Further comparison was also made among those who developed treatment failure and who did not and among the survivors and deaths.SAM children with danger signs of severe pneumonia more often experienced treatment failure (58% vs. 20%; p<0.001 and fatal outcome (21% vs. 4%; p<0.001 compared to those without danger signs. Only 6/111 (5.4% SAM children with danger signs of severe pneumonia and 12/296 (4.0% without danger signs had bacterial isolates from blood. In log-linear binomial regression analysis, after adjusting for potential confounders, danger signs of severe pneumonia, dehydration, hypocalcaemia, and bacteraemia were independently associated both with treatment failure and deaths in SAM children presenting with cough or respiratory difficulty and radiological pneumonia (p<0.01.The result suggests that SAM children with cough or respiratory difficulty and radiologic pneumonia who

  1. Altered surfactant homeostasis and recurrent respiratory failure secondary to TTF-1 nuclear targeting defect.

    Science.gov (United States)

    Peca, Donatella; Petrini, Stefania; Tzialla, Chryssoula; Boldrini, Renata; Morini, Francesco; Stronati, Mauro; Carnielli, Virgilio P; Cogo, Paola E; Danhaive, Olivier

    2011-08-25

    Mutations of genes affecting surfactant homeostasis, such as SFTPB, SFTPC and ABCA3, lead to diffuse lung disease in neonates and children. Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1)--critical for lung, thyroid and central nervous system morphogenesis and function--causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome. Molecular mechanisms involved in this syndrome are heterogeneous and poorly explored. We report a novel TTF-1 molecular defect causing recurrent respiratory failure episodes in an infant. The subject was an infant with severe neonatal respiratory distress syndrome followed by recurrent respiratory failure episodes, hypopituitarism and neurological abnormalities. Lung histology and ultrastructure were assessed by surgical biopsy. Surfactant-related genes were studied by direct genomic DNA sequencing and array chromatine genomic hybridization (aCGH). Surfactant protein expression in lung tissue was analyzed by confocal immunofluorescence microscopy. For kinetics studies, surfactant protein B and disaturated phosphatidylcholine (DSPC) were isolated from serial tracheal aspirates after intravenous administration of stable isotope-labeled (2)H(2)O and (13)C-leucine; fractional synthetic rate was derived from gas chromatography/mass spectrometry (2)H and (13)C enrichment curves. Six intubated infants with no primary lung disease were used as controls. Lung biopsy showed desquamative interstitial pneumonitis and lamellar body abnormalities suggestive of genetic surfactant deficiency. Genetic studies identified a heterozygous ABCA3 mutation, L941P, previously unreported. No SFTPB, SFTPC or NKX2.1 mutations or deletions were found. However, immunofluorescence studies showed TTF-1 prevalently expressed in type II cell cytoplasm instead of nucleus, indicating defective nuclear targeting. This pattern has not been reported in human and was not found in two healthy controls and

  2. Altered surfactant homeostasis and recurrent respiratory failure secondary to TTF-1 nuclear targeting defect

    Directory of Open Access Journals (Sweden)

    Carnielli Virgilio P

    2011-08-01

    Full Text Available Abstract Background Mutations of genes affecting surfactant homeostasis, such as SFTPB, SFTPC and ABCA3, lead to diffuse lung disease in neonates and children. Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1 - critical for lung, thyroid and central nervous system morphogenesis and function - causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome. Molecular mechanisms involved in this syndrome are heterogeneous and poorly explored. We report a novel TTF-1 molecular defect causing recurrent respiratory failure episodes in an infant. Methods The subject was an infant with severe neonatal respiratory distress syndrome followed by recurrent respiratory failure episodes, hypopituitarism and neurological abnormalities. Lung histology and ultrastructure were assessed by surgical biopsy. Surfactant-related genes were studied by direct genomic DNA sequencing and array chromatine genomic hybridization (aCGH. Surfactant protein expression in lung tissue was analyzed by confocal immunofluorescence microscopy. For kinetics studies, surfactant protein B and disaturated phosphatidylcholine (DSPC were isolated from serial tracheal aspirates after intravenous administration of stable isotope-labeled 2H2O and 13C-leucine; fractional synthetic rate was derived from gas chromatography/mass spectrometry 2H and 13C enrichment curves. Six intubated infants with no primary lung disease were used as controls. Results Lung biopsy showed desquamative interstitial pneumonitis and lamellar body abnormalities suggestive of genetic surfactant deficiency. Genetic studies identified a heterozygous ABCA3 mutation, L941P, previously unreported. No SFTPB, SFTPC or NKX2.1 mutations or deletions were found. However, immunofluorescence studies showed TTF-1 prevalently expressed in type II cell cytoplasm instead of nucleus, indicating defective nuclear targeting. This pattern has not been reported in human

  3. Data on respiratory variables in critically ill patients with acute respiratory failure placed on proportional assist ventilation with load adjustable gain factors (PAV+

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    Dimitris Georgopoulos

    2016-09-01

    Full Text Available The data show respiratory variables in 108 critically ill patients with acute respiratory failure placed on proportional assist ventilation with load adjustable gain factors (PAV+ after at least 36 h on passive mechanical ventilation. PAV+ was continued for 48 h until the patients met pre-defined criteria either for switching to controlled modes or for breathing without ventilator assistance. Data during passive mechanical ventilation and during PAV+ are reported. Data are acquired from the whole population, as well as from patients with and without acute respiratory distress syndrome. The reported variables are tidal volume, driving pressure (ΔP, the difference between static end-inspiratory plateau pressure and positive end-expiratory airway pressure, respiratory system compliance and resistance, and arterial blood gasses. The data are supplemental to our original research article, which described individual ΔP in these patients and examined how it related to ΔP when the same patients were ventilated with passive mechanical ventilation using the currently accepted lung-protective strategy “Driving pressure during assisted mechanical ventilation. Is it controlled by patient brain?” [1]. Keywords: Tidal volume, Compliance, Driving pressure

  4. The value of high-flow nasal cannula oxygen therapy after extubation in patients with acute respiratory failure

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    Hong-Zhuan Song

    Full Text Available OBJECTIVE: To investigate the value of high-flow nasal cannula oxygen therapy after extubation in patients with acute respiratory failure. METHODS: A single-center, prospective, randomized, controlled pilot trial was conducted between January 2013 and December 2014. Sixty enrolled patients were randomized immediately after extubation into either a high-flow nasal cannula group (n=30 or an air entrainment mask group (n=30 at a fixed inspired oxygen fraction (40%. The success rate of oxygen therapy, respiratory and hemodynamic parameters and subjective discomfort (using a visual analogue scale were assessed at 24h after extubation. RESULTS: The two groups were comparable at extubation. A total of 46 patients were successfully treated including 27 patients in the high-flow nasal cannula group and 19 patients in the air entrainment mask group. Compared to the air entrainment mask group, the success rate of oxygen therapy and the partial pressure of arterial oxygen were significantly higher and the respiratory rate was lower in the high-flow nasal cannula group. In addition, less discomfort related to interface displacement and airway dryness was observed in the high-flow nasal cannula group than in the air entrainment mask group. CONCLUSIONS: At a fixed inspired oxygen fraction, the application of a high-flow nasal cannula after extubation achieves a higher success rate of oxygen therapy and less discomfort at 24h than an air entrainment mask in patients with acute respiratory failure.

  5. Seronegative neuromyelitis optica presenting with life-threatening respiratory failure.

    Science.gov (United States)

    Nardone, Raffaele; Zuccoli, Giulio; Brigo, Francesco; Trinka, Eugen; Fitzgerald, Ryan T

    2016-11-01

    Dyspnea has rarely been reported as a presenting symptom in patients with neuromyelitis optica (NMO). We report an unusual case of NMO relapse presenting with rapidly progressive respiratory failure and briefly discuss the possible pathophysiological mechanisms of this potential life-threatening complication of NMO. The 58-year-old woman with a history of bilateral optic neuritis presented to the emergency department with rapidly worsening dyspnea. Cervical spine magnetic resonance imaging showed extensive abnormal signal with involvement of the medulla oblongata. Since in our patient chest radiography failed to disclose a diaphragmatic palsy that is commonly observed in patients with phrenic nerve involvement, this acute manifestation of the disease may be attributed to brainstem involvement instead of cervical myelitis. Clinicians should be aware of this atypical presentation of NMO, which needs to be promptly recognized and aggressively treated.

  6. Turnover rate of hypoxic cells in solid tumors

    International Nuclear Information System (INIS)

    Ljungkvist, A.S.E.; Bussink, J.; Rijken, P.F.J.W.; Van Der Kogel, A.J.

    2003-01-01

    Most solid tumors contain hypoxic cells, and both the amount and duration of tumor hypoxia has been shown to influence the effect of radiation treatment negatively. It is important to understand the dynamic processes within the hypoxic cell population in non-treated tumors, and the effect of different treatment modalities on the kinetics of hypoxic cells to be able to design optimal combined modality treatments. The turnover rate of hypoxic cells was analyzed in three different solid tumor models with a double bio-reductive hypoxic marker assay with sequential injection of the two hypoxic markers. Previously it was shown that this assay could be used to detect both a decrease and an increase of tumor hypoxia in relation to the tumor vasculature with high spatial resolution. In this study the first hypoxic marker, pimonidazole, was administered at variable times relative to tumor harvest, and the second hypoxic marker, CCI-103F, was injected at a fixed time before harvest. The hypoxic cell turnover rate was calculated as the loss of pimonidazole positive cells relative to CCI-103F. The murine C38 line had the fastest hypoxic turnover rate of 60% /24h and the human xenograft line SCCNij3 had the slowest hypoxic turnover rate of 30% /24 h. The hypoxic turnover rate was most heterogeneous in the SCCNij3 line that even contained viable groups of cells that had been hypoxic for at least 5 days. The human xenograft line MEC82 fell in between with a hypoxic turnover rate of 50% /24 h. The hypoxic cell turnover was related to the potential tumor volume doubling time (Tpot) with a Tpot of 26h in C38 and 103h in SCCNij3. The dynamics of hypoxic cells, quantified with a double hypoxic marker method, showed large differences in hypoxic cell turnover rate and were related to Tpot

  7. Afferent Neural Feedback Overrides the Modulating Effects of Arousal, Hypercapnia and Hypoxemia on Neonatal Cardio-respiratory Control.

    Science.gov (United States)

    Lumb, Kathleen J; Schneider, Jennifer M; Ibrahim, Thowfique; Rigaux, Anita; Hasan, Shabih U

    2018-04-20

    Evidence at whole animal, organ-system, and cellular and molecular levels suggests that afferent volume feedback is critical for establishment of adequate ventilation at birth. Due to the irreversible nature of vagal ablation studies to date, it was difficult to quantify the roles of afferent volume input, arousal and changes in blood gas tensions on neonatal respiratory control. During reversible perineural vagal block, profound apneas, and hypoxemia and hypercarbia were observed necessitating termination of perineural blockade. Respiratory depression and apneas were independent of the sleep states. We demonstrate that profound apneas and life-threatening respiratory failure in vagally denervated animals do not result from lack of arousal or hypoxemia. Change in sleep state and concomitant respiratory depression result from lack of afferent volume feedback, which appears to be critical for the maintenance of normal breathing patterns and adequate gas exchange during the early postnatal period. Afferent volume feedback plays a vital role in neonatal respiratory control. Mechanisms for the profound respiratory depression and life-threatening apneas observed in vagally denervated neonatal animals remain unclear. We investigated the roles of sleep states, hypoxic-hypercapnia and afferent volume feedback on respiratory depression using reversible perineural vagal block during early postnatal period. Seven lambs were instrumented during the first 48h of life to record/analyze sleep states, diaphragmatic electromyograph, arterial blood gas tensions, systemic arterial blood pressure and rectal temperature. Perineural cuffs were placed around the vagi to attain reversible blockade. Post-operatively, during the awake state, both vagi were blocked using 2% xylocaine for up to 30 minutes. Compared with baseline values, pHa, PaO 2 and SaO 2 decreased and PaCO 2 increased during perineural blockade (P Respiratory depression and apneas were independent of sleep states. This

  8. Tg(Th-Cre)FI172Gsat (Th-Cre) defines neurons that are required for full hypercapnic and hypoxic reflexes.

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    Sun, Jenny J; Ray, Russell S

    2017-08-15

    The catecholaminergic (CA) system has been implicated in many facets of breathing control and offers an important target to better comprehend the underlying etiologies of both developmental and adult respiratory pathophysiologies. Here, we used a noninvasive DREADD-based pharmacogenetic approach to acutely perturb Tg(Th-Cre)FI172Gsat ( Th-Cre )-defined neurons in awake and unrestrained mice in an attempt to characterize CA function in breathing. We report that clozapine-N-oxide (CNO)-DREADD-mediated inhibition of Th-Cre -defined neurons results in blunted ventilatory responses under respiratory challenge. Under a hypercapnic challenge (5% CO 2 /21% O 2 /74% N 2 ), perturbation of Th-Cre neurons results in reduced f R , [Formula: see text] and [Formula: see text] Under a hypoxic challenge (10% O 2 /90% N 2 ), we saw reduced f R , [Formula: see text] and [Formula: see text], in addition to instability in both interbreath interval and tidal volume, resulting in a Cheyne-Stokes-like respiratory pattern. These findings demonstrate the necessity of Th-Cre -defined neurons for the hypercapnic and hypoxic ventilatory responses and breathing stability during hypoxia. However, given the expanded non-CA expression domains of the Tg(Th-Cre)FI172Gsat mouse line found in the brainstem, full phenotypic effect cannot be assigned solely to CA neurons. Nonetheless, this work identifies a key respiratory population that may lead to further insights into the circuitry that maintains respiratory stability in the face of homeostatic challenges. © 2017. Published by The Company of Biologists Ltd.

  9. Extra-corporeal membrane oxygenation in the management of 2009 influenza A (H1N1) refractory respiratory failure.

    LENUS (Irish Health Repository)

    Das, J P

    2012-02-01

    Rapidly progressive acute respiratory failure attributed to 2009 H1N1 influenza A infection has been reported worldwide-3. Refractory hypoxaemia despite conventional mechanical ventilation and lung protective strategies has resulted in the use a combination of rescue therapies, such as conservative fluid management, prone positioning, inhaled nitric oxide, high frequency oscillatory ventilation and extracorporeal membrane oxygenation (ECMO)4. ECMO allows for pulmonary or cardiopulmonary support as an adjunct to respiratory and cardiac failure, minimising ventilator-associated lung injury (VALI). This permits treatment of the underlying disease process, while concurrently allowing for recovery of the acute lung injury. This case documents a previously healthy twenty-two year old Asian male patient with confirmed pandemic (H 1N1) 2009 influenza A who was successfully managed with ECMO in the setting of severe refractory hypoxaemia and progressive hypercapnia.

  10. Extra-corporeal membrane oxygenation in the management of 2009 influenza A (H1N1) refractory respiratory failure.

    LENUS (Irish Health Repository)

    Das, J P

    2011-03-01

    Rapidly progressive acute respiratory failure attributed to 2009 H1N1 influenza A infection has been reported worldwide-3. Refractory hypoxaemia despite conventional mechanical ventilation and lung protective strategies has resulted in the use a combination of rescue therapies, such as conservative fluid management, prone positioning, inhaled nitric oxide, high frequency oscillatory ventilation and extracorporeal membrane oxygenation (ECMO)4. ECMO allows for pulmonary or cardiopulmonary support as an adjunct to respiratory and cardiac failure, minimising ventilator-associated lung injury (VALI). This permits treatment of the underlying disease process, while concurrently allowing for recovery of the acute lung injury. This case documents a previously healthy twenty-two year old Asian male patient with confirmed pandemic (H 1N1) 2009 influenza A who was successfully managed with ECMO in the setting of severe refractory hypoxaemia and progressive hypercapnia.

  11. Ventilatory chemosensory drive is blunted in the mdx mouse model of Duchenne Muscular Dystrophy (DMD.

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    Matias Mosqueira

    Full Text Available Duchenne Muscular Dystrophy (DMD is caused by mutations in the DMD gene resulting in an absence of dystrophin in neurons and muscle. Respiratory failure is the most common cause of mortality and previous studies have largely concentrated on diaphragmatic muscle necrosis and respiratory failure component. Here, we investigated the integrity of respiratory control mechanisms in the mdx mouse model of DMD. Whole body plethysmograph in parallel with phrenic nerve activity recordings revealed a lower respiratory rate and minute ventilation during normoxia and a blunting of the hypoxic ventilatory reflex in response to mild levels of hypoxia together with a poor performance on a hypoxic stress test in mdx mice. Arterial blood gas analysis revealed low PaO2 and pH and high PaCO2 in mdx mice. To investigate chemosensory respiratory drive, we analyzed the carotid body by molecular and functional means. Dystrophin mRNA and protein was expressed in normal mice carotid bodies however, they are absent in mdx mice. Functional analysis revealed abnormalities in Dejours test and the early component of the hypercapnic ventilatory reflex in mdx mice. Together, these results demonstrate a malfunction in the peripheral chemosensory drive that would be predicted to contribute to the respiratory failure in mdx mice. These data suggest that investigating and monitoring peripheral chemosensory drive function may be useful for improving the management of DMD patients with respiratory failure.

  12. East coast fever caused by Theileria parva is characterized by macrophage activation associated with vasculitis and respiratory failure

    Science.gov (United States)

    Respiratory failure and death in East Coast Fever (ECF), a clinical syndrome of African cattle caused by the apicomplexan parasite Theileria parva, has historically been attributed to pulmonary infiltration by infected lymphocytes. However, immunohistochemical staining of tissue from T. parva infect...

  13. New avenues in hypoxic cell sensitization

    International Nuclear Information System (INIS)

    Huilgol, N.G.; Chatterjee, N.A.; Singh, B.B.

    1995-01-01

    Hypoxic cells in tumors represent a population of cells that are resistant to radiotherapy. Bio-reductive agents like RSU 1069, RBU 6145 and EOg and vasoactive drugs in conjunction with hypoxic cell sensitizers are being evaluated as hypoxic cell cytotoxins. Chlorpromazine a membrane active drug and AK-2123- a nitrotriazole with a potential to deplete intracellular thiols induced vasoconstriction and sensitize hypoxic cells have stretched the boundaries of innovation. A preliminary experience with these drugs is discussed. 8 refs., 2 tabs., 2 figs

  14. Chronic heart failure modifies respiratory mechanics in rats: a randomized controlled trial

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    Deise M. Pacheco

    2016-01-01

    Full Text Available ABSTRACT Objective To analyze respiratory mechanics and hemodynamic alterations in an experimental model of chronic heart failure (CHF following myocardial infarction. Method Twenty-seven male adult Wistar rats were randomized to CHF group (n=12 or Sham group (n=15. Ten weeks after coronary ligation or sham surgery, the animals were anesthetized and submitted to respiratory mechanics and hemodynamic measurements. Pulmonary edema as well as cardiac remodeling were measured. Results The CHF rats showed pulmonary edema 26% higher than the Sham group. The respiratory system compliance (Crs and the total lung capacity (TLC were lower (40% and 27%, respectively in the CHF rats when compared to the Sham group (P<0.01. There was also an increase in tissue resistance (Gti and elastance (Hti (28% and 45%, respectively in the CHF group. Moreover, left ventricular end-diastolic pressure was higher (32 mmHg vs 4 mmHg, P<0.01, while the left ventricular systolic pressure was lower (118 mmHg vs 130 mmHg, P=0.02 in the CHF group when compared to the control. Pearson’s correlation coefficient showed a negative association between pulmonary edema and Crs (r=–0.70, P=0.0001 and between pulmonary edema and TLC (r=–0.67,P=0.0034. Pulmonary edema correlated positively with Gti (r=0.68, P=0.001 and Hti (r=0.68, P=0.001. Finally, there was a strong positive relationship between pulmonary edema and heart weight (r=0.80, P=0.001. Conclusion Rats with CHF present important changes in hemodynamic and respiratory mechanics, which may be associated with alterations in cardiopulmonary interactions.

  15. In vitro effects of piracetam on the radiosensitivity of hypoxic cells (adaptation of MTT assay to hypoxic conditions)

    International Nuclear Information System (INIS)

    Gheuens, E.E.O.; Bruijn, E.A. de; Van der Heyden, S.; Van Oosterom, A.T.; Lagarde, P.; Pooter, C.M.J. de; Chomy, F.

    1995-01-01

    This paper describes the adaptation of the MTT assay to hypoxic conditions in order to test the in vitro effect of piracetam on hypoxic cells and particularly on the radiosensitivity of hypoxic cells since this drug has shown clinical effect on acute and chronic hypoxia. The V79 cell line was selected by reference to preliminary hypoxic experiments using clonogenic assay and euoxic experiments using clonogenic and MTT assays. Cell growth and survival in our hypoxic conditions were assessed using MTT assay with an enclosure and special 48-well plates both made of glass. Growth curves on glass plates after 1-hour exposure to nitrogen versus air were comparable, so there is no bias effect due to gas composition. Survival curves using MTT versus reference clonogenic assay were comparable after radiation exposure in eu- and hypoxic conditions, and confirm the validity of our original technique for creating hypoxia. The Oxygen Enhancement Ratio was of about 3 for 1-hour hypoxic exposure. Piracetam gave no cytotoxic effect up to 10 mM of piracetam. Growth curves after continuous drug exposure and 1-hour euoxic versus hypoxic exposure gave no cytotoxic effect up to 10 mM of piracetam. Survival curves after continuous drug exposure to 10 mM of piracetam gave no significant effect on the radiosensitivity of hypoxic V79 cells using MTT or clonogenic assay. (author). 32 refs., 6 figs

  16. Predicting success of high-flow nasal cannula in pneumonia patients with hypoxemic respiratory failure: The utility of the ROX index.

    Science.gov (United States)

    Roca, Oriol; Messika, Jonathan; Caralt, Berta; García-de-Acilu, Marina; Sztrymf, Benjamin; Ricard, Jean-Damien; Masclans, Joan R

    2016-10-01

    The purpose of the study is to describe early predictors and to develop a prediction tool that accurately identifies the need for mechanical ventilation (MV) in pneumonia patients with hypoxemic acute respiratory failure (ARF) treated with high-flow nasal cannula (HFNC). This is a 4-year prospective observational 2-center cohort study including patients with severe pneumonia treated with HFNC. High-flow nasal cannula failure was defined as need for MV. ROX index was defined as the ratio of pulse oximetry/fraction of inspired oxygen to respiratory rate. One hundred fifty-seven patients were included, of whom 44 (28.0%) eventually required MV (HFNC failure). After 12 hours of HFNC treatment, the ROX index demonstrated the best prediction accuracy (area under the receiver operating characteristic curve 0.74 [95% confidence interval, 0.64-0.84]; Pfailure in whom therapy can be continued after 12 hours. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Management of an elderly patient with respiratory failure due to double aortic arch

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    Changwan Ryu

    2016-01-01

    Full Text Available Vascular rings are congenital malformations of the aortic arch. A double aortic arch (DAA, the most common type of vascular ring, results from the failure of the fourth embryonic branchial arch to regress, leading to an ascending aorta that divides into a left and right arch that fuse together to completely encircle the trachea and esophagus. The subsequent DAA causes compressive effects on the trachea and esophagus that typically manifests in infancy or early childhood. Adult presentations, particularly in the elderly, are exceedingly rare. Historically such patients have a long-standing history of dyspnea on exertion and dysphagia, with many assumed to have obstructive lung or intrinsic cardiac disease. We describe a case of an elderly woman who presented with respiratory failure due to DAA. In her case, surgery was not feasible and we describe our experience with airway stenting.

  18. Ultrasound-guided transversus abdominis plane (TAP) block: a useful adjunct in the management of postoperative respiratory failure.

    Science.gov (United States)

    Singh, Mandeep; Chin, Ki Jinn; Chan, Vincent

    2011-06-01

    The ultrasound-guided transversus abdominis plane (TAP) block is a useful tool in controlling postoperative pain following abdominal surgery. The bilateral ultrasound-guided TAP blocks successfully managed the pain of a patient presenting with hypoxemia and respiratory failure in the Post-anesthesia Care Unit, following a laparotomy for small bowel obstruction during general anesthesia. The TAP block reduced systemic opioid requirements and opioid-induced sedation and respiratory depression, improved patient compliance with non-invasive positive pressure ventilation, and prevented the need for intubation and ventilation in the intensive care unit. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Can patients with moderate to severe acute respiratory failure from COPD be treated safely with noninvasive mechanical ventilation on the ward?

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    Yalcinsoy M

    2016-05-01

    Full Text Available Murat Yalcinsoy,1 Cuneyt Salturk,2 Selahattin Oztas,2 Sinem Gungor,2 Ipek Ozmen,2 Feyyaz Kabadayi,2 Aysem Askim Oztim,2 Emine Aksoy,2 Nalan Adıguzel,2 Ozlem Oruc,2 Zuhal Karakurt2 1Department of Pulmonary Medicine, Inonu University Medical Faculty, Turgut Ozal Medical Center, Malatya, 2Department of Pulmonary Medicine, Sureyyapaşa Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey Purpose: Noninvasive mechanical ventilation (NIMV usage outside of intensive care unit is not recommended in patients with COPD for severe acute respiratory failure (ARF. We assessed the factors associated with failure of NIMV in patients with ARF and severe acidosis admitted to the emergency department and followed on respiratory ward.Patients and methods: This is a retrospective observational cohort study conducted in a tertiary teaching hospital specialized in chest diseases and thoracic surgery between June 1, 2013 and May 31, 2014. COPD patients who were admitted to our emergency department due to ARF were included. Patients were grouped according to the severity of acidosis into two groups: group 1 (pH=7.20–7.25 and group 2 (pH=7.26–7.30.Results: Group 1 included 59 patients (mean age: 70±10 years, 30.5% female and group 2 included 171 patients (mean age: 67±11 years, 28.7% female. On multivariable analysis, partial arterial oxygen pressure to the inspired fractionated oxygen (PaO2/FiO2 ratio <200, delta pH value <0.30, and pH value <7.31 on control arterial blood gas after NIMV in the emergency room and peak C-reactive protein were found to be the risk factors for NIMV failure in COPD patients with ARF in the ward.Conclusion: NIMV is effective not only in mild respiratory failure but also with severe forms of COPD patients presenting with severe exacerbation. The determination of the failure criteria of NIMV and the expertise of the team is critical for treatment success. Keywords: noninvasive mechanical ventilation

  20. Measles and respiratory failure: Case report and review of the last European outbreaks

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    Leonel Lagunes

    2015-08-01

    Full Text Available Measles is an preventable acute viral illness, with the potential for severe and fatal complications. According to the European Centre for Disease Prevention and Control in the last surveillance report, a total of 10 271 cases of measles were reported from January to December 2013. And 127 of those were reported in Spain with a 2.7/1 million habitants rate. In 2010, the World Health Organization European Region made a new commitment to eradicate measles by 2015 in the zone, however, measles cases and outbreaks are still occurring in many countries. We present the last 2 cases with severe measles-associated respiratory failure and a review of the literature of the last European outbreaks. Two young adults were admitted in the intensive care unit due to respiratory failure with a confirmed measles infection. Both treated with high flow nasal cannula during 3 to 5 days; one had a pneumococcal pneumonia coinfection. An incomplete vaccination schedule was documented in one of them while the other did not remember his. Within 10 days of admission, both were discharged from intensive care unit and the hospital with no complications. Measles can present with a variety of symptoms in adults and is responsible for a high morbidity especially during outbreaks. Pneumonia is a severe complication of measles infection, commonly reported. Surveillance and vaccination programs should be strengthened in order to achieve measles elimination.

  1. Neuroleptic malignant-like syndrome with a slight elevation of creatine-kinase levels and respiratory failure in a patient with Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Wei L

    2014-02-01

    Full Text Available Li Wei,1,2 Yinghui Chen1,2 1Department of Neurology, Jinshan Hospital, 2Department of Neurology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China Abstract: Neuroleptic malignant-like syndrome (NMLS is a rare but catastrophic complication of drug treatment for Parkinson's disease (PD. Sudden withdrawal and abrupt reduction of antiparkinsonian drugs are major risk factors. Just as its name suggests, the clinical features of NMLS are similar to neuroleptic malignant syndrome, which is a dangerous adverse response to antipsychotic drugs. Both of these conditions can present with hyperthermia, marked muscle rigidity, altered consciousness, autonomic dysfunction, and elevated serum creatine-kinase (CK levels. However, we describe a special NMLS case with a slight elevation of CK levels and respiratory failure in the full course of her treatment. The patient, a 68-year-old woman with a 4-years history of Parkinson's disease, presented with hyperthermia and severe muscular rigidity. During the course of her treatment, her maximum temperature was extremely high (above 41°C. At the beginning, the diagnosis of NMLS secondary to dopamine decrease was difficult to make, because her initial blood examination revealed that her serum CK levels were mildly elevated and decreased to normal range rapidly. Although antiparkinsonian drugs and supportive treatment were applied, the patient developed an acute respiratory failure in the early course of treatment. This case report highlights that when confronted with Parkinson's patients with high body temperature and muscle rigidity, NMLS should be taken into consideration even if there is no CK elevation. Likewise, the need for supportive care is essential, because its complications are severe, even such as respiratory failure. Keywords: antiparkinsonian drugs, creatine kinase, parkinsonism–hyperpyrexia syndrome, respiratory failure

  2. Runners maintain locomotor-respiratory coupling following isocapnic voluntary hyperpnea to task failure.

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    Stickford, Abigail S L; Stickford, Jonathon L; Tanner, David A; Stager, Joel M; Chapman, Robert F

    2015-11-01

    Evidence has long suggested that mammalian ventilatory and locomotor rhythms are linked, yet determinants and implications of locomotor-respiratory coupling (LRC) continue to be investigated. Anecdotally, respiratory muscle fatigue seen at the end of heavy exercise may result in an uncoupling of movement-ventilation rhythms; however, there is no scientific evidence to substantiate this claim. We sought to determine whether or not fatigue of the respiratory muscles alters locomotor-respiratory coupling patterns typically observed in highly trained individuals while running. A related query was to examine the relationship between the potential changes in LRC and measures of running economy. Twelve male distance runners ran at four submaximal workloads (68-89 % VO2peak) on two separate days while LRC was quantified. One LRC trial served as a control (CON), while the other was performed following an isocapnic voluntary hyperpnea to task failure to induce respiratory muscle fatigue (FT+). LRC was assessed as stride-to-breathing frequency ratios (SF/fB) and degree of LRC (percentage of breaths occurring during the same decile of the step cycle). Hyperpnea resulted in significant declines in maximal voluntary inspiratory (MIP) and expiratory (MEP) mouth pressures (ΔMIP = -10 ± 12 cm H2O; ΔMEP = -6 ± 9 cm H2O). There were no differences in minute ventilation between CON and FT+ (CON, all speeds pooled = 104 ± 25 L min(-1); FT+ pooled = 106 ± 23 L min(-1)). Stride frequency was not different between trials; however, breathing frequency was significantly greater during FT+ compared to CON at all speeds (CON pooled = 47 ± 10 br min(-1); FT+ pooled = 52 ± 9 br min(-1)), resulting in smaller corresponding SF/fB. Yet, the degree of LRC was the same during CON and FT+ (CON pooled = 63 ± 15 %; FT+ pooled = 64 ± 18 %). The results indicate that trained runners are able to continue entraining breath and step cycles, despite marked changes in exercise breathing frequency

  3. Sequential Oxygenation Index and Organ Dysfunction Assessment within the First 3 Days of Mechanical Ventilation Predict the Outcome of Adult Patients with Severe Acute Respiratory Failure

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    Hsu-Ching Kao

    2013-01-01

    Full Text Available Objective. To determine early predictors of outcomes of adult patients with severe acute respiratory failure. Method. 100 consecutive adult patients with severe acute respiratory failure were evaluated in this retrospective study. Data including comorbidities, Sequential Organ Failure Assessment (SOFA score, Acute Physiological Assessment and Chronic Health Evaluation II (APACHE II score, PaO2, FiO2, PaO2/FiO2, PEEP, mean airway pressure (mPaw, and oxygenation index (OI on the 1st and the 3rd day of mechanical ventilation, and change in OI within 3 days were recorded. Primary outcome was hospital mortality; secondary outcome measure was ventilator weaning failure. Results. 38 out of 100 (38% patients died within the study period. 48 patients (48% failed to wean from ventilator. Multivariate analysis showed day 3 OI ( and SOFA ( score were independent predictors of hospital mortality. Preexisting cerebrovascular accident (CVA ( was the predictor of weaning failure. Results from Kaplan-Meier method demonstrated that higher day 3 OI was associated with shorter survival time (log-Rank test, . Conclusion. Early OI (within 3 days and SOFA score were predictors of mortality in severe acute respiratory failure. In the future, prospective studies measuring serial OIs in a larger scale of study cohort is required to further consolidate our findings.

  4. Cleistanthus collinus induces type I distal renal tubular acidosis and type II respiratory failure in rats.

    Science.gov (United States)

    Maneksh, Delinda; Sidharthan, Anita; Kettimuthu, Kavithapriya; Kanthakumar, Praghalathan; Lourthuraj, Amala A; Ramachandran, Anup; Subramani, Sathya

    2010-06-01

    A water decoction of the poisonous shrub Cleistanthus collinus is used for suicidal purposes. The mortality rate is 28%. The clinical profile includes distal renal tubular acidosis (DRTA) and respiratory failure. The mechanism of toxicity is unclear. To demonstrate features of C. collinus toxicity in a rat model and to identify its mechanism(s) of action. Rats were anesthetized and the carotid artery was cannulated. Electrocardiogram and respiratory movements were recorded. Either aqueous extract of C. collinus or control solution was administered intraperitoneally. Serial measurements of blood gases, electrolytes and urinary pH were made. Isolated brush border and basolateral membranes from rat kidney were incubated with C. collinus extract and reduction in ATPase activity was assessed. Venous blood samples from human volunteers and rats were incubated with an acetone extract of C. collinus and plasma potassium was estimated as an assay for sodium-potassium pump activity. The mortality was 100% in tests and 17% in controls. Terminal event in test animals was respiratory arrest. Controls had metabolic acidosis, respiratory compensation acidic urine and hyperkalemia. Test animals showed respiratory acidosis, alkaline urine and low blood potassium as compared to controls. C. collinus extract inhibited ATPase activity in rat kidney. Plasma K(+) did not increase in human blood incubated with C. collinus extract. Active principles of C. collinus inhibit proton pumps in the renal brush border, resulting in type I DRTA in rats. There is no inhibition of sodium-potassium pump activity. Test animals develop respiratory acidosis, and the immediate cause of death is respiratory arrest.

  5. Microvascular decompression surgery for vertebral artery compression of the medulla oblongata: 3 cases with respiratory failure and/or dysphagia.

    Science.gov (United States)

    Nakahara, Yukiko; Kawashima, Masatou; Matsushima, Toshio; Kouguchi, Motofumi; Takase, Yukinori; Nanri, Yusuke; Yakusiji, Yusuke

    2014-01-01

    It is well known that brainstem dysfunction may be caused by vascular compression of the medulla oblongata (MO). However, only a limited number of reports have found microvascular decompression (MVD) surgery to be an effective treatment for symptomatic patients with MO dysfunction, such as essential hypertension, pyramidal tract signs, dysphagia, and respiratory failure. This report describes 3 patients with vertebral artery compression of MO who presented with respiratory failure and/or dysphagia. MVD surgery using the transcondylar fossa approach was effective in relieving patient symptoms. Although the pathogenic mechanisms of symptomatic vertebral artery compression of MO remain unclear, we should recognize that MVD surgery is effective for selected patients with brainstem dysfunction. The transcondylar fossa approach and the stitched sling retraction technique are appropriate in MVD surgery to relieve vertebral artery compression of MO. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Functional and histopathological identification of the respiratory failure in a DMSXL transgenic mouse model of myotonic dystrophy

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    Petrica-Adrian Panaite

    2013-05-01

    Acute and chronic respiratory failure is one of the major and potentially life-threatening features in individuals with myotonic dystrophy type 1 (DM1. Despite several clinical demonstrations showing respiratory problems in DM1 patients, the mechanisms are still not completely understood. This study was designed to investigate whether the DMSXL transgenic mouse model for DM1 exhibits respiratory disorders and, if so, to identify the pathological changes underlying these respiratory problems. Using pressure plethysmography, we assessed the breathing function in control mice and DMSXL mice generated after large expansions of the CTG repeat in successive generations of DM1 transgenic mice. Statistical analysis of breathing function measurements revealed a significant decrease in the most relevant respiratory parameters in DMSXL mice, indicating impaired respiratory function. Histological and morphometric analysis showed pathological changes in diaphragmatic muscle of DMSXL mice, characterized by an increase in the percentage of type I muscle fibers, the presence of central nuclei, partial denervation of end-plates (EPs and a significant reduction in their size, shape complexity and density of acetylcholine receptors, all of which reflect a possible breakdown in communication between the diaphragmatic muscles fibers and the nerve terminals. Diaphragm muscle abnormalities were accompanied by an accumulation of mutant DMPK RNA foci in muscle fiber nuclei. Moreover, in DMSXL mice, the unmyelinated phrenic afferents are significantly lower. Also in these mice, significant neuronopathy was not detected in either cervical phrenic motor neurons or brainstem respiratory neurons. Because EPs are involved in the transmission of action potentials and the unmyelinated phrenic afferents exert a modulating influence on the respiratory drive, the pathological alterations affecting these structures might underlie the respiratory impairment detected in DMSXL mice. Understanding

  7. Plasma Endothelin-1 Levels in Preterm Neonatal Infants with Acute Respiratory Failure

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    D. V. Dmitriyev

    2008-01-01

    Full Text Available Increased pulmonary vascular resistance in preterm infants is associated with acute respiratory failure (ARF and at the same time endothelin-1 (E-1 plays an important role in neonatal pulmonary vascular responsiveness. Methods. Endothelin-1 levels were measured in two blood samples in 12 preterm infants with ARF and in 12 controls (at 32.2±1.3 and 29.8±1.2 weeks of gestation, respectively by enzyme immunoassay. For this, the first and second blood samples were taken at 18 to 40 hours after birth. Results. The plasma level of E-1 in the first sample did not differ between the neonates of both groups. In the second sample, significantly higher E-1 concentrations were observed in the newborns with ARF than in the controls. In the first sample, E-1 concentration were higher than in the second one in both groups (p<0.001. There was a significant positive correlation between the second E-1 sample and the SNAPPE 2 scale rating (r=0.38; p=0.02. The plasma level of E-1 in the first sample did not differ in both groups (11.9 and 12.2 pg/ml, respectively. Conclusion. Neonates with and without ARF had the similar plasma E-1 levels in the first sample, by taking into account the fact that the E-1 levels were higher in ARF than in the controls at 18 to 40 hour after birth. Increased vascular resistance in ARF may be associated with the high level of E-1. Key words: endothe-lin-1, acute respiratory failure.

  8. High prevalence of respiratory muscle weakness in hospitalized acute heart failure elderly patients.

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    Pedro Verissimo

    Full Text Available Respiratory Muscle Weakness (RMW has been defined when the maximum inspiratory pressure (MIP is lower than 70% of the predictive value. The prevalence of RMW in chronic heart failure patients is 30 to 50%. So far there are no studies on the prevalence of RMW in acute heart failure (AHF patients.Evaluate the prevalence of RMW in patients admitted because of AHF and the condition of respiratory muscle strength on discharge from the hospital.Sixty-three patients had their MIP measured on two occasions: at the beginning of the hospital stay, after they had reached respiratory, hemodynamic and clinical stability and before discharge from the hospital. The apparatus and technique to measure MIP were adapted because of age-related limitations of the patients. Data on cardiac ejection fraction, ECG, brain natriuretic peptide (BNP levels and on the use of noninvasive ventilation (NIV were collected.The mean age of the 63 patients under study was 75 years. On admission the mean ejection fraction was 33% (95% CI: 31-35 and the BNP hormone median value was 726.5 pg/ml (range: 217 to 2283 pg/ml; 65% of the patients used NIV. The median value of MIP measured after clinical stabilization was -52.7 cmH2O (range: -20 to -120 cmH2O; 76% of the patients had MIP values below 70% of the predictive value. On discharge, after a median hospital stay of 11 days, the median MIP was -53.5 cmH2O (range:-20 to -150 cmH2O; 71% of the patients maintained their MIP values below 70% of the predictive value. The differences found were not statistically significant.Elderly patients admitted with AHF may present a high prevalence of RMW on admission; this condition may be maintained at similar levels on discharge in a large percentage of these patients, even after clinical stabilization of the heart condition.

  9. Clinical characteristics, etiology, and prognosis of hypoxic hepatitis: an analysis of 68 cases

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    FAN Hebin

    2014-11-01

    Full Text Available ObjectiveTo investigate the clinical characteristics, etiology, and prognosis of hypoxic hepatitis (HH. MethodsThe medical records of 68 patients with HH admitted to our hospital from January 2002 to December 2012 were collected and reviewed. The common causes of HH were analyzed. The patients were divided into groups of survival and death according to the clinical outcomes. The age, sex, and the Sequential Organ Failure Assessment (SOFA score on admission were compared between groups. The clinical and laboratory data, including bilirubin (Bil, alkaline (ALP, gamma-glutamyl transpeptidase (GGT, international normalized ratio (INR, lactate dehydrogenase (LDH, alanine aminotransferase (ALT, and blood urea nitrogen (BUN, were monitored, and the peak of each parameter was compared between groups. Normally distributed continuous data were compared between the two groups using Student′s t-test, and non-normally distributed continuous data were compared using rank sum test. ResultsThe common causes of HH included heart failure (acute myocardial infarction and congestive heart failure, respiratory failure, septic shock, heat shock, and severe allergic reactions to bee sting. Sharply increasing levels of serum ALT and AST were observed in all patients. The 28-day in-hospital mortality rate was 33.8%. Significant differences between two groups were observed in age of admission (P<0.001, SOFA value (P<0.001, and peak levels of Bil (P<0.001, ALP (P<0.001, GGT (P= 0.001, INR (P<0.001, LDH (P<0.001, ALT (P=0.013, and BUN (P<0.001. The treatments of HH mainly targeted the primary disease, while adjuvant therapies such as nutritional support and liver protection were also needed. ConclusionThe prognosis of HH is poor and the mortality rate is high. The major cause of death is cardiogenic shock, followed by septic shock and acute myocardial infarction. Protecting vital organs from injury and preventing infection play important roles in improving

  10. Relationship between human respiratory reactivity and neutrophil metabolism under intermittent hypoxic influences in humans exposed to low-level radiation

    International Nuclear Information System (INIS)

    Serebrovskaya, T.V.; Oberenko, O.A.; Guseva, S.A.

    1996-01-01

    The group of 18 men exposed to radiation during amelioration work in the Chernobyl NPP was examined in the course of adaptation to intermittent hypoxia (rebreathing technique during 10 days of three dayly 5-7 min sessions with 15 min break). The starting level of ventilatory response to hypoxic stimulus (HVR) did not differ from the one in persons living in non-contaminated areas. This hypoxic training (HT) caused the increase of HVR, activity of NADPH-oxidase and cationic protein content in neutrophyls as well as various changes in mieloperoxidase activity. The correlation between respiration reactivity and deviations in neutrophil metabolism under HT was found. 14 refs., 2 figs

  11. Risk of Unsuccessful Noninvasive Ventilation for Acute Respiratory Failure in Heterogeneous Neuromuscular Diseases: A Retrospective Study.

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    Kataoka, Hiroshi; Nanaura, Hitoki; Kinugawa, Kaoru; Uchihara, Yuto; Ohara, Hiroya; Eura, Nobuyuki; Syobatake, Ryogo; Sawa, Nobuhiro; Takao, Kiriyama; Sugie, Kazuma; Ueno, Satoshi

    2017-02-20

    If invasive ventilation can be avoided by performing noninvasive mechanical ventilation (NIV) in patients with acute respiratory failure (ARF), the disease can be effectively managed. It is important to clarify the characteristics of patients with neuromuscular diseases in whom initial NIV is likely to be unsuccessful. We studied 27 patients in stable neuromuscular condition who initially received NIV to manage fatal ARF to identify differences in factors immediately before the onset of ARF among patients who receive continuous NIV support, patients who are switched from NIV to invasive ventilation, and patients in whom NIV is discontinued. Endpoints were evaluated 24 and 72 hours after the initiation of NIV. After 24 hours, all but 1 patient with amyotrophic lateral sclerosis (ALS) received continuous NIV support. 72 hours later, 5 patients were switched from NIV to invasive ventilation, and 5 patients continued to receive NIV support. 72 hours after the initiation of NIV, the proportion of patients with a diagnosis of ALS differed significantly among the three groups (P=0.039). NIV may be attempted to manage acute fatal respiratory failure associated with neuromuscular diseases, but clinicians should carefully manage the clinical course in patients with ALS.

  12. Risk of unsuccessful noninvasive ventilation for acute respiratory failure in heterogeneous neuromuscular diseases: a retrospective study

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    Hiroshi Kataoka

    2017-03-01

    Full Text Available If invasive ventilation can be avoided by performing noninvasive mechanical ventilation (NIV in patients with acute respiratory failure (ARF, the disease can be effectively managed. It is important to clarify the characteristics of patients with neuromuscular diseases in whom initial NIV is likely to be unsuccessful. We studied 27 patients in stable neuromuscular condition who initially received NIV to manage fatal ARF to identify differences in factors immediately before the onset of ARF among patients who receive continuous NIV support, patients who are switched from NIV to invasive ventilation, and patients in whom NIV is discontinued. Endpoints were evaluated 24 and 72 hours after the initiation of NIV. After 24 hours, all but 1 patient with amyotrophic lateral sclerosis (ALS received continuous NIV support. 72 hours later, 5 patients were switched from NIV to invasive ventilation, and 5 patients continued to receive NIV support. 72 hours after the initiation of NIV, the proportion of patients with a diagnosis of ALS differed significantly among the three groups (P=0.039. NIV may be attempted to manage acute fatal respiratory failure associated with neuromuscular diseases, but clinicians should carefully manage the clinical course in patients with ALS.

  13. Elevated Extravascular Lung Water Index (ELWI) as a Predictor of Failure of Continuous Positive Airway Pressure Via Helmet (Helmet-CPAP) in Patients With Acute Respiratory Failure After Major Surgery.

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    Redondo Calvo, Francisco Javier; Bejarano Ramirez, Natalia; Uña Orejon, Rafael; Villazala Garcia, Ruben; Yuste Peña, Ana Sofia; Belda, Francisco Javier

    2015-11-01

    NIV is increasingly used for prevention and treatment of respiratory complications and failure. Some of them are admitted to the PACU with advanced hemodynamic monitors which allow quantification of Extravascular Lung Water (EVLW) by transpulmonary thermodilution technique (TPTD) and Pulmonary Vascular Permeability (PVP) providing information on lung edema. The objective of this study was to ascertain if EVLW Index and PVP Index may predict failure (intubation) or success (non-intubation) in patients developing acute respiratory failure (ARF) in the postoperative period following major abdominal surgery, where the first line of treatment was non-invasive continuous positive airway pressure via a helmet. Hemodynamic variables, EVLWI and PVPI were monitored with a transpulmonary thermodilution hemodynamic monitor device (PiCCO™) before and after the application of CPAP. Avoidance of intubation was observed in 66% of patients with Helmet-CPAP. In these patients after the first hour of application of CPAP, PaO2/FiO2 ratio significantly increased (303.33±65.2 vs. 141.6±14.6, P<.01). Before starting Helmet-CPAP values of EVLWI and PVPI were significantly lower in non-intubated patients (EVLWI 8.6±1.08 vs. 11.8±0.99ml/kg IBW, P<.01 and PVPI 1.7±0.56 vs. 3.0±0.88, P<.01). An optimal cut-off value for EVLWI was established at 9.5, and at 2.45 for PVPI (sensitivity of 0.7; specificity of 0.9, P<.01). In this type of patient the physiological parameters that predict the failure of Helmet-CPAP with the greatest accuracy were the value of the EVLWI and PVPI before Helmet-CPAP institution and the PaO2/FiO2 ratio and the respiratory rate after one hour of CPAP. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

  14. High mortality from respiratory failure secondary to swine-origin influenza A (H1N1) in South Africa.

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    Koegelenberg, C F N; Irusen, E M; Cooper, R; Diacon, A H; Taljaard, J J; Mowlana, A; von Groote-Bidlingmaier, F; Bolliger, C T

    2010-05-01

    The novel influenza A (H1N1) pandemic affected South Africa late during the 2009 Southern hemisphere winter and placed an extra burden on a health care system already dealing with a high prevalence of chronic lung diseases and human immunodeficiency virus (HIV) infection. The aim of this study was to describe the epidemiological characteristics, clinical features, management and outcomes of patients with confirmed influenza A (H1N1) infection complicated by respiratory failure. We included all adult patients with confirmed influenza A (H1N1) infection that were referred to the medical intensive care unit of a large academic hospital in Cape Town for ventilatory support in this prospective observational study. A total of 19 patients (39.5 +/- 14.8 years) needed ventilatory support over a 6-week period. Of these, 15 were female and 16 had identifiable risk factors for severe disease, including pregnancy (n = 6), type 2 diabetes mellitus (n = 6), obesity (n = 4), HIV infection (n = 3), immunosuppressive therapy (n = 3) and active pulmonary tuberculosis (n = 2). The most frequent complications were acute renal failure (n = 13), acute respiratory distress syndrome (n = 12) and ventilator associated pneumonia (n = 10). Thirteen patients died (mortality: 68.4%). Fatal cases were significantly associated with an APACHE II score >or=20 (P = 0.034), but not with a P(a)O(2)/F(I)O(2) or=12 (P = 0.134). The majority of patients with respiratory failure secondary to influenza A (H1N1) infection were young females and had an underlying risk factor for severe disease. The condition had a high mortality, particularly amongst patients with an APACHE II score >or=20.

  15. A comparison of synchronized intermittent mandatory ventilation and pressure-regulated volume control ventilation in elderly patients with acute exacerbations of COPD and respiratory failure

    OpenAIRE

    Chang, Suchi; Shi, Jindong; Fu, Cuiping; Wu, Xu; Li, Shanqun

    2016-01-01

    Suchi Chang,1 Jindong Shi,2 Cuiping Fu,1 Xu Wu,1 Shanqun Li1 1Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, 2Department of Respiratory Medicine, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, People’s Republic of China Background: COPD is the third leading cause of death worldwide. Acute exacerbations of COPD may cause respiratory failure, requiring intensive care unit admission and mechanical ventilation. Inten...

  16. Postoperative rescue closure of patent foramen ovale in the clinical setting of acute hypoxemic respiratory failure and stroke following coronary artery bypass surgery

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    José L Díaz-Gómez

    2015-01-01

    Full Text Available We describe a case of intraoperative diagnosis and successful deferred percutaneous closure of a patent foramen ovale (PFO in the clinical setting of acute refractory hypoxemic respiratory failure and new-onset ischemic stroke in an elderly patient after coronary artery bypass graft. Perioperative morbidity (i.e. severe hypoxemia, worsening right ventricular dysfunction, and embolic stroke that is potentially related to intraoperatively diagnosed PFO during cardiac surgery can complicate management in the Intensive Care Unit and perhaps affect the patient′s outcome. Although the PFO closure can be challenging in the clinical setting of hypoxemic respiratory failure and stroke following cardiac surgery, it can be a reasonable perioperative option.

  17. Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD)

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    McCurdy, BR

    2012-01-01

    Executive Summary In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions. After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses. The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html. Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive

  18. Acute respiratory failure and mechanical ventilation in pregnant patient: A narrative review of literature

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    Pradeep Kumar Bhatia

    2016-01-01

    Full Text Available Physiological changes of pregnancy imposes higher risk of acute respiratory failure (ARF with even a slight insult and remains an important cause of maternal and fetal morbidity and mortality. Although pregnant women have different respiratory physiology and different causes of ARF, guidelines specific to ventilatory settings, goals of oxygenation and weaning process could not be framed due to lack of large-scale randomized controlled trials. During the 2009 H1N1 pandemic, pregnant women had higher morbidity and mortality compared to nonpregnant women. During this period, alternative strategies of ventilation such as high-frequency oscillatory ventilation, inhalational of nitric oxide, prone positioning, and extra corporeal membrane oxygenation were increasingly used as a desperate measure to rescue pregnant patients with severe hypoxemia who were not improving with conventional mechanical ventilation. This article highlights the causes of ARF and recent advances in invasive, noninvasive and alternative strategies of ventilation used during pregnancy.

  19. The hemodynamic effects of prolonged respiratory alkalosis in anesthetized newborn piglets.

    Science.gov (United States)

    Jundi, K; Barrington, K J; Henderson, C; Allen, R G; Finer, N N

    2000-04-01

    To test the hypothesis that prolonged alkalosis decreases cardiac output and, furthermore, exacerbates hypoxic pulmonary vasoconstriction, as respiratory alkalosis is frequently induced as a therapy for persistent pulmonary hypertension of the newborn despite a lack of controlled evidence of improved outcomes. Potential adverse effects of prolonged alkalosis have been demonstrated. Two groups (control, n = 6, and hypocapnic alkalosis, n = 6) of 1-3 day old fentanyl-anesthetized, vecuronium-paralyzed piglets were instrumented to measure cardiac index (CI) and mean systemic (MAP) and pulmonary (PAP) arterial pressures. Baseline values were recorded. Alveolar hypoxia was then induced to achieve an arterial oxygen saturation of between 50 and 60% for 15 min. Respiratory alkalosis was then induced, by increasing ventilation to achieve a pH between 7.55-7.60, and was continued for 240 min. Inspired carbon dioxide was used with hyperventilation in the control group to maintain pressure of arterial carbon dioxide (PaCO2) at 35-45 mmHg and pH of 7.35-7.45. Hypoxia was induced again at 15 and 240 min. Pulmonary and systemic vascular resistances (PVR and SVR) were calculated. Prolonged alkalosis led to a significant and progressive fall in mean MAP from 61 (SD 7) mmHg at the start of the study falling to 50 (SD 6.9, p = 0.043), with no effect on CI. Calculated SVR decreased (0.45 SD 0.03 vs 0.36 SD 0.05). There were no statistically significant changes in any of the variables in the control group. Neither acute nor prolonged respiratory alkalosis had a significant effect on hypoxic pulmonary vasoconstriction. Prolonged hyperventilation leads to systemic hypotension, however it does not exacerbate hypoxic pulmonary vasoconstriction.

  20. Chronic intermittent hyperoxia alters the development of the hypoxic ventilatory response in neonatal rats.

    Science.gov (United States)

    Logan, Sarah; Tobin, Kristina E; Fallon, Sarah C; Deng, Kevin S; McDonough, Amy B; Bavis, Ryan W

    2016-01-01

    Chronic exposure to sustained hyperoxia alters the development of the respiratory control system, but the respiratory effects of chronic intermittent hyperoxia have rarely been investigated. We exposed newborn rats to short, repeated bouts of 30% O2 or 60% O2 (5 bouts h(-1)) for 4-15 days and then assessed their hypoxic ventilatory response (HVR; 10 min at 12% O2) by plethysmography. The HVR tended to be enhanced by intermittent hyperoxia at P4 (early phase of the HVR), but it was significantly reduced at P14-15 (primarily late phase of the HVR) compared to age-matched controls; the HVR recovered when individuals were returned to room air and re-studied as adults. To investigate the role of carotid body function in this plasticity, single-unit carotid chemoafferent activity was recorded in vitro. Intermittent hyperoxia tended to decrease spontaneous action potential frequency under normoxic conditions but, contrary to expectations, hypoxic responses were only reduced at P4 (not at P14) and only in rats exposed to higher O2 levels (i.e., intermittent 60% O2). Rats exposed to intermittent hyperoxia had smaller carotid bodies, and this morphological change may contribute to the blunted HVR. In contrast to rats exposed to intermittent hyperoxia beginning at birth, two weeks of intermittent 60% O2 had no effect on the HVR or carotid body size of rats exposed beginning at P28; therefore, intermittent hyperoxia-induced respiratory plasticity appears to be unique to development. Although both intermittent and sustained hyperoxia alter carotid body development and the HVR of rats, the specific effects and time course of this plasticity differs. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Hypoxic cell turnover in different solid tumor lines

    International Nuclear Information System (INIS)

    Ljungkvist, Anna S.E.; Bussink, Johan; Kaanders, Johannes H.A.M.; Rijken, Paulus F.J.W.; Begg, Adrian C.; Raleigh, James A.; Kogel, Albert J. van der

    2005-01-01

    Purpose: Most solid tumors contain hypoxic cells, and the amount of tumor hypoxia has been shown to have a negative impact on the outcome of radiotherapy. The efficacy of combined modality treatments depends both on the sequence and timing of the treatments. Hypoxic cell turnover in tumors may be important for optimal scheduling of combined modality treatments, especially when hypoxic cell targeting is involved. Methods and Materials: Previously we have shown that a double bioreductive hypoxic marker assay could be used to detect changes of tumor hypoxia in relation to the tumor vasculature after carbogen and hydralazine treatments. This assay was used in the current study to establish the turnover rate of hypoxic cells in three different tumor models. The first hypoxic marker, pimonidazole, was administered at variable times before tumor harvest, and the second hypoxic marker, CCI-103F, was injected at a fixed time before harvest. Hypoxic cell turnover was defined as loss of pimonidazole (first marker) relative to CCI-103F (second marker). Results: The half-life of hypoxic cell turnover was 17 h in the murine C38 colon carcinoma line, 23 h and 49 h in the human xenograft lines MEC82 and SCCNij3, respectively. Within 24 h, loss of pimonidazole-stained areas in C38 and MEC82 occurred concurrent with the appearance of pimonidazole positive cell debris in necrotic regions. In C38 and MEC82, most of the hypoxic cells had disappeared after 48 h, whereas in SCCNij3, viable cells that had been labeled with pimonidazole were still observed after 5 days. Conclusions: The present study demonstrates that the double hypoxia marker assay can be used to study changes in both the proportion of hypoxic tumor cells and their lifespan at the same time. The present study shows that large differences in hypoxic cell turnover rates may exist among tumor lines, with half-lives ranging from 17-49 h

  2. [Magnesium sulphate in the treatment of ischemic-hypoxic neonatal encephalopathy].

    Science.gov (United States)

    Kornacka, M K

    2001-01-01

    Hypoxic-ischaemic encephalopathy (HIE) remains one of the most important neurological complications in full and near full term newborns. During HIE glutamate and other excitatory neurotransmitters are released and progressive energy failure in brain is observed. Toxicity of glutamate plays the main role in brain injury. Glutamate activates the specific receptors that, in turn, mediate an overwhelming influx of calcium into the postsynaptic neuron. The pathological changes are located particularly in hippocampus. Magnesium sulfate has been used safely for years to treat preclampsia. The animal experimental evidence support a neuroprotective role for magnesium in HIE.

  3. Relevance of chest sonography in the diagnosis of acute respiratory failure: Comparison with current diagnostic tools in intensive care units

    Directory of Open Access Journals (Sweden)

    Rasha Daabis

    2014-10-01

    Conclusions: Lung ultrasound provided an immediate diagnosis of the underlying etiology of acute respiratory failure in most cases; it can therefore be added to the armamentarium of ICU where urgent decisions are needed for rapid diagnosis and management of patients with ARF.

  4. Cardiac biomarkers in neonatal hypoxic ischaemia.

    LENUS (Irish Health Repository)

    Sweetman, D

    2012-04-01

    Following a perinatal hypoxic-ischaemic insult, term infants commonly develop cardiovascular dysfunction. Troponin-T, troponin-I and brain natriuretic peptide are sensitive indicators of myocardial compromise. The long-term effects of cardiovascular dysfunction on neurodevelopmental outcome following perinatal hypoxic ischaemia remain controversial. Follow-up studies are warranted to ensure optimal cardiac function in adulthood. CONCLUSION: Cardiac biomarkers may improve the diagnosis of myocardial injury, help guide management, estimate mortality risk and may also aid in longterm neurodevelopmental outcome prediction following neonatal hypoxic-ischaemia.

  5. Management of respiratory symptoms in ALS.

    LENUS (Irish Health Repository)

    Hardiman, Orla

    2012-02-01

    Respiratory insufficiency is a frequent feature of ALS and is present in almost all cases at some stage of the illness. It is the commonest cause of death in ALS. FVC is used as important endpoint in many clinical trials, and in decision-making events for patients with ALS, although there are limitations to its predictive utility. There are multiple causes of respiratory muscle failure, all of which act to produce a progressive decline in pulmonary function. Diaphragmatic fatigue and weakness, coupled with respiratory muscle weakness, lead to reduced lung compliance and atelectasis. Increased secretions increase the risk of aspiration pneumonia, which further compromises respiratory function. Bulbar dysfunction can lead to nutritional deficiency, which in turn increases the fatigue of respiratory muscles. Early recognition of respiratory decline and symptomatic intervention, including non-invasive ventilation can significantly enhance both quality of life and life expectancy in ALS. Patients with respiratory failure should be advised to consider an advance directive to avoid emergency mechanical ventilation.

  6. Management of respiratory symptoms in ALS.

    LENUS (Irish Health Repository)

    Hardiman, Orla

    2011-03-01

    Respiratory insufficiency is a frequent feature of ALS and is present in almost all cases at some stage of the illness. It is the commonest cause of death in ALS. FVC is used as important endpoint in many clinical trials, and in decision-making events for patients with ALS, although there are limitations to its predictive utility. There are multiple causes of respiratory muscle failure, all of which act to produce a progressive decline in pulmonary function. Diaphragmatic fatigue and weakness, coupled with respiratory muscle weakness, lead to reduced lung compliance and atelectasis. Increased secretions increase the risk of aspiration pneumonia, which further compromises respiratory function. Bulbar dysfunction can lead to nutritional deficiency, which in turn increases the fatigue of respiratory muscles. Early recognition of respiratory decline and symptomatic intervention, including non-invasive ventilation can significantly enhance both quality of life and life expectancy in ALS. Patients with respiratory failure should be advised to consider an advance directive to avoid emergency mechanical ventilation.

  7. Risk of Unsuccessful Noninvasive Ventilation for Acute Respiratory Failure in Heterogeneous Neuromuscular Diseases: A Retrospective Study

    OpenAIRE

    Kataoka, Hiroshi; Nanaura, Hitoki; Kinugawa, Kaoru; Uchihara, Yuto; Ohara, Hiroya; Eura, Nobuyuki; Syobatake, Ryogo; Sawa, Nobuhiro; Takao, Kiriyama; Sugie, Kazuma; Ueno, Satoshi

    2017-01-01

    If invasive ventilation can be avoided by performing noninvasive mechanical ventilation (NIV) in patients with acute respiratory failure (ARF), the disease can be effectively managed. It is important to clarify the characteristics of patients with neuromuscular diseases in whom initial NIV is likely to be unsuccessful. We studied 27 patients in stable neuromuscular condition who initially received NIV to manage fatal ARF to identify differences in factors immediately before the onset of ARF a...

  8. Prone position for acute respiratory failure in adults.

    Science.gov (United States)

    Bloomfield, Roxanna; Noble, David W; Sudlow, Alexis

    2015-11-13

    Acute hypoxaemia de novo or on a background of chronic hypoxaemia is a common reason for admission to intensive care and for provision of mechanical ventilation. Various refinements of mechanical ventilation or adjuncts are employed to improve patient outcomes. Mortality from acute respiratory distress syndrome, one of the main contributors to the need for mechanical ventilation for hypoxaemia, remains approximately 40%. Ventilation in the prone position may improve lung mechanics and gas exchange and could improve outcomes. The objectives of this review are (1) to ascertain whether prone ventilation offers a mortality advantage when compared with traditional supine or semi recumbent ventilation in patients with severe acute respiratory failure requiring conventional invasive artificial ventilation, and (2) to supplement previous systematic reviews on prone ventilation for hypoxaemic respiratory failure in an adult population. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 1), Ovid MEDLINE (1950 to 31 January 2014), EMBASE (1980 to 31 January 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 31 January 2014) and Latin American Caribbean Health Sciences Literature (LILACS) (1992 to 31 January 2014) in Ovid MEDLINE for eligible randomized controlled trials. We also searched for studies by handsearching reference lists of relevant articles, by contacting colleagues and by handsearching published proceedings of relevant journals. We applied no language constraints, and we reran the searches in CENTRAL, MEDLINE, EMBASE, CINAHL and LILACS in June 2015. We added five new studies of potential interest to the list of "Studies awaiting classification" and will incorporate them into formal review findings during the review update. We included randomized controlled trials (RCTs) that examined the effects of prone position versus supine/semi recumbent position during conventional mechanical ventilation in

  9. Use of Lung Opening Maneuver in Patients with Acute Respiratory Failure After Cardiosurgical Operations

    Directory of Open Access Journals (Sweden)

    A. A. Yeremenko

    2006-01-01

    Full Text Available Postoperative respiratory failure is a most common complication and a main cause of postoperative death. The lung opening maneuver is a most effective method of respiratory therapy for this syndrome.Objective. To evaluate the impact of recruiting maneuver on gas exchange parameters, the biomechanical properties of the lung, and hemodynamic parameters. To determine whether the lung opening maneuver can be fully performed in patients undergoing cardiac surgery.Materials and methods. The study covered 19 patients aged 53 to 70 years who had postoperative failure. The indication for the recruiting maneuver was a decrease in the oxygenation index below 250 mm Hg during assisted ventilation (AV with FiO2>0.5, an inspiratory-expira-tory phase ratio of 1:1 to 3:1, and a positive end-expiratory pressure of 5—10 cm H2O.Results. A decrease in the oxygenation index to 139±36 mm Hg was observed before the recruiting maneuver was applied. Cd;n. averaged 41.1±8.4 ml/cm H2O. After use of the recruiting maneuver, there were increases in the oxygenation index up to 371±121 mm Hg and in Cd;n. up to 64.3±10 ml/cm H2O in all the patients. When the recruiting maneuver was employed, 14 patients were observed to have elevated blood pressures corrected with a vasopressor. One patient developed pneumothorax that was drained in proper time.Conclusion. The application of the lung opening maneuver leads to a considerable improvement of gas exchange parameters and lung mechanical properties.

  10. STUDY OF FACTORS INFLUENCING EARLY SYMPTOMATIC IMPROVEMENT, RETURN TO NORMOXIA AND RADIOLOGICAL RESOLUTION IN SWINE FLU PATIENTS WITH RESPIRATORY FAILURE IN RICU

    Directory of Open Access Journals (Sweden)

    Vamsidhar Reddy Manne

    2017-05-01

    Full Text Available BACKGROUND Since 2009, swine influenza outbreaks have been recorded virtually every year, although their extent and severity have varied widely. Localised outbreaks are taking place at variable intervals, usually every 1-3 years. The most recent outbreak has been from December 2016 through April 2017. We still are in the midst of one. This study of factors influencing early clinical and radiological improvement and reversion to normoxia in swine flu patients with respiratory failure helps in saving precious lives. MATERIALS AND METHODS This is a cross-sectional study conducted at RICU, Department of Pulmonary Medicine, S.V.R.R. Government General Hospital/S.V. Medical College, Tirupathi, Andhra Pradesh, between January 2017 and April 2017. Study sample was the total number of swine flu patients admitted to the RICU of the Department of Pulmonary Medicine with respiratory failure. RESULTS Out of 42 patients who tested positive for swine flu, 37 had respiratory failure and were immediately admitted in RICU. Oxygen support, oseltamivir and higher antibiotics were immediately started, injectable steroids given where necessary. Comorbidities were meticulously managed. 19 were males and 18 were females. 21 patients (>50% were above 50 years. Cough and breathlessness were present in all patients (100%. At admission, all 37 showed SpO2 <85% and at discharge all of them were normoxic. 18 patients had either multilobar pneumonia or ARDS on CXR, which had resolved by the time of discharge. The shortest duration of stay was 7 days and the longest duration of stay was 11 days. 35 patients were discharged and 2 patients died. CONCLUSION Good oxygenation, starting of oseltamivir on day 1 of admission prevents further complications and hastens recovery. Swine flu patients with normal chest x-ray and no comorbidities can still end up with respiratory failure. Steroids decrease cough and breathlessness, but have no role in hastening recovery. No residual symptoms

  11. Mixed Acid-Base Disorders, Hydroelectrolyte Imbalance and Lactate Production in Hypercapnic Respiratory Failure: The Role of Noninvasive Ventilation

    Science.gov (United States)

    Terzano, Claudio; Di Stefano, Fabio; Conti, Vittoria; Di Nicola, Marta; Paone, Gregorino; Petroianni, Angelo; Ricci, Alberto

    2012-01-01

    Background Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV) when treating hypercapnic respiratory failure. Methods Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO2 and PaCO2 and blood lactate were checked at the 1st, 2nd, 6th and 24th hours after starting NIV. Results Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7%) mixed respiratory acidosis–metabolic alkalosis, 10/36 (27.8%) respiratory acidosis and 3/5 (60%) mixed respiratory-metabolic acidosis patients (p = 0.026), with durations of 45.1±9.8, 36.2±8.9 and 53.3±4.1 hours, respectively (p = 0.016). The duration of ventilation was associated with higher blood lactate (prespiratory acidosis patients. Hypovolemic hyponatremia with hypochloremia and hypokalemia occurred in 10 mixed respiratory acidosis–metabolic alkalosis patients, and euvolemic hypochloremia occurred in the other 7 patients with this mixed acid-base disorder. Conclusions Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV. The combination of mixed acid-base disorders and hydro-electrolyte disturbances should be further investigated. PMID:22539963

  12. Mixed acid-base disorders, hydroelectrolyte imbalance and lactate production in hypercapnic respiratory failure: the role of noninvasive ventilation.

    Science.gov (United States)

    Terzano, Claudio; Di Stefano, Fabio; Conti, Vittoria; Di Nicola, Marta; Paone, Gregorino; Petroianni, Angelo; Ricci, Alberto

    2012-01-01

    Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV) when treating hypercapnic respiratory failure. Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO(2) and PaCO(2) and blood lactate were checked at the 1st, 2nd, 6th and 24th hours after starting NIV. Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7%) mixed respiratory acidosis-metabolic alkalosis, 10/36 (27.8%) respiratory acidosis and 3/5 (60%) mixed respiratory-metabolic acidosis patients (p = 0.026), with durations of 45.1 ± 9.8, 36.2 ± 8.9 and 53.3 ± 4.1 hours, respectively (p = 0.016). The duration of ventilation was associated with higher blood lactate (prespiratory acidosis patients. Hypovolemic hyponatremia with hypochloremia and hypokalemia occurred in 10 mixed respiratory acidosis-metabolic alkalosis patients, and euvolemic hypochloremia occurred in the other 7 patients with this mixed acid-base disorder. Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV. The combination of mixed acid-base disorders and hydro-electrolyte disturbances should be further investigated.

  13. Effects of sensitizers on cell respiration. 3. The effects of hypoxic cell radiosensitizers on oxidative metabolism and the radiation response of an in vitro tumour model

    Energy Technology Data Exchange (ETDEWEB)

    Durand, R E [Wisconsin Clinical Cancer Center, Madison (USA). Dept. of Human Oncology; Biaglow, J E; Greenstock, C L

    1978-06-01

    Physiological factors are important when considering the effects of radiosensitizers on the radiation response of complex systems such as multi-cellular spheroids. In this system, under conditions of unlimited nutrient supply, cells are rendered hypoxic by metabolism. Thus, using the spheroid system as an in vitro model of the tumour-cell microenvironment, we have determined the relative contribution of radiosensitization and respiratory effects of a number of electron-affinic sensitizers having potential clinical use. These studies are indicative of physiological responses at the cellular level, and suggest optimal drug administration schemes for obtaining maximal radiation response in vivo with hypoxic cell sensitizers.

  14. Cost-effectiveness of noninvasive ventilation for chronic obstructive pulmonary disease-related respiratory failure in Indian hospitals without ICU facilities

    Directory of Open Access Journals (Sweden)

    Shraddha P Patel

    2015-01-01

    Full Text Available Introduction: The majority of Indian hospitals do not provide intensive care unit (ICU care or ward-based noninvasive positive pressure ventilation (NIV. Because no mechanical ventilation or NIV is available in these hospitals, the majority of patients suffering from respiratory failure die. Objective: To perform a cost-effective analysis of two strategies (ward-based NIV with concurrent standard treatment vs standard treatment alone in chronic obstructive pulmonary disease (COPD respiratory failure patients treated in Indian hospitals without ICU care. Materials and Methods: A decision-analytical model was created to compare the cost-effectiveness for the two strategies. Estimates from the literature were used for parameters in the model. Future costs were discounted at 3%. All costs were reported in USD (2012. One-way, two-way, and probabilistic sensitivity analysis were performed. The time horizon was lifetime and perspective was societal. Results: The NIV strategy resulted in 17.7% more survival and was slightly more costly (increased cost of $101 (USD 2012 but resulted in increased quality-adjusted life-years (QALYs (1.67 QALY. The cost-effectiveness (2012 USD/QALY in the standard and NIV groups was $78/QALY ($535.02/6.82 and $75/QALY ($636.33/8.49, respectively. Incremental cost-effectiveness ratio (ICER was only $61 USD/QALY. This was substantially lower than the gross domestic product (GDP per capita for India (1489 USD, suggesting the NIV strategy was very cost effective. Using a 5% discount rate resulted in only minimally different results. Probabilistic analysis suggests that NIV strategy was preferred 100% of the time when willingness to pay was >$250 2012 USD. Conclusion: Ward-based NIV treatment is cost-effective in India, and may increase survival of patients with COPD respiratory failure when ICU is not available.

  15. Negative-pressure in treatment of persistent post-traumatic subcutaneous emphysema with respiratory failure: Case report and literature review

    Directory of Open Access Journals (Sweden)

    Jakov Mihanović

    2018-02-01

    Full Text Available Subcutaneous emphysema may aggravate traumatic pneumothorax treatment, especially when mechanical ventilation is required. Expectative management usually suffices, but when respiratory function is impaired surgical treatment might be indicated. Historically relevant methods are blowhole incisions and placement of various drains, often with related wound complications. Since the first report of negative pressure wound therapy for the treatment of severe subcutaneous emphysema in 2009, only few publications on use of commercially available sets were published. We report on patient injured in a motor vehicle accident who had serial rib fractures and bilateral pneumothorax managed initially in another hospital. Due to respiratory deterioration, haemodynamic instability and renal failure patient was transferred to our Intensive Care Unit. Massive and persistent subcutaneous emphysema despite adequate thoracic drainage with respiratory deterioration and potentially injurious mechanical ventilation with high airway pressures was the indication for active surgical treatment. Negative-pressure wound therapy dressing was applied on typical blowhole incisions which resulted in swift emphysema regression and respiratory improvement. Negative pressure wound therapy for decompression of severe subcutaneous emphysema represents simple, effective and relatively unknown technique that deserves wider attention.

  16. Validation of a Novel Molecular Host Response Assay to Diagnose Infection in Hospitalized Patients Admitted to the ICU With Acute Respiratory Failure.

    Science.gov (United States)

    Koster-Brouwer, Maria E; Verboom, Diana M; Scicluna, Brendon P; van de Groep, Kirsten; Frencken, Jos F; Janssen, Davy; Schuurman, Rob; Schultz, Marcus J; van der Poll, Tom; Bonten, Marc J M; Cremer, Olaf L

    2018-03-01

    Discrimination between infectious and noninfectious causes of acute respiratory failure is difficult in patients admitted to the ICU after a period of hospitalization. Using a novel biomarker test (SeptiCyte LAB), we aimed to distinguish between infection and inflammation in this population. Nested cohort study. Two tertiary mixed ICUs in the Netherlands. Hospitalized patients with acute respiratory failure requiring mechanical ventilation upon ICU admission from 2011 to 2013. Patients having an established infection diagnosis or an evidently noninfectious reason for intubation were excluded. None. Blood samples were collected upon ICU admission. Test results were categorized into four probability bands (higher bands indicating higher infection probability) and compared with the infection plausibility as rated by post hoc assessment using strict definitions. Of 467 included patients, 373 (80%) were treated for a suspected infection at admission. Infection plausibility was classified as ruled out, undetermined, or confirmed in 135 (29%), 135 (29%), and 197 (42%) patients, respectively. Test results correlated with infection plausibility (Spearman's rho 0.332; p < 0.001). After exclusion of undetermined cases, positive predictive values were 29%, 54%, and 76% for probability bands 2, 3, and 4, respectively, whereas the negative predictive value for band 1 was 76%. Diagnostic discrimination of SeptiCyte LAB and C-reactive protein was similar (p = 0.919). Among hospitalized patients admitted to the ICU with clinical uncertainty regarding the etiology of acute respiratory failure, the diagnostic value of SeptiCyte LAB was limited.

  17. Mixed acid-base disorders, hydroelectrolyte imbalance and lactate production in hypercapnic respiratory failure: the role of noninvasive ventilation.

    Directory of Open Access Journals (Sweden)

    Claudio Terzano

    Full Text Available BACKGROUND: Hypercapnic Chronic Obstructive Pulmonary Disease (COPD exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV when treating hypercapnic respiratory failure. METHODS: Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO(2 and PaCO(2 and blood lactate were checked at the 1st, 2nd, 6th and 24th hours after starting NIV. RESULTS: Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7% mixed respiratory acidosis-metabolic alkalosis, 10/36 (27.8% respiratory acidosis and 3/5 (60% mixed respiratory-metabolic acidosis patients (p = 0.026, with durations of 45.1 ± 9.8, 36.2 ± 8.9 and 53.3 ± 4.1 hours, respectively (p = 0.016. The duration of ventilation was associated with higher blood lactate (p<0.001, lower pH (p = 0.016, lower serum sodium (p = 0.014 and lower chloride (p = 0.038. Hyponatremia without hypervolemic hypochloremia occurred in 11 respiratory acidosis patients. Hypovolemic hyponatremia with hypochloremia and hypokalemia occurred in 10 mixed respiratory acidosis-metabolic alkalosis patients, and euvolemic hypochloremia occurred in the other 7 patients with this mixed acid-base disorder. CONCLUSIONS: Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV. The combination of mixed acid-base disorders and hydro-electrolyte disturbances should be further investigated.

  18. Hypoxic training: Clinical benefits on cardiometabolic risk factors.

    Science.gov (United States)

    Wee, Justin; Climstein, Mike

    2015-01-01

    The main aim of this review was to evaluate the effectiveness of hypoxic training on the modulation of cardiometabolic risk factors. Literature review. An electronic search encompassing five databases (PUBMED, EMBASE, MEDLINE, CINAHL, and SPORTDiscus) was conducted. A total of 2138 articles were retrieved. After excluding non-relevant articles, duplications and outcomes not related to cardiometabolic risk factors, 25 articles were chosen for review. Body weight and body composition were reported to be significantly improved when hypoxic training (≥1700 m) was used in conjunction with exercise regimes, at least three times a week, however extreme altitudes (>5000 m) resulted in a loss of fat-free muscle mass. Fasting blood glucose levels generally improved over time (≥21 days) at moderate levels of altitude (1500 m-3000 m), although reductions in blood glucose tolerance were observed when subjects were exposed to extreme hypoxia (>4000 m). Resting systolic and diastolic blood pressure levels improved as much as 26 mmHg and 13 mmHg respectively, with hypoxic training (1285 m-2650 m) in medicated, stable hypertensive subjects. Effects of hypoxic training when used in combination with exercise training on cholesterol levels were mixed. While there were improvements in total cholesterol (-4.2% to -30%) and low-density lipoprotein (-2.6% to -14.3%) reported as a result of hypoxic training, available evidence does not substantiate hypoxic training for the improvement of high-density lipoprotein and triglycerides. In conclusion, hypoxic training may be used as an adjunct treatment to modify some cardiometabolic risk factors. Measurement of hypoxic load may be used to individualize and ascertain appropriate levels of hypoxic training. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  19. Correlations between respiratory and functional variables in heart failure

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    Fábio Cangeri Di Naso

    2009-09-01

    Full Text Available Background: Respiratory alterations can impact on the functional performance of patients with heart failure. Aim: To correlate maximum inspiratory muscular force and lung function variables with functional capacity in heart failure patients. Methods: A transversal study January-July 2007 with 42 chronic heart disease patients (28 males with no prior pulmonary illness. The patients were in New York Heart Association Functional Class I, II and III. The variables used were maximum inspiratory pressure, forced vital capacity and forced expiratory volume in the first second. Respiratory variables measured were distance covered in the six-minute walk test, NYHA functional class and the physical functioning domain of the Short Form-36 Quality of Life Questionnaire. Results: Maximum inspiratory pressure correlated with the six-minute walk test (r = 0.543 and p < 0.001, functional capacity (r = −0.566 and p < 0.001 and the physical functioning domain score of the Short Form-36 (r = 0.459 and p = 0.002. The same was true of forced vital capacity and the six-minute walk test (r = 0.501 and p = 0.001, functional capacity (r = −0.477 and p = 0.001 and Short Form-36 (r = 0.314 and p = 0.043 variables. Forced expiratory volume correlated with the distance covered in the six-minute walk test (r = 0.514 and p < 0.001 and functional capacity (r = −0.383 and p = 0.012. Conclusion: Lung function and inspiratory muscular force respiratory variables correlated with functional variables in patients with heart failure. Resumo: Fundamento: Alterações respiratórias podem influenciar o desempenho funcional em doentes com insuficiência cardíaca (IC. Objectivo: Correlacionar a força muscular inspiratória máxima (PImax e as variáveis da função pulmonar com a capacidade funcional em doentes com IC. Métodos: Estudo transversal

  20. Hypoxic hypoxia as a means of modifying radiosensibility

    International Nuclear Information System (INIS)

    Neumeister, K.; Niemiec, C.; Bolck, M.; Jahns, J.; Kamprad, F.; Arnold, P.; Johannsen, U.; Koch, F.; Mehlhorn, G.

    1977-01-01

    Following an overview of the various possibilities of creating hypoxia in mammals, the problem of reducing radioresistance of hypoxic tumor cells is treated. Furthermore, the results of irradiation experiments with mice, rats and pigs breathing hypoxic mixtures of O 2 and N 2 are given and discussed with a view to applying hypoxic hypoxia in the radiotherapy of human tumors. (author)

  1. Radioresistance and hypoxic cells

    International Nuclear Information System (INIS)

    Ando, Koichi

    1989-01-01

    Current progress to explore further understanding of tumor hypoxia was reviewed. At subcellular level, hypoxia induces specific proteins, inhibits DNA synthesis as well as initiation of DNA replicon. Radioresistant characteristics of hypoxic cells is questioned in condition where irradiated cells were kept hypoxia during colony formation. Chronically hypoxic cells recovered from the inner layer of V79 multicellular spheroids are more sensitive to radiation than those from the oxic, outer layer. A novel sandwich culture method, which enables to reoxygenate chronic hypoxia, implies that chronically hypoxic cells are less sensitive to radiation after reoxygenation than oxic cells. For in vivo tumor, two types of tumor hypoxia are reported: diffusion-limited, chronic hypoxia and perfusion-limited, acute hypoxia. Evidence supporting the existence of perfusion-limited hypoxia is provided by an elegant method using vital staining and cell sorter. Data of our own laboratory also implies 2 types of tumor hypoxia; fractional hypoxia and incomplete hypoxia. Fractional hypoxia corresponds to a radioresistant tail on a biphasic tumor cell survival curves while tumors with incomplete hypoxia demonstrate only single component with radioresistant characteristics, instead. (author)

  2. Impaired ventilatory and thermoregulatory responses to hypoxic stress in newborn Phox2b heterozygous knockout mice

    Directory of Open Access Journals (Sweden)

    Nelina eRamanantsoa

    2011-09-01

    Full Text Available The Phox2b gene is necessary for the development of the autonomic nervous system, and especially, of respiratory neuronal circuits. In the present study, we examined the role of Phox2b in ventilatory and thermoregulatory responses to hypoxic stress, which are closely related in the postnatal period. Hypoxic stress was generated by strong thermal stimulus, combined or not with reduced inspired O2. To this end, we exposed 6-day-old Phox2b+/- pups and their wild-type littermates (Phox2b+/+ to hypoxia (10% O2 or hypercapnia (8% CO2 under thermoneutral (33°C or cold (26°C conditions. We found that Phox2b+/- pups showed less normoxic ventilation (VE in the cold than Phox2b+/+ pups. Phox2b+/- pups also showed lower oxygen consumption (VO2 in the cold, reflecting reduced thermogenesis and a lower body temperature. Furthermore, while the cold depressed ventilatory responses to hypoxia and hypercapnia in both genotype groups, this effect was less pronounced in Phox2b+/- pups. Finally, because serotonin (5-HT neurons are pivotal to respiratory and thermoregulatory circuits and depend on Phox2b for their differentiation, we studied 5-HT metabolism using high-pressure liquid chromatography, and found that it was altered in Phox2b+/- pups. We conclude that Phox2b haploinsufficiency alters the ability of newborns to cope with metabolic challenges, possibly due to 5-HT signaling impairments.

  3. Chronic heart failure

    OpenAIRE

    Hopper, Ingrid; Easton, Kellie

    2017-01-01

    1. The common symptoms and signs of chronic heart failure are dyspnoea, ankle swelling, raised jugular venous pressure and basal crepitations. Other conditions may be confused with chronic heart failure, including dependent oedema or oedema due to renal or hepatic disease. Shortness of breath may be due to respiratory disease or severe anaemia. Heart failure secondary to lung disease (cor pulmonale) should be distinguished from congestive cardiac failure. Heart failure may also present with l...

  4. Dose dependent effect of progesterone on hypoxic ventilatory response in newborn rats.

    Science.gov (United States)

    Hichri, Oubeidallah; Laurin, Jean-C; Julien, Cécile A; Joseph, Vincent; Bairam, Aida

    2012-01-01

    The effect of progesterone as a respiratory stimulant in newborn subjects is less known than that in adults. This study investigated the dose-response curve (0, 2, 4, and 8 mg/kg, ip) of progesterone on ventilation in non-anesthetized newborn rats at 4- and 12-days old using plethysmography. Progesterone had no effects in the regulation of normoxic ventilation. However, it enhanced the response to moderate hypoxia (FiO(2) 12%, 20 min) in 4- but not in 12-days old pups. This response was similar between the dose of 4 and 8 mg/kg. These observations suggested that progesterone enhances in age- and dose-dependent manner the hypoxic ventilatory response in newborn rats.

  5. A comparison of synchronized intermittent mandatory ventilation and pressure-regulated volume control ventilation in elderly patients with acute exacerbations of COPD and respiratory failure

    Directory of Open Access Journals (Sweden)

    Chang SC

    2016-05-01

    Full Text Available Suchi Chang,1 Jindong Shi,2 Cuiping Fu,1 Xu Wu,1 Shanqun Li1 1Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, 2Department of Respiratory Medicine, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, People’s Republic of China Background: COPD is the third leading cause of death worldwide. Acute exacerbations of COPD may cause respiratory failure, requiring intensive care unit admission and mechanical ventilation. Intensive care unit patients with acute exacerbations of COPD requiring mechanical ventilation have higher mortality rates than other hospitalized patients. Although mechanical ventilation is the most effective intervention for these conditions, invasive ventilation techniques have yielded variable effects. Objective: We evaluated pressure-regulated volume control (PRVC ventilation treatment efficacy and preventive effects on pulmonary barotrauma in elderly COPD patients with respiratory failure. Patients and methods: Thirty-nine intubated patients were divided into experimental and control groups and treated with the PRVC and synchronized intermittent mandatory ventilation – volume control methods, respectively. Vital signs, respiratory mechanics, and arterial blood gas analyses were monitored for 2–4 hours and 48 hours. Results: Both groups showed rapidly improved pH, partial pressure of oxygen (PaO2, and PaO2 per fraction of inspired O2 levels and lower partial pressure of carbon dioxide (PaCO2 levels. The pH and PaCO2 levels at 2–4 hours were lower and higher, respectively, in the test group than those in the control group (P<0.05 for both; after 48 hours, blood gas analyses showed no statistical difference in any marker (P>0.05. Vital signs during 2–4 hours and 48 hours of treatment showed no statistical difference in either group (P>0.05. The level of peak inspiratory pressure in the experimental group after mechanical ventilation for 2–4 hours and 48

  6. A case of severe and rigid congenital thoracolumbar lordoscoliosis with diastematomyelia presenting with type 2 respiratory failure: managed by staged correction with controlled axial traction.

    Science.gov (United States)

    Kanagaraju, Vijayanth; Chhabra, H S; Srivastava, Abhishek; Mahajan, Rajat; Kaul, Rahul; Bhatia, Pallav; Tandon, Vikas; Nanda, Ankur; Sangondimath, Gururaj; Patel, Nishit

    2016-10-01

    Congenital lordoscoliosis is an uncommon pathology and its management poses formidable challenge especially in the presence of type 2 respiratory failure and intraspinal anomalies. In such patients standard management protocols are not applicable and may require multistage procedure to minimize risk and optimize results. A 15-year-old girl presented in our hospital emergency services with severe breathing difficulty. She had a severe and rapidly progressing deformity in her back, noted since 6 years of age, associated with severe respiratory distress requiring oxygen and BiPAP support. She was diagnosed to have a severe and rigid congenital right thoracolumbar lordoscoliosis (coronal Cobb's angle: 105° and thoracic lordosis -10°) with type 1 split cord malformation with bony septum extending from T11 to L3. This leads to presentation of restrictive lung disease with type 2 respiratory failure. As her lung condition did not allow for any major procedure, we did a staged procedure rather than executing in a single stage. Controlled axial traction by halogravity was applied initially followed by halo-femoral traction. Four weeks later, this was replaced by halo-pelvic distraction device after a posterior release procedure with asymmetric pedicle substraction osteotomies at T7 and T10. Halo-pelvic distraction continued for 4 more weeks to optimize and correct the deformity. Subsequently definitive posterior stabilization and fusion was done. The detrimental effect of diastematomyelia resection in such cases is clearly evident from literature, so it was left unresected. A good scoliotic correction with improved respiratory function was achieved. Three years follow-up showed no loss of deformity correction, no evidence of pseudarthrosis and a good clinical outcome with reasonably balanced spine. The management of severe and rigid congenital lordoscoliotic deformities with intraspinal anomalies is challenging. Progressive reduction in respiratory volume in untreated

  7. Respiratory failure following delayed intrathecal morphine pump refill: a valuable, but costly lesson.

    Science.gov (United States)

    Ruan, Xiulu; Couch, J Patrick; Liu, HaiNan; Shah, Rinoo V; Wang, Frank; Chiravuri, Srinivas

    2010-01-01

    Spinal analgesia, mediated by opioid receptors, requires only a fraction of the opioid dose that is needed systemically. By infusing a small amount of opioid into the cerebrospinal fluid in close proximity to the receptor sites in the spinal cord, profound analgesia may be achieved while sparing some of the side effects due to systemic opioids. Intraspinal drug delivery (IDD) has been increasingly used in patients with intractable chronic pain, when these patients have developed untoward side effects with systemic opioid usage. The introduction of intrathecal opioids has been considered one of the most important breakthroughs in pain management in the past three decades. A variety of side effects associated with the long-term usage of IDD have been recognized. Among them, respiratory depression is the most feared. To describe a severe adverse event, i.e., respiratory failure, following delayed intrathecal morphine pump refill. A 65-year-old woman with intractable chronic low back pain, due to degenerative disc disease, and was referred to our clinic for an intraspinal drug delivery evaluation, after failing to respond to multidisciplinary pain treatment. Following a psychological evaluation confirming her candidacy, she underwent an outpatient patient-controlled continuous epidural morphine infusion trial. The infusion trial lasted 12 days and was beneficial in controlling her pain. The patient reported more than 90% pain reduction with improved distance for ambulation. She subsequently consented and was scheduled for permanent intrathecal morphine pump implantation. The intrathecal catheter was inserted at right paramedian L3-L4, with catheter tip advanced to L1, confirmed under fluoroscopy. Intrathecal catheter placement was confirmed by positive CSF flow and by myelogram. A non-programmable Codman 3000 constant-flow rate infusion pump was placed in the right mid quandrant between right rib cage and right iliac crest. The intrathecal infusion consisted of

  8. Respiratory Failure Associated with the Lipodystrophy Syndrome in an HIV-Positive Patient with Compromised Lung Function

    Directory of Open Access Journals (Sweden)

    Natasha Press

    2001-01-01

    Full Text Available Protease inhibitors, used as treatment in human immunodeficiency virus (HIV infection, are associated with a syndrome of peripheral lipodystrophy, central adiposity, hyperlipidemia and insulin resistance. An HIV-positive patient with chronic obstructive pulmonary disease is presented who developed the lipodystrophy syndrome that is associated with the use of protease inhibitors. It is postulated that the lipodystrophy syndrome further compromised his lung function, leading to respiratory failure. Patients who have pulmonary disease and are taking protease inhibitors require monitoring of clinical status and pulmonary function tests.

  9. Severe respiratory failure as a presenting feature of an interstitial lung disease associated with anti-synthetase syndrome (ASS).

    Science.gov (United States)

    Piroddi, Ines Maria Grazia; Ferraioli, Gianluca; Barlascini, Cornelius; Castagneto, Corrado; Nicolini, Antonello

    2016-07-01

    Anti-synthetase syndrome (ASS) is defined as a heterogeneous connective tissue disorder characterized by the association of an interstitial lung disease (ILD) with or without inflammatory myositis with the presence of anti-aminoacyl-tRNA-synthetase antibodies. ILD is one of the major extra-muscular manifestations of polymyositis and dermatomyositis. We report a case of a patient with dyspnea, cough, and intermittent fever as well as ILD associated ASS in the absence of muscular involvement. This patient was admitted to the emergency department with severe respiratory failure requiring non-invasive ventilation. Our patient's case demonstrates that the diagnosis of ASS may not be obvious. However, its diagnosis leads to appropriate and potentially life-saving treatment. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  10. Modulation of radioprotective effects of respiratory hypoxia by changing the duration of hypoxia before irradiation and by combining hypoxia and administration of hemopoiesis-stimulating agents

    International Nuclear Information System (INIS)

    Vacek, A.; Hofer, M.

    2001-01-01

    Aim: Analysis of radioprotective effect of respiratory hypoxia on hemopoietic tissue and enhancement of this effect by hemopoietic activation. Material and methods: In mice breathing hypoxic gas mixture during total body gamma irradiation the recovery of pluripotent and committed granulocyte-macrophage progenitor cells and animal lethality were determined. Results: In mice forced to breathe 10% O 2 and 8% O 2 during irradiation, the oxygen tension in the spleen decreased to 40% and 20%, respectively, of control values. Hypoxia mitigated the lethal effect of gamma-rays and improved the recovery of hemopoiesis in compartments of pluripotent and committed progenitor cells. Enhancement of the proliferative activity in hemopoietic tissue by a cytokine (rmGM-CSF) or an immunomodulator (dextran sulfate) increased the effect of hypoxic radioprotection, while elimination of proliferative cells by hydroxyurea decreased the radioprotective effect. Adaptation of experimental animals to hypoxic conditions was found to reduce the radioprotective effect without influencing tissue partial oxygen pressure lowered by hypoxic conditions. Conclusion: The data presented confirm the radioprotective effect of 10% and 8% O 2 respiratory hypoxia on hemopoiesis. These findings may represent a way out for further experimental and clinical research aimed at considering differential protection of various tissues by hypoxia. (orig.) [de

  11. Osteomalacia, severe thoracic deformities and respiratory failure in a young woman with anorexia nervosa.

    Science.gov (United States)

    Watanabe, Daisuke; Hotta, Mari; Ichihara, Atsuhiro

    2015-01-01

    The recent trends in avoiding sunbathing and eating fewer fish products have resulted in a high prevalence of vitamin D deficiency in the general Japanese population. We herein report the case of a young woman with enduring anorexia nervosa (AN) who suffered from osteomalacia, thoracic deformities and respiratory failure. Her vitamin D deficiency had been overlooked for years. Although the serum 25-hyroxyvitamin D [25(OH)D] level is a marker of vitamin D stores, it is not routinely examined because the cost is not covered by the national health insurance program. However, measuring the serum 25(OH)D levels in AN patients with hypocalcemia is recommended to prevent osteomalacia and osteoporosis.

  12. Impaired Ventilatory and Thermoregulatory Responses to Hypoxic Stress in Newborn Phox2b Heterozygous Knock-Out Mice

    Science.gov (United States)

    Ramanantsoa, Nelina; Matrot, Boris; Vardon, Guy; Lajard, Anne-Marie; Voituron, Nicolas; Dauger, Stéphane; Denjean, André; Hilaire, Gérard; Gallego, Jorge

    2011-01-01

    The Phox2b genesis necessary for the development of the autonomic nervous system, and especially, of respiratory neuronal circuits. In the present study, we examined the role of Phox2b in ventilatory and thermoregulatory responses to hypoxic stress, which are closely related in the postnatal period. Hypoxic stress was generated by strong thermal stimulus, combined or not with reduced inspired O2. To this end, we exposed 6-day-old Phox2b+/− pups and their wild-type littermates (Phox2b+/+) to hypoxia (10% O2) or hypercapnia (8% CO2) under thermoneutral (33°C) or cold (26°C) conditions. We found that Phox2b+/− pups showed less normoxic ventilation (VE) in the cold than Phox2b+/+ pups. Phox2b+/− pups also showed lower oxygen consumption (VO2) in the cold, reflecting reduced thermogenesis and a lower body temperature. Furthermore, while the cold depressed ventilatory responses to hypoxia and hypercapnia in both genotype groups, this effect was less pronounced in Phox2b+/− pups. Finally, because serotonin (5-HT) neurons are pivotal to respiratory and thermoregulatory circuits and depend on Phox2b for their differentiation, we studied 5-HT metabolism using high pressure liquid chromatography, and found that it was altered in Phox2b+/− pups. We conclude that Phox2b haploinsufficiency alters the ability of newborns to cope with metabolic challenges, possibly due to 5-HT signaling impairments. PMID:21977017

  13. Acute respiratory distress syndrome and acute renal failure from Plasmodium ovale infection with fatal outcome.

    Science.gov (United States)

    Lau, Yee-Ling; Lee, Wenn-Chyau; Tan, Lian-Huat; Kamarulzaman, Adeeba; Syed Omar, Sharifah Faridah; Fong, Mun-Yik; Cheong, Fei-Wen; Mahmud, Rohela

    2013-11-04

    Plasmodium ovale is one of the causative agents of human malaria. Plasmodium ovale infection has long been thought to be non-fatal. Due to its lower morbidity, P. ovale receives little attention in malaria research. Two Malaysians went to Nigeria for two weeks. After returning to Malaysia, they fell sick and were admitted to different hospitals. Plasmodium ovale parasites were identified from blood smears of these patients. The species identification was further confirmed with nested PCR. One of them was successfully treated with no incident of relapse within 12-month medical follow-up. The other patient came down with malaria-induced respiratory complication during the course of treatment. Although parasites were cleared off the circulation, the patient's condition worsened. He succumbed to multiple complications including acute respiratory distress syndrome and acute renal failure. Sequencing of the malaria parasite DNA from both cases, followed by multiple sequence alignment and phylogenetic tree construction suggested that the causative agent for both malaria cases was P. ovale curtisi. In this report, the differences between both cases were discussed, and the potential capability of P. ovale in causing severe complications and death as seen in this case report was highlighted. Plasmodium ovale is potentially capable of causing severe complications, if not death. Complete travel and clinical history of malaria patient are vital for successful diagnoses and treatment. Monitoring of respiratory and renal function of malaria patients, regardless of the species of malaria parasites involved is crucial during the course of hospital admission.

  14. Lung microvascular transport properties measured by multiple indicator dilution methods in patients with adult respiratory distress syndrome. A comparison between patients reversing respiratory failure and those failing to reverse

    International Nuclear Information System (INIS)

    Harris, T.R.; Bernard, G.R.; Brigham, K.L.; Higgins, S.B.; Rinaldo, J.E.; Borovetz, H.S.; Sibbald, W.J.; Kariman, K.; Sprung, C.L.

    1990-01-01

    We conducted indicator dilution studies on the lungs of patients in the early phases of adult respiratory distress syndrome (ARDS) to test the hypothesis that capillary permeability was increased in patients with respiratory failure. Indicator dilution studies were performed using 51Cr-erythrocytes, 125I-albumin, 14C-urea, and 3H-water as tracers. The injectate was infused as a bolus into a central venous line. Peripheral arterial blood was collected and counted for radioactivity. Mathematical analysis of the indicator curves yielded cardiac output, measures of the product of capillary permeability and surface area for urea (PS and D1/2S), the intravascular lung volume (Vv), and the extravascular lung water volume (Ve). Permeability was separated from surface area by normalizing PS and D1/2S to Vv. Patients could be divided into 16 in whom blood gas determinations and radiologic criteria for ARDS were reversed and 23 in whom they were not. We examined indicator dilution and other measures of lung function in the two groups to determine whether significant differences in microvascular function existed. PS and PS/Vv were significantly higher in the nonreversal patients. Ve was above normal, but not different between groups. Linear regression analysis showed significant correlations for all of the following in the nonreversal group: Ve and all measures of permeability, pulmonary vascular resistance (PVR), and the inverse of permeability-surface area measures and AaDO2 and PVR. Only measures of Ve and PS correlated in the reversal group. These results support the hypothesis that capillary permeability is increased in patients with early ARDS and continuing respiratory failure

  15. Practical approach to management of respiratory complications in neurological disorders

    Directory of Open Access Journals (Sweden)

    Mangera Z

    2012-03-01

    Full Text Available Zaheer Mangera, Kirat Panesar, Himender MakkerRespiratory Medicine, North Middlesex University Hospital, London, UKAbstract: Patients with certain neurological diseases are at increased risk of developing chest infections as well as respiratory failure due to muscular weakness. In particular, patients with certain neuromuscular disorders are at higher risk. These conditions are often associated with sleep disordered breathing. It is important to identify patients at risk of respiratory complications early in the course of their disease, although patients with neuromuscular disorders often present in the acute setting with respiratory involvement. This review of the respiratory complications of neurological disorders, with a particular focus on neuromuscular disorders, explores why this happens and looks at how to recognize, investigate, and manage these patients effectively.Keywords: respiratory failure, respiratory muscle weakness

  16. A comparison of synchronized intermittent mandatory ventilation and pressure-regulated volume control ventilation in elderly patients with acute exacerbations of COPD and respiratory failure.

    Science.gov (United States)

    Chang, Suchi; Shi, Jindong; Fu, Cuiping; Wu, Xu; Li, Shanqun

    2016-01-01

    COPD is the third leading cause of death worldwide. Acute exacerbations of COPD may cause respiratory failure, requiring intensive care unit admission and mechanical ventilation. Intensive care unit patients with acute exacerbations of COPD requiring mechanical ventilation have higher mortality rates than other hospitalized patients. Although mechanical ventilation is the most effective intervention for these conditions, invasive ventilation techniques have yielded variable effects. We evaluated pressure-regulated volume control (PRVC) ventilation treatment efficacy and preventive effects on pulmonary barotrauma in elderly COPD patients with respiratory failure. Thirty-nine intubated patients were divided into experimental and control groups and treated with the PRVC and synchronized intermittent mandatory ventilation - volume control methods, respectively. Vital signs, respiratory mechanics, and arterial blood gas analyses were monitored for 2-4 hours and 48 hours. Both groups showed rapidly improved pH, partial pressure of oxygen (PaO2), and PaO2 per fraction of inspired O2 levels and lower partial pressure of carbon dioxide (PaCO2) levels. The pH and PaCO2 levels at 2-4 hours were lower and higher, respectively, in the test group than those in the control group (P0.05). Vital signs during 2-4 hours and 48 hours of treatment showed no statistical difference in either group (P>0.05). The level of peak inspiratory pressure in the experimental group after mechanical ventilation for 2-4 hours and 48 hours was significantly lower than that in the control group (P0.05). Among elderly COPD patients with respiratory failure, application of PRVC resulted in rapid improvement in arterial blood gas analyses while maintaining a low peak inspiratory pressure. PRVC can reduce pulmonary barotrauma risk, making it a safer protective ventilation mode than synchronized intermittent mandatory ventilation - volume control.

  17. Involvement of SIRT1 in hypoxic down-regulation of c-Myc and β-catenin and hypoxic preconditioning effect of polyphenols

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Kyung-Soo [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Park, Jun-Ik [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Kim, Mi-Ju; Kim, Hak-Bong; Lee, Jae-Won [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Dao, Trong Tuan; Oh, Won Keun [BK21 Project Team, College of Pharmacy, Chosun University, Gwangju (Korea, Republic of); Kang, Chi-Dug, E-mail: kcdshbw@pusan.ac.kr [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Kim, Sun-Hee, E-mail: ksh7738@pusan.ac.kr [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of)

    2012-03-01

    SIRT1 has been found to function as a Class III deacetylase that affects the acetylation status of histones and other important cellular nonhistone proteins involved in various cellular pathways including stress responses and apoptosis. In this study, we investigated the role of SIRT1 signaling in the hypoxic down-regulations of c-Myc and β-catenin and hypoxic preconditioning effect of the red wine polyphenols such as piceatannol, myricetin, quercetin and resveratrol. We found that the expression of SIRT1 was significantly increased in hypoxia-exposed or hypoxic preconditioned HepG2 cells, which was closely associated with the up-regulation of HIF-1α and down-regulation of c-Myc and β-catenin expression via deacetylation of these proteins. In addition, blockade of SIRT1 activation using siRNA or amurensin G, a new potent SIRT1 inhibitor, abolished hypoxia-induced HIF-1α expression but increased c-Myc and β-catenin expression. SIRT1 was also found to stabilize HIF-1α protein and destabilize c-Myc, β-catenin and PHD2 under hypoxia. We also found that myricetin, quercetin, piceatannol and resveratrol up-regulated HIF-1α and down-regulated c-Myc, PHD2 and β-catenin expressions via SIRT1 activation, in a manner that mimics hypoxic preconditioning. This study provides new insights of the molecular mechanisms of hypoxic preconditioning and suggests that polyphenolic SIRT1 activators could be used to mimic hypoxic/ischemic preconditioning. -- Graphical abstract: Polyphenols mimicked hypoxic preconditioning by up-regulating HIF-1α and SIRT1 and down-regulating c-Myc, PHD2, and β-catenin. HepG2 cells were pretreated with the indicated doses of myricetin (MYR; A), quercetin (QUR; B), or piceatannol (PIC; C) for 4 h and then exposed to hypoxia for 4 h. Levels of HIF-1α, SIRT1, c-Myc, β-catenin, and PHD2 were determined by western blot analysis. The data are representative of three individual experiments. Highlights: ► SIRT1 expression is increased in hypoxia

  18. Involvement of SIRT1 in hypoxic down-regulation of c-Myc and β-catenin and hypoxic preconditioning effect of polyphenols

    International Nuclear Information System (INIS)

    Hong, Kyung-Soo; Park, Jun-Ik; Kim, Mi-Ju; Kim, Hak-Bong; Lee, Jae-Won; Dao, Trong Tuan; Oh, Won Keun; Kang, Chi-Dug; Kim, Sun-Hee

    2012-01-01

    SIRT1 has been found to function as a Class III deacetylase that affects the acetylation status of histones and other important cellular nonhistone proteins involved in various cellular pathways including stress responses and apoptosis. In this study, we investigated the role of SIRT1 signaling in the hypoxic down-regulations of c-Myc and β-catenin and hypoxic preconditioning effect of the red wine polyphenols such as piceatannol, myricetin, quercetin and resveratrol. We found that the expression of SIRT1 was significantly increased in hypoxia-exposed or hypoxic preconditioned HepG2 cells, which was closely associated with the up-regulation of HIF-1α and down-regulation of c-Myc and β-catenin expression via deacetylation of these proteins. In addition, blockade of SIRT1 activation using siRNA or amurensin G, a new potent SIRT1 inhibitor, abolished hypoxia-induced HIF-1α expression but increased c-Myc and β-catenin expression. SIRT1 was also found to stabilize HIF-1α protein and destabilize c-Myc, β-catenin and PHD2 under hypoxia. We also found that myricetin, quercetin, piceatannol and resveratrol up-regulated HIF-1α and down-regulated c-Myc, PHD2 and β-catenin expressions via SIRT1 activation, in a manner that mimics hypoxic preconditioning. This study provides new insights of the molecular mechanisms of hypoxic preconditioning and suggests that polyphenolic SIRT1 activators could be used to mimic hypoxic/ischemic preconditioning. -- Graphical abstract: Polyphenols mimicked hypoxic preconditioning by up-regulating HIF-1α and SIRT1 and down-regulating c-Myc, PHD2, and β-catenin. HepG2 cells were pretreated with the indicated doses of myricetin (MYR; A), quercetin (QUR; B), or piceatannol (PIC; C) for 4 h and then exposed to hypoxia for 4 h. Levels of HIF-1α, SIRT1, c-Myc, β-catenin, and PHD2 were determined by western blot analysis. The data are representative of three individual experiments. Highlights: ► SIRT1 expression is increased in hypoxia

  19. [Late respiratory function complications following burns].

    Science.gov (United States)

    Ernesto, S; Marduel, Y; Freymond, N; Pacheco, Y; Devouassoux, G

    2008-03-01

    Twenty five per cent of thermal injuries are associated with secondary respiratory events linked to several mechanisms. In the acute phase of the accident oedema of the airways, the fume inhalation syndrome and ARDS are the most common causes responsible for death in 60% of cases. Late respiratory complications are little known and neglected. They comprise obstructive ventilatory defects due to the inhalation syndrome and restrictive defects secondary to ARDS or to dermal injury. We report the case of a female patient, extensively burnt 2 years previously, admitted to hospital with severe acute respiratory failure complicating COPD. The presence of both restrictive and obstructive defects led to the suggestion of alternative underlying mechanisms such as the pulmonary consequences of ARDS and extensive dermal scars. The latter were responsible for an armour like thickening of the skin of the thorax compatible with the restrictive defect. These functional abnormalities and the potential severity of acute respiratory failure are indications for regular pulmonary follow-up of patients with severe circumferential scarring of the thorax who are at high risk for respiratory complications.

  20. Effects of hypercapnia and NO synthase inhibition in sustained hypoxic pulmonary vasoconstriction

    Science.gov (United States)

    2012-01-01

    Background Acute respiratory disorders may lead to sustained alveolar hypoxia with hypercapnia resulting in impaired pulmonary gas exchange. Hypoxic pulmonary vasoconstriction (HPV) optimizes gas exchange during local acute (0-30 min), as well as sustained (> 30 min) hypoxia by matching blood perfusion to alveolar ventilation. Hypercapnia with acidosis improves pulmonary gas exchange in repetitive conditions of acute hypoxia by potentiating HPV and preventing pulmonary endothelial dysfunction. This study investigated, if the beneficial effects of hypercapnia with acidosis are preserved during sustained hypoxia as it occurs, e.g in permissive hypercapnic ventilation in intensive care units. Furthermore, the effects of NO synthase inhibitors under such conditions were examined. Method We employed isolated perfused and ventilated rabbit lungs to determine the influence of hypercapnia with or without acidosis (pH corrected with sodium bicarbonate), and inhibitors of endothelial as well as inducible NO synthase on acute or sustained HPV (180 min) and endothelial permeability. Results In hypercapnic acidosis, HPV was intensified in sustained hypoxia, in contrast to hypercapnia without acidosis when HPV was amplified during both phases. L-NG-Nitroarginine (L-NNA), a non-selective NO synthase inhibitor, enhanced acute as well as sustained HPV under all conditions, however, the amplification of sustained HPV induced by hypercapnia with or without acidosis compared to normocapnia disappeared. In contrast 1400 W, a selective inhibitor of inducible NO synthase (iNOS), decreased HPV in normocapnia and hypercapnia without acidosis at late time points of sustained HPV and selectively reversed the amplification of sustained HPV during hypercapnia without acidosis. Hypoxic hypercapnia without acidosis increased capillary filtration coefficient (Kfc). This increase disappeared after administration of 1400 W. Conclusion Hypercapnia with and without acidosis increased HPV during

  1. Effects of hypercapnia and NO synthase inhibition in sustained hypoxic pulmonary vasoconstriction

    Directory of Open Access Journals (Sweden)

    Ketabchi Farzaneh

    2012-01-01

    Full Text Available Abstract Background Acute respiratory disorders may lead to sustained alveolar hypoxia with hypercapnia resulting in impaired pulmonary gas exchange. Hypoxic pulmonary vasoconstriction (HPV optimizes gas exchange during local acute (0-30 min, as well as sustained (> 30 min hypoxia by matching blood perfusion to alveolar ventilation. Hypercapnia with acidosis improves pulmonary gas exchange in repetitive conditions of acute hypoxia by potentiating HPV and preventing pulmonary endothelial dysfunction. This study investigated, if the beneficial effects of hypercapnia with acidosis are preserved during sustained hypoxia as it occurs, e.g in permissive hypercapnic ventilation in intensive care units. Furthermore, the effects of NO synthase inhibitors under such conditions were examined. Method We employed isolated perfused and ventilated rabbit lungs to determine the influence of hypercapnia with or without acidosis (pH corrected with sodium bicarbonate, and inhibitors of endothelial as well as inducible NO synthase on acute or sustained HPV (180 min and endothelial permeability. Results In hypercapnic acidosis, HPV was intensified in sustained hypoxia, in contrast to hypercapnia without acidosis when HPV was amplified during both phases. L-NG-Nitroarginine (L-NNA, a non-selective NO synthase inhibitor, enhanced acute as well as sustained HPV under all conditions, however, the amplification of sustained HPV induced by hypercapnia with or without acidosis compared to normocapnia disappeared. In contrast 1400 W, a selective inhibitor of inducible NO synthase (iNOS, decreased HPV in normocapnia and hypercapnia without acidosis at late time points of sustained HPV and selectively reversed the amplification of sustained HPV during hypercapnia without acidosis. Hypoxic hypercapnia without acidosis increased capillary filtration coefficient (Kfc. This increase disappeared after administration of 1400 W. Conclusion Hypercapnia with and without acidosis

  2. Effects of hypercapnia and NO synthase inhibition in sustained hypoxic pulmonary vasoconstriction.

    Science.gov (United States)

    Ketabchi, Farzaneh; Ghofrani, Hossein A; Schermuly, Ralph T; Seeger, Werner; Grimminger, Friedrich; Egemnazarov, Bakytbek; Shid-Moosavi, S Mostafa; Dehghani, Gholam A; Weissmann, Norbert; Sommer, Natascha

    2012-01-31

    Acute respiratory disorders may lead to sustained alveolar hypoxia with hypercapnia resulting in impaired pulmonary gas exchange. Hypoxic pulmonary vasoconstriction (HPV) optimizes gas exchange during local acute (0-30 min), as well as sustained (> 30 min) hypoxia by matching blood perfusion to alveolar ventilation. Hypercapnia with acidosis improves pulmonary gas exchange in repetitive conditions of acute hypoxia by potentiating HPV and preventing pulmonary endothelial dysfunction. This study investigated, if the beneficial effects of hypercapnia with acidosis are preserved during sustained hypoxia as it occurs, e.g in permissive hypercapnic ventilation in intensive care units. Furthermore, the effects of NO synthase inhibitors under such conditions were examined. We employed isolated perfused and ventilated rabbit lungs to determine the influence of hypercapnia with or without acidosis (pH corrected with sodium bicarbonate), and inhibitors of endothelial as well as inducible NO synthase on acute or sustained HPV (180 min) and endothelial permeability. In hypercapnic acidosis, HPV was intensified in sustained hypoxia, in contrast to hypercapnia without acidosis when HPV was amplified during both phases. L-NG-Nitroarginine (L-NNA), a non-selective NO synthase inhibitor, enhanced acute as well as sustained HPV under all conditions, however, the amplification of sustained HPV induced by hypercapnia with or without acidosis compared to normocapnia disappeared. In contrast 1400 W, a selective inhibitor of inducible NO synthase (iNOS), decreased HPV in normocapnia and hypercapnia without acidosis at late time points of sustained HPV and selectively reversed the amplification of sustained HPV during hypercapnia without acidosis. Hypoxic hypercapnia without acidosis increased capillary filtration coefficient (Kfc). This increase disappeared after administration of 1400 W. Hypercapnia with and without acidosis increased HPV during conditions of sustained hypoxia. The

  3. [Spinal muscular atrophy and respiratory failure. How do primary care pediatricians act in a simulated scenario?].

    Science.gov (United States)

    Agra Tuñas, M C; Sánchez Santos, L; Busto Cuiñas, M; Rodríguez Núñez, A

    2015-11-01

    Spinal muscular atrophy type 1 (SMA-1) tends to be fatal in the first year of life if there is no ventilatory support. The decision whether to start such support is an ethical conflict for healthcare professionals. A scenario of acute respiratory failure in an infant with SMA-1 has been included in a training program using advanced simulation for Primary Care pediatricians (PCP). The performances of 34 groups of 4 pediatricians, who participated in 17 courses, were systematically analyzed. Clinical, ethical and communication aspects with parents were evaluated. The initial technical assistance (Administration of oxygen and immediate ventilatory support) was correctly performed by 94% of the teams. However, the PCP had problems in dealing with the ethical aspects of the case. Of the 85% of the teams that raised the ethical conflict with parents, 29% did so on their own initiative, 23% actively excluded them, and only 6% involved them and took their opinion into account in making decisions. Only 11.7% asked about the quality of life of children and 12% for their knowledge of the prognosis of the disease. None explained treatment alternatives, nor tried to contact the pediatrician responsible for the child. When faced with a simulated SMA-1 infant with respiratory failure, PCP have difficulties in interacting with the family, and to involve it in the decision making process. Practical training of all pediatricians should include case scenarios with an ethical clinical problem. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  4. Development of a real-time imaging system for hypoxic cell apoptosis

    Directory of Open Access Journals (Sweden)

    Go Kagiya

    2016-01-01

    Full Text Available Hypoxic regions within the tumor form due to imbalances between cell proliferation and angiogenesis; specifically, temporary closure or a reduced flow due to abnormal vasculature. They create environments where cancer cells acquire resistance to therapies. Therefore, the development of therapeutic approaches targeting the hypoxic cells is one of the most crucial challenges for cancer regression. Screening potential candidates for effective diagnostic modalities even under a hypoxic environment would be an important first step. In this study, we describe the development of a real-time imaging system to monitor hypoxic cell apoptosis for such screening. The imaging system is composed of a cyclic luciferase (luc gene under the control of an improved hypoxic-responsive promoter. The cyclic luc gene product works as a caspase-3 (cas-3 monitor as it gains luc activity in response to cas-3 activation. The promoter composed of six hypoxic responsible elements and the CMV IE1 core promoter drives the effective expression of the cyclic luc gene in hypoxic conditions, enhancing hypoxic cell apoptosis visualization. We also confirmed real-time imaging of hypoxic cell apoptosis in the spheroid, which shares properties with the tumor. Thus, this constructed system could be a powerful tool for the development of effective anticancer diagnostic modalities.

  5. Emersion behaviour underlies variation in gill morphology and aquatic respiratory function in the amphibious fish Kryptolebias marmoratus.

    Science.gov (United States)

    Turko, A J; Tatarenkov, A; Currie, S; Earley, R L; Platek, A; Taylor, D S; Wright, P A

    2018-04-13

    Fishes acclimated to hypoxic environments often increase gill surface area to improve O 2 uptake. In some species, surface area is increased via reduction of an interlamellar cell mass (ILCM) that fills water channels between gill lamellae. Amphibious fishes, however, may not increase gill surface area in hypoxic water because these species can, instead, leave water and breathe air. To differentiate between these possibilities, we compared wild amphibious mangrove rivulus Kryptolebias marmoratus from two habitats that varied in O 2 availability - a hypoxic freshwater pool versus nearly anoxic crab burrows. Fish captured from crab burrows had less gill surface area (as ILCMs were enlarged by ∼32%), increased rates of normoxic O 2 consumption and increased critical O 2 tension compared with fish from the freshwater pool. Thus, wild mangrove rivulus do not respond to near-anoxic water by decreasing metabolism or increasing O 2 extraction. Instead, fish from the crab burrow habitat spent three times longer out of water, which probably caused the observed changes in gill morphology and respiratory phenotype. We also tested whether critical O 2 tension is influenced by genetic heterozygosity, as K. marmoratus is one of only two hermaphroditic vertebrate species that can produce both self-fertilized (inbred) or out-crossed (more heterozygous) offspring. We found no evidence for inbreeding depression, suggesting that self-fertilization does not impair respiratory function. Overall, our results demonstrate that amphibious fishes that inhabit hypoxic aquatic habitats can use a fundamentally different strategy from that used by fully aquatic water-breathing fishes, relying on escape behaviour rather than metabolic depression or increased O 2 extraction ability. © 2018. Published by The Company of Biologists Ltd.

  6. Lung Volume Reduction Surgery for Respiratory Failure in Infants With Bronchopulmonary Dysplasia.

    Science.gov (United States)

    Sohn, Bongyeon; Park, Samina; Park, In Kyu; Kim, Young Tae; Park, June Dong; Park, Sung-Hye; Kang, Chang Hyun

    2018-04-01

    Lung volume reduction surgery (LVRS) can be performed in patients with severe emphysematous disease. However, LVRS in pediatric patients has not yet been reported. Here, we report our experience with 2 cases of pediatric LVRS. The first patient was a preterm infant girl with severe bronchopulmonary dysplasia, pulmonary hypertension, and hypothyroidism. The emphysematous portion of the right lung was removed via sternotomy and right hemiclamshell incision. The patient was discharged on full-time home ventilator support for 3 months after the surgery. Since then, her respiratory function has improved continuously. She no longer needs oxygen supplementation or ventilator care. Her T-cannula was removed recently. The second patient was also a preterm infant girl with bronchopulmonary dysplasia. She was born with pulmonary hypertension and multiple congenital anomalies, including an atrial septal defect. Despite receiving the best supportive care, she could not be taken off the mechanical ventilator because of severe hypercapnia. We performed LVRS on the right lung via thoracotomy. She was successfully weaned off the mechanical ventilator 1 month after the surgery. She was discharged without severe complications at 3 months after the operation. At present, she is growing well with the help of intermittent home ventilator support. She can now tolerate an oral diet. Our experience shows that LVRS can be considered as a treatment option for pediatric patients with severe emphysematous lung. It is especially helpful for discontinuing prolonged mechanical ventilator care for patients with respiratory failure. Copyright © 2018 by the American Academy of Pediatrics.

  7. CT diagnosis of hypoxic ischemic encephalopathy

    International Nuclear Information System (INIS)

    Zhao Xiang; Ma Jiwei; Wu Lide

    2004-01-01

    Objective: To explore CT characteristics of hypoxic ischemic encephalopathy (HIE), and to improve the accuracy of CT diagnosis. Methods: 50 cases of neonatal asphyxia in perinatal period diagnosed as hypoxic ischemic encephalopathy by CT was analyzed. Results: The main manifestation of hypoxic ischemic encephalopathy is cerebral edema and intracranial hemorrhage. Focal or diffuse hypo-dense lesion and hyper-dense area in various location and morphology were seen on CT images. (1) Localized diffuse hypo-dense area in 1 or 2 cerebral lobe were found in 17 cases, and the lesions were localized in frontal lobe (n=6), in frontotemporal lobe (n=5), and in temporo-occipital lobe (n=6). (2) Hypo-density region involving more than three cerebral lobes were found in 18 cases, and abnormalities were found in frontotemporal and parietal lobe (n=8), accompanying with subarachnoid hemorrhage (n=2); in frontal, temporal and occipital lobe (n=6), in which cerebral hemorrhage was complicated (n=1); and in other cerebral lobe (n=4). (3) Diffuse low-density region in all cerebral lobe were found in 15 cases, in which subarachnoid hemorrhage was complicated in 4 cases, and ventricular hemorrhage was found in 2 case. Conclusion: CT imaging plays an important role in diagnosis of hypoxic ischemic encephalopathy and has shown its clinical value

  8. Hepatocytes Determine the Hypoxic Microenvironment and Radiosensitivity of Colorectal Cancer Cells Through Production of Nitric Oxide That Targets Mitochondrial Respiration

    International Nuclear Information System (INIS)

    Jiang, Heng; Verovski, Valeri N.; Leonard, Wim; Law, Ka Lun; Vermeersch, Marieke; Storme, Guy; Van den Berge, Dirk; Gevaert, Thierry; Sermeus, Alexandra; De Ridder, Mark

    2013-01-01

    Purpose: To determine whether host hepatocytes may reverse hypoxic radioresistance through nitric oxide (NO)-induced oxygen sparing, in a model relevant to colorectal cancer (CRC) liver metastases. Methods and Materials: Hepatocytes and a panel of CRC cells were incubated in a tissue-mimetic coculture system with diffusion-limited oxygenation, and oxygen levels were monitored by an oxygen-sensing fluorescence probe. To activate endogenous NO production, cocultures were exposed to a cytokine mixture, and the expression of inducible nitric oxide synthase was analyzed by reverse transcription–polymerase chain reaction, Western blotting, and NO/nitrite production. The mitochondrial targets of NO were examined by enzymatic activity. To assess hypoxic radioresponse, cocultures were irradiated and reseeded for colonies. Results: Resting hepatocytes consumed 10-40 times more oxygen than mouse CT26 and human DLD-1, HT29, HCT116, and SW480 CRC cells, and thus seemed to be the major effectors of hypoxic conditioning. As a result, hepatocytes caused uniform radioprotection of tumor cells at a 1:1 ratio. Conversely, NO-producing hepatocytes radiosensitized all CRC cell lines more than 1.5-fold, similar to the effect of selective mitochondrial inhibitors. The radiosensitizing effect was associated with a respiratory self-arrest of hepatocytes at the level of aconitase and complex II, which resulted in profound reoxygenation of tumor cells through oxygen sparing. Nitric oxide–producing hepatocytes were at least 10 times more active than NO-producing macrophages to reverse hypoxia-induced radioresistance. Conclusions: Hepatocytes were the major determinants of the hypoxic microenvironment and radioresponse of CRC cells in our model of metabolic hypoxia. We provide evidence that reoxygenation and radiosensitization of hypoxic CRC cells can be achieved through oxygen sparing induced by endogenous NO production in host hepatocytes

  9. Hepatocytes Determine the Hypoxic Microenvironment and Radiosensitivity of Colorectal Cancer Cells Through Production of Nitric Oxide That Targets Mitochondrial Respiration

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Heng; Verovski, Valeri N.; Leonard, Wim; Law, Ka Lun; Vermeersch, Marieke; Storme, Guy; Van den Berge, Dirk; Gevaert, Thierry; Sermeus, Alexandra [Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels (Belgium); De Ridder, Mark, E-mail: mark.deridder@uzbrussel.be [Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels (Belgium)

    2013-03-01

    Purpose: To determine whether host hepatocytes may reverse hypoxic radioresistance through nitric oxide (NO)-induced oxygen sparing, in a model relevant to colorectal cancer (CRC) liver metastases. Methods and Materials: Hepatocytes and a panel of CRC cells were incubated in a tissue-mimetic coculture system with diffusion-limited oxygenation, and oxygen levels were monitored by an oxygen-sensing fluorescence probe. To activate endogenous NO production, cocultures were exposed to a cytokine mixture, and the expression of inducible nitric oxide synthase was analyzed by reverse transcription–polymerase chain reaction, Western blotting, and NO/nitrite production. The mitochondrial targets of NO were examined by enzymatic activity. To assess hypoxic radioresponse, cocultures were irradiated and reseeded for colonies. Results: Resting hepatocytes consumed 10-40 times more oxygen than mouse CT26 and human DLD-1, HT29, HCT116, and SW480 CRC cells, and thus seemed to be the major effectors of hypoxic conditioning. As a result, hepatocytes caused uniform radioprotection of tumor cells at a 1:1 ratio. Conversely, NO-producing hepatocytes radiosensitized all CRC cell lines more than 1.5-fold, similar to the effect of selective mitochondrial inhibitors. The radiosensitizing effect was associated with a respiratory self-arrest of hepatocytes at the level of aconitase and complex II, which resulted in profound reoxygenation of tumor cells through oxygen sparing. Nitric oxide–producing hepatocytes were at least 10 times more active than NO-producing macrophages to reverse hypoxia-induced radioresistance. Conclusions: Hepatocytes were the major determinants of the hypoxic microenvironment and radioresponse of CRC cells in our model of metabolic hypoxia. We provide evidence that reoxygenation and radiosensitization of hypoxic CRC cells can be achieved through oxygen sparing induced by endogenous NO production in host hepatocytes.

  10. Hypoxic training methods for improving endurance exercise performance

    Directory of Open Access Journals (Sweden)

    Jacob A. Sinex

    2015-12-01

    Full Text Available Endurance athletic performance is highly related to a number of factors that can be altered through altitude and hypoxic training including increases in erythrocyte volume, maximal aerobic exercise capacity, capillary density, and economy. Physiological adaptations in response to acute and chronic exposure to hypoxic environments are well documented and range from short-term detrimental effects to longer-term adaptations that can improve performance at altitude and in sea-level competitions. Many altitude and hypoxic training protocols have been developed, employing various combinations of living and training at sea-level, low, moderate, and high altitudes and utilizing natural and artificial altitudes, with varying degrees of effectiveness. Several factors have been identified that are associated with individual responses to hypoxic training, and techniques for identifying those athletes most likely to benefit from hypoxic training continue to be investigated. Exposure to sufficiently high altitude (2000–3000 m for more than 12 h/day, while training at lower altitudes, for a minimum of 21 days is recommended. Timing of altitude training related to competition remains under debate, although general recommendations can be considered.

  11. TWO CASES OF TYPE II RESPIRATORY FAILURE IN COPD TREATED IN KATURI MEDICAL COLLEGE HOSPITAL, GUNTUR AND AN OVERVIEW OF TREATMENT OF ACUTE EXACERBATION AND RESPIRATORY FAILURE

    Directory of Open Access Journals (Sweden)

    Ramakrishna

    2015-04-01

    Full Text Available Treatment of Type II Respiratory Failure in a COPD patient is a difficult task for the ICU and Pulmonary physician. Multi factorial and multi - disciplinary approach is required . Our experience of two cases treated recently in Katuri medical College Hospita l have common features. One is a male of 54 years age and the other is a female of similar age. Both of them were obese and were nonsmokers. Both were poor and could not afford any ICU treatment on their own. Both were rescued by State sponsored Arogyasree programme. Both of them had the advantage of support from their families. Aided by Arogyasree programme, dedicated staff of ICU, Pulmonology, ENT departments , timely interventions with electrolyte balance, balanced antibiotic therapy, Noninvasive and inva sive ventilator strategies, Nutritional support, Blood transfusions, Timely Tracheostomy and excellent nursing care and drug administration in ICU both patients recovered back to normalcy . Initially both required home oxygen therapy and both were subsequen tly seen maintaining normal oxygenation status even without oxygen causing happiness to family members and the treating physicians

  12. [Follow-up of newborns with hypoxic-ischaemic encephalopathy].

    Science.gov (United States)

    Martínez-Biarge, M; Blanco, D; García-Alix, A; Salas, S

    2014-07-01

    Hypothermia treatment for newborn infants with hypoxic-ischemic encephalopathy reduces the number of neonates who die or have permanent neurological deficits. Although this therapy is now standard of care, neonatal hypoxic-ischaemic encephalopathy still has a significant impact on the child's neurodevelopment and quality of life. Infants with hypoxic-ischaemic encephalopathy should be enrolled in multidisciplinary follow-up programs in order to detect impairments, to initiate early intervention, and to provide counselling and support for families. This article describes the main neurodevelopmental outcomes after term neonatal hypoxic-ischaemic encephalopathy. We offer recommendations for follow-up based on the infant's clinical condition and other prognostic indicators, mainly neonatal neuroimaging. Other aspects, such as palliative care and medico-legal issues, are also briefly discussed. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  13. Hypoxic enhancement of exosome release by breast cancer cells

    International Nuclear Information System (INIS)

    King, Hamish W; Michael, Michael Z; Gleadle, Jonathan M

    2012-01-01

    Exosomes are nanovesicles secreted by tumour cells which have roles in paracrine signalling during tumour progression, including tumour-stromal interactions, activation of proliferative pathways and bestowing immunosuppression. Hypoxia is an important feature of solid tumours which promotes tumour progression, angiogenesis and metastasis, potentially through exosome-mediated signalling. Breast cancer cell lines were cultured under either moderate (1% O 2 ) or severe (0.1% O 2 ) hypoxia. Exosomes were isolated from conditioned media and quantitated by nanoparticle tracking analysis (NTA) and immunoblotting for the exosomal protein CD63 in order to assess the impact of hypoxia on exosome release. Hypoxic exosome fractions were assayed for miR-210 by real-time reverse transcription polymerase chain reaction and normalised to exogenous and endogenous control genes. Statistical significance was determined using the Student T test with a P value of < 0.05 considered significant. Exposure of three different breast cancer cell lines to moderate (1% O 2 ) and severe (0.1% O 2 ) hypoxia resulted in significant increases in the number of exosomes present in the conditioned media as determined by NTA and CD63 immunoblotting. Activation of hypoxic signalling by dimethyloxalylglycine, a hypoxia-inducible factor (HIF) hydroxylase inhibitor, resulted in significant increase in exosome release. Transfection of cells with HIF-1α siRNA prior to hypoxic exposure prevented the enhancement of exosome release by hypoxia. The hypoxically regulated miR-210 was identified to be present at elevated levels in hypoxic exosome fractions. These data provide evidence that hypoxia promotes the release of exosomes by breast cancer cells, and that this hypoxic response may be mediated by HIF-1α. Given an emerging role for tumour cell-derived exosomes in tumour progression, this has significant implications for understanding the hypoxic tumour phenotype, whereby hypoxic cancer cells may release

  14. Assessment of blood gas parameters and the degree of inflammation in noninvasive positive pressure ventilation combined with aminophylline treatment of COPD complicated with type II respiratory failure

    Directory of Open Access Journals (Sweden)

    Jin-Ru Zhang

    2016-10-01

    Full Text Available Objective: To analyze the effect of noninvasive positive pressure ventilation combined with aminophylline therapy on blood gas parameters and the degree of inflammation in patients with COPD and type II respiratory failure. Methods: A total of 80 patients with COPD and type Ⅱ respiratory failure were randomly divided into observation group and control group (n=40, control group received symptomatic treatment + aminophylline treatment, observation group received symptomatic treatment + aminophylline + noninvasive positive pressure ventilation treatment, and then differences in blood gas parameters, pulmonary function parameters, hemorheology parameters and inflammatory factor levels were compared between two groups of patients after treatment. Results: Radial artery pH and PO2 values of observation group after treatment were higher than those of control group while PCO2, Cl- and CO2CP values were lower than those of control group; pulmonary function parameters FVC, FEV1, FEF25-75, MMF, PEF and FRC values of observation group after treatment were higher than those of control group; whole blood viscosity (150 s- and 10 s-, plasma viscosity, fibrinogen, erythrocyte aggregation index and erythrocyte rigidity index values in peripheral venous blood of observation group after treatment were lower than those of control group; serum IL-17, IL-33, TREM-1, sICAM-1 and PGE2 levels of observation group after treatment were lower than those of control group. Conclusion: Noninvasive positive pressure ventilation combined with aminophylline can optimize the respiratory function of patients with COPD and type II respiratory failure and improve blood gas parameters and the degree of inflammation.

  15. Participation of the dorsal periaqueductal grey matter in the hypoxic ventilatory response in unanaesthetized rats.

    Science.gov (United States)

    Lopes, L T; Biancardi, V; Vieira, E B; Leite-Panissi, C; Bícego, K C; Gargaglioni, L H

    2014-07-01

    Although periaqueductal grey matter activation is known to elicit respiratory and cardiovascular responses, the role of this midbrain area in the compensatory responses to hypoxia is still unknown. To test the participation of the periaqueductal grey matter in cardiorespiratory and thermal responses to hypoxia in adult male Wistar rats, we performed a chemical lesion of the dorsolateral/dorsomedial or the ventrolateral/lateral periaqueductal grey matter using ibotenic acid. Pulmonary ventilation, mean arterial pressure, heart rate and body temperature were measured in unanaesthetized rats during normoxic and hypoxic exposure (5, 15, 30 min, 7% O2). An ibotenic acid lesion of the dorsolateral/dorsomedial periaqueductal grey matter caused a higher increase in pulmonary ventilation (67.1%, 1730±282.5 mL kg(-1) min(-1)) compared to the Sham group (991.4±194 mL kg(-1) min(-1)) after 15 min in hypoxia, whereas for the ventrolateral/Lateral periaqueductal grey matter lesion, no differences were observed between groups. Mean arterial pressure, heart rate and body temperature were not affected by a dorsolateral/dorsomedial or ventrolateral/lateral periaqueductal grey matter lesion. Middle to caudal portions of the dorsolateral/dorsomedial periaqueductal grey matter neurones modulate the hypoxic ventilatory response, exerting an inhibitory modulation during low O2 situations. In addition, the middle to caudal portions of the dorsolateral/dorsomedial or ventrolateral/lateral periaqueductal grey matter do not appear to exert a tonic role on cardiovascular or thermal parameters during normoxic and hypoxic conditions. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  16. Hypoxic stress-induced changes in ribosomes of maize seedling roots

    International Nuclear Information System (INIS)

    Bailey-Serres, J.; Freeling, M.

    1990-01-01

    The hypoxic stress response of Zea mays L. seedling roots involves regulation of gene expression at transcriptional and posttranscriptional levels. We investigated the effect of hypoxia on the translational machinery of seedling roots. The levels of monoribosomes and ribosomal subunits increased dramatically within 1 hour of stress. Prolonged hypoxia resulted in continued accumulation of nontranslating ribosomes, as well as increased levels of small polyribosomes. The return of seedlings to normal aerobic conditions resulted in recovery of normal polyribosome levels. Comparison of ribosomal proteins from control and hypoxic roots revealed differences in quantity and electrophoretic mobility. In vivo labeling of roots with [ 35 S]methionine revealed variations in newly synthesized ribosomal proteins. In vivo labeling of roots with [ 32 P]orthophosphate revealed a major reduction in the phosphorylation of a 31 kilodalton ribosomal protein in hypoxic stressed roots. In vitro phosphorylation of ribosomal proteins by endogenous kinases was used to probe for differences in ribosome structure and composition. The patterns of in vitro kinased phosphoproteins of ribosomes from control and hypoxic roots were not identical. Variation in phosphoproteins of polyribosomes from control and hypoxic roots, as well as among polyribosomes from hypoxic roots were observed. These results indicate that modification of the translational machinery occurs in response to hypoxic stress

  17. Respiratory responses of the air-breathing fish Hoplosternum littorale to hypoxia and hydrogen sulfide.

    Science.gov (United States)

    Affonso, E G; Rantin, F T

    2005-07-01

    The present study analyzes the respiratory responses of the neotropical air-breathing fish Hoplosternum littorale to graded hypoxia and increased sulfide concentrations. The oxygen uptake (VO2), critical O2 tension (PcO2), respiratory (fR) and air-breathing (fRA) frequencies in response to graded hypoxia were determined for fish acclimated to 28 degrees C. H. littorale was able to maintain a constant VO2 down to a PcO2 of 50 mm Hg, below which fish became dependent on the environmental O2 even with significant increases in fR. The fRA was kept constant around 1 breath h(-1) above 50 mm Hg and increased significantly below 40 mm Hg, reaching maximum values (about 4.5 breaths h(-1)) at 10 mm Hg. The lethality to sulfide concentrations under normoxic and hypoxic conditions were also determined along with the fRA. For the normoxic fish the sulfide lethal limit was about 70 microM, while in the hypoxic ones this limit increased to 87 muM. The high sulfide tolerance of H. littorale may be attributed to the air-breathing capability, which is stimulated by this compound.

  18. Application of altitude/hypoxic training by elite athletes.

    Science.gov (United States)

    Wilber, Randall L

    2007-09-01

    At the Olympic level, differences in performance are typically less than 0.5%. This helps explain why many contemporary elite endurance athletes in summer and winter sport incorporate some form of altitude/hypoxic training within their year-round training plan, believing that it will provide the "competitive edge" to succeed at the Olympic level. The purpose of this paper is to describe the practical application of altitude/hypoxic training as used by elite athletes. Within the general framework of the paper, both anecdotal and scientific evidence will be presented relative to the efficacy of several contemporary altitude/hypoxic training models and devices currently used by Olympic-level athletes for the purpose of legally enhancing performance. These include the three primary altitude/hypoxic training models: 1) live high+train high (LH+TH), 2) live high+train low (LH+TL), and 3) live low+train high (LL+TH). The LH+TL model will be examined in detail and will include its various modifications: natural/terrestrial altitude, simulated altitude via nitrogen dilution or oxygen filtration, and hypobaric normoxia via supplemental oxygen. A somewhat opposite approach to LH+TL is the altitude/hypoxic training strategy of LL+TH, and data regarding its efficacy will be presented. Recently, several of these altitude/hypoxic training strategies and devices underwent critical review by the World Anti-Doping Agency (WADA) for the purpose of potentially banning them as illegal performance-enhancing substances/methods. This paper will conclude with an update on the most recent statement from WADA regarding the use of simulated altitude devices.

  19. Cost-effectiveness of Out-of-Hospital Continuous Positive Airway Pressure for Acute Respiratory Failure.

    Science.gov (United States)

    Thokala, Praveen; Goodacre, Steve; Ward, Matt; Penn-Ashman, Jerry; Perkins, Gavin D

    2015-05-01

    We determine the cost-effectiveness of out-of-hospital continuous positive airway pressure (CPAP) compared with standard care for adults presenting to emergency medical services with acute respiratory failure. We developed an economic model using a United Kingdom health care system perspective to compare the costs and health outcomes of out-of-hospital CPAP to standard care (inhospital noninvasive ventilation) when applied to a hypothetical cohort of patients with acute respiratory failure. The model assigned each patient a probability of intubation or death, depending on the patient's characteristics and whether he or she had out-of-hospital CPAP or standard care. The patients who survived accrued lifetime quality-adjusted life-years (QALYs) and health care costs according to their age and sex. Costs were accrued through intervention and hospital treatment costs, which depended on patient outcomes. All results were converted into US dollars, using the Organisation for Economic Co-operation and Development purchasing power parities rates. Out-of-hospital CPAP was more effective than standard care but was also more expensive, with an incremental cost-effectiveness ratio of £20,514 per QALY ($29,720/QALY) and a 49.5% probability of being cost-effective at the £20,000 per QALY ($29,000/QALY) threshold. The probability of out-of-hospital CPAP's being cost-effective at the £20,000 per QALY ($29,000/QALY) threshold depended on the incidence of eligible patients and varied from 35.4% when a low estimate of incidence was used to 93.8% with a high estimate. Variation in the incidence of eligible patients also had a marked influence on the expected value of sample information for a future randomized trial. The cost-effectiveness of out-of-hospital CPAP is uncertain. The incidence of patients eligible for out-of-hospital CPAP appears to be the key determinant of cost-effectiveness. Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All

  20. Hypoxic sensitizers (A review)

    International Nuclear Information System (INIS)

    Ohno, Tadao; Shikita, Mikio

    1976-01-01

    Since the early works of Bridges (1960) and Adams (1963), electron-affinic compounds have long been the subject of a number of studies in the search for a drug which sensitizes radio-resistant hypoxic tumor cells for improvement of radiotherapy of cancer. However, clinical application of this kind of drugs has been hampered by the fact that most of the compounds which exhibited radiosensitizing action in vitro exerted no such action against hypoxic tumor cells in vivo, because of rapid metabolical decomposition or because of great toxicity in vivo. Low solubility of these compounds in aqueous solution was another problem which made it difficult to use the compounds in proper concentrations. The authors have found that furylfuramide (AF-2), possesses a typical radiosensitizing potency. The radiosensitizing action of AF-2 was demonstrated in hypoxic yeasts as well as in mouse leukemic cells (L-5178 Y). Injection of 4.7 μg of AF-2 into a mouse mammary carcinoma 5 min before a single dose (3500 rad) of x-irradiation reduced regrowth of the tumors to a greater extent than irradiation alone, giving an enhancing ratio of 1.6. The effect of AF-2 was insignificant when radiation was given in divided doses (800 rad for 5 times) with the drug injected each time prior to irradiation. (auth.)

  1. Testing of new hypoxic cell sensitizers in vivo

    International Nuclear Information System (INIS)

    Stone, H.B.; Sinesi, M.S.

    1982-01-01

    We tested five agents as potential sensitizers of hypoxic cells in vivo in mammary tumors in C3H mice in comparison with misonidazole. The LD/sub 50/2/ for desmethylmisonidazole was 2.7 mg/g body wt, compared to 1.3 for misonidazole. It was as effective in reducing the TCD 50 of MDAH-MCa-4 as were equitoxic doses of misonidazole. the LD/sub 50/2/ of SR-2508 was 3.3 mg/g and was as effective a sensitizer as misonidazole. Ro 07-0741 was more toxic, with an LD/sub 50/2/ of 0.6 mg/g, but was as effective as misonidazole at equitoxic doses. NP-1 was also more toxic than misonidazole (LA/sub 50/2/ = 04 mg/g) but was a less effective sensitizer. Rotenone, which causes sensitization by inhibiting cellular respiration, thus increasing the diffusion distance of oxygen, was extremely toxic (LD/sub 50/2/ - 0.003 mg/g), and systemic respiratory inhibition and the radioprotective effects of the dimethyl sulfoxide used to dissolve it rendered it totally ineffective as a sensitizer in vivo

  2. Evaluation of Hemodynamic Changes and Respiratory Physical Findings in Patients with Pulmonary Embolism

    Directory of Open Access Journals (Sweden)

    Masome Rabieepour

    2014-07-01

    Full Text Available Introduction: Pulmonary thromboembolism (PTE is a potentially fatal disease with nonspecific symptoms and signs. Patients with Pulmonary embolism often have dyspnea, chest pain, haemoptysis, tachycardia tachypnea and respiratory physical finding including hypoxia and decreased ETCO2. Daily patients with Pulmonary embolism are very few in hospital course and we aimed to determine clinical and paraclinical findings in hospital pulmonary embolism patients. Methods: we assessed in hospital course of 104 patients with pulmonary embolism with symptom (dyspnea, chest pain, and hemoptysis and signs (tachypnea, tachycardia, DVT signs, blood pressure and respiratory physical findings (PO2, ETCO2. Results: majority of patients had risk factor for PTE; the most common was cancer. 21.2% of patients had apparent DVT in Doppler sonography. Isolated dyspnea (38%, chest pain with and without hemoptysis (60% and syncope (2% were observed in patients. Mean duration of dyspnea resolution was 3.4 days. Mean duration of chest pain resolution was 1.76 days. Mean duration of hemoptysis resolution was 2 days. 64.4% of the patients were hypoxic and mean duration of hypoxic resolution was 2.63 days. Mean duration of tachycardia resolution was 2.37 days. No relation was observed between size of PTE and mortality or hypotension and PO2. Mean ETCO2 was 23±2 mmHg and 86.5% of patients had ETCO2 lower than 28. Mean duration of ETCO2 resolution was 3.6 days. Most common physical finding that resolved later than others was ETCO2. In 32.7% of patients, ETCO2 did not resolve.   Key words: Pulmonary thromboembolism; Tachycardia; Tachypnea; Hemoptysis; Hypoxic; ETCO2

  3. Toxic clinical hypoxic radiation sensitizers plus radiation-induced toxicity

    International Nuclear Information System (INIS)

    Richmond, R.C.

    1984-01-01

    The operational definition espoused twelve years ago that clinical hypoxic radiation sensitizers should be nontoxic interferes with the recognition and research of useful radiation sensitizers. Eight years ago the toxic antitumor drug cis-dichlorodiammineplatinum(II) was reported to be a hypoxic radiation sensitizer and the selective antitumor action of this drug was stressed as potentially creating tumor-targeted radiation sensitization. This rationale of oxidative antitumor drugs as toxic and targeted clinical sensitizers is useful, and has led to the study reported here. The antitumor drug cis-(1,1-cyclobutane-dicarboxylato)diammineplatinum(II), or JM-8, is being tested in clinical trials. Cells of S. typhimurium in PBS in the presence of 0.2mM JM-8 are found to be sensitized to irradiation under hypoxic, but not oxic, conditions. JM-8 is nontoxic to bacteria at this concentration, but upon irradiation the JM-8 solution becomes highly toxic. This radiation induced toxicity of JM-8 preferentially develops from hypoxic solution, and thus contributes to the rationale of hypoxic tumor cell destruction

  4. PKA activity exacerbates hypoxia-induced ROS formation and hypoxic injury in PC-12 cells.

    Science.gov (United States)

    Gozal, Evelyne; Metz, Cynthia J; Dematteis, Maurice; Sachleben, Leroy R; Schurr, Avital; Rane, Madhavi J

    2017-09-05

    Hypoxia is a primary factor in many pathological conditions. Hypoxic cell death is commonly attributed to metabolic failure and oxidative injury. cAMP-dependent protein kinase A (PKA) is activated in hypoxia and regulates multiple enzymes of the mitochondrial electron transport chain, thus may be implicated in cellular energy depletion and hypoxia-induced cell death. Wild type (WT) PC-12 cells and PKA activity-deficient 123.7 PC-12 cells were exposed to 3, 6, 12 and 24h hypoxia (0.1% or 5% O 2 ). Hypoxia, at 24h 0.1% O 2 , induced cell death and increased reactive oxygen species (ROS) in WT PC-12 cells. Despite lower ATP levels in normoxic 123.7 cells than in WT cells, hypoxia only decreased ATP levels in WT cells. However, menadione-induced oxidative stress similarly affected both cell types. While mitochondrial COX IV expression remained consistently higher in 123.7 cells, hypoxia decreased COX IV expression in both cell types. N-acetyl cysteine antioxidant treatment blocked hypoxia-induced WT cell death without preventing ATP depletion. Transient PKA catα expression in 123.7 cells partially restored hypoxia-induced ROS but did not alter ATP levels or COX IV expression. We conclude that PKA signaling contributes to hypoxic injury, by regulating oxidative stress rather than by depleting ATP levels. Therapeutic strategies targeting PKA signaling may improve cellular adaptation and recovery in hypoxic pathologies. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Effect of fractionated hyperthermia on hypoxic cells in vitro

    International Nuclear Information System (INIS)

    Nielson, O.S.

    1981-01-01

    The lethal response of asynchronous exponentially growing mouse lung (L1A2) cells heated to 42 0 C under hypoxic conditions was demonstrated in vitro. Acutely hypoxic cells (i.e. heated immediately after 30 min of N 2 +CO 2 gassing) and aerobic cells treated under the same extracellular pH were equally sensitive to a single hyperthermic treatment, and incubation under hypoxia for up to 24 hours prior to treatment did not influence cell survival. Similarly, under controlled pH conditions (pH within 7.0 to 7.4) recovery from hyperthermic damage demonstrated by two-dose hyperthermic fractionation (each of 1.5 hours at 42 0 C) was identical in hypoxic and aerobic cells, and the highest recovery was found at a 10-hour interval Preheating for 1.5 hours at 42 0 C induced thermal resistance. to a second treatment at 42 0 C (thermotolerance). At the 10-hour interval the degree of thermotolerance was not influenced by incubation under hypoxic conditions (thermotolerance ratio, TTR = 4.7 in both aerobic and hypoxic cells). The data indicate that hypoxic conditions do not influence the heat response in L1A2 cells to either a single or a two-dose fractionated hyperthermic treatment in which hypoxia or aerobic conditions were maintained in the interval between the heat treatments. (author)

  6. Diaphragm Muscle Weakness Following Acute Sustained Hypoxic Stress in the Mouse Is Prevented by Pretreatment with N-Acetyl Cysteine

    Directory of Open Access Journals (Sweden)

    Andrew J. O’Leary

    2018-01-01

    Full Text Available Oxygen deficit (hypoxia is a major feature of cardiorespiratory diseases characterized by diaphragm dysfunction, yet the putative role of hypoxic stress as a driver of diaphragm dysfunction is understudied. We explored the cellular and functional consequences of sustained hypoxic stress in a mouse model. Adult male mice were exposed to 8 hours of normoxia, or hypoxia (FiO2 = 0.10 with or without antioxidant pretreatment (N-acetyl cysteine, 200 mg/kg i.p.. Ventilation and metabolism were measured. Diaphragm muscle contractile function, myofibre size and distribution, gene expression, protein signalling cascades, and oxidative stress (TBARS were determined. Hypoxia caused pronounced diaphragm muscle weakness, unrelated to increased respiratory muscle work. Hypoxia increased diaphragm HIF-1α protein content and activated MAPK, mTOR, Akt, and FoxO3a signalling pathways, largely favouring protein synthesis. Hypoxia increased diaphragm lipid peroxidation, indicative of oxidative stress. FoxO3 and MuRF-1 gene expression were increased. Diaphragm 20S proteasome activity and muscle fibre size and distribution were unaffected by acute hypoxia. Pretreatment with N-acetyl cysteine substantially enhanced cell survival signalling, prevented hypoxia-induced diaphragm oxidative stress, and prevented hypoxia-induced diaphragm dysfunction. Hypoxia is a potent driver of diaphragm weakness, causing myofibre dysfunction without attendant atrophy. N-acetyl cysteine protects the hypoxic diaphragm and may have application as a potential adjunctive therapy.

  7. Sulphonylurea drugs reduce hypoxic damage in the isolated perfused rat kidney.

    Science.gov (United States)

    Engbersen, R; Moons, M M; Wouterse, A C; Dijkman, H B; Kramers, C; Smits, P; Russel, F G

    2000-08-01

    Sulphonylurea drugs have been shown to protect against hypoxic damage in isolated proximal tubules of the kidney. In the present study we investigated whether these drugs can protect against hypoxic damage in a whole kidney preparation. Tolbutamide (200 microM) and glibenclamide (10 microM) were applied to the isolated perfused rat kidney prior to changing the gassing from oxygen to nitrogen for 30 min. Hypoxic perfusions resulted in an increased fractional excretion of glucose (FE % glucose 14.3+/-1.5 for hypoxic perfusions vs 4.9+/-1.6 for normoxic perfusions, mean +/- s.e. mean, P<0.05), which could be completely restored by 200 microM tolbutamide (5.7+/-0.4 for tolbutamide vs 14.3+/-1.5 for untreated hypoxic kidneys, P<0.01). Furthermore, tolbutamide reduced the total amount of LDH excreted in the urine (220+/-100 mU for tolbutamide vs. 1220+/-160 mU for untreated hypoxic kidneys, P<0.01). Comparable results were obtained with glibenclamide (10 microM). In agreement with the effect on functional parameters, ultrastructural analysis of proximal tubules showed increased brush border preservation in tolbutamide treated kidneys compared to untreated hypoxic kidneys. We conclude that glibenclamide and tolbutamide are both able to reduce hypoxic damage to proximal tubules in the isolated perfused rat kidney when applied in the appropriate concentrations.

  8. Ocular Tropism of Respiratory Viruses

    Science.gov (United States)

    Rota, Paul A.; Tumpey, Terrence M.

    2013-01-01

    SUMMARY Respiratory viruses (including adenovirus, influenza virus, respiratory syncytial virus, coronavirus, and rhinovirus) cause a broad spectrum of disease in humans, ranging from mild influenza-like symptoms to acute respiratory failure. While species D adenoviruses and subtype H7 influenza viruses are known to possess an ocular tropism, documented human ocular disease has been reported following infection with all principal respiratory viruses. In this review, we describe the anatomical proximity and cellular receptor distribution between ocular and respiratory tissues. All major respiratory viruses and their association with human ocular disease are discussed. Research utilizing in vitro and in vivo models to study the ability of respiratory viruses to use the eye as a portal of entry as well as a primary site of virus replication is highlighted. Identification of shared receptor-binding preferences, host responses, and laboratory modeling protocols among these viruses provides a needed bridge between clinical and laboratory studies of virus tropism. PMID:23471620

  9. Hypothermia therapy for newborns with hypoxic ischemic encephalopathy.

    Science.gov (United States)

    Silveira, Rita C; Procianoy, Renato S

    2015-01-01

    Therapeutic hypothermia reduces cerebral injury and improves the neurological outcome secondary to hypoxic ischemic encephalopathy in newborns. It has been indicated for asphyxiated full-term or near-term newborn infants with clinical signs of hypoxic-ischemic encephalopathy (HIE). A search was performed for articles on therapeutic hypothermia in newborns with perinatal asphyxia in PubMed; the authors chose those considered most significant. There are two therapeutic hypothermia methods: selective head cooling and total body cooling. The target body temperature is 34.5 °C for selective head cooling and 33.5 °C for total body cooling. Temperatures lower than 32 °C are less neuroprotective, and temperatures below 30 °C are very dangerous, with severe complications. Therapeutic hypothermia must start within the first 6h after birth, as studies have shown that this represents the therapeutic window for the hypoxic-ischemic event. Therapy must be maintained for 72 h, with very strict control of the newborn's body temperature. It has been shown that therapeutic hypothermia is effective in reducing neurologic impairment, especially in full-term or near-term newborns with moderate hypoxic-ischemic encephalopathy. Therapeutic hypothermia is a neuroprotective technique indicated for newborn infants with perinatal asphyxia and hypoxic-ischemic encephalopathy. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  10. Inhibition of glycolysis by misonidazole in hypoxic cells

    International Nuclear Information System (INIS)

    Ling, L.; Sutherland, R.

    1984-01-01

    Inhibition of glycolysis has been postulated to be a mechanism of misonidazole (MISO) toxicity in hypoxic cells. To investigate the effect of MISO on glycolysis, glucose transport and its consumption and lactate formation were measured. Exponential EMT6 cells (10/sup 6/ cells/ml) were made hypoxix by continuous gassing in 3% CO/sub 2/ in N/sub 2/. They were then treated with 5mM MISO for various times, then washed and analysed for their rates of anaerobic glycolysis. Glucose and lactate content were determined enzymatically. The rates of both glucose consumption and lactate formation decreased after 30 min hypoxic incubation with MISO. After 90 min, the rates were not measurable even though the cells still excluded Trypan Blue. There was, however, a parallel decrease in plating efficiency. These data suggest that the inhibition of glycolysis is an important mechanism of hypoxic toxicity of MISO. To locate the site of inhibition, studies were initiated to look at glucose transport by following the uptake of /sup 14/-C-3-0-methyl-glucose, a nonmetabolised glucose analog. Results obtained so far indicate that up to 90 min of hypoxic incubation with MISO, there was no change in the kinetics of the uptake of his analog. Therefore, the results showed that in hypoxic cells treated with MISO, the glucose transport system was unaffected. However, there was a rapid decrease in anaerobic glycolysis

  11. Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)

    DEFF Research Database (Denmark)

    Kvisgaard, Lise Kirstine

    This PhD thesis presents the diversity of Porcine Reproductive and Respiratory Syndrome viruses (PRRSV) circulating in the Danish pig population. PRRS is a disease in pigs caused by the PRRS virus resulting in reproductive failures in sows and gilts and respiratory diseases in pigs . Due to genetic...

  12. Phrenic and hypoglossal nerve activity during respiratory response to hypoxia in 6-OHDA unilateral model of Parkinson's disease.

    Science.gov (United States)

    Andrzejewski, Kryspin; Budzińska, Krystyna; Kaczyńska, Katarzyna

    2017-07-01

    Parkinson's disease (PD) patients apart from motor dysfunctions exhibit respiratory disturbances. Their mechanism is still unknown and requires investigation. Our research was designed to examine the activity of phrenic (PHR) and hypoglossal (HG) nerves activity during a hypoxic respiratory response in the 6-hydroxydopamine (6-OHDA) model of PD. Male adult Wistar rats were injected unilaterally with 6-OHDA (20μg) or the vehicle into the right medial forebrain bundle (MFB). Two weeks after the surgery the activity of the phrenic and hypoglossal nerve was registered in anesthetized, vagotomized, paralyzed, and mechanically ventilated rats under normoxic and hypoxic conditions. Lesion effectiveness was confirmed by the cylinder test, performed before the MFB injection and 14days after, before the respiratory experiment. 6-OHDA lesioned animals showed a significant increase in normoxic inspiratory time. Expiratory time and total time of the respiratory cycle were prolonged in PD rats after hypoxia. The amplitude of the PHR activity and its minute activity were increased in comparison to the sham group at recovery time and during 30s of hypoxia. The amplitude of the HG activity was increased in response to hypoxia in 6-OHDA lesioned animals. The degeneration of dopaminergic neurons decreased the pre-inspiratory/inspiratory ratio of the hypoglossal burst amplitude during and after hypoxia. Unilateral MFB lesion changed the activity of the phrenic and hypoglossal nerves. The altered pre-inspiratory hypoglossal nerve activity indicates modifications to the central mechanisms controlling the activity of the HG nerve and may explain respiratory disorders seen in PD, i.e. apnea. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Radiosensitization of hypoxic tumor cells in vitro by nitric oxide

    International Nuclear Information System (INIS)

    Griffin, Robert J.; Makepeace, Carol M.; Hur, Won-Joo; Song, Chang W.

    1996-01-01

    Purpose: The effects of nitric oxide (NO) on the radiosensitivity of SCK tumor cells in oxic and hypoxic environments in vitro were studied. Methods and Materials: NO was delivered to cell suspensions using the NO donors 2,2-diethyl-1-nitroso-oxyhydrazine sodium salt (DEA/NO), and a spermine/nitric oxide complex (SPER/NO), which release NO at half-lives of 2.1 min and 39 min at pH 7.4, respectively. The cells were suspended in media containing DEA/NO or SPER/NO for varying lengths of time under oxic or hypoxic conditions, irradiated, and the clonogenicity determined. Results: Both compounds markedly radiosensitized the hypoxic cells. The drug enhancement ratios (DER) for 0.1, 1.0, and 2.0 mM DEA/NO were 2.0, 2.3 and 3.0, respectively, and those for 0.1, 1.0, and 2.0 mM SPER/NO were 1.6, 2.3, and 2.8, respectively. Aerobic cells were not radiosensitized by DEA/NO or SPER/NO. When DEA/NO and SPER/NO were incubated in solution overnight to allow release of NO, they were found to have no radiosensitizing effect under hypoxic or oxic conditions indicating the sensitization by the NO donors was due to the NO molecule released from these drugs. At the higher concentrations, SPER/NO was found to be cytotoxic in aerobic conditions but not in hypoxic conditions. DEA/NO was only slightly toxic to the cells in both aerobic and hypoxic conditions. Conclusions: NO released from NO donors DEA/NO and SPER/NO is as effective as oxygen to radiosensitize hypoxic cells in vitro. Its application to the radiosensitization of hypoxic cells in solid tumors remains to be investigated

  14. Hypoxic conditioning as a new therapeutic modality

    Directory of Open Access Journals (Sweden)

    Samuel eVerges

    2015-06-01

    Full Text Available Preconditioning refers to a procedure by which a single noxious stimulus below the threshold of damage is applied to the tissue in order to increase resistance to the same or even different noxious stimuli given above the threshold of damage. Hypoxic preconditioning relies on complex and active defenses that organisms have developed to counter the adverse consequences of oxygen deprivation. The protection it confers against ischemic attack for instance as well as the underlying biological mechanisms have been extensively investigated in animal models. Based on these data, hypoxic conditioning (consisting in recurrent exposure to hypoxia has been suggested a potential non-pharmacological therapeutic intervention to enhance some physiological functions in individuals in whom acute or chronic pathological events are anticipated or existing. In addition to healthy subjects, some benefits have been reported in patients with cardiovascular and pulmonary diseases as well as in overweight and obese individuals. Hypoxic conditioning consisting in sessions of intermittent exposure to moderate hypoxia repeated over several weeks may induce hematological, vascular, metabolic and neurological effects. This review addresses the existing evidence regarding the use of hypoxic conditioning as a potential therapeutic modality and emphasizes on many remaining issues to clarify and future researches to be performed in the field.

  15. Perinatal Hypoxic-Ischemic brain injury; MR findings

    International Nuclear Information System (INIS)

    Park, Dong Woo; Seo, Chang Hye

    1994-01-01

    To characterize the MR findings of hypoxic-ischemic brain injury and to assess the value of the MR imaging. SE T1-, T2-weighted, and IR brain MR images of 44 infants and children with the past history of perinatal hypoxic insults were reviewed. Abnormal brain MR findings of 8 patients with birth history of prematurity and 36 patients with birth history of full-term/posterm including 7 with severe anoxic insult history, were compared in regard to the location and the character of the lesions. MRI demonstrated the followings; (1)abnormal signal intensity lesions of subcortical and/or deep cerebral white matter, cortex, and deep gray matter, (2)atrophy of the cerebral white matter, cortex and corpus callosum, with/without ventriculomegaly, and (3)delay in myelination. Periventricular and deep white matter lesions were demonstrated in the prematurity, the deep white matter lesions and/ or subcortical white matter lesions in the term/post-term, and deep gray matter lesions in the 7 patients with severe anoxic insults history. MR imaging was useful in the diagnosis of the hypoxic-ischemic brain injury, and the white and gray matter lesions were correlated with the time of the injury and the severity of hypoxic insult

  16. Respiratory muscle strength and muscle endurance are not affected by acute metabolic acidemia.

    NARCIS (Netherlands)

    Nizet, T.A.C.; Heijdra, Y.F.; Elshout, F.J.J. van den; Ven, M.J.T. van de; Bosch, F.H.; Mulder, P.H.M. de; Folgering, H.T.M.

    2009-01-01

    Respiratory muscle fatigue in asthma and chronic obstructive lung disease (COPD) contributes to respiratory failure with hypercapnia, and subsequent respiratory acidosis. Therapeutic induction of acute metabolic acidosis further increases the respiratory drive and, therefore, may diminish

  17. [Temporary disappearance of EEG activity during reversible respiratory failure in rabbits and cats].

    Science.gov (United States)

    Jurco, M; Tomori, Z; Tkácová, R; Calfa, J

    1989-02-01

    The dynamics of changes of EEG activity was studied on the model of reversible respiratory failure in rabbits and cats in pentobarbital anesthesia. During N2 inhalation, apnea of 60 second duration, and subsequent resuscitation the electrocorticogram in bifrontal and bioccipital connection was recorded. Evaluation of 19 episodes of apnea in 7 rabbits and of 25 episodes in 8 cats yielded the following results: 1. During hyperventilation induced by N2 inhalation a certain activation of the EEG was observed (spindles more pronounced, increased occurrence rate of discharges of the reticular activation system). 2. At the onset of apnea the EEG was still distinct, suggesting that primary apnea is presumably not caused by anoxia and the accompanying electric silence of the structures that control respiration. 3. Disappearance of EEG occurred within 50 seconds from the onset of apnea in rabbits and within 30 seconds in cats. 4. After repeated episodes of apnea lasting for 60 sec., artificial ventilation mostly resulted in normalization of EEG.

  18. Effect of noninvasive mechanical ventilation in elderly patients with hypercapnic acute-on-chronic respiratory failure and a do-not-intubate order

    Directory of Open Access Journals (Sweden)

    Paolo Scarpazza

    2008-10-01

    Full Text Available Paolo Scarpazza1, Cristoforo Incorvaia2, Giuseppe di Franco1, Stefania Raschi1, Pierfranco Usai1, Monica Bernareggi1, Cristiano Bonacina1, Chiara Melacini1, Silvia Vanni1, Serena Bencini1, Chiara Pravettoni2, Giuseppe Di Cara3, Mona-Rita Yacoub4, Gian Galeazzo Riario-Sforza2, Enrico Guffanti5, Walter Casali11Divisione di Broncopneumotisiologia, Ospedale Civile, Vimercate, Italy; 2Pulmonary rehabilitation, Istituti Clinici di Perfezionamento, Milan, Italy; 3University Department of Medical and Surgical Specialties and Public Health, Perugia, Italy; 4Allergy and Immunology Unit, IRCCS San Raffaele Hospital, Milan, Italy; 5Pulmonary rehabilitation, INRCA, Casatenovo, ItalyAbstract: Noninvasive mechanical ventilation (NIMV is effective in the treatment of patients with acute respiratory failure (ARF. It proved to reduce the need of endotracheal intubation (ETI, the incidence of ETI-associated pneumonia, and mortality compared to nonventilated patients. A particular aspect concerns the outcome of NIMV in patients referring to an emergency room (ER for ARF, and with a do-not-intubate (DNI status due to advanced age or critical conditions. The aim of our study is to assess the outcome of NIMV in a group of elderly patients with acute hypercapnic ARF who had a DNI status. An overall number of 62 subjects (30 males, 32 females, mean age 81 ± 4.8 years, range 79–91 years referred to our semi-intensive respiratory department were enrolled in the study. The underlying diseases were severe chronic obstructive pulmonary disease (COPD in 50/62 subjects, restrictive thoracic disorders in 7/62 subjects, and multiorgan failure in 5/62 subjects. Fifty-four/62 patients were successfully treated with NIMV while 2/62 did not respond to NIMV and were therefore submitted to ETI (one survived. Among NIMV-treated patients, death occurred in 6 patients after a mean of 9.9 days; the overall rate of NIMV failure was 12.9%. Negative prognostic factors for NIMV response

  19. Assessment of heart rate, acidosis, consciousness, oxygenation, and respiratory rate to predict noninvasive ventilation failure in hypoxemic patients.

    Science.gov (United States)

    Duan, Jun; Han, Xiaoli; Bai, Linfu; Zhou, Lintong; Huang, Shicong

    2017-02-01

    To develop and validate a scale using variables easily obtained at the bedside for prediction of failure of noninvasive ventilation (NIV) in hypoxemic patients. The test cohort comprised 449 patients with hypoxemia who were receiving NIV. This cohort was used to develop a scale that considers heart rate, acidosis, consciousness, oxygenation, and respiratory rate (referred to as the HACOR scale) to predict NIV failure, defined as need for intubation after NIV intervention. The highest possible score was 25 points. To validate the scale, a separate group of 358 hypoxemic patients were enrolled in the validation cohort. The failure rate of NIV was 47.8 and 39.4% in the test and validation cohorts, respectively. In the test cohort, patients with NIV failure had higher HACOR scores at initiation and after 1, 12, 24, and 48 h of NIV than those with successful NIV. At 1 h of NIV the area under the receiver operating characteristic curve was 0.88, showing good predictive power for NIV failure. Using 5 points as the cutoff value, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for NIV failure were 72.6, 90.2, 87.2, 78.1, and 81.8%, respectively. These results were confirmed in the validation cohort. Moreover, the diagnostic accuracy for NIV failure exceeded 80% in subgroups classified by diagnosis, age, or disease severity and also at 1, 12, 24, and 48 h of NIV. Among patients with NIV failure with a HACOR score of >5 at 1 h of NIV, hospital mortality was lower in those who received intubation at ≤12 h of NIV than in those intubated later [58/88 (66%) vs. 138/175 (79%); p = 0.03). The HACOR scale variables are easily obtained at the bedside. The scale appears to be an effective way of predicting NIV failure in hypoxemic patients. Early intubation in high-risk patients may reduce hospital mortality.

  20. Postnatal morphology of hematoencephalic barrier in hypoxic lesion

    Directory of Open Access Journals (Sweden)

    E. V. Kikhtenko

    2012-12-01

    Full Text Available In infants with perinatal hypoxic lesion of the central nervous system swelling and death of the endothelium, thickening of the capillary basement membranes, karyorrhexis and plasmorrhexis of astrocytes are observed. The severity and degree of pathological changes depends on the time of hypoxic exposure (antenatal or intrapartum period and the term of postnatal life.

  1. Satellite-based empirical models linking river plume dynamics with hypoxic area andvolume

    Science.gov (United States)

    Satellite-based empirical models explaining hypoxic area and volume variation were developed for the seasonally hypoxic (O2 < 2 mg L−1) northern Gulf of Mexico adjacent to the Mississippi River. Annual variations in midsummer hypoxic area and ...

  2. Adult respiratory distress syndrome

    International Nuclear Information System (INIS)

    Murphy, C.H.; Colvin, R.S.

    1987-01-01

    Due to improved emergency resuscitation procedures, and with advancing medical technology in the field of critical care, an increasing number of patients survive the acute phase of shock and catastrophic trauma. Patients who previously died of massive sepsis, hypovolemic or hypotensive shock, multiple fractures, aspiration, toxic inhalation, and massive embolism are now surviving long enough to develop previously unsuspected and unrecognized secondary effects. With increasing frequency, clinicians are recognizing the clinical and radiographic manifestations of pathologic changes in the lungs occurring secondary to various types of massive insult. This paper gives a list of diseases that have been shown to precipitate or predispose to diffuse lung damage. Various terms have been used to describe the lung damage and respiratory failure secondary to these conditions. The term adult respiratory distress syndrome (ARDS) is applied to several cases of sudden respiratory failure in patients with previously healthy lungs following various types of trauma or shock. Numerous investigations and experiments have studied the pathologic changes in ARDS, and, while there is still no clear indication of why it develops, there is now some correlation of the sequential pathologic developments with the clinical and radiographic changes

  3. Using the prone position for ventilated patients with respiratory failure: a review.

    Science.gov (United States)

    Wright, Angie D; Flynn, Maria

    2011-01-01

    this review explored the evidence relating to prone positioning in ventilated patients diagnosed with respiratory failure, including acute lung injury (ALI) or adult respiratory distress syndrome (ARDS). mortality rates for ventilated patients with ALI or ARDS are high, and there is a growing body of evidence suggesting that the position these patients are nursed in may influence clinical outcomes. However, there are no guidelines to inform nursing practice in positioning these patients. Medline, Scopus, Cinahl and the Cochrane Library databases were searched for original research reports or systematic reviews of evidence between 2000 and 2009. Reference lists of retrieved papers were hand searched and included studies were analysed using the Critical Appraisal and Skills Programme framework. A narrative data synthesis considered the strengths and limitations of studies, and findings were collated and interpreted. Application of the search strategy identified a systematic review, currently underway, which has not yet reported and 14 relevant studies eligible for inclusion in this review. Analysis showed considerable variation in study design, but suggests that PaO(2) /FiO(2) ratio, incidence of VAP and mortality may be positively affected by prone positioning. evidence of the clinical benefits associated with prone positioning is inconclusive and provides little guidance for nursing practice. There is a need for further research into the clinical outcomes of prone positioning, and greater understanding of the practicalities of prone positioning critically ill patients is required. nurses have a central role to play in the continual assessment and management of this patient group, including the position they are nursed in, not only to ensure the best clinical outcomes but also to provide care and comfort to the patient and their family. It is therefore important that their nursing practice and interventions are informed by the best available evidence.

  4. The Use of Benzodiazepine Receptor Agonists and Risk of Respiratory Failure in Patients with Chronic Obstructive Pulmonary Disease: A Nationwide Population-Based Case-Control Study

    Science.gov (United States)

    Chen, Su-Jung; Yeh, Chiu-Mei; Chao, Tze-Fan; Liu, Chia-Jen; Wang, Kang-Ling; Chen, Tzeng-Ji; Chou, Pesus; Wang, Fu-Der

    2015-01-01

    Study Objectives: Insomnia is prevalent in patients with chronic obstructive pulmonary disease (COPD), and benzodiazepine receptor agonists (BZRAs) are the most commonly used drugs despite their adverse effects on respiratory function. The aim of this study was to investigate whether the use of BZRAs was associated with an increased risk of respiratory failure (RF) in COPD patients. Design: Matched case-control study. Setting: National Health Insurance Research Database (NHIRD) in Taiwan. Participants: The case group consisted of 2,434 COPD patients with RF, and the control group consisted of 2,434 COPD patients without RF, matched for age, sex, and date of enrollment. Measurements and Results: Exposure to BZRAs during the 180-day period preceding the index date was analyzed and compared in the case and control groups. Conditional logistic regression was performed, and the use of BZRAs was associated with an increased risk of RF (adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.14–2.13). In subgroup analysis, we found that the benzodiazepine (BZD) users had a higher risk of RF (aOR 1.58, 95% CI 1.14–2.20), whereas the risk in non-benzodiazepine (non-BZD) users was insignificant (aOR 0.85, 95% CI 0.51–1.44). A greater than 2-fold increase in risk was found in those who received two or more kinds of BZRAs and those using a combination of BZD and non-BZD medications. Conclusions: The use of benzodiazepine receptor agonists was a significant risk factor for respiratory failure in patients with chronic obstructive pulmonary disease (COPD). Compared to benzodiazepine, the prescription of non-benzodiazepine may be safer for the management of insomnia in COPD patients. Citation: Chen SJ, Yeh CM, Chao TF, Liu CJ, Wang KL, Chen TJ, Chou P, Wang FD. The use of benzodiazepine receptor agonists and risk of respiratory failure in patients with chronic obstructive pulmonary disease: a nationwide population-based case-control study. SLEEP 2015;38(7):1045–1050

  5. [3H]-nitrendipine binding in membranes obtained from hypoxic and reoxygenated heart.

    Science.gov (United States)

    Matucci, R; Bennardini, F; Sciammarella, M L; Baccaro, C; Stendardi, I; Franconi, F; Giotti, A

    1987-04-01

    We compared the binding properties of [3H]-nitrendipine in heart membranes from normal guinea-pig heart and from hypoxic or hypoxic and reoxygenated heart. The [3H]-nitrendipine binds a single class of high capacity (Bmax 667.2 +/- 105.2) with high affinity (KD 0.14 +/- 0.02) binding sites. By contrast, in membranes of hypoxic and reoxygenated heart the Bmax decreases significantly while it remains unaffected during hypoxia. Xanthinoxidase activity is increased in hypoxic-reoxygenated hearts.

  6. Potentially three distinct roles for hypoxic cell sensitizers in the clinic

    International Nuclear Information System (INIS)

    Chapman, J.D.; Raleigh, J.A.; Pedersen, J.E.; Ngan, J.; Shum, F.Y.

    1979-01-01

    Nitroaromatic drugs have been applied to radiation therapy on the basis of their effectiveness to enhance radiation damages selectively in hypoxic mammalian cells at nontoxic concentration. Such sensitizers could improve the rate of local tumor control by conventional radiotherapy in such cases that the resistance due to hypoxia in a limiting factor. The selective cytotoxicity of the drug to hypoxic cells is the second distinct action. A third potential role for nitroaromatic drugs could involve their use for the diagnosis of the number and location of hypoxic cells within tumors. The gain in therapeutic ratio by a factor from 5 to 10 is necessary before the full clinical impact of hypoxic cell radiosensitizers can be evaluated. The drugs selected for the use as clinical radiosensitizers were originally developed as the antibacterial agents with selective activity against anaerobes. The hypoxic cells in tumors are usually resistant to chemotherapy as well as resistant to radiation, and this specific drug action of sensitizers combined with that of an agent effective against oxygenated and cycling cells could possibly produce improved tumor cures. Electron-affinitive chemicals become selectively bound to the macromolecules of hypoxic mammalian cells by radiation-induced chemical reaction. This technique was used to identify by autoradiographic procedures the location of the radioactive nitrofurazone bound to hypoxic cells within multicellular spheroids. (Yamashita, S.)

  7. State of the art. Neonatal respiratory failure.

    Science.gov (United States)

    Parker, L A

    1999-12-01

    Advances in ventilatory management of respiratory distress in the newborn have made dramatic strides during the last decade. Innovative treatments such as PTV, HFV, liquid ventilation, and NO therapy are just beginning to have an impact on the care of neonates in the NICU. These treatment modalities should continue to have an effect on the care of the newborn infant well into the future.

  8. Palytoxin-induced acute respiratory failure

    Directory of Open Access Journals (Sweden)

    Lokendra K. Thakur

    2017-01-01

    Full Text Available Palytoxin is one of the most potent toxins known to mankind and poses a high risk to humans through ingestion, inhalation and dermal routes [1,2]. Although the exact mechanism of action is unknown it is postulated that palytoxin binds to the Na+/K + ATPase pump resulting in K+ efflux, Ca2+ influx and membrane depolarization leading to widespread secondary pharmacological actions [2]. Palytoxin is highly toxic and can affect multiple organs causing severe symptoms including death. Palytoxin poisoning is mainly developed after ingesting seafood. We are reporting a case of suspected inhalational palytoxin poisoning in a healthy healthcare provider from who developed severe respiratory distress within 12 hours of exposure to vapors. We have highlighted diagnostic clues and clinical features in the patients' history that may help intensivists to diagnose a case of ARDS secondary to palytoxin poisoning.

  9. Priming of the Cells: Hypoxic Preconditioning for Stem Cell Therapy.

    Science.gov (United States)

    Wei, Zheng Z; Zhu, Yan-Bing; Zhang, James Y; McCrary, Myles R; Wang, Song; Zhang, Yong-Bo; Yu, Shan-Ping; Wei, Ling

    2017-10-05

    Stem cell-based therapies are promising in regenerative medicine for protecting and repairing damaged brain tissues after injury or in the context of chronic diseases. Hypoxia can induce physiological and pathological responses. A hypoxic insult might act as a double-edged sword, it induces cell death and brain damage, but on the other hand, sublethal hypoxia can trigger an adaptation response called hypoxic preconditioning or hypoxic tolerance that is of immense importance for the survival of cells and tissues. This review was based on articles published in PubMed databases up to August 16, 2017, with the following keywords: "stem cells," "hypoxic preconditioning," "ischemic preconditioning," and "cell transplantation." Original articles and critical reviews on the topics were selected. Hypoxic preconditioning has been investigated as a primary endogenous protective mechanism and possible treatment against ischemic injuries. Many cellular and molecular mechanisms underlying the protective effects of hypoxic preconditioning have been identified. In cell transplantation therapy, hypoxic pretreatment of stem cells and neural progenitors markedly increases the survival and regenerative capabilities of these cells in the host environment, leading to enhanced therapeutic effects in various disease models. Regenerative treatments can mobilize endogenous stem cells for neurogenesis and angiogenesis in the adult brain. Furthermore, transplantation of stem cells/neural progenitors achieves therapeutic benefits via cell replacement and/or increased trophic support. Combinatorial approaches of cell-based therapy with additional strategies such as neuroprotective protocols, anti-inflammatory treatment, and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the recent progress regarding cell types and applications in regenerative medicine as well as future applications.

  10. Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung

    LENUS (Irish Health Repository)

    Sands, Michelle

    2011-01-25

    Abstract Background Chronic alveolar hypoxia, due to residence at high altitude or chronic obstructive lung diseases, leads to pulmonary hypertension, which may be further complicated by right heart failure, increasing morbidity and mortality. In the non-diseased lung, angiogenesis occurs in chronic hypoxia and may act in a protective, adaptive manner. To date, little is known about the behaviour of individual vascular endothelial growth factor (VEGF) family ligands in hypoxia-induced pulmonary angiogenesis. The aim of this study was to examine the expression of placenta growth factor (PlGF) and VEGFB during the development of hypoxic pulmonary angiogenesis and their functional effects on the pulmonary endothelium. Methods Male Sprague Dawley rats were exposed to conditions of normoxia (21% O2) or hypoxia (10% O2) for 1-21 days. Stereological analysis of vascular structure, real-time PCR analysis of vascular endothelial growth factor A (VEGFA), VEGFB, placenta growth factor (PlGF), VEGF receptor 1 (VEGFR1) and VEGFR2, immunohistochemistry and western blots were completed. The effects of VEGF ligands on human pulmonary microvascular endothelial cells were determined using a wound-healing assay. Results Typical vascular remodelling and angiogenesis were observed in the hypoxic lung. PlGF and VEGFB mRNA expression were significantly increased in the hypoxic lung. Immunohistochemical analysis showed reduced expression of VEGFB protein in hypoxia although PlGF protein was unchanged. The expression of VEGFA mRNA and protein was unchanged. In vitro PlGF at high concentration mimicked the wound-healing actions of VEGFA on pulmonary microvascular endothelial monolayers. Low concentrations of PlGF potentiated the wound-healing actions of VEGFA while higher concentrations of PlGF were without this effect. VEGFB inhibited the wound-healing actions of VEGFA while VEGFB and PlGF together were mutually antagonistic. Conclusions VEGFB and PlGF can either inhibit or potentiate the

  11. microRNA regulation of the embryonic hypoxic response in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Kagias, Konstantinos; Pocock, Roger

    2015-01-01

    Layered strategies to combat hypoxia provide flexibility in dynamic oxygen environments. Here we show that multiple miRNAs are required for hypoxic survival responses during C. elegans embryogenesis. Certain miRNAs promote while others antagonize the hypoxic survival response. We found...... of the full mRNA target repertoire of these miRNAs will reveal the miRNA-regulated network of hypoxic survival mechanisms in C. elegans....

  12. Hypoxic contraction of cultured pulmonary vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Murray, T.R.; Chen, L.; Marshall, B.E.; Macarak, E.J.

    1990-01-01

    The cellular events involved in generating the hypoxic pulmonary vasoconstriction response are not clearly understood, in part because of the multitude of factors that alter pulmonary vascular tone. The goal of the present studies was to determine if a cell culture preparation containing vascular smooth muscle (VSM) cells could be made to contract when exposed to a hypoxic atmosphere. Cultures containing only fetal bovine pulmonary artery VSM cells were assessed for contractile responses to hypoxic stimuli by two methods. In the first, tension forces generated by cells grown on a flexible growth surface (polymerized polydimethyl siloxane) were manifested as wrinkles and distortions of the surface under the cells. Wrinkling of the surface was noted to progressively increase with time as the culture medium bathing the cells was made hypoxic (PO2 approximately 25 mmHg). The changes were sometimes reversible upon return to normoxic conditions and appeared to be enhanced in cells already exhibiting evidence of some baseline tone. Repeated passage in culture did not diminish the hypoxic response. Evidence for contractile responses to hypoxia was also obtained from measurements of myosin light chain (MLC) phosphorylation. Conversion of MLC to the phosphorylated species is an early step in the activation of smooth muscle contraction. Lowering the PO2 in the culture medium to 59 mmHg caused a 45% increase in the proportion of MLC in the phosphorylated form as determined by two-dimensional gel electrophoresis. Similarly, cultures preincubated for 4 h with 32P and then exposed to normoxia or hypoxia for a 5-min experimental period showed more than twice as much of the label in MLCs of the hypoxic cells

  13. Presentation of Neuromyelitis Optica with Recurrent Severe Myelitis and Acute Respiratory Failure in an Old Woman

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    Saeed Razmeh

    2017-06-01

    Full Text Available Neuromyelitis Optica (NMO is a rare disease of the central nervous system that causes optic nerve and spinal cord involvement. The our patient first developed acute paraplegia that was treated with intravenous methylprednisolone with diagnosis of acute thoracic myelitis according to magnetic resonance imaging (MRI finding , concurrently with tapering of oral prednisolone, again affected by quadriplegia and respiratory failure. She was seropositivity for NMO-IgG that was negative in first admission and MRI of spine shows hyperintense lesion in whole cervical and upper thoracic MRI. With considering the findings, NMO was diagnosed and the plasmapheresis starts for her. We report a case of this syndrome because it can increase the physician’s awareness of the unusual manifestations of this syndrome.

  14. Acute Respiratory Failure Induced by Magnesium Replacement in a 62-Year-Old Woman with Myasthenia Gravis.

    Science.gov (United States)

    Singh, Paramveer; Idowu, Olakunle; Malik, Imrana; Nates, Joseph L

    2015-10-01

    Magnesium is known to act at the neuromuscular junction by inhibiting the presynaptic release of acetylcholine and desensitizing the postsynaptic membrane. Because of these effects, magnesium has been postulated to potentiate neuromuscular weakness. We describe the case of a 62-year-old woman with myasthenia gravis and a metastatic thymoma who was admitted to our intensive care unit for management of a myasthenic crisis. The patient's neuromuscular weakness worsened in association with standard intravenous magnesium replacement, and the exacerbated respiratory failure necessitated intubation, mechanical ventilation, and an extended stay in the intensive care unit. The effect of magnesium replacement on myasthenia gravis patients has not been well documented, and we present this case to increase awareness and stimulate research. In addition, we discuss the relevant medical literature.

  15. [Sleep apnea and heart failure: pathophysiology, diagnosis and therapy].

    Science.gov (United States)

    Monda, Cinzia; Scala, Oriana; Paolillo, Stefania; Savarese, Gianluigi; Cecere, Milena; D'Amore, Carmen; Parente, Antonio; Musella, Francesca; Mosca, Susanna; Filardi, Pasquale Perrone

    2010-11-01

    Sleep apnea, defined as a pathologic pause in breathing during sleep >10 s, promotes the progression of chronic heart failure and may be a predictor of poor prognosis. It causes, in fact, several mechanical, hemodynamic, chemical and inflammatory changes that negatively compromise cardiovascular homeostasis of heart failure patients. Sleep apnea is recognized as sleep apnea syndrome when specific symptoms, such as sleepiness and headache during the daytime and snoring, are present and is diagnosed with an overnight test called polysomnography. There are two different forms of sleep apnea, central and obstructive. Breathing is interrupted by the loss of respiratory drive and the lack of respiratory effort in the central form, which affects about 40-60% of heart failure patients. In obstructive sleep apnea, breathing stops when throat muscles relax, despite respiratory effort. This form affects about 3% of the general population, while it is present in at least 30% of heart failure patients. The diagnosis of sleep disorders in heart failure becomes very important to help patients adopting lifestyle changes and starting specific therapies to improve quality of life and retard the progression of chronic heart failure.

  16. Acute renal failure: Nephrosonographic findings in asphyxiated neonates

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    Mohd. Ashraf

    2011-01-01

    Full Text Available To determine the incidence of acute renal failure (ARF and nephrosonographic findings among asphyxiated neonates, and to correlate this with uric acid levels and the severity of hypoxic encephalopathy, we studied 80 full-term appropriate-for-date singleton neonates with perinatal asphyxia, and 30 healthy full-term neonates as controls from March 2006 to February 2007. A detailed history, thorough clinical examination along with investigations, including urine examination, 24-h urine collection, ultrasonography of abdomen and cranium, serum electrolytes, blood urea nitrogen, serum creatinine, and serum uric acid were obtained. ARF developed in 45% (36/80 of the asphyxiated neonates. Forty-eight (60% neonates showed significant elevation of blood urea and 41 (51.3% neonates had significant elevation of serum creatinine than the control group (P < 0.001. Sixty-two (77.5% neonates developed significant elevation of serum uric acid levels, and nephrosonography revealed hyperechogenicity in all of them, while only two among the healthy neonates showed the raised uric acid levels (P < 0.001. Nonoliguric renal failure was seen 28/36 (77.8% of the neonates with ARF, whereas eight (22.2% neonates had oliguric renal failure. Eight (27.8% patients among ARF patients maintained abnormal biochemical parameters after 2 weeks, and of whom four patients died after variable lengths of time with a mortality rate of 11.11%. Kidneys are the most common organs involved in perinatal asphyxia, and uric acid might be a causative factor for failure in addition to hypoxic insult. Routine use of kidney function test, along with abdominal ultrasonography form an important screening tool to detect any additional morbidity in these patients.

  17. The lifetime of hypoxic human tumor cells

    International Nuclear Information System (INIS)

    Durand, Ralph E.; Sham, Edward

    1998-01-01

    Purpose: For hypoxic and anoxic cells in solid tumors to be a therapeutic problem, they must live long enough to be therapeutically relevant, or else be rapidly recruited into the proliferating compartment during therapy. We have, therefore, estimated lifetime and recruitment rate of hypoxic human tumor cells in multicell spheroids in vitro, or in xenografted tumors in SCID mice. Materials and Methods: Cell turnover was followed by flow cytometry techniques, using antibodies directed at incorporated halogenated pyrimidines. The disappearance of labeled cells was quantified, and verified to be cell loss rather than label dilution. Repopulation was studied in SiHa tumor xenografts during twice-daily 2.5-Gy radiation exposures. Results: The longevity of hypoxic human tumor cells in spheroids or xenografts exceeded that of rodent cell lines, and cell turnover was slower in xenografts than under static growth as spheroids. Human tumor cells remained viable in the hypoxic regions of xenografts for 4-10 days, compared to 3-5 days in spheroids, and 1-3 days for most rodent cells in spheroids. Repopulation was observed within the first few radiation treatments for the SiHa xenografts and, with accumulated doses of more than 10 Gy, virtually all recovered cells had progressed through at least one S-phase. Conclusion: Our results suggest an important difference in the ability of human vs. rodent tumor cells to withstand hypoxia, and raise questions concerning the increased longevity seen in vivo relative to the steady-state spheroid system

  18. Hypoxic tumor environments exhibit disrupted collagen I fibers and low macromolecular transport.

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    Samata M Kakkad

    Full Text Available Hypoxic tumor microenvironments result in an aggressive phenotype and resistance to therapy that lead to tumor progression, recurrence, and metastasis. While poor vascularization and the resultant inadequate drug delivery are known to contribute to drug resistance, the effect of hypoxia on molecular transport through the interstitium, and the role of the extracellular matrix (ECM in mediating this transport are unexplored. The dense mesh of fibers present in the ECM can especially influence the movement of macromolecules. Collagen 1 (Col1 fibers form a key component of the ECM in breast cancers. Here we characterized the influence of hypoxia on macromolecular transport in tumors, and the role of Col1 fibers in mediating this transport using an MDA-MB-231 breast cancer xenograft model engineered to express red fluorescent protein under hypoxia. Magnetic resonance imaging of macromolecular transport was combined with second harmonic generation microscopy of Col1 fibers. Hypoxic tumor regions displayed significantly decreased Col1 fiber density and volume, as well as significantly lower macromolecular draining and pooling rates, than normoxic regions. Regions adjacent to severely hypoxic areas revealed higher deposition of Col1 fibers and increased macromolecular transport. These data suggest that Col1 fibers may facilitate macromolecular transport in tumors, and their reduction in hypoxic regions may reduce this transport. Decreased macromolecular transport in hypoxic regions may also contribute to poor drug delivery and tumor recurrence in hypoxic regions. High Col1 fiber density observed around hypoxic regions may facilitate the escape of aggressive cancer cells from hypoxic regions.

  19. Maternal and Fetal Recovery After Severe Respiratory Failure: A Case Report of Air Transportation of a Pregnant Woman on ECMO Using the CentriMag Transporter System.

    Science.gov (United States)

    Kaliyev, Rymbay; Kapyshev, Timur; Goncharov, Alex; Lesbekov, Timur; Pya, Yuri

    2015-01-01

    Use of extracorporeal membrane oxygenation (ECMO) for severe cardiopulmonary failure has increased because of improved outcomes. A specially designed ECMO transport system allows for safe transport of patients over long distances. We report a 28-year-old pregnant woman (26 weeks gestation) with acute respiratory distress syndrome in whom ECMO support was necessary for survival, and she was transported to another facility 1,155 km away with the aid of the portable ECMO system. Transport was uneventful, and the patient's condition remained stable. Acute respiratory distress syndrome improved gradually until the patient was discharged from the hospital with excellent maternal and fetal outcome.

  20. SUMO Signaling by Hypoxic Inactivation of SUMO-Specific Isopeptidases

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    Kathrin Kunz

    2016-09-01

    Full Text Available Post-translational modification of proteins with ubiquitin-like SUMO modifiers is a tightly regulated and highly dynamic process. The SENP family of SUMO-specific isopeptidases comprises six cysteine proteases. They are instrumental in counterbalancing SUMO conjugation, but their regulation is not well understood. We demonstrate that in hypoxic cell extracts, the catalytic activity of SENP family members, in particular SENP1 and SENP3, is inhibited in a rapid and fully reversible process. Comparative mass spectrometry from normoxic and hypoxic cells defines a subset of hypoxia-induced SUMO1 targets, including SUMO ligases RanBP2 and PIAS2, glucose transporter 1, and transcriptional regulators. Among the most strongly induced targets, we identified the transcriptional co-repressor BHLHE40, which controls hypoxic gene expression programs. We provide evidence that SUMOylation of BHLHE40 is reversed by SENP1 and contributes to transcriptional repression of the metabolic master regulator gene PGC-1α. We propose a pathway that connects oxygen-controlled SENP activity to hypoxic reprogramming of metabolism.

  1. Prolonged lateral steep position impairs respiratory mechanics during continuous lateral rotation therapy in respiratory failure.

    Science.gov (United States)

    Schellongowski, Peter; Losert, Heidrun; Locker, Gottfried J; Laczika, Klaus; Frass, Michael; Holzinger, Ulrike; Bojic, Andja; Staudinger, Thomas

    2007-04-01

    To establish whether prolonged lateral steep position during continuous rotation therapy leads to improvement on pulmonary gas exchange, respiratory mechanics and hemodynamics. Prospective observational study. Intensive care unit of a university hospital. Twelve consecutive patients suffering from acute lung injury or adult respiratory distress syndrome undergoing continuous rotation therapy. Blood gas analysis, static lung compliance, blood pressure, cardiac index and pulmonary shunt fraction were measured in supine as well as in left and right lateral steep position at 62 degrees during continuous rotation therapy (phase I). Rotation was then stopped for 30 min with the patients in supine position, left and right lateral steep position, and the same measurements were performed every 10 min (phase II). Phase I and II revealed no significant changes in PaO(2)/FiO(2) ratio, mean arterial blood pressure, pulmonary shunt fraction, or cardiac index. Significantly lower static compliance was observed in lateral steep position than in supine position (pposition than in left and right lateral steep position (ppositioning impairs the compliance of the respiratory system. Prolonged lateral steep position does not lead to benefits with respect to oxygenation or hemodynamics. Individual response to the different positions is unpredictable. The pauses in "extreme" positions should be as short as possible.

  2. Anemia and performance status as prognostic markers in acute hypercapnic respiratory failure due to chronic obstructive pulmonary disease

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    Haja Mydin H

    2013-03-01

    Full Text Available Helmy Haja Mydin, Stephen Murphy, Howell Clague, Kishore Sridharan, Ian K TaylorDepartment of Respiratory Medicine, Sunderland Royal Infirmary, Sunderland, United KingdomBackground: In patients with acute hypercapnic respiratory failure (AHRF during exacerbations of COPD, mortality can be high despite noninvasive ventilation (NIV. For some, AHRF is terminal and NIV is inappropriate. However there is no definitive method of identifying patients who are unlikely to survive. The aim of this study was to identify factors associated with inpatient mortality from AHRF with respiratory acidosis due to COPD.Methods: COPD patients presenting with AHRF and who were treated with NIV were studied prospectively. The forced expiratory volume in 1 second (FEV1, World Health Organization performance status (WHO-PS, clinical observations, a composite physiological score (Early Warning Score, routine hematology and biochemistry, and arterial blood gases prior to commencing NIV, were recorded.Results: In total, 65 patients were included for study, 29 males and 36 females, with a mean age of 71 ± 10.5 years. Inpatient mortality in the group was 33.8%. Mortality at 30 days and 12 months after admission were 38.5% and 58.5%, respectively. On univariate analysis, the variables associated with inpatient death were: WHO-PS ≥ 3, long-term oxygen therapy, anemia, diastolic blood pressure < 70 mmHg, Early Warning Score ≥ 3, severe acidosis (pH < 7.20, and serum albumin < 35 g/L. On multivariate analysis, only anemia and WHO-PS ≥ 3 were significant. The presence of both predicted 68% of inpatient deaths, with a specificity of 98%.Conclusion: WHO-PS ≥ 3 and anemia are prognostic factors in AHRF with respiratory acidosis due to COPD. A combination of the two provides a simple method of identifying patients unlikely to benefit from NIV.Keywords: acute exacerbations of COPD, noninvasive ventilation, emphysema, prognostic markers

  3. Hypoxic stress induces, but cannot sustain trophoblast stem cell differentiation to labyrinthine placenta due to mitochondrial insufficiency

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    Yufen Xie

    2014-11-01

    Full Text Available Dysfunctional stem cell differentiation into placental lineages is associated with gestational diseases. Of the differentiated lineages available to trophoblast stem cells (TSC, elevated O2 and mitochondrial function are necessary to placental lineages at the maternal–placental surface and important in the etiology of preeclampsia. TSC lineage imbalance leads to embryonic failure during uterine implantation. Stress at implantation exacerbates stem cell depletion by decreasing proliferation and increasing differentiation. In an implantation site O2 is normally ~2%. In culture, exposure to 2% O2 and fibroblast growth factor 4 (FGF4 enabled the highest mouse TSC multipotency and proliferation. In contrast, hypoxic stress (0.5% O2 initiated the most TSC differentiation after 24 h despite exposure to FGF4. However, hypoxic stress supported differentiation poorly after 4–7 days, despite FGF4 removal. At all tested O2 levels, FGF4 maintained Warburg metabolism; mitochondrial inactivity and aerobic glycolysis. However, hypoxic stress suppressed mitochondrial membrane potential and maintained low mitochondrial cytochrome c oxidase (oxidative phosphorylation/OxPhos, and high pyruvate kinase M2 (glycolysis despite FGF4 removal. Inhibiting OxPhos inhibited optimum differentiation at 20% O2. Moreover, adding differentiation-inducing hyperosmolar stress failed to induce differentiation during hypoxia. Thus, differentiation depended on OxPhos at 20% O2; hypoxic and hyperosmolar stresses did not induce differentiation at 0.5% O2. Hypoxia-limited differentiation and mitochondrial inhibition and activation suggest that differentiation into two lineages of the labyrinthine placenta requires O2 > 0.5–2% and mitochondrial function. Stress-activated protein kinase increases an early lineage and suppresses later lineages in proportion to the deviation from optimal O2 for multipotency, thus it is the first enzyme reported to prioritize differentiation.

  4. Gold nanoparticle cellular uptake, toxicity and radiosensitisation in hypoxic conditions

    International Nuclear Information System (INIS)

    Jain, Suneil; Coulter, Jonathan A.; Butterworth, Karl T.; Hounsell, Alan R.; McMahon, Stephen J.; Hyland, Wendy B.; Muir, Mark F.; Dickson, Glenn R.; Prise, Kevin M.; Currell, Fred J.; Hirst, David G.; O’Sullivan, Joe M.

    2014-01-01

    Background and purpose: Gold nanoparticles (GNPs) are novel agents that have been shown to cause radiosensitisation in vitro and in vivo. Tumour hypoxia is associated with radiation resistance and reduced survival in cancer patients. The interaction of GNPs with cells in hypoxia is explored. Materials and methods: GNP uptake, localization, toxicity and radiosensitisation were assessed in vitro under oxic and hypoxic conditions. Results: GNP cellular uptake was significantly lower under hypoxic than oxic conditions. A significant reduction in cell proliferation in hypoxic MDA-MB-231 breast cancer cells exposed to GNPs was observed. In these cells significant radiosensitisation occurred in normoxia and moderate hypoxia. However, in near anoxia no significant sensitisation occurred. Conclusions: GNP uptake occurred in hypoxic conditions, causing radiosensitisation in moderate, but not extreme hypoxia in a breast cancer cell line. These findings may be important for the development of GNPs for cancer therapy

  5. A scenario and forecast model for Gulf of Mexico hypoxic area and volume

    Science.gov (United States)

    Scavia, Donald; Evans, Mary Anne; Obenour, Daniel R.

    2013-01-01

    For almost three decades, the relative size of the hypoxic region on the Louisiana-Texas continental shelf has drawn scientific and policy attention. During that time, both simple and complex models have been used to explore hypoxia dynamics and to provide management guidance relating the size of the hypoxic zone to key drivers. Throughout much of that development, analyses had to accommodate an apparent change in hypoxic sensitivity to loads and often cull observations due to anomalous meteorological conditions. Here, we describe an adaptation of our earlier, simple biophysical model, calibrated to revised hypoxic area estimates and new hypoxic volume estimates through Bayesian estimation. This application eliminates the need to cull observations and provides revised hypoxic extent estimates with uncertainties, corresponding to different nutrient loading reduction scenarios. We compare guidance from this model application, suggesting an approximately 62% nutrient loading reduction is required to reduce Gulf hypoxia to the Action Plan goal of 5,000 km2, to that of previous applications. In addition, we describe for the first time, the corresponding response of hypoxic volume. We also analyze model results to test for increasing system sensitivity to hypoxia formation, but find no strong evidence of such change.

  6. Sex-specific effects of daily gavage with a mixed progesterone and glucocorticoid receptor antagonist on hypoxic ventilatory response in newborn rats.

    Science.gov (United States)

    Fournier, Stéphanie; Doan, Van Diep; Joseph, Vincent

    2012-01-01

    We tested the hypothesis that daily gavage with mifepristone, a mixed progesterone/glucocorticoid receptor antagonist would alter hypoxic ventilatory response (HVR) in newborn male and female rats. Rats were treated with mifepristone (40µg/g/day), or vehicle between postnatal days 3-12, and used at 10-12 days of age to record baseline ventilatory and metabolic values using whole body plethysmography. HVR was tested by exposing the animals to 14% and 12% O(2) for 20 minutes each. HVR was enhanced by mifepristone treatment, mainly due to an effect on tidal volume that remained higher in mifepristone treated rats during both levels of hypoxic exposure. This effect was sex-specific being apparent only in male rats. In Vehicle treated rats, HVR was higher in females than in males, which was also due to a higher tidal volume in hypoxia (at 14 and 12% O(2)). We conclude that the activity of the progesterone and/or glucocorticoid receptors modulates respiratory control in rat pups, and that these effects are different in males and females.

  7. Predictive value of daily living score in acute respiratory failure of COPD patients requiring invasive mechanical ventilation pilot study.

    Science.gov (United States)

    Langlet, Ketty; Van Der Linden, Thierry; Launois, Claire; Fourdin, Caroline; Cabaret, Philippe; Kerkeni, Nadia; Barbe, Coralie; Lebargy, François; Deslée, Gaetan

    2012-10-18

    Mechanical ventilation (MV) is imperative in many forms of acute respiratory failure (ARF) in COPD patients. Previous studies have shown the difficulty to identify parameters predicting the outcome of COPD patients treated by invasive MV. Our hypothesis was that a non specialized score as the activities daily living (ADL) score may help to predict the outcome of these patients. We studied the outcome of 25 COPD patients admitted to the intensive care unit for ARF requiring invasive MV. The patients were divided into those weaning success (group A n = 17, 68%) or failure (group B n = 8, 32%). We investigated the correlation between the ADL score and the outcome and mortality. The ADL score was higher in group A (5.1 ±1.1 vs 3.7 ± 0.7 in group B, p success and mortality at 6 months, suggesting that the assessment of daily activities should be an important component of ARF management in COPD patients.

  8. Hypoxic fraction and binding of misonidazole in EMT6/Ed multicellular tumor spheroids

    International Nuclear Information System (INIS)

    Franko, A.J.

    1985-01-01

    Misonidazole has been shown to bind selectively to hypoxic cells in tissue culture and to cells which are presumed to be chronically hypoxic in EMT6 spheroids and tumors. Thus it has considerable potential as a marker of hypoxic cells in vivo. To further evaluate this potential EMT6/Ed spheroids were used to quantitate misonidazole binding under conditions which resulted in hypoxic fractions between 0 and 1. The patterns of binding of 14 C-labeled misonidazole determined by autoradiography were consistent with the regions of radiobiological hypoxia as predicted by oxygen diffusion theory. The overall uptake of 3 H-labeled misonidazole by spheroids correlated well with the hypoxic fraction, although binding to aerobic cells and necrotic tissue contributed appreciably to the total label in the spheroids. It is concluded that misonidazole is an excellent marker of hypoxia in EMT6/Ed spheroids at the microscopic level, and the total amount bound per spheroid provides a potentially useful measure of the hypoxic fraction

  9. Hypoxic training increases maximal oxygen consumption in Thoroughbred horses well-trained in normoxia.

    Science.gov (United States)

    Ohmura, Hajime; Mukai, Kazutaka; Takahashi, Yuji; Takahashi, Toshiyuki; Jones, James H

    2017-01-01

    Hypoxic training is effective for improving athletic performance in humans. It increases maximal oxygen consumption (V̇O 2 max) more than normoxic training in untrained horses. However, the effects of hypoxic training on well-trained horses are unclear. We measured the effects of hypoxic training on V̇O 2 max of 5 well-trained horses in which V̇O 2 max had not increased over 3 consecutive weeks of supramaximal treadmill training in normoxia which was performed twice a week. The horses trained with hypoxia (15% inspired O 2 ) twice a week. Cardiorespiratory valuables were analyzed with analysis of variance between before and after 3 weeks of hypoxic training. Mass-specific V̇O 2 max increased after 3 weeks of hypoxic training (178 ± 10 vs. 194 ± 12.3 ml O 2 (STPD)/(kg × min), Phorses, at least for the durations of time evaluated in this study. Training while breathing hypoxic gas may have the potential to enhance normoxic performance of Thoroughbred horses.

  10. Activation of radiosensitizers by hypoxic cells

    Energy Technology Data Exchange (ETDEWEB)

    Olive, P L; Durand, R E [Wisconsin Clinical Cancer Center, Madison (USA). Dept. of Human Oncology

    1978-06-01

    Hypoxic cells metabolize nitroheterocyclic compounds to produce toxic intermediates capable of affecting the survival of neighboring oxygenated cells. Mutagenesis experiments with E. coli WP-2 343 (deficient in nitro-reductase) indicated that reduction of nitroheterocyclics outside bacteria causes killing and mutations within bacteria, presumably due to the transfer of the 'active' specie(s). Using animal tissue slices to reduce nitrofurans, cultured L-929 cells incubated under aerobic conditions were far more sensitive to the toxic and DNA damaging effects of these drugs. Transfer of the active species also occurs in a tissue-like environment in multicell spheroids where the presence of a hypoxic central core served to convert the nitroheterocyclics to intermediates which also damaged the neighbouring oxygenated cells.

  11. A low protein diet increases the hypoxic tolerance in Drosophila.

    Directory of Open Access Journals (Sweden)

    Paul Vigne

    2006-12-01

    Full Text Available Dietary restriction is well known to increase the life span of a variety of organisms from yeast to mammals, but the relationships between nutrition and the hypoxic tolerance have not yet been considered. Hypoxia is a major cause of cell death in myocardial infarction and stroke. Here we forced hypoxia-related death by exposing one-day-old male Drosophila to chronic hypoxia (5% O(2 and analysed their survival. Chronic hypoxia reduced the average life span from 33.6 days to 6.3 days when flies were fed on a rich diet. A demographic analysis indicated that chronic hypoxia increased the slope of the mortality trajectory and not the short-term risk of death. Dietary restriction produced by food dilution, by yeast restriction, or by amino acid restriction partially reversed the deleterious action of hypoxia. It increased the life span of hypoxic flies up to seven days, which represented about 25% of the life time of an hypoxic fly. Maximum survival of hypoxic flies required only dietary sucrose, and it was insensitive to drugs such as rapamycin and resveratrol, which increase longevity of normoxic animals. The results thus uncover a new link between protein nutrition, nutrient signalling, and resistance to hypoxic stresses.

  12. Considerations on hypoxic conditions. On the past setback of classic radiation biology

    International Nuclear Information System (INIS)

    Nakatsugawa, Shigekazu; Klimova, S.V.; Tamasu, Shogo; Nakamura, Hideaki; Murayama, Chieko

    2002-01-01

    Considerations on hypoxic cancer cell environment are made on classic radiation biology concept and on a new proposal of the anti-cancer strategy. Classic radiation biology knowledge of hypoxic cancer cells has produced many of clinical trials, which, however, have failed after all. This is because the knowledge is that the cells are recognized to be in a rather static hypoxic condition. Based on authors' investigations, made is the proposal that improvement of dynamic, acute hypoxic conditions yielded via blood circulation between the heterogeneous malignant cancer cells and the dynamic homeostatic systems of normal cells including immunity is important as one of cancer therapy approaches. (N.I.)

  13. Placental Inflammatory Changes and Bacterial Infection in Premature Neonates with Respiratory Failure

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    S. A. Perepelitsa

    2012-01-01

    Full Text Available Objective: to reveal a relationship of placental inflammatory changes to bacterial infection in premature neonates with respiratory failure. Material and methods. Bronchoalveolar aspirate was bacteriologically studied in 157 premature neonates with respiratory distress syndrome (NRDS; the total and differential leukocyte counts were measured in their peripheral blood. The levels of the cytokines IL-1^3, IL-4, IL-6, and TNF-a were studied in different biological fluids of mothers and their babies; the placentas were also morphologically examined. Results. An analysis of bacterial cultures from the tracheobronchial tree revealed no growth of bacterial microflora in 61.8% of cases, Enterococcus faecalis and Staphylococcus epidermidis were isolated in 6.4 and 8.3% of the infants, respectively; Staphylococcus haemolyticus, Staphylococcus capitis, Enterobacter agglomerans, and hemolytic group A Streptococcus were seen in 1.9% each; moreover, 1.3% of the newborn infants were found to have Bacillus spp., Staphylococcus aureus, Escherichia coli, Acinetobacter spp., and Serratia marcescens. Other microorganisms and a microbial association were encountered in 8.9% of cases. Placental morphological examination revealed different inflammatory changes concurrent with chronic and acute placental insufficiency. The investigation demonstrated that the maternal peripheral plasma levels of IL-1^, IL-4, IL-6, and TNF-a were within the physiological range at the end of the first period of delivery. The amniotic fluid displayed elevated IL-6 and TNF-a concentrations and normal IL-4 and IL-1e levels, suggesting that there was an intrauterine inflammatory process. Conclusion. Premature birth is associated with various placental inflammatory changes, which causes intrauterine stimulation of macrophages in the chorionic villi. Specific immune defense mechanisms that prevent the development of a fetal infectious process, i.e. the maternal infectious process, may induce

  14. Hypoxia-Induced Signaling Promotes Prostate Cancer Progression: Exosomes Role as Messenger of Hypoxic Response in Tumor Microenvironment

    Science.gov (United States)

    Deep, Gagan; Panigrahi, Gati K.

    2017-01-01

    Prostate cancer (PCA) is the leading malignancy in men and the second leading cause of cancer-related deaths. Hypoxia (low O2 condition) is considered an early event in prostate carcinogenesis associated with an aggressive phenotype. In fact, clinically, hypoxia and hypoxia-related biomarkers are associated with treatment failure and disease progression. Hypoxia-inducible factor 1 (HIF-1) is the key factor that is activated under hypoxia, and mediates adaptation of cells to hypoxic conditions through regulating the expression of genes associated with angiogenesis, epithelial-to-mesenchymal transition (EMT), metastasis, survival, proliferation, metabolism, stemness, hormone-refractory progression, and therapeutic resistance. Besides HIF-1, several other signaling pathways including PI3K/Akt/mTOR, NADPH oxidase (NOX), Wnt/β-catenin, and Hedgehog are activated in cancer cells under hypoxic conditions, and also contribute in hypoxia-induced biological effects in HIF-1-dependent and -independent manners. Hypoxic cancer cells cause extensive changes in the tumor microenvironment both local and distant, and recent studies have provided ample evidence supporting the crucial role of nanosized vesicles “exosomes” in mediating hypoxia-induced tumor microenvironment remodeling. Exosomes’ role has been reported in hypoxia-induced angiogenesis, stemness, activation of cancer-associated fibroblasts (CAFs), and EMT. Together, existing literature suggests that hypoxia plays a predominant role in PCA growth and progression, and PCA could be effectively prevented and treated via targeting hypoxia/hypoxia-related signaling pathways. PMID:27279239

  15. Respiratory Disorders in Complicated Cervical Spine Injury

    Directory of Open Access Journals (Sweden)

    S. A. Pervukhin

    2016-01-01

    Full Text Available Objective. Evaluating the results of respiratory therapy in patients with complicated traumatic injury of the cervical spine.Materials and methods. A retrospective comparative analysis of the clinical course was carried out in 52 patients with complicated traumatic injury of the cervical spine: group A: complete spinal cord injury (ASIA A, 37 patients and group B: incomplete injury (ASIA B, 15 patients. The severity of patients' status on integral scales, parameters of the respiratory pattern and thoracopulmonary compliance, gas composition, and acidbase status of the blood were assessed. Data on patients who required prolonged mechanical ventilation, duration of mechanical ventilation, incidence of nosocomial pneumonia, duration of stay in the ICU, time of hospital treatment, and mortality were included in the analysis. Results. The average APACHE II and SOFA scores were higher in group A patients. The development of the acute respiratory failure required longterm mechanical ventilation (more than 48 hours in 91.4% of group A patients and in 53.3% of group B patients. Ventilatorassociated pneumonia complicated the disease in 81.3% of group A patients and 62.5% of group B patients and was accompanied by sepsis in 25% and 12.5% of cases, respectively. Statistically significant deterioration of biomechanical properties and gas exchange function of the lungs was observed in patients complicated with septic pneumonia.Conclusion. Patients with complicated ASIA A and ASIA B cervical spine injuries demonstrate the presence of respiratory failure of neurogenic origin. In addition, the infectious bronchopulmonary complications aggravated respiratory failure in patients with ASIA A injury in 70.3% versus 33.3% in patients with ASIA B. Developmentof pulmonogenic sepsis led to deterioration of the biomechanical and gas exchange functions of the lungs and increased the likelihood of unfavorable outcome of the disease in 77.8% of cases. The high

  16. Tonometry revisited: perfusion-related, metabolic, and respiratory components of gastric mucosal acidosis in acute cardiorespiratory failure.

    Science.gov (United States)

    Jakob, Stephan M; Parviainen, Ilkka; Ruokonen, Esko; Kogan, Alexander; Takala, Jukka

    2008-05-01

    Mucosal pH (pHi) is influenced by local perfusion and metabolism (mucosal-arterial pCO2 gradient, DeltapCO2), systemic metabolic acidosis (arterial bicarbonate), and respiration (arterial pCO2). We determined these components of pHi and their relation to outcome during the first 24 h of intensive care. We studied 103 patients with acute respiratory or circulatory failure (age, 63+/-2 [mean+/-SEM]; Acute Physiology and Chronic Health Evaluation II score, 20+/-1; Sequential Organ Failure Assessment score, 8+/-0). pHi, and the effects of bicarbonate and arterial and mucosal pCO2 on pHi, were assessed at admission, 6, and 24 h. pHi was reduced (at admission, 7.27+/-0.01) due to low arterial bicarbonate and increased DeltapCO2. Low pHi (or=7.32 at admission; P=0.061) was associated with an increased DeltapCO2 in 59% of patients (mortality, 47% vs. 4% for patients with low pHi and normal DeltapCO2; P=0.0003). An increased versus normal DeltapCO2, regardless of pHi, was associated with increased mortality at admission (51% vs. 5%; Pacidosis. Inadequate tissue perfusion may persist despite stable hemodynamics and contributes to poor outcome.

  17. Concordance between hypoxic challenge testing and predictive equations for hypoxic flight assessment in chronic obstructive pulmonary disease patients prior to air travel

    Directory of Open Access Journals (Sweden)

    Mohie Aldeen Abd Alzaher Khalifa

    2016-10-01

    Conclusions: The present study supports on-HCT as a reliable, on-invasive and continuous methods determining the requirement for in-flight O2 are relatively constant. Predictive equations considerably overestimate the need for in-flight O2 compared to hypoxic inhalation test. Predictive equations are cheap, readily available methods of flight assessment, but this study shows poor agreement between their predictions and the measured individual hypoxic responses during HCT.

  18. Postoperative respiratory muscle dysfunction: pathophysiology and preventive strategies.

    Science.gov (United States)

    Sasaki, Nobuo; Meyer, Matthew J; Eikermann, Matthias

    2013-04-01

    Postoperative pulmonary complications are responsible for significant increases in hospital cost as well as patient morbidity and mortality; respiratory muscle dysfunction represents a contributing factor. Upper airway dilator muscles functionally resist the upper airway collapsing forces created by the respiratory pump muscles. Standard perioperative medications (anesthetics, sedatives, opioids, and neuromuscular blocking agents), interventions (patient positioning, mechanical ventilation, and surgical trauma), and diseases (lung hyperinflation, obesity, and obstructive sleep apnea) have differential effects on the respiratory muscle subgroups. These effects on the upper airway dilators and respiratory pump muscles impair their coordination and function and can result in respiratory failure. Perioperative management strategies can help decrease the incidence of postoperative respiratory muscle dysfunction. Such strategies include minimally invasive procedures rather than open surgery, early and optimal mobilizing of respiratory muscles while on mechanical ventilation, judicious use of respiratory depressant anesthetics and neuromuscular blocking agents, and noninvasive ventilation when possible.

  19. Hypoxia modifies the feeding preferences of Drosophila. Consequences for diet dependent hypoxic survival

    Directory of Open Access Journals (Sweden)

    Frelin Christian

    2010-05-01

    Full Text Available Abstract Background Recent attention has been given to the relationships between diet, longevity, aging and resistance to various forms of stress. Flies do not simply ingest calories. They sense different concentrations of carbohydrate and protein macronutrients and they modify their feeding behavior in response to changes in dietary conditions. Chronic hypoxia is a major consequence of cardiovascular diseases. Dietary proteins have recently been shown to decrease the survival of chronically hypoxic Drosophila. Whether flies modify their feeding behavior in response to hypoxia is not currently known. This study uses the recently developed capillary feeding assay to analyze the feeding behavior of normoxic and chronically hypoxic Drosophila melanogaster. Results The intakes rates of sucrose and yeast by normoxic or chronically hypoxic flies (5% O2 were analyzed under self selecting and "no choice" conditions. Chronically hypoxic flies fed on pure yeast diets or mixed diets under self selection conditions stopped feeding on yeast. Flies fed on mixed diets under "no choice" conditions reduced their food intakes. Hypoxia did not modify the adaptation of flies to diluted diets or to imbalanced diets. Mortality was assessed in parallel experiments. Dietary yeast had two distinct effects on hypoxic flies (i a repellent action which eventually led to starvation and which was best observed in the absence of dietary sucrose and (ii a toxic action which led to premature death. Finally we determined that hypoxic survivals were correlated to the intakes of sucrose, which suggested that dietary yeast killed flies by reducing their intake of sucrose. The feeding preferences of adult Drosophila were insensitive to NO scavengers, NO donor molecules and inhibitors of phosphodiesterases which are active on Drosophila larvae. Conclusion Chronically hypoxic flies modify their feeding behavior. They avoid dietary yeast which appears to be toxic. Hypoxic survival is

  20. Activation of radiosensitizers by hypoxic cells

    International Nuclear Information System (INIS)

    Olive, P.L.; Durand, R.E.

    1978-01-01

    Hypoxic cells metabolize nitroheterocyclic compounds to produce toxic intermediates capable of affecting the survival of neighboring oxygenated cells. Mutagenesis experiments with E. coli WP-2 343 (deficient in nitro-reductase) indicated that reduction of nitroheterocyclics outside bacteria causes killing and mutations within bacteria, presumably due to the transfer of the 'active' specie(s). Using animal tissue slices to reduce nitrofurans, cultured L-929 cells incubated under aerobic conditions were far more sensitive to the toxic and DNA damaging effects of these drugs. Transfer of the active species also occurs in a tissue-like environment in multicell spheroids where the presence of a hypoxic central core served to convert the nitroheterocyclics to intermediates which also damaged the neighbouring oxygenated cells. (author)

  1. Ultrastructural alterations in hypoxic EMT-6/RO cells treated with misonidazole

    International Nuclear Information System (INIS)

    Wilbur, D.C.; Mulcahy, R.T.

    1984-01-01

    Ultrastructural alterations in hypoxic EMT-6 tumor cells were quantitatively analyzed as a function of time in the presence and absence of 1.0mM MISO. Control and MISO-treated monolayer cultures were maintained in hypoxic chambers at 37 0 C. At intervals after initiation of hypoxia, the cells were fixed and prepared for electron microscopy. The major ultrastructural alterations observed in untreated and MISO-treated hypoxic cells included mitochondrial swelling and accumulation of cytoplasmic lipid vacuoles. Mean mitochondrial area and relative cytoplasmic area occupied by lipid vacuoles were determined morphometrically. Mitochondrial damage was also scored qualitatively based on distortions in configuration. In the absence of MISO both parameters of mitochondrial injury increased over a period of two hours, after which little further change was noted. A progressive increase in lipid vacuolization was also seen. In the presence of MISO, mitochondrial swelling and lipid vacuole formation were significantly increased. The proportion of irreversibly damaged mitochondria was markedly enhanced. MISO treatment also accelerated the expression of these changes. The accelerated expression of hypoxic-related injury in MISO treated cells suggests that cytotoxicity is related to accentuation of hypoxic injury, perhaps by inhibition of glycolysis

  2. [The changes of physiological reactivity of cardiorespiratory system to respiratory homeostasis with the use of complex stimulation of special work capacity].

    Science.gov (United States)

    Lysenko, O M

    2012-01-01

    We present the influence of the program of special additional stimulation of work capacity of high-performance athletes on the sensitivity of cardiorespiratory system to hypercapnic and hypoxic shifts in respiratory homeostasis. We found that under the influence of the pre-start complex a decrease in the sensitivity of ventilator responses to CO2-H+ stimuli in combination with a reduction in the thresholds of the reaction take place. This creates conditions for increased mobilization properties of the cardiorespiratory system and economization of its reaction under conditions of changes of respiratory homeostasis characteristic of intense training and competitive loads in the sport.

  3. Systematic review of non-invasive positive pressure ventilation for chronic respiratory failure.

    Science.gov (United States)

    Hannan, Liam M; Dominelli, Giulio S; Chen, Yi-Wen; Darlene Reid, W; Road, Jeremy

    2014-02-01

    This systematic review examined the effect of non-invasive positive pressure ventilation (NIPPV) on patient reported outcomes (PROs) and survival for individuals with or at risk of chronic respiratory failure (CRF). Randomised controlled trials (RCTs) and prospective non-randomised studies in those treated with NIPPV for CRF were identified from electronic databases, reference lists and grey literature. Diagnostic groups included in the review were amyotrophic lateral sclerosis/motor neuron disease (ALS/MND), Duchenne muscular dystrophy (DMD), restrictive thoracic disease (RTD) and obesity hypoventilation syndrome (OHS). Eighteen studies were included and overall study quality was weak. Those with ALS/MND had improved somnolence and fatigue as well as prolonged survival with NIPPV. For OHS, improvements in somnolence and fatigue, dyspnoea and sleep quality were demonstrated, while for RTD, measures of dyspnoea, sleep quality, physical function and health, mental and emotional health and social function improved. There was insufficient evidence to form conclusions regarding the effect of NIPPV for those with DMD. This review has demonstrated that NIPPV influences PROs differently depending on the underlying cause of CRF. These findings may provide assistance to patients and clinicians to determine the relative costs and benefits of NIPPV therapy and also highlight areas in need of further research. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung

    Directory of Open Access Journals (Sweden)

    McLoughlin Paul

    2011-01-01

    Full Text Available Abstract Background Chronic alveolar hypoxia, due to residence at high altitude or chronic obstructive lung diseases, leads to pulmonary hypertension, which may be further complicated by right heart failure, increasing morbidity and mortality. In the non-diseased lung, angiogenesis occurs in chronic hypoxia and may act in a protective, adaptive manner. To date, little is known about the behaviour of individual vascular endothelial growth factor (VEGF family ligands in hypoxia-induced pulmonary angiogenesis. The aim of this study was to examine the expression of placenta growth factor (PlGF and VEGFB during the development of hypoxic pulmonary angiogenesis and their functional effects on the pulmonary endothelium. Methods Male Sprague Dawley rats were exposed to conditions of normoxia (21% O2 or hypoxia (10% O2 for 1-21 days. Stereological analysis of vascular structure, real-time PCR analysis of vascular endothelial growth factor A (VEGFA, VEGFB, placenta growth factor (PlGF, VEGF receptor 1 (VEGFR1 and VEGFR2, immunohistochemistry and western blots were completed. The effects of VEGF ligands on human pulmonary microvascular endothelial cells were determined using a wound-healing assay. Results Typical vascular remodelling and angiogenesis were observed in the hypoxic lung. PlGF and VEGFB mRNA expression were significantly increased in the hypoxic lung. Immunohistochemical analysis showed reduced expression of VEGFB protein in hypoxia although PlGF protein was unchanged. The expression of VEGFA mRNA and protein was unchanged. In vitro PlGF at high concentration mimicked the wound-healing actions of VEGFA on pulmonary microvascular endothelial monolayers. Low concentrations of PlGF potentiated the wound-healing actions of VEGFA while higher concentrations of PlGF were without this effect. VEGFB inhibited the wound-healing actions of VEGFA while VEGFB and PlGF together were mutually antagonistic. Conclusions VEGFB and PlGF can either inhibit or

  5. Interstitial Lung Disease in a 70-Year-Old Man with Ulcerative Colitis.

    Science.gov (United States)

    Collins, Hampton W; Frye, Jeanetta W

    2018-01-01

    Interstitial lung disease is a rare but increasingly recognized extraintestinal manifestation of inflammatory bowel disease that can have devastating consequences if left untreated. We report a case of ulcerative colitis-associated interstitial lung disease presenting with acute hypoxic respiratory failure during an ulcerative colitis flare. Gastroenterologists and pulmonologists should be aware of the numerous bronchopulmonary signs and symptoms that can suggest systemic illness in inflammatory bowel disease.

  6. Pilot study of a new device to titrate oxygen flow in hypoxic patients on long-term oxygen therapy.

    Science.gov (United States)

    Cirio, Serena; Nava, Stefano

    2011-04-01

    The O(2) Flow Regulator (Dima, Bologna, Italy) is a new automated oxygen regulator that titrates the oxygen flow based on a pulse-oximetry signal to maintain a target S(pO(2)). We tested the device's safety and efficacy. We enrolled 18 subjects with chronic lung disease, exercise-induced desaturation, and on long-term oxygen therapy, in a randomized crossover study with 2 constant-work-load 15-min cycling exercise tests, starting with the patient's previously prescribed usual oxygen flow. In one test the oxygen flow was titrated manually by the respiratory therapist, and in the other test the oxygen flow was titrated by the O(2) Flow Regulator, to maintain an S(pO(2)) of 94%. We measured S(pO(2)) throughout each test, the time spent by the respiratory therapist to set the device or to manually regulate the oxygen flow, and the total number of respiratory-therapist titration interventions during the trial. There were no differences in symptoms or heart rate between the exercise tests. Compared to the respiratory-therapist-controlled tests, during the O(2) Flow Regulator tests S(pO(2)) was significantly higher (95 ± 2% vs 93 ± 3%, P = .04), significantly less time was spent below the target S(pO(2)) (171 ± 187 s vs 340 ± 220 s, P less respiratory therapist time (5.6 ± 3.7 min vs 2.0 ± 0.1 min, P = .005). The O(2) Flow Regulator may be a safe and effective alternative to manual oxygen titration during exercise in hypoxic patients. It provided stable S(pO(2)) and avoided desaturations in our subjects.

  7. High-frequency oscillatory ventilation in pediatric acute hypoxemic respiratory failure: disease-specific morbidity survival analysis.

    Science.gov (United States)

    Babbitt, Christopher J; Cooper, Michael C; Nussbaum, Eliezer; Liao, Eileen; Levine, Glenn K; Randhawa, Inderpal S

    2012-12-01

    Multiple ventilatory strategies for acute hypoxemic respiratory failure (AHRF) in children have been advocated, including high-frequency oscillatory ventilation (HFOV). Despite the frequent deployment of HFOV, randomized controlled trials remain elusive and currently there are no pediatric trials looking at its use. Our longitudinal study analyzed the predictive clinical outcome of HFOV in pediatric AHRF given disease-specific morbidity. A retrospective 8-year review on pediatric intensive care unit admissions with AHRF ventilated by HFOV was performed. Primary outcomes included survival, morbidity, length of stay (LOS), and factors associated with survival or mortality. A total of 102 patients underwent HFOV with a 66 % overall survival rate. Survivors had a greater LOS than nonsurvivors (p = 0.001). Mortality odds ratio (OR) for patients without bronchiolitis was 8.19 (CI = 1.02, 65.43), and without pneumonia it was 3.07 (CI = 1.12, 8.39). A lower oxygenation index (OI) after HFOV commencement and at subsequent time points analyzed predicted survival. After 24 h, mortality was associated with an OI > 35 [OR = 31.11 (CI = 3.25, 297.98)]. Sepsis-related mortality was associated with a higher baseline FiO(2) (0.88 vs. 0.65), higher OI (42 vs. 22), and augmented metabolic acidosis (pH of 7.25 vs. 7.32) evaluated 4 h on HFOV (p < 0.05). High-frequency oscillatory ventilation may be safely utilized. It has a 66 % overall survival rate in pediatric AHRF of various etiologies. Patients with morbidity limited to the respiratory system and optimized oxygenation indices are most likely to survive on HFOV.

  8. Long-term non-invasive ventilation reduces readmissions in COPD patients with two or more episodes of acute hypercapnic respiratory failure

    DEFF Research Database (Denmark)

    Ankjærgaard, Kasper Linde; Maibom, Sophia Liff; Wilcke, Jon Torgny

    2016-01-01

    BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients who have had an episode of acute hypercapnic respiratory failure (AHRF) have a large 1-year risk of death or readmission. Acute non-invasive ventilation (NIV) has been shown to be an effective treatment of AHRF; and long-term NIV.......88 (p=0.0092). Four patients (20%) died in 1 year. LTNIV tended to reduce arterial CO2. No changes were found in lung function. CONCLUSIONS: LTNIV seems effective in reducing recurrent AHRF and readmissions in a highly select group of patients with severe, unstable COPD and frequent AHRF....

  9. Analysis and modeling of ensemble recordings from respiratory pre-motor neurons indicate changes in functional network architecture after acute hypoxia

    Directory of Open Access Journals (Sweden)

    Roberto F Galán

    2010-09-01

    Full Text Available We have combined neurophysiologic recording, statistical analysis, and computational modeling to investigate the dynamics of the respiratory network in the brainstem. Using a multielectrode array, we recorded ensembles of respiratory neurons in perfused in situ rat preparations that produce spontaneous breathing patterns, focusing on inspiratory pre-motor neurons. We compared firing rates and neuronal synchronization among these neurons before and after a brief hypoxic stimulus. We observed a significant decrease in the number of spikes after stimulation, in part due to a transient slowing of the respiratory pattern. However, the median interspike interval did not change, suggesting that the firing threshold of the neurons was not affected but rather the synaptic input was. A bootstrap analysis of synchrony between spike trains revealed that, both before and after brief hypoxia, up to 45 % (but typically less than 5 % of coincident spikes across neuronal pairs was not explained by chance. Most likely, this synchrony resulted from common synaptic input to the pre-motor population, an example of stochastic synchronization. After brief hypoxia most pairs were less synchronized, although some were more, suggesting that the respiratory network was “rewired” transiently after the stimulus. To investigate this hypothesis, we created a simple computational model with feed-forward divergent connections along the inspiratory pathway. Assuming that 1 the number of divergent projections was not the same for all presynaptic cells, but rather spanned a wide range and 2 that the stimulus increased inhibition at the top of the network; this model reproduced the reduction in firing rate and bootstrap-corrected synchrony subsequent to hypoxic stimulation observed in our experimental data.

  10. Low-dose dexamethasone-supplemented fluid resuscitation reverses endotoxin-induced acute renal failure and prevents cortical microvascular hypoxia

    NARCIS (Netherlands)

    Johannes, Tanja; Mik, Egbert G.; Klingel, Karin; Dieterich, Hans-Jürgen; Unertl, Klaus E.; Ince, Can

    2009-01-01

    There is growing evidence that impairment in intrarenal oxygenation and hypoxic injury might contribute to the pathogenesis of septic renal failure. An important molecule known to act on the renal microvascular tone and therefore consequently being involved in the regulation of intrarenal oxygen

  11. Use and Outcomes of Noninvasive Ventilation for Acute Respiratory Failure in Different Age Groups.

    Science.gov (United States)

    Ozsancak Ugurlu, Aylin; Sidhom, Samy S; Khodabandeh, Ali; Ieong, Michael; Mohr, Chester; Lin, Denis Y; Buchwald, Irwin; Bahhady, Imad; Wengryn, John; Maheshwari, Vinay; Hill, Nicholas S

    2016-01-01

    The prevalence of chronic disease and do-not-intubate status increases with age. Thus, we aimed to determine characteristics and outcomes associated with noninvasive ventilation (NIV) use for acute respiratory failure (ARF) in different age groups. A database comprising prospective data collected on site on all adult patients with ARF requiring ventilatory support from 8 acute care hospitals in Massachusetts was used. From a total of 1,225 ventilator starts, overall NIV utilization, success, and in-hospital mortality rates were 22, 54, and 18% in younger (18-44 y); 34, 65, and 13% in middle-aged (45-64 y); 49, 68, and 17% in elderly (65-79 y); and 47, 76, and 24% in aged (≥ 80 y) groups, respectively (P age (25, 57, 57, and 74% and 7, 12, 18, and 31%, respectively, in the 4 age groups [P age groups (P = .27 and P = .98, respectively). NIV use and a do-not-intubate status are more frequent in subjects with ARF ≥ 65 y than in those age groups. (ClinicalTrials.gov registration NCT00458926.). Copyright © 2016 by Daedalus Enterprises.

  12. Archaeal enrichment in the hypoxic zone in the northern Gulf of Mexico.

    Science.gov (United States)

    Gillies, Lauren E; Thrash, J Cameron; deRada, Sergio; Rabalais, Nancy N; Mason, Olivia U

    2015-10-01

    Areas of low oxygen have spread exponentially over the past 40 years, and are cited as a key stressor on coastal ecosystems. The world's second largest coastal hypoxic (≤ 2 mg of O2 l(-1)) zone occurs annually in the northern Gulf of Mexico. The net effect of hypoxia is the diversion of energy flow away from higher trophic levels to microorganisms. This energy shunt is consequential to the overall productivity of hypoxic water masses and the ecosystem as a whole. In this study, water column samples were collected at 39 sites in the nGOM, 21 of which were hypoxic. Analysis of the microbial community along a hypoxic to oxic dissolved oxygen gradient revealed that the relative abundance (iTag) of Thaumarchaeota species 16S rRNA genes (> 40% of the microbial community in some hypoxic samples), the absolute abundance (quantitative polymerase chain reaction; qPCR) of Thaumarchaeota 16S rRNA genes and archaeal ammonia-monooxygenase gene copy number (qPCR) were significantly higher in hypoxic samples. Spatial interpolation of the microbial and chemical data revealed a continuous, shelfwide band of low dissolved oxygen waters that were dominated by Thaumarchaeota (and Euryarchaeota), amoA genes and high concentrations of phosphate in the nGOM, thus implicating physicochemical forcing on microbial abundance. © 2015 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.

  13. Excluding infection through procalcitonin testing improves outcomes of congestive heart failure patients presenting with acute respiratory symptoms: results from the randomized ProHOSP trial.

    Science.gov (United States)

    Schuetz, Philipp; Kutz, Alexander; Grolimund, Eva; Haubitz, Sebastian; Demann, Désirée; Vögeli, Alaadin; Hitz, Fabienne; Christ-Crain, Mirjam; Thomann, Robert; Falconnier, Claudine; Hoess, Claus; Henzen, Christoph; Marlowe, Robert J; Zimmerli, Werner; Mueller, Beat

    2014-08-20

    We sought to determine whether exclusion of infection and antibiotic stewardship with the infection biomarker procalcitonin improves outcomes in congestive heart failure (CHF) patients presenting to emergency departments with respiratory symptoms and suspicion of respiratory infection. We performed a secondary analysis of patients with a past medical history of CHF formerly included in a Swiss multicenter randomized-controlled trial. The trial compared antibiotic stewardship according to a procalcitonin algorithm or state-of-the-art guidelines (controls). The primary endpoint was a 30-day adverse outcome (death, intensive care unit admission); the secondary endpoints included a 30-day antibiotic exposure. In the 110/233 analyzed patients (47.2%) with low initial procalcitonin (<0.25 μg/L), suggesting the absence of systemic bacterial infection, those randomized to procalcitonin guidance (n=50) had a significantly lower adverse outcome rate compared to controls (n=60): 4% vs. 20% (absolute difference -16.0%, 95% confidence interval (CI) -28.4% to -3.6%, P=0.01), and significantly reduced antibiotic exposure [days] (mean 3.7 ± 4.0 vs. 6.5 ± 4.4, difference -2.8 [95% CI, -4.4 to -1.2], P<0.01). When initial procalcitonin was ≥0.25 μg/L, procalcitonin-guided patients had significantly reduced antibiotic exposure due to early stop of therapy without any difference in adverse outcomes (25.8% vs. 24.6%, difference [95% CI] 1.2% [-14.5% to 16.9%, P=0.88]). CHF patients presenting to the emergency department with respiratory symptoms and suspicion for respiratory infection had decreased antibiotic exposure and improved outcomes when procalcitonin measurement was used to exclude bacterial infection and guide antibiotic treatment. These data provide further evidence for the potential harmful effects of antibiotic / fluid treatment when used instead of diuretics and heart failure medication in clinically symptomatic CHF patients without underlying infection. Copyright

  14. [Neuromuscular disease: respiratory clinical assessment and follow-up].

    Science.gov (United States)

    Martínez Carrasco, C; Villa Asensi, J R; Luna Paredes, M C; Osona Rodríguez de Torres, F B; Peña Zarza, J A; Larramona Carrera, H; Costa Colomer, J

    2014-10-01

    Patients with neuromuscular disease are an important group at risk of frequently suffering acute or chronic respiratory failure, which is their main cause of death. They require follow-up by a pediatric respiratory medicine specialist from birth or diagnosis in order to confirm the diagnosis and treat any respiratory complications within a multidisciplinary context. The ventilatory support and the cough assistance have improved the quality of life and long-term survival for many of these patients. In this paper, the authors review the pathophysiology, respiratory function evaluation, sleep disorders, and the most frequent respiratory complications in neuromuscular diseases. The various treatments used, from a respiratory medicine point of view, will be analyzed in a next paper. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  15. An HRE-Binding Py-Im Polyamide Impairs Hypoxic Signaling in Tumors.

    Science.gov (United States)

    Szablowski, Jerzy O; Raskatov, Jevgenij A; Dervan, Peter B

    2016-04-01

    Hypoxic gene expression contributes to the pathogenesis of many diseases, including organ fibrosis, age-related macular degeneration, and cancer. Hypoxia-inducible factor-1 (HIF1), a transcription factor central to the hypoxic gene expression, mediates multiple processes including neovascularization, cancer metastasis, and cell survival. Pyrrole-imidazole polyamide 1: has been shown to inhibit HIF1-mediated gene expression in cell culture but its activity in vivo was unknown. This study reports activity of polyamide 1: in subcutaneous tumors capable of mounting a hypoxic response and showing neovascularization. We show that 1: distributes into subcutaneous tumor xenografts and normal tissues, reduces the expression of proangiogenic and prometastatic factors, inhibits the formation of new tumor blood vessels, and suppresses tumor growth. Tumors treated with 1: show no increase in HIF1α and have reduced ability to adapt to the hypoxic conditions, as evidenced by increased apoptosis in HIF1α-positive regions and the increased proximity of necrotic regions to vasculature. Overall, these results show that a molecule designed to block the transcriptional activity of HIF1 has potent antitumor activity in vivo, consistent with partial inhibition of the tumor hypoxic response. Mol Cancer Ther; 15(4); 608-17. ©2015 AACR. ©2015 American Association for Cancer Research.

  16. Enhanced induction of SCEs in hypoxic mammalian cells by ionizing radiation

    International Nuclear Information System (INIS)

    Tofilon, P.J.; Meyn, R.E.

    1985-01-01

    Ionizing radiation is, in general, a poor inducer of sister chromatoid exchanges (SCEs). However, the authors previously observed an increase in X-ray induced DNA-protein crosslinks in hypoxic cells, as compared to aerated cells, suggesting that in the absence of oxygen, X rays induce a qualitatively different DNA lesion. Therefore, they examined the effect of X-rays on SCE induction under hypoxic conditions. CHO cells were rendered hypoxic by incubation at 37 0 for 3 hr. in evacuated glass ampules and irradiated with graded doses of X-rays. After irradiation, cells were incubated in medium containing BrdUrd and the SCE assay performed. At each dose tested (0-900 rads) the number of SCEs induced by X-rays in hypoxic cells was approximately 2.5 fold the number induced in aerated cells. When a 16-hr. repair-incubation interval was allowed between irradiation and BrdUrd labeling, the number of SCEs returned to background levels. In further experiments, repair-deficient cells, incapable of completely removing crosslinks from their DNA, did not completely restore SCE levels to background within the repair period. These data provide further evidence suggesting that hypoxic cells respond differently to radiation in a qualitative sense, in addition to the well known quantitative sense

  17. Compression of the medulla oblongata and acute respiratory failure caused by rupture of a thrombosed large aneurysm of the anterior inferior cerebellar artery.

    Science.gov (United States)

    Oyama, Hirofumi; Kito, Akira; Maki, Hideki; Hattori, Kenichi; Tanahashi, Kuniaki

    2010-01-01

    A 65-year-old female presented with an extremely rare case of a ruptured thrombosed large aneurysm of the anterior inferior cerebellar artery (AICA) in which a local hematoma compressed the medulla oblongata and caused acute respiratory failure. She first presented with dizziness, general fatigue, and nausea 2 months before admission. She was hospitalized for intense general fatigue, nausea, and occipitalgia. Computed tomography and T(1)-weighted magnetic resonance imaging showed a heterogeneous lesion around the right cerebello-medullary cistern. Angiography revealed a fusiform aneurysm of the right AICA. Asphyxia occurred 4 days after admission and the patient underwent an emergency operation. No subarachnoid hematoma was present, but a hematoma around the ruptured portion markedly compressed the medulla oblongata. The medulla oblongata was adequately decompressed after subtotal removal of the aneurysm. The patient's respiratory status and consciousness level recovered after the operation.

  18. Airway Reflux, Cough and Respiratory Disease

    Science.gov (United States)

    Molyneux, Ian D.; Morice, Alyn H.

    2011-01-01

    It is increasingly accepted that the effects of gastro-oesophageal reflux are not limited to the gastrointestinal tract. The adjacent respiratory structures are also at risk from material ejected from the proximal oesophagus as a result of the failure of anatomical and physiological barriers. There is evidence of the influence of reflux on several respiratory and otorhinological conditions and although in many cases the precise mechanism has yet to be elucidated, the association alone opens potential novel avenues of therapy to clinicians struggling to treat patients with apparently intractable respiratory complaints. This review provides a description of the airway reflux syndrome, its effects on the lung and current and future therapeutic options. PMID:23251752

  19. Effect of adjuvant noninvasive positive pressure ventilation on blood gas parameters, cardiac function and inflammatory state in patients with COPD and type II respiratory failure

    Directory of Open Access Journals (Sweden)

    You-Ming Zhu1

    2017-03-01

    Full Text Available Objective: T o analyze the effect of adjuvant noninvasive positive pressure ventilation on blood gas parameters, cardiac function and inflammatory state in patients with chronic obstructive pulmonary disease (COPD and type II respiratory failure. Methods: 90 patients with COPD and type II respiratory failure were randomly divided into observation group and control group (n=45. Control group received conventional therapy, observation group received conventional therapy + adjuvant noninvasive positive pressure ventilation, and differences in blood gas parameters, cardiac function, inflammatory state, etc., were compared between two groups of patients 2 weeks after treatment. Results: Arterial blood gas parameters pH and alveolar-arterial partial pressure of oxygen [P(A-aO2] levels of observation group were higher than those of control group while, potassium ion (K+, chloride ion (Cl﹣ and carbon dioxide combining power (CO2CP levels were lower than those of control group 2 weeks after treatment; echocardiography parameters Doppler-derived tricuspid lateral annular systolic velocity (DTIS and pulmonary arterial velocity (PAV levels were lower than those of control group (P<0.05 while pulmonary artery accelerating time (PAACT, left ventricular enddiastolic dimension (LVDd and right atrioventricular tricuspid annular plane systolic excursion (TAPSE levels were higher than those of control group (P<0.05; serum cardiac function indexes adiponectin (APN, Copeptin, N-terminal pro-B-type natriuretic peptide (NT-proBNP, cystatin C (CysC, growth differentiation factor-15 (GDF-15 and heart type fatty acid binding protein (H-FABP content were lower than those of control group (P<0.05; serum inflammatory factors hypersensitive C-reactive protein (hs-CRP, tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β, IL-8, IL-10, and transforming growth factor-β1 (TGF-β1 content were lower than those of control group (P<0.05. Conclusions: Adjuvant

  20. Hypoxic survival strategies in two fishes: extreme anoxia tolerance in the North European crucian carp and natural hypoxic preconditioning in a coral-reef shark.

    Science.gov (United States)

    Nilsson, Göran E; Renshaw, Gillian M C

    2004-08-01

    Especially in aquatic habitats, hypoxia can be an important evolutionary driving force resulting in both convergent and divergent physiological strategies for hypoxic survival. Examining adaptations to anoxic/hypoxic survival in hypoxia-tolerant animals may offer fresh ideas for the treatment of hypoxia-related diseases. Here, we summarise our present knowledge of two fishes that have evolved to survive hypoxia under very different circumstances. The crucian carp (Carassius carassius) is of particular interest because of its extreme anoxia tolerance. During the long North European winter, it survives for months in completely oxygen-deprived freshwater habitats. The crucian carp also tolerates a few days of anoxia at room temperature and, unlike anoxia-tolerant freshwater turtles, it is still physically active in anoxia. Moreover, the crucian carp does not appear to reduce neuronal ion permeability during anoxia and may primarily rely on more subtle neuromodulatory mechanisms for anoxic metabolic depression. The epaulette shark (Hemiscyllium ocellatum) is a tropical marine vertebrate. It lives on shallow reef platforms that repeatedly become cut off from the ocean during periods of low tides. During nocturnal low tides, the water [O(2)] can fall by 80% due to respiration of the coral and associated organisms. Since the tides become lower and lower over a period of a few days, the hypoxic exposure during subsequent low tides will become progressively longer and more severe. Thus, this shark is under a natural hypoxic preconditioning regimen. Interestingly, hypoxic preconditioning lowers its metabolic rate and its critical P(O(2)). Moreover, repeated anoxia appears to stimulate metabolic depression in an adenosine-dependent way.

  1. Predictive value of daily living score in acute respiratory failure of COPD patients requiring invasive mechanical ventilation pilot study

    Directory of Open Access Journals (Sweden)

    Langlet Ketty

    2012-10-01

    Full Text Available Abstract Background Mechanical ventilation (MV is imperative in many forms of acute respiratory failure (ARF in COPD patients. Previous studies have shown the difficulty to identify parameters predicting the outcome of COPD patients treated by invasive MV. Our hypothesis was that a non specialized score as the activities daily living (ADL score may help to predict the outcome of these patients. Methods We studied the outcome of 25 COPD patients admitted to the intensive care unit for ARF requiring invasive MV. The patients were divided into those weaning success (group A n = 17, 68% or failure (group B n = 8, 32%. We investigated the correlation between the ADL score and the outcome and mortality. Results The ADL score was higher in group A (5.1 ±1.1 vs 3.7 ± 0.7 in group B, p  Conclusion Our pilot study demonstrates that the ADL score is predictive of weaning success and mortality at 6 months, suggesting that the assessment of daily activities should be an important component of ARF management in COPD patients.

  2. Exploratory Use of Decision Tree Analysis in Classification of Outcome in Hypoxic-Ischemic Brain Injury.

    Science.gov (United States)

    Phan, Thanh G; Chen, Jian; Singhal, Shaloo; Ma, Henry; Clissold, Benjamin B; Ly, John; Beare, Richard

    2018-01-01

    Prognostication following hypoxic ischemic encephalopathy (brain injury) is important for clinical management. The aim of this exploratory study is to use a decision tree model to find clinical and MRI associates of severe disability and death in this condition. We evaluate clinical model and then the added value of MRI data. The inclusion criteria were as follows: age ≥17 years, cardio-respiratory arrest, and coma on admission (2003-2011). Decision tree analysis was used to find clinical [Glasgow Coma Score (GCS), features about cardiac arrest, therapeutic hypothermia, age, and sex] and MRI (infarct volume) associates of severe disability and death. We used the area under the ROC (auROC) to determine accuracy of model. There were 41 (63.7% males) patients having MRI imaging with the average age 51.5 ± 18.9 years old. The decision trees showed that infarct volume and age were important factors for discrimination between mild to moderate disability and severe disability and death at day 0 and day 2. The auROC for this model was 0.94 (95% CI 0.82-1.00). At day 7, GCS value was the only predictor; the auROC was 0.96 (95% CI 0.86-1.00). Our findings provide proof of concept for further exploration of the role of MR imaging and decision tree analysis in the early prognostication of hypoxic ischemic brain injury.

  3. Periodicity during hypercapnic and hypoxic stimulus is crucial in distinct aspects of phrenic nerve plasticity.

    Science.gov (United States)

    Stipica, I; Pavlinac Dodig, I; Pecotic, R; Dogas, Z; Valic, Z; Valic, M

    2016-01-01

    This study was undertaken to determine pattern sensitivity of phrenic nerve plasticity in respect to different respiratory challenges. We compared long-term effects of intermittent and continuous hypercapnic and hypoxic stimuli, and combined intermittent hypercapnia and hypoxia on phrenic nerve plasticity. Adult, male, urethane-anesthetized, vagotomized, paralyzed, mechanically ventilated Sprague-Dawley rats were exposed to: acute intermittent hypercapnia (AIHc or AIHc(O2)), acute intermittent hypoxia (AIH), combined intermittent hypercapnia and hypoxia (AIHcH), continuous hypercapnia (CHc), or continuous hypoxia (CH). Peak phrenic nerve activity (pPNA) and burst frequency were analyzed during baseline (T0), hypercapnia or hypoxia exposures, at 15, 30, and 60 min (T60) after the end of the stimulus. Exposure to acute intermittent hypercapnia elicited decrease of phrenic nerve frequency from 44.25+/-4.06 at T0 to 35.29+/-5.21 at T60, (P=0.038, AIHc) and from 45.5+/-2.62 to 37.17+/-3.68 breaths/min (P=0.049, AIHc(O2)), i.e. frequency phrenic long term depression was induced. Exposure to AIH elicited increase of pPNA at T60 by 141.0+/-28.2 % compared to baseline (P=0.015), i.e. phrenic long-term facilitation was induced. Exposure to AIHcH, CHc, or CH protocols failed to induce long-term plasticity of the phrenic nerve. Thus, we conclude that intermittency of the hypercapnic or hypoxic stimuli is needed to evoke phrenic nerve plasticity.

  4. Hypoxic Living and Exercise Training Alter Adipose Tissue Leptin/Leptin Receptor in Rats

    Directory of Open Access Journals (Sweden)

    Yingli Lu

    2016-11-01

    Full Text Available Background: Hypobaric hypoxia results in weight loss in obese individuals, and exercise training is advocated for the treatment of obesity and its related metabolic dysfunctions. The purpose of this study was to investigate the effects of hypoxic living and exercise training on obesity and adipose tissue leptin/leptin receptor in dietary-induced obese rats. Methods: One hundred and thirty high-fat diet fed Sprague-Dawley rats were assigned into one of the following groups (n=10 each: control, sedentary hypoxic living for 1 to 4 weeks (SH1, SH2, SH3, and SH4, living and exercise training in normoxic conditions for 1 to 4 weeks (TN1, TN2, TN3, and TN4, and living and exercise training in hypoxic conditions for 1 to 4 weeks (TN1, TN2, TN3, and TN4. Epididymal adipose tissue expression levels of leptin and leptin receptor were determined. Results: Compared to hypoxic living and living and exercise training in normoxic conditions, living and exercise training in hypoxic conditions for 3-4 weeks resulted in lower Lee index (P<0.05 to P<0.01, and higher expression of leptin and leptin receptor (P<0.05 to P<0.01 in adipose tissue. Conclusion: In a rodent model of altitude training, living and exercise training in hypoxic conditions resulted in greater alterations in obesity and adipose tissue leptin/leptin receptor than hypoxic living alone and living and exercise training in normoxic conditions.

  5. Hypoksisk hepatitis

    DEFF Research Database (Denmark)

    Amadid, Hanan; Schiødt, Frank Vinholt

    2014-01-01

    Hypoxic hepatitis (HH), also known as ischaemic hepatitis or shock liver, is an acute liver injury caused by hepatic hypoxia. Cardiac failure, respiratory failure and septic shock are the main underlying conditions. In each of these conditions, several haemodynamic mechanisms lead to hepatic...... hypoxia. A shock state is observed in only 50% of cases. Thus, shock liver and ischaemic hepatitis are misnomers. HH can be a diagnostic pitfall but the diagnosis can be established when three criteria are met. Prognosis is poor and prompt identification and treatment of the underlying conditions...

  6. Radiosensitization effect of CMNa on hypoxic pancreatic cancer cell in vitro

    International Nuclear Information System (INIS)

    Yin Lijie; Zhang Li; Ding Tiangui; Peng Zhaoxiang; Yu Huan; Gao Yuwei

    2006-01-01

    Objective: To investigate the effects of glycodidazolum natrium (CMNa) on pancreatic cancer cells under hypoxic condition. Methods: The human pancreatic cancer Panc-1 cells were exposed to a single fraction of high-dose γ-ray radiation either with CMNa or under hypoxic condition. The percentage of dead cells was detected with a multiwell plated reader, and fluorescence intensities of propidium iodide were measured before and after digitonin treatment. The sensitizing effect of CMNa on cell killing induced by high-dose irradiation was evaluated by time and concentration dependence. The selective radiosensitive effect of CMNa on hypoxia was evaluated by flow cytometry. Results: The death rate of pancreatic cancer Panc-1 cells paralleled with the increasing concentration of CMNa under hypoxic condition after 30 gray irradiation. The selective radiosensitive effect of CMNa on hypoxia was time-dependent. Conclusions: CMNa can enhance the radiosensitivity of pancreatic cancer Pane-1 cells under hypoxic condition with high-dose irradiation. (authors)

  7. X-ray picture of the respiratory distress syndrome (shock lung)

    International Nuclear Information System (INIS)

    Sharov, B.K.; Ana'ev, V.M.; Kiseleva, M.N.

    1993-01-01

    X-Ray picture of the respiratory distress syndrome (shock lung) in 78 patients exposed to high temperature as a result of gas condensate explosion is analyzed. X-ray and morphologic fundings in these patients are compared to those in 13 similar patients in whom acute respiratory failure developed because of other causes. Morphologic basis of the4 majority of x-ray signs of acute respiratory distress has been investigated. A relationship between respiratory distress syndrome development and changes in the heart size has been revealed, which may serve the prediction criterion

  8. LW6, a hypoxia-inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells.

    Science.gov (United States)

    Sato, Mariko; Hirose, Katsumi; Kashiwakura, Ikuo; Aoki, Masahiko; Kawaguchi, Hideo; Hatayama, Yoshiomi; Akimoto, Hiroyoshi; Narita, Yuichiro; Takai, Yoshihiro

    2015-09-01

    Hypoxia‑inducible factor 1 (HIF‑1) activates the transcription of genes that act upon the adaptation of cancer cells to hypoxia. LW6, an HIF‑1 inhibitor, was hypothesized to improve resistance to cancer therapy in hypoxic tumors by inhibiting the accumulation of HIF‑1α. A clear anti‑tumor effect under low oxygen conditions would indicate that LW6 may be an improved treatment strategy for cancer in hypoxia. In the present study, the HIF‑1 inhibition potential of LW6 on the growth and apoptosis of A549 lung cancer cells in association with oxygen availability was evaluated. LW6 was observed to inhibit the expression of HIF‑1α induced by hypoxia in A549 cells at 20 mM, independently of the von Hippel‑Lindau protein. In addition, at this concentration, LW6 induced hypoxia‑selective apoptosis together with a reduction in the mitochondrial membrane potential. The intracellular reactive oxygen species levels increased in LW6‑treated hypoxic A549 cells and LW6 induced a hypoxia‑selective increase of mitochondrial O2•‑. In conclusion, LW6 inhibited the growth of hypoxic A549 cells by affecting the mitochondria. The inhibition of the mitochondrial respiratory chain is suggested as a potentially effective strategy to target apoptosis in cancer cells.

  9. Myxedema Coma with Reversible Cardiopulmonary Failure: a Rare Entity in 21St Century.

    Science.gov (United States)

    Dhakal, Prajwal; Pant, Manisha; Acharya, Pranab Sharma; Dahal, Sumit; Bhatt, Vijaya Raj

    2015-09-01

    Myxedema coma, a rare entity in 21st century in developed nations, is a decompensated phase of hypothyroidism with high mortality rates. We describe a young woman with myxedema, who developed respiratory failure, congestive heart failure and significant pericardial effusion, some of the uncommon manifestations. Decreased cardiac contractility can result in cardiomyopathy and heart failure. As illustrated by this case, myxedema can also result in significant pericardial effusion due to increased vascular permeability. Myxedema can further be complicated by alveolar hypoventilation and respiratory failure secondary to the lack of central drive as well as respiratory muscle weakness. Prompt therapy with thyroid hormone replacement, glucocorticoid therapy, aggressive supportive care and management of the precipitating event can save lives and reverse the cardiopulmonary symptoms, as in our patient. Hence, physicians should have a high index of suspicion for myxedema coma in patients with unexplained cardiopulmonary failure. Our report is, therefore, aimed at bringing awareness about the rare but fatal manifestations of myxedema coma.

  10. Critically Ill Patients With the Middle East Respiratory Syndrome: A Multicenter Retrospective Cohort Study.

    Science.gov (United States)

    Arabi, Yaseen M; Al-Omari, Awad; Mandourah, Yasser; Al-Hameed, Fahad; Sindi, Anees A; Alraddadi, Basem; Shalhoub, Sarah; Almotairi, Abdullah; Al Khatib, Kasim; Abdulmomen, Ahmed; Qushmaq, Ismael; Mady, Ahmed; Solaiman, Othman; Al-Aithan, Abdulsalam M; Al-Raddadi, Rajaa; Ragab, Ahmed; Al Mekhlafi, Ghaleb A; Al Harthy, Abdulrahman; Kharaba, Ayman; Ahmadi, Mashael Al; Sadat, Musharaf; Mutairi, Hanan Al; Qasim, Eman Al; Jose, Jesna; Nasim, Maliha; Al-Dawood, Abdulaziz; Merson, Laura; Fowler, Robert; Hayden, Frederick G; Balkhy, Hanan H

    2017-10-01

    To describe patient characteristics, clinical manifestations, disease course including viral replication patterns, and outcomes of critically ill patients with severe acute respiratory infection from the Middle East respiratory syndrome and to compare these features with patients with severe acute respiratory infection due to other etiologies. Retrospective cohort study. Patients admitted to ICUs in 14 Saudi Arabian hospitals. Critically ill patients with laboratory-confirmed Middle East respiratory syndrome severe acute respiratory infection (n = 330) admitted between September 2012 and October 2015 were compared to consecutive critically ill patients with community-acquired severe acute respiratory infection of non-Middle East respiratory syndrome etiology (non-Middle East respiratory syndrome severe acute respiratory infection) (n = 222). None. Although Middle East respiratory syndrome severe acute respiratory infection patients were younger than those with non-Middle East respiratory syndrome severe acute respiratory infection (median [quartile 1, quartile 3] 58 yr [44, 69] vs 70 [52, 78]; p < 0.001), clinical presentations and comorbidities overlapped substantially. Patients with Middle East respiratory syndrome severe acute respiratory infection had more severe hypoxemic respiratory failure (PaO2/FIO2: 106 [66, 160] vs 176 [104, 252]; p < 0.001) and more frequent nonrespiratory organ failure (nonrespiratory Sequential Organ Failure Assessment score: 6 [4, 9] vs 5 [3, 7]; p = 0.002), thus required more frequently invasive mechanical ventilation (85.2% vs 73.0%; p < 0.001), oxygen rescue therapies (extracorporeal membrane oxygenation 5.8% vs 0.9%; p = 0.003), vasopressor support (79.4% vs 55.0%; p < 0.001), and renal replacement therapy (48.8% vs 22.1%; p < 0.001). After adjustment for potential confounding factors, Middle East respiratory syndrome was independently associated with death compared to non-Middle East respiratory syndrome severe acute respiratory

  11. Pediatric Specialty Care Model for Management of Chronic Respiratory Failure: Cost and Savings Implications and Misalignment With Payment Models.

    Science.gov (United States)

    Graham, Robert J; McManus, Michael L; Rodday, Angie Mae; Weidner, Ruth Ann; Parsons, Susan K

    2018-05-01

    To describe program design, costs, and savings implications of a critical care-based care coordination model for medically complex children with chronic respiratory failure. All program activities and resultant clinical outcomes were tracked over 4 years using an adapted version of the Care Coordination Measurement Tool. Patient characteristics, program activity, and acute care resource utilization were prospectively documented in the adapted version of the Care Coordination Measurement Tool and retrospectively cross-validated with hospital billing data. Impact on total costs of care was then estimated based on program outcomes and nationally representative administrative data. Tertiary children's hospital. Critical Care, Anesthesia, Perioperative Extension and Home Ventilation Program enrollees. None. The program provided care for 346 patients and families over the study period. Median age at enrollment was 6 years with more than half deriving secondary respiratory failure from a primary neuromuscular disease. There were 11,960 encounters over the study period, including 1,202 home visits, 673 clinic visits, and 4,970 telephone or telemedicine encounters. Half (n = 5,853) of all encounters involved a physician and 45% included at least one care coordination activity. Overall, we estimated that program interventions were responsible for averting 556 emergency department visits and 107 hospitalizations. Conservative monetization of these alone accounted for annual savings of $1.2-2 million or $407/pt/mo net of program costs. Innovative models, such as extension of critical care services, for high-risk, high-cost patients can result in immediate cost savings. Evaluation of financial implications of comprehensive care for high-risk patients is necessary to complement clinical and patient-centered outcomes for alternative care models. When year-to-year cost variability is high and cost persistence is low, these savings can be estimated from documentation within care

  12. Clinical outcomes of isolated renal failure compared to other forms of organ failure in patients with severe acute pancreatitis.

    Science.gov (United States)

    Gougol, Amir; Dugum, Mohannad; Dudekula, Anwar; Greer, Phil; Slivka, Adam; Whitcomb, David C; Yadav, Dhiraj; Papachristou, Georgios I

    2017-08-07

    To assess differences in clinical outcomes of isolated renal failure (RF) compared to other forms of organ failure (OF) in patients with severe acute pancreatitis (SAP). Using a prospectively maintained database of patients with acute pancreatitis admitted to a tertiary medical center between 2003 and 2016, those with evidence of persistent OF were classified to renal, respiratory, cardiovascular, or multi-organ (2 or more organs). Data regarding demographics, comorbidities, etiology of acute pancreatitis, and clinical outcomes were prospectively recorded. Differences in clinical outcomes after development of isolated RF in comparison to other forms of OF were determined using independent t and Mann-Whitney U tests for continues variables, and χ 2 test for discrete variables. Among 500 patients with acute pancreatitis, 111 patients developed persistent OF: mean age was 54 years, and 75 (67.6%) were male. Forty-three patients had isolated OF: 17 (15.3%) renal, 25 (21.6%) respiratory, and 1 (0.9%) patient with cardiovascular failure. No differences in demographics, etiology of acute pancreatitis, systemic inflammatory response syndrome scores, or development of pancreatic necrosis were seen between patients with isolated RF vs isolated respiratory failure. Patients with isolated RF were less likely to require nutritional support (76.5% vs 96%, P = 0.001), ICU admission (58.8% vs 100%, P = 0.001), and had shorter mean ICU stay (2.4 d vs 15.7 d, P pancreatitis.

  13. The effects of carbon monoxide on respiratory chemoreflexes in humans

    International Nuclear Information System (INIS)

    Vesely, A.E.; Somogyi, R.B.; Sasano, Hiroshi; Sasano, Nobuko; Fisher, J.A.; Duffin, James

    2004-01-01

    As protection against low-oxygen and high-carbon-dioxide environments, the respiratory chemoreceptors reflexly increase breathing. Since CO is also frequently present in such environments, it is important to know whether CO affects the respiratory chemoreflexes responsiveness. Although the peripheral chemoreceptors fail to detect hypoxia produced by CO poisoning, whether CO affects the respiratory chemoreflex responsiveness to carbon dioxide is unknown. The responsiveness of 10 healthy male volunteers were assessed before and after inhalation of ∼1200 ppm CO in air using two iso-oxic rebreathing tests; hypoxic, to emphasize the peripheral chemoreflex, and hyperoxic, to emphasize the central chemoreflex. Although mean (SEM) COHb values of 10.2 (0.2)% were achieved, no statistically significant effects of CO were observed. The average differences between pre- and post-CO values for ventilation response threshold and sensitivity were -0.5 (0.9) mmHg and 0.8 (0.3) L/min/mmHg, respectively, for hyperoxia, and 0.7 (1.1) mmHg and 1.2 (0.8) L/min/mmHg, respectively, for hypoxia. The 95% confidence intervals for the effect of CO were small. We conclude that environments with low levels of CO do not have a clinically significant effect acutely on either the central or the peripheral chemoreflex responsiveness to carbon dioxide

  14. Hypoxic preconditioning induces neuroprotective stanniocalcin-1 in brain via IL-6 signaling

    DEFF Research Database (Denmark)

    Westberg, Johan A; Serlachius, Martina; Lankila, Petri

    2007-01-01

    BACKGROUND AND PURPOSE: Exposure of animals for a few hours to moderate hypoxia confers relative protection against subsequent ischemic brain damage. This phenomenon, known as hypoxic preconditioning, depends on new RNA and protein synthesis, but its molecular mechanisms are poorly understood...... originally reported expression of mammalian STC-1 in brain neurons and showed that STC-1 guards neurons against hypercalcemic and hypoxic damage. METHODS: We treated neural Paju cells with IL-6 and measured the induction of STC-1 mRNA. In addition, we quantified the effect of hypoxic preconditioning on Stc-1...... mRNA levels in brains of wild-type and IL-6 deficient mice. Furthermore, we monitored the Stc-1 response in brains of wild-type and transgenic mice, overexpressing IL-6 in the astroglia, before and after induced brain injury. RESULTS: Hypoxic preconditioning induced an upregulated expression of Stc...

  15. Hypoxic pretreatment protects against neuronal damage of the rat hippocampus induced by severe hypoxia.

    Science.gov (United States)

    Gorgias, N; Maidatsi, P; Tsolaki, M; Alvanou, A; Kiriazis, G; Kaidoglou, K; Giala, M

    1996-04-01

    The present study investigates whether under conditions of successive hypoxic exposures pretreatment with mild (15% O(2)) or moderate (10% O(2)) hypoxia, protects hippocampal neurones against damage induced by severe (3% O(2)) hypoxia. The ultrastructural findings were also correlated with regional superoxide dismutase (SOD) activity changes. In unpretreated rats severe hypoxia induced ultrastructural changes consistent with the aspects of delayed neuronal death (DND). However, in preexposed animals hippocampal damage was attenuated in an inversely proportional way with the severity of the hypoxic pretreatment. The ultrastructural hypoxic tolerance findings were also closely related to increased regional SOD activity levels. Thus the activation of the endogenous antioxidant defense by hypoxic preconditioning, protects against hippocampal damage induced by severe hypoxia. The eventual contribution of increased endogenous adenosine and/or reduced excitotoxicity to induce hypoxic tolerance is discussed.

  16. Preclinical assessment of hypoxic marker specificity and sensitivity

    International Nuclear Information System (INIS)

    Iyer, Renuka V.; Engelhardt, Edward L.; Stobbe, Corinne C.; Schneider, Richard F.; Chapman, J. Donald

    1998-01-01

    Purpose: In the search for a sensitive, accurate, and noninvasive technique for quantifying human tumor hypoxia, our laboratory has synthesized several potential radiodiagnostic agents. The purpose of this study was to assess and compare the hypoxic marking properties of both radioiodinated and Tc-99m labeled markers in appropriate test systems which can predict for in vivo activity. Materials and Methods: Preclinical assessment of hypoxic marker specificity and sensitivity employed three laboratory assays with tumor cells in vitro and in vivo. Radiolabeled marker uptake and/or binding to whole EMT-6 tumor cells under extremely hypoxic and aerobic conditions was measured and their ratio defined hypoxia-specific factor (HSF). Marker specificity to hypoxic tumor tissue was estimated from its selective avidity to two rodent tumors in vivo, whose radiobiologic hypoxic fractions (HF) had been measured. The ratios of % injected dose/gram (%ID/g) of marker at various times in EMT-6 tumor tissue relative to that in the blood and muscle of scid mice were used to quantify hypoxia-specific activity. This tumor in this host exhibited an average radiobiologic HF of ∼35%. As well, nuclear medicine images were acquired from R3327-AT (HF ≅15%) and R3327-H (no measurable HF) prostate carcinomas growing in rats to distinguish between marker avidity due to hypoxia versus perfusion. Results: The HSF for FC-103 and other iodinated markers were higher (5-40) than those for FC-306 and other Tc-99m labeled markers. The latter did not show hypoxia-specific uptake into cells in vitro. Qualitative differences were observed in the biodistribution and clearance kinetics of the iodinated azomycin nucleosides relative to the technetium chelates. The largest tumor/blood (T/B) and tumor/muscle (T/M) ratios were observed for compounds of the azomycin nucleoside class in EMT-6 tumor-bearing scid mice. These markers also showed a 3-4 x higher uptake into R3327-AT tumors relative to the well

  17. Physiological Responses to Two Hypoxic Conditioning Strategies in Healthy Subjects.

    Science.gov (United States)

    Chacaroun, Samarmar; Borowik, Anna; Morrison, Shawnda A; Baillieul, Sébastien; Flore, Patrice; Doutreleau, Stéphane; Verges, Samuel

    2016-01-01

    Objective: Hypoxic exposure can be used as a therapeutic tool by inducing various cardiovascular, neuromuscular, and metabolic adaptations. Hypoxic conditioning strategies have been evaluated in patients with chronic diseases using either sustained (SH) or intermittent (IH) hypoxic sessions. Whether hypoxic conditioning via SH or IH may induce different physiological responses remains to be elucidated. Methods: Fourteen healthy active subjects (7 females, age 25 ± 8 years, body mass index 21.5 ± 2.5 kg·m -2 ) performed two interventions in a single blind, randomized cross-over design, starting with either 3 x SH (48 h apart), or 3 x IH (48 h apart), separated by a 2 week washout period. SH sessions consisted of breathing a gas mixture with reduced inspiratory oxygen fraction (FiO 2 ), continuously adjusted to reach arterial oxygen saturations (SpO 2 ) of 70-80% for 1 h. IH sessions consisted of 5 min with reduced FiO 2 (SpO 2 = 70-80%), followed by 3-min normoxia, repeated seven times. During the first (S1) and third (S3) sessions of each hypoxic intervention, cardiorespiratory parameters, and muscle and pre-frontal cortex oxygenation (near infrared spectroscopy) were assessed continuously. Results : Minute ventilation increased significantly during IH sessions (+2 ± 2 L·min -1 ) while heart rate increased during both SH (+11 ± 4 bpm) and IH (+13 ± 5 bpm) sessions. Arterial blood pressure increased during all hypoxic sessions, although baseline normoxic systolic blood pressure was reduced from S1 to S3 in IH only (-8 ± 11 mmHg). Muscle oxygenation decreased significantly during S3 but not S1, for both hypoxic interventions (S3: SH -6 ± 5%, IH -3 ± 4%); pre-frontal oxygenation decreased in S1 and S3, and to a greater extent in SH vs. IH (-13 ± 3% vs. -6 ± 6%). Heart rate variability indices indicated a significantly larger increase in sympathetic activity in SH vs. IH (lower SDNN, PNN50, and RMSSD values in SH). From S1 to S3, further reduction in heart

  18. Low-dose radiation suppresses Pokemon expression under hypoxic conditions.

    Science.gov (United States)

    Kim, Seung-Whan; Yu, Kweon; Shin, Kee-Sun; Kwon, Kisang; Hwang, Tae-Sik; Kwon, O-Yu

    2014-01-01

    Our previous data demonstrated that CoCl2-induced hypoxia controls endoplasmic reticulum (ER) stress-associated and other intracellular factors. One of them, the transcription factor Pokemon, was differentially regulated by low-dose radiation (LDR). There are limited data regarding how this transcription factor is involved in expression of the unfolded protein response (UPR) under hypoxic conditions. The purpose of this study was to obtain clues on how Pokemon is involved in the UPR. Pokemon was selected as a differentially expressed gene under hypoxic conditions; however, its regulation was clearly repressed by LDR. It was also demonstrated that both expression of ER chaperones and ER stress sensors were affected by hypoxic conditions, and the same results were obtained when cells in which Pokemon was up- or down-regulated were used. The current state of UPR and LDR research associated with the Pokemon pathway offers an important opportunity to understand the oncogenesis, senescence, and differentiation of cells, as well as to facilitate introduction of new therapeutic radiopharmaceuticals.

  19. In vivo assay of the radiation sensitivity of hypoxic tumour cells. Influence of radiation quality and hypoxic sensitization

    International Nuclear Information System (INIS)

    Porschen, W.; Bosiljanoff, P.; Gewehr, K.; Muehlensiepen, H.; Feinendegen, L.E.

    1977-01-01

    In order to measure quantitatively tumour cell kinetics in living mice, tumour bearing animals (sarcoma-180) received intravenously 5-iodo-2'-deoxyuridine (IUdR), a thymidine analogue, which was labelled with 125 I or with 131 I, both of which can be easily externally counted by their gamma emission. IUdR is stably bound to DNA, reutilization is minimal and the measured activity loss from the tumour later than 50 hours after injection signals cell loss or cell death. The effect of irradiation on euoxic and average tumour cells was studied by sequentially labelling the tumour bearing animals first with 125 IUdR and, 70 hours later, with 131 IUdR. At the time of the second injection the average tumour cell population is labelled by the first injection of 125 IUdR, and the second injection of 131 IUdR nearly exclusively tags the perivascular tumour cells; these are euoxic in contrast to the average tumour cell, a large proportion of which is hypoxic. The radiation-induced activity loss rates from the two labelled tumour cell populations indicate the sensitivities of the two populations. At dose levels that cause identical effects on euoxic cells, the ratio of radiation-induced enhancement of cell loss rates for euoxic cells to average cells was 2.6 for 60 Co gamma radiation, 1.4 for 15MeV neutron irradiation, and 1.0 for alpha irradiation (1.5.MeV). The effect of five hypoxic cell sensitizers was analysed. The sensitization was limited to hypoxic cells, and the most effective drug was Ro-07-0582, showing at the 50% level of maximum effect a dose modifying factor of 1.5. Sensitization was highest when the drug was given 15 min prior to irradiation. Hyperthermia affected nearly exclusively hypoxic cells and showed a dose modifying factor of about 2 when the tumours were heated at 42 0 C for 30 min immediately after irradiation. The resulting enhancement of effect was reduced when hyperthermia was applied prior to irradiation. (author)

  20. Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions

    Science.gov (United States)

    Felfoul, Ouajdi; Mohammadi, Mahmood; Taherkhani, Samira; de Lanauze, Dominic; Zhong Xu, Yong; Loghin, Dumitru; Essa, Sherief; Jancik, Sylwia; Houle, Daniel; Lafleur, Michel; Gaboury, Louis; Tabrizian, Maryam; Kaou, Neila; Atkin, Michael; Vuong, Té; Batist, Gerald; Beauchemin, Nicole; Radzioch, Danuta; Martel, Sylvain

    2016-11-01

    Oxygen-depleted hypoxic regions in the tumour are generally resistant to therapies. Although nanocarriers have been used to deliver drugs, the targeting ratios have been very low. Here, we show that the magneto-aerotactic migration behaviour of magnetotactic bacteria, Magnetococcus marinus strain MC-1 (ref. 4), can be used to transport drug-loaded nanoliposomes into hypoxic regions of the tumour. In their natural environment, MC-1 cells, each containing a chain of magnetic iron-oxide nanocrystals, tend to swim along local magnetic field lines and towards low oxygen concentrations based on a two-state aerotactic sensing system. We show that when MC-1 cells bearing covalently bound drug-containing nanoliposomes were injected near the tumour in severe combined immunodeficient beige mice and magnetically guided, up to 55% of MC-1 cells penetrated into hypoxic regions of HCT116 colorectal xenografts. Approximately 70 drug-loaded nanoliposomes were attached to each MC-1 cell. Our results suggest that harnessing swarms of microorganisms exhibiting magneto-aerotactic behaviour can significantly improve the therapeutic index of various nanocarriers in tumour hypoxic regions.

  1. treatment of common respiratory infections: the antibiotic dilemma

    African Journals Online (AJOL)

    Enrique

    HIV infection. Chronic cardiovascular disease. Leukaemia/lymphoma. Chronic respiratory disease. Myeloma. Other chronic medical conditions. Other malignancies. Diabetes mellitus. Chronic renal failure. Cirrhosis. Nephrotic syndrome. Alcoholism. Organ transplants. Special environments. Immunosuppressive medication.

  2. The Use of Benzodiazepine Receptor Agonists and Risk of Respiratory Failure in Patients with Chronic Obstructive Pulmonary Disease: A Nationwide Population-Based Case-Control Study.

    Science.gov (United States)

    Chen, Su-Jung; Yeh, Chiu-Mei; Chao, Tze-Fan; Liu, Chia-Jen; Wang, Kang-Ling; Chen, Tzeng-Ji; Chou, Pesus; Wang, Fu-Der

    2015-07-01

    Insomnia is prevalent in patients with chronic obstructive pulmonary disease (COPD), and benzodiazepine receptor agonists (BZRAs) are the most commonly used drugs despite their adverse effects on respiratory function. The aim of this study was to investigate whether the use of BZRAs was associated with an increased risk of respiratory failure (RF) in COPD patients. Matched case-control study. National Health Insurance Research Database (NHIRD) in Taiwan. The case group consisted of 2,434 COPD patients with RF, and the control group consisted of 2,434 COPD patients without RF, matched for age, sex, and date of enrollment. Exposure to BZRAs during the 180-day period preceding the index date was analyzed and compared in the case and control groups. Conditional logistic regression was performed, and the use of BZRAs was associated with an increased risk of RF (adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.14-2.13). In subgroup analysis, we found that the benzodiazepine (BZD) users had a higher risk of RF (aOR 1.58, 95% CI 1.14-2.20), whereas the risk in non-benzodiazepine (non-BZD) users was insignificant (aOR 0.85, 95% CI 0.51-1.44). A greater than 2-fold increase in risk was found in those who received two or more kinds of BZRAs and those using a combination of BZD and non-BZD medications. The use of benzodiazepine receptor agonists was a significant risk factor for respiratory failure in patients with chronic obstructive pulmonary disease (COPD). Compared to benzodiazepine, the prescription of non-benzodiazepine may be safer for the management of insomnia in COPD patients. © 2015 Associated Professional Sleep Societies, LLC.

  3. Sudden death of a child due to respiratory diphtheria.

    Science.gov (United States)

    Swain, Rajanikanta; Behera, Chittaranjan; Arava, Sudheer Kumar; Kundu, Naveen

    2016-06-01

    A four-year-old girl presented to the emergency department with respiratory distress. Death occurred despite attempted resuscitation. The illness was not clinically diagnosed. Her father revealed that she had a fever and sore throat for the last four days and was not immunised for diphtheria. Characteristic gross and microscopic pathology of respiratory diphtheria and microbiological findings were observed. The cause of death was acute respiratory failure consequent upon upper airway obstruction from diphtheria. Forensic pathologists should remember that the diphtheria cases can cause sudden death especially in developing countries. © The Author(s) 2016.

  4. Radiosensitization of hypoxic tumor cells by simultaneous administration of hyperthermia and nitroimidazoles

    International Nuclear Information System (INIS)

    Hofer, K.G.; Hofer, M.G.; Ieracitano, J.; McLaughlin, W.H.

    1977-01-01

    The radiation response of oxygenated and hypoxic L1210 leukemia cells subjected to in vivo treatments with hyperthermia and/or chemical radiosensitizers was evaluated with the [ 125 I]iododeoxyuridine prelabeling assay. X irradiation of L1210 cells at body temperatures of 41 0 C or higher resulted in strongly enhanced tumor cell death. The magnitude of this thermal effect increased with increasing temperatures. Hypoxic L1210 cells were particularly sensitive to heat induced enhancement of radiation damage, i.e., the sensitizing effects were more pronounced and occurred at lower temperatures. Chemical radiosensitizers (metronidazole, Ro 7-0582) selectively sensitized hypoxic L1210 populations; fully oxygenated cells were not affected. Considerable radiosensitization was achieved at nontoxic dose levels of the two sensitizers. Experiments designed to determine the degree of radiosensititization as a function of drug dose showed that Ro 7-0582 was consistently more effective than metronidazole in sensitizing hypoxic tumor populations. At the highest drug dose used (3 mg/g body wt) the DMF was 2.2 for metronidazole and 2.8 for Ro 7-0582. Combined administration of hyperthermia and Ro 7-0582 (or metronidazole) produced synergistic potentiation of radiation damage in hypoxic L1210 populations (DMF of 4.2). Under optimal conditions, hypoxic L1210 cells subjected simultaneously to both modes of radiosensitization became more radiosensitive than untreated, fully oxygenated L1210 cells. Experiments on two other tumor lines (BP-8 murine sarcoma and Ehrlich ascites cells) indicate that such synergistic radiosensitization effects are not unique to L1210 cells

  5. Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis

    Directory of Open Access Journals (Sweden)

    De-An Zhao

    Full Text Available Abstract Background and objectives: Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. Methods: A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Results: Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Conclusions: Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis.

  6. Metabolic profiling of hypoxic cells revealed a catabolic signature required for cell survival.

    Directory of Open Access Journals (Sweden)

    Christian Frezza

    Full Text Available Hypoxia is one of the features of poorly vascularised areas of solid tumours but cancer cells can survive in these areas despite the low oxygen tension. The adaptation to hypoxia requires both biochemical and genetic responses that culminate in a metabolic rearrangement to counter-balance the decrease in energy supply from mitochondrial respiration. The understanding of metabolic adaptations under hypoxia could reveal novel pathways that, if targeted, would lead to specific death of hypoxic regions. In this study, we developed biochemical and metabolomic analyses to assess the effects of hypoxia on cellular metabolism of HCT116 cancer cell line. We utilized an oxygen fluorescent probe in anaerobic cuvettes to study oxygen consumption rates under hypoxic conditions without the need to re-oxygenate the cells and demonstrated that hypoxic cells can maintain active, though diminished, oxidative phosphorylation even at 1% oxygen. These results were further supported by in situ microscopy analysis of mitochondrial NADH oxidation under hypoxia. We then used metabolomic methodologies, utilizing liquid chromatography-mass spectrometry (LC-MS, to determine the metabolic profile of hypoxic cells. This approach revealed the importance of synchronized and regulated catabolism as a mechanism of adaptation to bioenergetic stress. We then confirmed the presence of autophagy under hypoxic conditions and demonstrated that the inhibition of this catabolic process dramatically reduced the ATP levels in hypoxic cells and stimulated hypoxia-induced cell death. These results suggest that under hypoxia, autophagy is required to support ATP production, in addition to glycolysis, and that the inhibition of autophagy might be used to selectively target hypoxic regions of tumours, the most notoriously resistant areas of solid tumours.

  7. In vitro effects of piracetam on the radiosensitivity of hypoxic cells (adaptation of MTT assay to hypoxic conditions); Effets in vitro du piracetam sur la radiosensibilite des cellules hypoxiques (adapatation du test au MTT aux conditions d`hypoxie)

    Energy Technology Data Exchange (ETDEWEB)

    Gheuens, E.E.O.; Bruijn, E.A. de; Van der Heyden, S.; Van Oosterom, A.T. [Universitaire Instelling Antwerpen, Antwerp (Belgium); Lagarde, P. [Universitaire Instelling Antwerpen, Antwerp (Belgium)]|[Institut Bergonie, 33 - Bordeaux (France); Pooter, C.M.J. de [Universitaire Instelling Antwerpen, Antwerp (Belgium)]|[Hopital de Middelheim, Anvers (Belgium); Chomy, F. [Institut Bergonie, 33 - Bordeaux (France)

    1995-12-31

    This paper describes the adaptation of the MTT assay to hypoxic conditions in order to test the in vitro effect of piracetam on hypoxic cells and particularly on the radiosensitivity of hypoxic cells since this drug has shown clinical effect on acute and chronic hypoxia. The V79 cell line was selected by reference to preliminary hypoxic experiments using clonogenic assay and euoxic experiments using clonogenic and MTT assays. Cell growth and survival in our hypoxic conditions were assessed using MTT assay with an enclosure and special 48-well plates both made of glass. Growth curves on glass plates after 1-hour exposure to nitrogen versus air were comparable, so there is no bias effect due to gas composition. Survival curves using MTT versus reference clonogenic assay were comparable after radiation exposure in eu- and hypoxic conditions, and confirm the validity of our original technique for creating hypoxia. The Oxygen Enhancement Ratio was of about 3 for 1-hour hypoxic exposure. Piracetam gave no cytotoxic effect up to 10 mM of piracetam. Growth curves after continuous drug exposure and 1-hour euoxic versus hypoxic exposure gave no cytotoxic effect up to 10 mM of piracetam. Survival curves after continuous drug exposure to 10 mM of piracetam gave no significant effect on the radiosensitivity of hypoxic V79 cells using MTT or clonogenic assay. (author). 32 refs., 6 figs.

  8. ACUTE RESPIRATORY SYNCYTIAL VIRUS INFECTION IN CHILDREN IN THE AGE ASPECT

    Directory of Open Access Journals (Sweden)

    V. B. Rovny

    2013-01-01

    Full Text Available The clinical features of laboratory-confirmed acute respiratory syncytial virus infection (ARSVI are described in 221 children of the age from 1 month to 5 years. Febrile fever has been recorded in 76% of patients with ARSVI, and significantly more often in children in the second year of life (92%, but the difference in the temerature or duration has not been found. 98% of children have had symptoms of the lower respiratory tract lesions. The most common ARSVI manifestations in the patients of the first year of life were obstructive diseases of the lower respiratory tract (obstructive bronchitis in 53% and bronchiolitis in 11% of children, in the patients of the second year of life — pneumonia (28%, p < 0,05 and catarrhal otitis (26%; p < 0,05. Bronchial obstruction syndrome in children of the first year of life was characterized by the significantly higher frequency (73% and the maximal duration (9,7 ± 1,08 days. The largest number of cases of the severe respiratory failure has been recorded among patients of the second year of life (3 degree of respiratory failure in 22% of patients, p < 0,05.

  9. Gold namoprtices enhance anti-tumor effect of radiotherapy to hypoxic tumor

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Sun; Lee, Eun Jung; Kim, Jae Won; Keum, Ki Chang; Koom, Woong Sub [Dept. of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Chung, Ui Seok; Koh, Won Gun [Dept. of Chemical and Biomolecular Engineering, Yonsei University, Seoul (Korea, Republic of)

    2016-09-15

    Hypoxia can impair the therapeutic efficacy of radiotherapy (RT). Therefore, a new strategy is necessary for enhancing the response to RT. In this study, we investigated whether the combination of nanoparticles and RT is effective in eliminating the radioresistance of hypoxic tumors. Gold nanoparticles (GNPs) consisting of a silica core with a gold shell were used. CT26 colon cancer mouse model was developed to study whether the combination of RT and GNPs reduced hypoxia-induced radioresistance. Hypoxia inducible factor-1α (HIF-1α) was used as a hypoxia marker. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were conducted to evaluate cell death. Hypoxic tumor cells had an impaired response to RT. GNPs combined with RT enhanced anti-tumor effect in hypoxic tumor compared with RT alone. The combination of GNPs and RT decreased tumor cell viability compare to RT alone in vitro. Under hypoxia, tumors treated with GNPs + RT showed a higher response than that shown by tumors treated with RT alone. When a reactive oxygen species (ROS) scavenger was added, the enhanced antitumor effect of GNPs + RT was diminished. In the present study, hypoxic tumors treated with GNPs + RT showed favorable responses, which might be attributable to the ROS production induced by GNPs + RT. Taken together, GNPs combined with RT seems to be potential modality for enhancing the response to RT in hypoxic tumors.

  10. Gold namoprtices enhance anti-tumor effect of radiotherapy to hypoxic tumor

    International Nuclear Information System (INIS)

    Kim, Mi Sun; Lee, Eun Jung; Kim, Jae Won; Keum, Ki Chang; Koom, Woong Sub; Chung, Ui Seok; Koh, Won Gun

    2016-01-01

    Hypoxia can impair the therapeutic efficacy of radiotherapy (RT). Therefore, a new strategy is necessary for enhancing the response to RT. In this study, we investigated whether the combination of nanoparticles and RT is effective in eliminating the radioresistance of hypoxic tumors. Gold nanoparticles (GNPs) consisting of a silica core with a gold shell were used. CT26 colon cancer mouse model was developed to study whether the combination of RT and GNPs reduced hypoxia-induced radioresistance. Hypoxia inducible factor-1α (HIF-1α) was used as a hypoxia marker. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were conducted to evaluate cell death. Hypoxic tumor cells had an impaired response to RT. GNPs combined with RT enhanced anti-tumor effect in hypoxic tumor compared with RT alone. The combination of GNPs and RT decreased tumor cell viability compare to RT alone in vitro. Under hypoxia, tumors treated with GNPs + RT showed a higher response than that shown by tumors treated with RT alone. When a reactive oxygen species (ROS) scavenger was added, the enhanced antitumor effect of GNPs + RT was diminished. In the present study, hypoxic tumors treated with GNPs + RT showed favorable responses, which might be attributable to the ROS production induced by GNPs + RT. Taken together, GNPs combined with RT seems to be potential modality for enhancing the response to RT in hypoxic tumors

  11. Reconstitution activity of hypoxic cultured human cord blood CD34-positive cells in NOG mice

    International Nuclear Information System (INIS)

    Shima, Haruko; Takubo, Keiyo; Iwasaki, Hiroko; Yoshihara, Hiroki; Gomei, Yumiko; Hosokawa, Kentaro; Arai, Fumio; Takahashi, Takao; Suda, Toshio

    2009-01-01

    Hematopoietic stem cells (HSCs) reside in hypoxic areas of the bone marrow. However, the role of hypoxia in the maintenance of HSCs has not been fully characterized. We performed xenotransplantation of human cord blood cells cultured in hypoxic or normoxic conditions into adult NOD/SCID/IL-2Rγ null (NOG) mice. Hypoxic culture (1% O 2 ) for 6 days efficiently supported the maintenance of HSCs, although cell proliferation was suppressed compared to the normoxic culture. In contrast, hypoxia did not affect in vitro colony-forming ability. Upregulation of a cell cycle inhibitor, p21, was observed in hypoxic culture. Immunohistochemical analysis of recipient bone marrow revealed that engrafted CD34 + CD38 - cord blood HSCs were hypoxic. Taken together, these results demonstrate the significance of hypoxia in the maintenance of quiescent human cord blood HSCs.

  12. Extracorporeal carbon dioxide removal for patients with acute respiratory failure secondary to the acute respiratory distress syndrome: a systematic review

    Science.gov (United States)

    2014-01-01

    Acute respiratory distress syndrome (ARDS) continues to have significant mortality and morbidity. The only intervention proven to reduce mortality is the use of lung-protective mechanical ventilation strategies, although such a strategy may lead to problematic hypercapnia. Extracorporeal carbon dioxide removal (ECCO2R) devices allow uncoupling of ventilation from oxygenation, thereby removing carbon dioxide and facilitating lower tidal volume ventilation. We performed a systematic review to assess efficacy, complication rates, and utility of ECCO2R devices. We included randomised controlled trials (RCTs), case–control studies and case series with 10 or more patients. We searched MEDLINE, Embase, LILACS (Literatura Latino Americana em Ciências da Saúde), and ISI Web of Science, in addition to grey literature and clinical trials registries. Data were independently extracted by two reviewers against predefined criteria and agreement was reached by consensus. Outcomes of interest included mortality, intensive care and hospital lengths of stay, respiratory parameters and complications. The review included 14 studies with 495 patients (two RCTs and 12 observational studies). Arteriovenous ECCO2R was used in seven studies, and venovenous ECCO2R in seven studies. Available evidence suggests no mortality benefit to ECCO2R, although post hoc analysis of data from the most recent RCT showed an improvement in ventilator-free days in more severe ARDS. Organ failure-free days or ICU stay have not been shown to decrease with ECCO2R. Carbon dioxide removal was widely demonstrated as feasible, facilitating the use of lower tidal volume ventilation. Complication rates varied greatly across the included studies, representing technological advances. There was a general paucity of high-quality data and significant variation in both practice and technology used among studies, which confounded analysis. ECCO2R is a rapidly evolving technology and is an efficacious treatment to enable

  13. Modulation of aerial respiratory behaviour in a pond snail.

    Science.gov (United States)

    Lukowiak, Ken; Martens, Kara; Orr, Mike; Parvez, Kashif; Rosenegger, David; Sangha, Susan

    2006-11-01

    Aerial respiratory in Lymnaea is driven by a three-neuron CPG whose sufficiency and necessity has been directly demonstrated. While this CPG is 'hard-wired' it displays a tremendous amount of plasticity. That is, it is possible by employing specific training procedures to alter how it functions in a specific hypoxic environment. Thus, it is possible to study directly the causal mechanisms of long-term memory formation, forgetting, and modulation of the memory at a single cell level. Thus, it is possible to use a relatively simple three-neuron CPG to study not only important questions concerning regulation of important homeostatic mechanisms but to also use it to study how learning and non-declarative memory are mediated at a cellular level.

  14. Apoptosis, energy metabolism, and fraction of radiobiologically hypoxic cells: a study of human melanoma multicellular spheroids.

    Science.gov (United States)

    Rofstad, E K; Eide, K; Skøyum, R; Hystad, M E; Lyng, H

    1996-09-01

    The magnitude of the fraction of radiobiologically hypoxic cells in tumours is generally believed to reflect the efficiency of the vascular network. Theoretical studies have suggested that the hypoxic fraction might also be influenced by biological properties of the tumour cells. Quantitative experimental results of cell energy metabolism, hypoxia- induced apoptosis, and radiobiological hypoxia are reported here. Human melanoma multicellular spheroids (BEX-c and WIX-c) were used as tumour models to avoid confounding effects of the vascular network. Radiobiological studies showed that the fractions of hypoxic cells in 1000-microM spheroids were 32 +/- 12% (BEX-c) and 2.5 +/- 1.1% (WIX-c). The spheroid hypoxic volume fractions (28 +/- 6% (BEX-c) and 1.4 +/- 7% (WIX-c)), calculated from the rate of oxygen consumption per cell, the cell packing density, and the thickness of the viable rim, were similar to the fractions of radiobiologically hypoxic cells. Large differences between tumours in fraction of hypoxic cells are therefore not necessarily a result of differences in the efficiency of the vascular network. Studies of monolayer cell cultures, performed to identify the biological properties of the BEX-c and WIX-c cells leading to this large difference in fraction of hypoxic cells, gave the following results: (1) WIX-c showed lower cell surviving fractions after exposure to hypoxia than BEX-c, (2) WIX-c showed higher glucose uptake and lactate release rates than BEX-c both under aerobic and hypoxic conditions, and (3) hypoxia induced apoptosis in WIX-c but not in BEX-c. These observations suggested that the difference between BEX-c and WIX-c spheroids in fraction of hypoxic cells resulted partly from differences in cell energy metabolism and partly from a difference in capacity to retain viability under hypoxic stress. The induction of apoptosis by hypoxia was identified as a phenomenon which has an important influence on the magnitude of the fraction of

  15. Hypoxia-activated prodrug TH-302 decreased survival rate of canine lymphoma cells under hypoxic condition.

    Science.gov (United States)

    Yamazaki, Hiroki; Lai, Yu-Chang; Tateno, Morihiro; Setoguchi, Asuka; Goto-Koshino, Yuko; Endo, Yasuyuki; Nakaichi, Munekazu; Tsujimoto, Hajime; Miura, Naoki

    2017-01-01

    We tested the hypotheses that hypoxic stimulation enhances growth potentials of canine lymphoma cells by activating hypoxia-inducible factor 1α (HIF-1α), and that the hypoxia-activated prodrug (TH-302) inhibits growth potentials in the cells. We investigated how hypoxic culture affects the growth rate, chemoresistance, and invasiveness of canine lymphoma cells and doxorubicin (DOX)-resistant lymphoma cells, and influences of TH-302 on survival rate of the cells under hypoxic conditions. Our results demonstrated that hypoxic culture upregulated the expression of HIF-1α and its target genes, including ATP-binding cassette transporter B1 (ABCB1), ATP-binding cassette transporter G2 (ABCG2), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and survivin, and enhanced the growth rate, DOX resistance, and invasiveness of the cells. Additionally, TH-302 decreased the survival rate of the cells under hypoxic condition. Our studies suggest that hypoxic stimulation may advance the tumorigenicity of canine lymphoma cells, favoring malignant transformation. Therefore, the data presented may contribute to the development of TH-302-based hypoxia-targeting therapies for canine lymphoma.

  16. The hTERT promoter enhances the antitumor activity of an oncolytic adenovirus under a hypoxic microenvironment.

    Directory of Open Access Journals (Sweden)

    Yuuri Hashimoto

    Full Text Available Hypoxia is a microenvironmental factor that contributes to the invasion, progression and metastasis of tumor cells. Hypoxic tumor cells often show more resistance to conventional chemoradiotherapy than normoxic tumor cells, suggesting the requirement of novel antitumor therapies to efficiently eliminate the hypoxic tumor cells. We previously generated a tumor-specific replication-competent oncolytic adenovirus (OBP-301: Telomelysin, in which the human telomerase reverse transcriptase (hTERT promoter drives viral E1 expression. Since the promoter activity of the hTERT gene has been shown to be upregulated by hypoxia, we hypothesized that, under hypoxic conditions, the antitumor effect of OBP-301 with the hTERT promoter would be more efficient than that of the wild-type adenovirus 5 (Ad5. In this study, we investigated the antitumor effects of OBP-301 and Ad5 against human cancer cells under a normoxic (20% oxygen or a hypoxic (1% oxygen condition. Hypoxic condition induced nuclear accumulation of the hypoxia-inducible factor-1α and upregulation of hTERT promoter activity in human cancer cells. The cytopathic activity of OBP-301 was significantly higher than that of Ad5 under hypoxic condition. Consistent with their cytopathic activity, the replication of OBP-301 was significantly higher than that of Ad5 under the hypoxic condition. OBP-301-mediated E1A was expressed within hypoxic areas of human xenograft tumors in mice. These results suggest that the cytopathic activity of OBP-301 against hypoxic tumor cells is mediated through hypoxia-mediated activation of the hTERT promoter. Regulation of oncolytic adenoviruses by the hTERT promoter is a promising antitumor strategy, not only for induction of tumor-specific oncolysis, but also for efficient elimination of hypoxic tumor cells.

  17. Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) in children and adults

    DEFF Research Database (Denmark)

    Gebistorf, Fabienne; Karam, Oliver; Wetterslev, Jørn

    2016-01-01

    BACKGROUND: Acute hypoxaemic respiratory failure (AHRF) and mostly acute respiratory distress syndrome (ARDS) are critical conditions. AHRF results from several systemic conditions and is associated with high mortality and morbidity in individuals of all ages. Inhaled nitric oxide (INO) has been...

  18. [Management and treatment of respiratory failure associated with amyotrophic lateral sclerosis].

    Science.gov (United States)

    Danel-Brunaud, V; Perez, T; Just, N; Destée, A

    2005-04-01

    In amyotrophic lateral sclerosis (ALS), respiratory muscle involvement is highly predictive of survival and quality of life (QOL). There is compelling evidence that non invasive ventilation (NIV) prolongs survival by several months and improves QOL more than any other currently available treatment. Frequent testing of pulmonary function and regular evaluations are recommended since 1999 by the American Academy of Neurology in order to take appropriate treatment decisions. There are numerous tests available to evaluate respiratory status in ALS and it is important to know their sensitivity and specificity to recognize clinical risk situations. Some recent data suggest that sniff nasal pressure and maximal inspiratory pressure (MIP) can be performed reliably by most ALS patients and are more sensitive to decrements in inspiratory muscle strength than spirometry or arterial blood gasometry. Airway obstruction caused by ineffective coughing is the principal cause of intolerance to NIV. Several factors other than respiratory muscle strength may affect pulmonary function: postural changes, nutritional status, infectious disease, drugs. The neurologist has to coordinate multidisciplinary care, with attention to individual patient preferences, and with a frank and compassionate discussion between the patient, the family, the physicians and the caregivers.

  19. Effects on respiratory homeostasis of prolonged, continuous hyperoxia at 1.5 to 3.0 ATA in man in Predictive Studies V

    Science.gov (United States)

    Gelfand, R.; Clark, J. M.; Lambertsen, C. J.; Pisarello, J. B.

    1987-01-01

    Prolonged exposures of men to continuous hyperoxia at 3.0, 2.5, 2.0, and 1.5 ATA were conducted to define CNS oxygen tolerance and to investigate the effects of prolonged hyperoxia on CNS and other organ functions. Altered respiratory homeostasis was evident during exposures of men to 2.5 and 3.0 ATA O2 as nonprogressive increment in ventilation and reciprocal decrement in PET(CO2). These changes were progressive during exposure at 1.5 ATA O2. Mean values of respiratory reactivity at CO2 were somewhat increased following prolonged hyperoxia at 1.5 and 2.5 ATA, compared to preexposure mean values. Hypoxic ventilatory response was unchanged or enhanced after oxygen exposures at 1.5 and 2.5 ATA. Observed respiratory and body temperature changes were not of sufficient magnitude to impair function.

  20. Severe Respiratory Acidosis in Status Epilepticus as a Possible Etiology of Sudden Death in Lesch-Nyhan Disease: A Case Report and Review of the Literature.

    Science.gov (United States)

    Christy, Alison; Nyhan, William; Wilson, Jenny

    2017-01-01

    Lesch-Nyhan disease (LND) is an X-linked disorder of purine metabolism, associated with self-mutilation, dystonia, and chorea. Seizures are uncommon in LND. Patients with LND are at risk for sudden and unexpected death. The etiology of this is unknown, but appears to occur from a respiratory process. We propose that respiratory failure secondary to subclinical seizure may lead to sudden death in these patients. We report a case of an 11-year-old boy with LND who had two episodes of nocturnal gasping. The second event was immediately followed by a 10 min generalized seizure. Upon arrival at the hospital, an arterial blood gas test revealed a severe respiratory acidosis. Following aggressive treatment of his seizures, this patient did well, and was discharged home on oxcarbazepine with rectal diazepam. No further seizures have been noted in 1 year of follow-up. In this case report and review, we hypothesize that sudden death from respiratory failure in Lesch-Nyhan disease may in some cases be due to seizure-induced respiratory failure, akin to sudden unexpected death in epilepsy (SUDEP). We suggest screening for paroxysmal respiratory events; consideration of electroencephalography for patients with LND presenting in respiratory distress or failure; and consideration of more aggressive treatment of seizures in these patients. Brief Summary:We present an 11-year-old boy with Lesch-Nyhan disease (LND) who developed respiratory failure and severe respiratory acidosis from his first known seizure, which evolved to subclinical status epilepticus. We propose that patients with LND have a predisposition to respiratory failure and sudden death, which in some cases may be provoked by seizure (sudden unexpected death in epilepsy, or SUDEP).

  1. Extracorporeal respiratory support in adult patients

    Directory of Open Access Journals (Sweden)

    Thiago Gomes Romano

    Full Text Available ABSTRACT In patients with severe respiratory failure, either hypoxemic or hypercapnic, life support with mechanical ventilation alone can be insufficient to meet their needs, especially if one tries to avoid ventilator settings that can cause injury to the lungs. In those patients, extracorporeal membrane oxygenation (ECMO, which is also very effective in removing carbon dioxide from the blood, can provide life support, allowing the application of protective lung ventilation. In this review article, we aim to explore some of the most relevant aspects of using ECMO for respiratory support. We discuss the history of respiratory support using ECMO in adults, as well as the clinical evidence; costs; indications; installation of the equipment; ventilator settings; daily care of the patient and the system; common troubleshooting; weaning; and discontinuation.

  2. [Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis].

    Science.gov (United States)

    Zhao, De-An; Bi, Ling-Yun; Huang, Qian; Zhang, Fang-Min; Han, Zi-Ming

    Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  3. Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis.

    Science.gov (United States)

    Zhao, De-An; Bi, Ling-Yun; Huang, Qian; Zhang, Fang-Min; Han, Zi-Ming

    Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  4. Effects of Hypoxic Training versus Normoxic Training on Exercise Performance in Competitive Swimmers

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    Hun-Young Park, Kiwon Lim

    2017-12-01

    Full Text Available In swimming competition, optimal swimming performance is characterized by a variety of interchangeable components, such as aerobic exercise capacity, anaerobic power and muscular function. Various hypoxic training methods would potentiate greater performance improvements compared to similar training at sea-level. Therefore, this study aimed to evaluate the effects of six-weeks of hypoxic training on exercise performance in moderately trained competitive swimmers. Twenty swimmers were equally divided into a normoxic training group (n = 10 for residing and training at sea-level (PIO2 = 149.7 mmHg, and a hypoxic training group (n = 10 for residing at sea-level but training at 526 mmHg hypobaric hypoxic condition (PIO2 = 100.6 mmHg. Aerobic exercise capacity, anaerobic power, muscular function, hormonal response and 50 and 400 m swimming performance were measured before and after training, which was composed of warm-up, continuous training, interval training, elastic resistance training, and cool-down. The training frequency was 120 min, 3 days per week for 6 weeks. Muscular function and hormonal response parameters showed significant interaction effects (all p 0.288 in muscular strength and endurance, growth hormone; GH, insulin like growth factor-1; IGF-1, and vascular endothelial growth factor; VEGF. The other variables demonstrated no significant interaction effects. However, a hypoxic training group also showed significantly increased maximal oxygen consumption; VO2max (p = 0.001, peak anaerobic power (p = 0.001, and swimming performances for 50 m (p = 0.000 and 400 m (p = 0.000. These results indicated that the hypoxic training method proposed in our study is effective for improvement of muscular strength and endurance in moderately trained competitive swimmers compared to control group. However, our hypoxic training method resulted in unclear changes in aerobic exercise capacity (VO2max, anaerobic power, and swimming performance of 50 m and

  5. Acute Tetraparesis with Respiratory Failure after Steroid Administration in a Patient with a Dural Arteriovenous Fistula at the Craniocervical Junction

    Science.gov (United States)

    Takahashi, Hisashi; Ueshima, Taiki; Goto, Daiki; Kimura, Tadashi; Yuki, Natsuko; Inoue, Yasuo; Yoshioka, Akira

    2017-01-01

    A 63-year-old man developed vomiting, paraparesis, dysuria, bulbar palsy, and orthostatic hypotension over a period of 5 months. Neuroradiological examinations showed a swollen lower brainstem with a dural arteriovenous fistula at the craniocervical junction (DAVF-CCJ). A steroid was administered intravenously in the hospital to relieve brainstem edema. A few hours later, however, the patient developed acute tetraparesis with respiratory failure. Recently, there have been several reports describing the acute worsening of paraparesis in patients with a spinal dural arteriovenous fistula after steroid treatment. In addition to these reports, the present case suggests the risk of administering steroids to patients with DAVF-CCJ, especially those with brainstem dysfunction. PMID:29225249

  6. Comparison of Comfort and Effectiveness of Total Face Mask and Oronasal Mask in Noninvasive Positive Pressure Ventilation in Patients with Acute Respiratory Failure: A Clinical Trial.

    Science.gov (United States)

    Sadeghi, Somayeh; Fakharian, Atefeh; Nasri, Peiman; Kiani, Arda

    2017-01-01

    Background . There is a growing controversy about the use of oronasal masks (ONM) or total facemask (TFM) in noninvasive positive pressure ventilation (NPPV), so we designed a trial to compare the uses of these two masks in terms of effectiveness and comfort. Methods . Between February and November 2014, a total of 48 patients with respiratory failure were studied. Patients were randomized to receive NPPV via ONM or TFM. Data were recorded at 60 minutes and six and 24 hours after intervention. Patient comfort was assessed using a questionnaire. Data were analyzed using t -test and chi-square test. Repeated measures ANOVA and Mann-Whitney U test were used to compare clinical and laboratory data. Results . There were no differences in venous blood gas (VBG) values between the two groups ( P > 0.05). However, at six hours, TFM was much more effective in reducing the partial pressure of carbon dioxide (PCO2) ( P = 0.04). Patient comfort and acceptance were statistically similar in both groups ( P > 0.05). Total time of NPPV was also similar in the two groups ( P > 0.05). Conclusions . TFM was superior to ONM in acute phase of respiratory failure but not once the patients were out of acute phase.

  7. Comparison of Comfort and Effectiveness of Total Face Mask and Oronasal Mask in Noninvasive Positive Pressure Ventilation in Patients with Acute Respiratory Failure: A Clinical Trial

    Directory of Open Access Journals (Sweden)

    Somayeh Sadeghi

    2017-01-01

    Full Text Available Background. There is a growing controversy about the use of oronasal masks (ONM or total facemask (TFM in noninvasive positive pressure ventilation (NPPV, so we designed a trial to compare the uses of these two masks in terms of effectiveness and comfort. Methods. Between February and November 2014, a total of 48 patients with respiratory failure were studied. Patients were randomized to receive NPPV via ONM or TFM. Data were recorded at 60 minutes and six and 24 hours after intervention. Patient comfort was assessed using a questionnaire. Data were analyzed using t-test and chi-square test. Repeated measures ANOVA and Mann–Whitney U test were used to compare clinical and laboratory data. Results. There were no differences in venous blood gas (VBG values between the two groups (P>0.05. However, at six hours, TFM was much more effective in reducing the partial pressure of carbon dioxide (PCO2 (P=0.04. Patient comfort and acceptance were statistically similar in both groups (P>0.05. Total time of NPPV was also similar in the two groups (P>0.05. Conclusions. TFM was superior to ONM in acute phase of respiratory failure but not once the patients were out of acute phase.

  8. Anti-hypoxic activity of the ethanol extract from Portulaca oleracea in mice.

    Science.gov (United States)

    Chen, Cheng-Jie; Wang, Wan-Yin; Wang, Xiao-Li; Dong, Li-Wei; Yue, Yi-Tian; Xin, Hai-Liang; Ling, Chang-Quan; Li, Min

    2009-07-15

    To investigate the effects of the ethanol extract from Portulaca oleracea (EEPO) on hypoxia models mice and to find the possible mechanism of its anti-hypoxic actions so as to elucidate the anti-hypoxia activity and provide scientific basis for the clinical use of Portulaca oleracea. EEPO was evaluated on anti-hypoxic activity in several hypoxia mice models, including closed normobaric hypoxia and sodium nitrite or potassium cyanide toxicosis. To verify the possible mechanism(s), we detected the activities of pyruvate kinase (PK), phosphofructokinase (PFK), lactate dehydrogenase (LDH) and the level of adenosine triphosphate (ATP) in mice cortices. Given orally, the EEPO at doses of 100, 200, 400 mg/kg could dose-dependently enhance the survival time of mice in both of the normobaric and chemical hypoxia models. The activity of the glycolysis enzymes and the level of ATP were higher than those of the control. In the pentobarbital sodium-induced sleeping time test and the open-field test, EEPO neither significantly enhanced the pentobarbital sodium-induced sleeping time nor impaired the motor performance, indicating that the observed anti-hypoxic activity was unlikely due to sedation or motor abnormality. These results demonstrated that the EEPO possessed notable anti-hypoxic activity, which might be related to promoting the activity of the key enzymes in glycolysis and improving the level of ATP in hypoxic mice.

  9. Developmental hyperoxia alters CNS mechanisms underlying hypoxic ventilatory depression in neonatal rats.

    Science.gov (United States)

    Hill, Corey B; Grandgeorge, Samuel H; Bavis, Ryan W

    2013-12-01

    Newborn mammals exhibit a biphasic hypoxic ventilatory response (HVR), but the relative contributions of carotid body-initiated CNS mechanisms versus central hypoxia on ventilatory depression during the late phase of the HVR are not well understood. Neonatal rats (P4-5 or P13-15) were treated with a nonselective P2 purinergic receptor antagonist (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, or PPADS; 125mgkg(-1), i.p.) to pharmacologically denervate the peripheral chemoreceptors. At P4-5, rats reared in normoxia showed a progressive decline in ventilation during a 10-min exposure to 12% O2 (21-28% decrease from baseline). No hypoxic ventilatory depression was observed in the older group of neonatal rats (i.e., P13-15), suggesting that the contribution of central hypoxia to hypoxic ventilatory depression diminishes with age. In contrast, rats reared in moderate hyperoxia (60% O2) from birth exhibited no hypoxic ventilatory depression at either age studied. Systemic PPADS had no effect on the ventilatory response to 7% CO2, suggesting that the drug did not cross the blood-brain barrier. These findings indicate that (1) CNS hypoxia depresses ventilation in young, neonatal rats independent of carotid body activation and (2) hyperoxia alters the development of CNS pathways that modulate the late phase of the hypoxic ventilatory response. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. A novel technique in airway management of neonates with occipital encephalocele.

    Science.gov (United States)

    Rangaswamy, N; Pramanik, A K

    2014-11-01

    Airway stabilization in neonates with occipital encephalocele (OE) is critical during surgery or if they develop hypoxic-respiratory failure. Endotracheal intubation can be challenging due to difficulty in positioning the head in a patient with large occipital mass. We describe a novel technique for positioning neonates with large OE using a commonly used hospital apparatus which facilitated appropriate positioning of the baby and successful endotracheal intubation with ease and no additional staff.

  11. Detection of hypoxic fractions in murine tumors by comet assay: Comparison with other techniques

    International Nuclear Information System (INIS)

    Hu, Q.; Kavanagh, M.C.; Newcombe, D.

    1995-01-01

    The alkaline comet assay was used to detect the hypoxic fractions of murine tumors. A total of four tumor types were tested using needle aspiration biopsies taken immediately after a radiation dose of 15 Gy. Initial studies confirmed that the normalized tail moment, a parameter reflecting single-strand DNA breaks induced by the radiation, was linearly related to radiation dose. Further, it was shown that for a mixed population (1:1) of cells irradiated under air-breathing or hypoxic conditions, the histogram of normal tail moment values obtained from analyzing 400 cells in the population had a double peak which, when fitted with two Gaussian distributions, gave a good estimate of the proportion of the two subpopulations. For the four tumor types, the means of the calculated hypoxic fractions from four or five individual tumors were 0.15 ± 0.04 for B16F1, 0.08 ± 0.04 for KHT-LP1, 0.17 ± 0.04 for RIF-1 and 0.04 ± 0.01 for SCCVII. Analysis of variance showed that the hypoxic fraction in KHT-LP1 tumors is significantly lower than those of the other three tumors (P = 0.026) but that there is no significant difference in hypoxic fraction between B16F1, RIF-1 and SCCVII tumors (P = 0.574). Results from multiple samples taken from each of five RIF-1 tumors showed that the intertumor heterogeneity of hypoxic fractions was greater than that within the same tumor. The mean hypoxic fraction obtained using the comet assay for the four tumor types was compared with the hypoxic fraction determined by the clonogenic assay, or median pO 2 values, or [ 3 H]misonidazole binding in the same tumor types. The values of hypoxic fraction obtained with the comet assay were two to four times lower than those measured by the paired survival method. Preliminary results obtained with a dose of 5 Gy were consistent with those obtained using 15 Gy. These results suggest the further development of the comet assay for clinical studies. 21 refs., 7 figs., 5 tabs

  12. Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections.

    Science.gov (United States)

    Gerber, Jeffrey S; Ross, Rachael K; Bryan, Matthew; Localio, A Russell; Szymczak, Julia E; Wasserman, Richard; Barkman, Darlene; Odeniyi, Folasade; Conaboy, Kathryn; Bell, Louis; Zaoutis, Theoklis E; Fiks, Alexander G

    2017-12-19

    Acute respiratory tract infections account for the majority of antibiotic exposure in children, and broad-spectrum antibiotic prescribing for acute respiratory tract infections is increasing. It is not clear whether broad-spectrum treatment is associated with improved outcomes compared with narrow-spectrum treatment. To compare the effectiveness of broad-spectrum and narrow-spectrum antibiotic treatment for acute respiratory tract infections in children. A retrospective cohort study assessing clinical outcomes and a prospective cohort study assessing patient-centered outcomes of children between the ages of 6 months and 12 years diagnosed with an acute respiratory tract infection and prescribed an oral antibiotic between January 2015 and April 2016 in a network of 31 pediatric primary care practices in Pennsylvania and New Jersey. Stratified and propensity score-matched analyses to account for confounding by clinician and by patient-level characteristics, respectively, were implemented for both cohorts. Broad-spectrum antibiotics vs narrow-spectrum antibiotics. In the retrospective cohort, the primary outcomes were treatment failure and adverse events 14 days after diagnosis. In the prospective cohort, the primary outcomes were quality of life, other patient-centered outcomes, and patient-reported adverse events. Of 30 159 children in the retrospective cohort (19 179 with acute otitis media; 6746, group A streptococcal pharyngitis; and 4234, acute sinusitis), 4307 (14%) were prescribed broad-spectrum antibiotics including amoxicillin-clavulanate, cephalosporins, and macrolides. Broad-spectrum treatment was not associated with a lower rate of treatment failure (3.4% for broad-spectrum antibiotics vs 3.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 0.3% [95% CI, -0.4% to 0.9%]). Of 2472 children enrolled in the prospective cohort (1100 with acute otitis media; 705, group A streptococcal pharyngitis; and 667, acute sinusitis), 868

  13. Recurrent Acute Respiratory Infections in Children: Effectiveness and Safety of Phytotherapy

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    V. P. Vavilova

    2015-01-01

    Full Text Available Recurrent respiratory infections in children lead to physical development disorders, formation of chronic nidi of infection, failure of adaptive mechanisms and degradation o immunobiological resisting barriers; this causes development of new diseases. Results of the presented non interventional clinical study confirm high safety profile and effectiveness of a therapeutic phytopreparation for recurrent respiratory infections. 

  14. A Molecular and Whole Body Insight of the Mechanisms Surrounding Glucose Disposal and Insulin Resistance with Hypoxic Treatment in Skeletal Muscle

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    R. W. A. Mackenzie

    2016-01-01

    Full Text Available Although the mechanisms are largely unidentified, the chronic or intermittent hypoxic patterns occurring with respiratory diseases, such as chronic pulmonary disease or obstructive sleep apnea (OSA and obesity, are commonly associated with glucose intolerance. Indeed, hypoxia has been widely implicated in the development of insulin resistance either via the direct action on insulin receptor substrate (IRS and protein kinase B (PKB/Akt or indirectly through adipose tissue expansion and systemic inflammation. Yet hypoxia is also known to encourage glucose transport using insulin-dependent mechanisms, largely reliant on the metabolic master switch, 5′ AMP-activated protein kinase (AMPK. In addition, hypoxic exposure has been shown to improve glucose control in type 2 diabetics. The literature surrounding hypoxia-induced changes to glycemic control appears to be confusing and conflicting. How is it that the same stress can seemingly cause insulin resistance while increasing glucose uptake? There is little doubt that acute hypoxia increases glucose metabolism in skeletal muscle and does so using the same pathway as muscle contraction. The purpose of this review paper is to provide an insight into the mechanisms underpinning the observed effects and to open up discussions around the conflicting data surrounding hypoxia and glucose control.

  15. [Palliative surgical correction of respiratory insufficiency in diffusive pulmonary emphysema].

    Science.gov (United States)

    Gorbunkov, S D; Varlamov, V V; Cherny, S M; Lukina, O V; Kiryukhina, L D; Romanikhin, A I; Zinchenko, A V; Akopov, A L

    To analyze early postoperative period in patients with diffuse pulmonary emphysema after palliative surgical correction of respiratory failure. The study included 196 patients who underwent bullectomy (n=111) and surgical reduction of pulmonary volume (n=85). Overall morbidity and mortality were 40.8% and 12.2% respectively. Among patients older than 60 years these values were significantly higher (58.0% and 22.6% respectively). It was shown that age over 60 years is associated with high risk of complications and mortality after excision of large and giant bulls. In patients pulmonary volume. Selection of patients for palliative surgical correction of respiratory failure is generally corresponded to that for lung transplantation. However, these methods should be considered complementary rather competing.

  16. Current issues in the respiratory care of patients with amyotrophic lateral sclerosis

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    Marco Orsini

    2015-10-01

    Full Text Available Amyotrophic lateral sclerosis is a progressive neuromuscular disease, resulting in respiratory muscle weakness, reduced pulmonary volumes, ineffective cough, secretion retention, and respiratory failure. Measures as vital capacity, maximal inspiratory and expiratory pressures, sniff nasal inspiratory pressure, cough peak flow and pulse oximetry are recommended to monitor the respiratory function. The patients should be followed up by a multidisciplinary team, focused in improving the quality of life and deal with the respiratory symptoms. The respiratory care approach includes airway clearance techniques, mechanically assisted cough and noninvasive mechanical ventilation. Vaccination and respiratory pharmacological support are also recommended. To date, there is no enough evidence supporting the inspiratory muscle training and diaphragmatic pacing.

  17. Clinical characteristics of the respiratory and cardiovascular systems in patients with combination of chronic obstructive pulmonary disease and heart failure

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    I. I. Vyshnyvetskyy

    2017-06-01

    Full Text Available The aim of our work was to assess the respiratory and cardiovascular systems of patients with a combination of chronic obstructive pulmonary disease (COPD and congestive heart failure (CHF. Materials and methods. The study included 177 patients who had been diagnosed COPD by criteria GOLD. CHF was diagnosed in 77 (43.5 % cases – 29 (16.4 % with reduced systolic function and 48 (27.1 % with preserved systolic function. We analyzed some important parameters characterizing respiratory and cardiovascular systems. We tried to identify statistically significant difference of parameters between patients with COPD and those with COPD and CHF. Moreover, patients with CHF were evaluated as a whole, and separately with reduced and with preserved systolic function. Results. Thus, we observed significant deterioration in general clinical, laboratory, spirometric and echocardiographic parameters depending on the presence and severity of CHF in patients with COPD. In particular, the presence of CHF, especially with impaired systolic function significantly impair indicators such as incidence of cardiac arrhythmias and signs of ischemia on the ECG, NT-proBNP levels, prevalence of concentric, eccentric hypertrophy and concentric LV remodeling and diastolic dysfunction type "relaxation disorder", and incidence of a-wave absence during assessment of motion of the rear pulmonary artery valve wall. Listed changes as well as some of the tendencies that have not reached a certain level of significance, indicate that patients with COPD and concomitant CHF, especially with impaired systolic function, worsens general clinical parameters (breath rate, systolic blood pressure, heart rate, frequency arrhythmias and myocardial ischemia on ECG; laboratory levels of hemoglobin, hematocrit, cholesterol, glomerular filtration rate; spirometric indicators of bronchial obstruction (FEV1, FVC, instant volume expiratory flow rates; echocardiographic indicators suggest the

  18. Transcriptome analysis of severe hypoxic stress during development in zebrafish

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    I.G. Woods

    2015-12-01

    Full Text Available Hypoxia causes critical cellular injury both in early human development and in adulthood, leading to cerebral palsy, stroke, and myocardial infarction. Interestingly, a remarkable phenomenon known as hypoxic preconditioning arises when a brief hypoxia exposure protects target organs against subsequent, severe hypoxia. Although hypoxic preconditioning has been demonstrated in several model organisms and tissues including the heart and brain, its molecular mechanisms remain poorly understood. Accordingly, we used embryonic and larval zebrafish to develop a novel vertebrate model for hypoxic preconditioning, and used this model to identify conserved hypoxia-regulated transcripts for further functional study as published in Manchenkov et al. (2015 in G3: Genes|Genomes|Genetics. In this Brief article, we provide extensive annotation for the most strongly hypoxia-regulated genes in zebrafish, including their human orthologs, and describe in detail the methods used to identify, filter, and annotate hypoxia-regulated transcripts for downstream functional and bioinformatic assays using the source data provided in Gene Expression Omnibus Accession GSE68473.

  19. Superfractionation as a potential hypoxic cell radiosensitizer: prediction of an optimum dose per fraction

    International Nuclear Information System (INIS)

    Dasu, Alexandru; Denekamp, Juliana

    1999-01-01

    Purpose: A dose 'window of opportunity' has been identified in an earlier modeling study if the inducible repair variant of the LQ model is adopted instead of the pure LQ model, and if all survival curve parameters are equally modified by the presence or absence of oxygen. In this paper we have extended the calculations to consider survival curve parameters from 15 sets of data obtained for cells tested at low doses using clonogenic assays. Methods and Materials: A simple computer model has been used to simulate the response of each cell line to various doses per fraction in multifraction schedules, with oxic and hypoxic cells receiving the same fractional dose. We have then used pairs of simulated survival curves to estimate the effective hypoxic protection (OER') as a function of the dose per fraction. Results: The resistance of hypoxic cells is reduced by using smaller doses per fraction than 2 Gy in all these fractionated clinical simulations, whether using a simple LQ model, or the more complex LQ/IR model. If there is no inducible repair, the optimum dose is infinitely low. If there is inducible repair, there is an optimum dose per fraction at which hypoxic protection is minimized. This is usually around 0.5 Gy. It depends on the dose needed to induce repair being higher in hypoxia than in oxygen. The OER' may even go below unity, i.e. hypoxic cells may be more sensitive than oxic cells. Conclusions: If oxic and hypoxic cells are repeatedly exposed to doses of the same magnitude, as occurs in clinical radiotherapy, the observed hypoxic protection varies with the fractional dose. The OER' is predicted to diminish at lower doses in all cell lines. The loss of hypoxic resistance with superfractionation is predicted to be proportional to the capacity of the cells to induce repair, i.e. their intrinsic radioresistance at a dose of 2 Gy

  20. Tei index in neonatal respiratory distress and perinatal asphyxia

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    Ahmed Anwer Attia Khattab

    2015-09-01

    Full Text Available Cardiovascular compromise is a common complication of neonatal respiratory distress and perinatal asphyxia. Tei index is a Doppler-derived index for the assessment of overall left ventricular function that combines systolic and diastolic time intervals. Aim: Assess the role of MPI versus cardiac troponin I as early indicator of hypoxic cardiac damage in neonates with respiratory distress or perinatal asphyxia. The present work was conducted on forty neonates, 15 with neonatal respiratory distress (group I, 15 with perinatal asphyxia (group II, and 10 apparently healthy neonates as a control (group III. All have: Detailed history-thorough clinical examination-Plain X-ray-ECG-Two dimensional, M-mode and Doppler echocardiographic examination with the measurement of both myocardial performance index (MPI of the right and left ventricle-Serum cardiac troponin I. Results: There was statistically significant increase in serum cardiac troponin I in groups I and II than group III. Left and right ventricular myocardial performance index (MPI were increased in group I and II than the control group. No correlation between Tei index and each of postnatal age, apgar score at 5-min, heart rate, serum cardiac troponin I, ejection fraction and fractional shortening, but there was direct relationship between MPI and LVEDD and inverse relationship between MPI and each of EF% and FS%. But there was significant correlation between L.V. MPI and gestational age. Conclusion: Tei index was higher in neonates with respiratory distress and neonates with perinatal asphyxia than in normal neonates despite normal or even increased ejection fraction which indicates that these patients may have subclinical ventricular dysfunction which should be followed up carefully.

  1. CT in the evaluation of patients on ECMO due to acute respiratory failure

    International Nuclear Information System (INIS)

    Lidegran, Marika; Jorulf, Haakan; Palmer, Kenneth; Linden, Viveka

    2002-01-01

    Heading AbstractBackground. In patients with acute severe respiratory failure (ARF) treated with extracorporeal membrane oxygenation (ECMO) the radiological evaluation has until now almost exclusively relied on bedside radiography and US. At St. Goeran/Karolinska ECMO centre CT has become a routine complement to bedside examinations.Objective. To review retrospectively the frequency, indications and findings on CT of patients with ARF on ECMO and to evaluate the risk of complications associated with transportation for CT examinations.Materials and methods. One hundred twelve neonates, children and adults were treated with ECMO from May 1994 to January 2001. Forty-six per cent of these patients had CT examinations on one or more occasions during ECMO, giving a total number of 238 examination sites on 104 occasions. All CT examinations were performed in the Paediatric Radiology Department and included a 10-min transport using a mobile ECMO system.Results. CT was more often performed in older patients and in patients with long ECMO runs. The main indications were suspected complications of ECMO and/or the underlying disease or a delay in clinical improvement. In 57% of the CT occasions, significant findings affecting treatment were revealed. There were no complications associated with the examinations or transport.Conclusions. CT is safe and useful in evaluation of patients with ARF during ECMO. (orig.)

  2. Astrocyte-derived proinflammatory cytokines induce hypomyelination in the periventricular white matter in the hypoxic neonatal brain.

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    Yiyu Deng

    Full Text Available Hypoxic exposure in the perinatal period causes periventricular white matter damage (PWMD, a condition associated with myelination abnormalities. Under hypoxic conditions, glial cells were activated and released a large number of inflammatory mediators in the PWM in neonatal brain, which may result in oligodendrocyte (OL loss and axonal injury. This study aims to determine if astrocytes are activated and generate proinflammatory cytokines that may be coupled with the oligodendroglial loss and hypomyelination observed in hypoxic PWMD. Twenty-four 1-day-old Wistar rats were exposed to hypoxia for 2 h. The rats were then allowed to recover under normoxic conditions for 7 or 28 days before being killed. Another group of 24 rats kept outside the chamber was used as age-matched controls. Upregulated expression of TNF-α and IL-1β was observed in astrocytes in the PWM of P7 hypoxic rats by double immunofluorescence, western blotting and real time RT-PCR. This was linked to apoptosis and enhanced expression of TNF-R1 and IL-1R1 in APC(+ OLs. PLP expression was decreased significantly in the PWM of P28d hypoxic rats. The proportion of myelinated axons was markedly reduced by electron microscopy (EM and the average g-ratios were higher in P28d hypoxic rats. Upregulated expression of TNF-α and IL-1β in primary cultured astrocytes as well as their corresponding receptors in primary culture APC(+ oligodendrocytes were detected under hypoxic conditions. Our results suggest that following a hypoxic insult, astrocytes in the PWM of neonatal rats produce inflammatory cytokines such as TNF-α and IL-1β, which induce apoptosis of OLs via their corresponding receptors associated with them. This results in hypomyelination in the PWM of hypoxic rats.

  3. More than meets the eye: infant presenting with hypoxic ischaemic encephalopathy.

    Science.gov (United States)

    Sen, Kuntal; Agarwal, Rajkumar

    2018-04-05

    We report a newborn infant who presented with poor Apgar scores and umbilical artery acidosis leading to the diagnosis of hypoxic ischaemic encephalopathy. During the course of the infant's hospitalisation, subsequent workup revealed an underlying genetic cause that masqueraded as hypoxic ischaemic encephalopathy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Rehabilitation of patients admitted to a respiratory intensive care unit.

    Science.gov (United States)

    Nava, S

    1998-07-01

    Pulmonary rehabilitation has been shown to be of benefit to clinically stable patients with chronic obstructive pulmonary disease (COPD). This study examined the effect of pulmonary rehabilitation on some physiologic variables in COPD patients recovering from an episode of acute respiratory failure. A prospective, randomized study. A respiratory intensive care unit (RICU). Eighty COPD patients recovering from an episode of acute respiratory failure were randomized in a 3:1 fashion to receive stepwise pulmonary rehabilitation (group A, n=60 patients) or standard medical therapy (group B, n=20 patients). Improvements in exercise tolerance, sense of breathlessness, respiratory muscle function, and pulmonary function test values were measured, respectively, by exercise capacity (6-minute walking distance [6MWD]), dyspnea score (Visual Analog Scale [VAS]), maximal inspiratory pressure (MIP), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC). Group A received pulmonary rehabilitation that consisted of passive mobilization (step I), early deambulation (step II), respiratory and lower skeletal muscle training (step III), and if the patients were able, complete lower extremity training on a treadmill (step IV). Group B received standard medical therapy plus a basic deambulation program. Sixty-one of 80 patients were mechanically ventilated at admission to the unit and most of them were bedridden. Twelve of the 60 group A patients and 4 of the 20 group B patients died during their RICU stay, and 9 patients required invasive mechanical ventilation at home after their discharge. The total length of RICU stay was 38+/-14 days for patients in group A versus 33.2+/-11 days for those in group B. Most patients from both groups regained the ability to walk, either unaided or aided. At discharge, 6 MWD results were significantly improved (p respiratory failure and who, in most cases, required mechanical ventilation benefited from comprehensive early

  5. Respiratory difficulties and breathing disorders in achondroplasia.

    Science.gov (United States)

    Afsharpaiman, S; Saburi, A; Waters, Karen A

    2013-12-01

    Respiratory difficulties and breathing disorders in achondroplasia are thought to underlie the increased risk for sudden infant death and neuropsychological deficits seen in this condition. This review evaluates literature regarding respiratory dysfunctions and their sequelae in patients with achondroplasia. The limited number of prospective studies of respiratory disease in achondroplasia means that observational studies and case series provide a large proportion of the data regarding the spectrum of respiratory diseases in achondroplasia and their treatments. Amongst clinical respiratory problems described, snoring is the commonest observed abnormality, but the reported incidence of obstructive sleep apnoea (OSA) shows wide variance (10% to 75%). Reported treatments of OSA include adenotonsillectomy, the use of CPAP, and surgical improvement of the airway, including mid-face advancement. Otolaryngologic manifestations are also common. Respiratory failure due to small thoracic volumes is reported, but uncommon. Mortality rate at all ages was 2.27 (CI: 1.7-3.0) with age-specific mortality increased at all ages. Sudden death was most common in infants and children. Cardiovascular events are the main cause of mortality in adults. Despite earlier recognition and treatment of respiratory complications of achondroplasia, increased mortality rates and other complications remain high. Future and ongoing evaluation of the prevalence and impact of respiratory disorders, particularly OSA, in achondroplasia is recommended. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  6. Hypoxic cytotoxicity of chlorpromazine and the modification of radiation response in E. coli B/r

    International Nuclear Information System (INIS)

    Shenoy, M.A.; Singh, B.B.

    1978-01-01

    Chlorpromazine (0.1 mM) was cytotoxic to E. coli B/r cells under hypoxic but not euoxic conditions. Under nitrogen bubbling, there was no further enhancement in cellular lethality beyond 45 min contact time. The presence of the free drug seemed necessary for the cytocidal action to be demonstrated. Hypoxic cytotoxicity increased steadily with temperature between 30 and 37 0 C. Treatment of cells with N-ethyl maleimide (0.5 mM) completely abolished the subsequent hypoxic cytotoxicity of chlorpromazine (0.1 mM). Hypoxic gamma irradiation of cells pretreated for 45 min with chlorpromazine under nitrogen bubbling gave a DMF for survival of almost twice that produced by oxygen. Irradiation under aerobic conditions of cells subjected to the same pretreatment produced only the normal oxygen effect. The results indicate that the differential cytotoxicity of chlorpromazine is due to its effect on the changes induced in the membrane-associated biochemical state of the cells under euoxic and hypoxic conditions. (U.K.)

  7. THE SUCCESSFUL TREATMENT OF A PERIPHERAL VENO-VENOUS EXTRACORPOREAL MEMBRANE OXYGENATION FOR SEVERE ACUTE RESPIRATORY FAILURE IN THE EARLY PERIOD AFTER ADULT LIVER TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    V. N. Poptsov

    2014-01-01

    Full Text Available Aim: of our clinical study was to present own experience of veno-venous extracorporeal membrane oxygenation (VV ECMO for the treatment of an adult patient (female, 28 yrs, 150 cm, 35 kg with acute respiratory distress syndrome (ARDS in the early period after liver transplantation against satisfactory liver graft function. Materials and methods. Double-lumen cannula 22 F was placed percutaneously in the right internal jugular vein. The ext- racorporeal contour reduced in length and the polymethylpeptene oxygenator (priming volume 175 ml were also. Results. In 1 hour after the beginning of VV ECMO, we registered the noted improvement of arterial blood gas and acid-base balance (regress of respiratory acidosis, improvement of arterial oxygenation which allowed us to use the «protective» mode of mechanical ventilation. Improvement of gas exchange and regress of clinical and radiological manifestations of ARDS allowed for VV ECMO weaning and decannulation on day 7. The patient was discharged from ICU and then from our Centre to a homestay respectively on the 9th and 16th day after VV ECMO weaning with the satisfactory liver graft and lungs function. Conclusion. VV ECMO can be successfully applied to correct the life-threatening acute respiratory failure in the early period after liver transplantation. 

  8. Reduced hypoxic ventilatory response with preserved blood oxygenation in yoga trainees and Himalayan Buddhist monks at altitude: evidence of a different adaptive strategy?

    Science.gov (United States)

    Bernardi, Luciano; Passino, Claudio; Spadacini, Giammario; Bonfichi, Maurizio; Arcaini, Luca; Malcovati, Luca; Bandinelli, Gabriele; Schneider, Annette; Keyl, Cornelius; Feil, Paul; Greene, Richard E; Bernasconi, Carlo

    2007-03-01

    Yoga induces long-term changes in respiratory function and control. We tested whether it represents a successful strategy for high-altitude adaptation. We compared ventilatory, cardiovascular and hematological parameters in: 12 Caucasian yoga trainees and 12 control sea-level residents, at baseline and after 2-week exposure to high altitude (Pyramid Laboratory, Nepal, 5,050 m), 38 active lifestyle high-altitude natives (Sherpas) and 13 contemplative lifestyle high-altitude natives with practice of yoga-like respiratory exercises (Buddhist monks) studied at 5,050 m. At baseline, hypoxic ventilatory response (HVR), red blood cell count and hematocrit were lower in Caucasian yoga trainees than in controls. After 14 days at altitude, yoga trainees showed similar oxygen saturation, blood pressure, RR interval compared to controls, but lower HVR (-0.44 +/- 0.08 vs. -0.98 +/- 0.21 l/min/m/%SaO(2), P monks was lower than in Sherpas (-0.23 +/- 0.05 vs. -0.63 +/- 0.09 l/min/m/%SaO(2), P monks as compared to Sherpas. In conclusion, Caucasian subjects practicing yoga maintain a satisfactory oxygen transport at high altitude, with minimal increase in ventilation and with reduced hematological changes, resembling Himalayan natives. Respiratory adaptations induced by the practice of yoga may represent an efficient strategy to cope with altitude-induced hypoxia.

  9. Everything that wheezes… Late presentation of an aspirated foreign body as a cause of near fatal respiratory distress

    OpenAIRE

    L. Hindle*

    2013-01-01

    Aspirated foreign bodies are a common cause of mortality in children. They can be difficult to diagnose if the aspiration is not witnessed or if the object is not radiopaque, as this case illustrates. Case report: A 4 year old boy with a history of previous TB presented with respiratory distress after a week of fever and cough. No history of choking or foreign body was elicited. On examination the child was distressed, hypoxic and febrile. On auscultation bilateral coarse crackles and an e...

  10. Dinitrobenzamide mustard prodrugs - hypoxic cytotoxins and dual substrates for E.coli nitroreductase

    International Nuclear Information System (INIS)

    Patterson, A.V.; Hogg, A.; Pullen, S.; Degenkolbe, A.; Li, D.; Chappell, A.; Ying, S.; Atwell, G.J.; Denny, W.A.; Anderson, R.F.; Wilson, W.R.

    2003-01-01

    Conditional replicating adenoviral vectors (CRAds) have received considerable attention as therapeutic tools in combination with radiotherapy. Viral distribution and micro-regional geometry are likely to be important issues in the treatment of human solid tumours with gene therapy, particularly following intravenous virus administration. The use of CRAds that are 'armed' with enzyme/prodrug systems may overcome some of the perceived limitations; CRAds can redistribute and self-amplify in a cytolytic fashion whilst prodrug metabolites may elicit a local bystander effect. Either or both of these cytotoxic properties could have favourable interactions with radiotherapy (IR). Nevertheless, they may be insufficient to avoid pockets of vector-naive tumour cells beyond the diffusion limits of cytotoxic prodrug metabolites, such as when perivascular seeding occurs. Under such circumstances hypoxic tumour cells may represent the least accessible compartment for vector transfection; the same tumour subpopulation that is likely to be radioresistant. E.coli nitroreductase (NTR) can bioactivate dinitrobenzamide mustards (DNBMs) and is a promising enzyme/prodrug system for 'arming' CRAds. Notably DNMBs can also be activated by endogenous human reductases under low oxygen conditions providing an opportunity to identify dual hypoxic cytotoxins/NTR substrates that may circumvent some of the geometry issues and provide complementarity with IR. To identify a prodrug for NTR that is also active as a hypoxic cytotoxin in vivo. From a set of 164 DNB prodrugs, 19 with favourable activity in vitro against a panel of four NTR-expressing cancer cells were selected and screened for activity as hypoxic cytotoxins in vitro. Measured E17 values ranged from -444 to -366 mV. Seven DNBMs possessed acceptable hypoxic selectivity against the human NSCLC cell line A549WT or clones engineered to overexpress either a human single-electron reductase, cytochrome P450 reductase (A549P450R), or oxic

  11. Validity, prognostic value and optimal cutoff of respiratory muscle strength in patients with chronic heart failure changes with beta-blocker treatment.

    Science.gov (United States)

    Frankenstein, Lutz; Nelles, Manfred; Meyer, F Joachim; Sigg, Caroline; Schellberg, Dieter; Remppis, B Andrew; Katus, Hugo A; Zugck, Christian

    2009-08-01

    Training studies frequently use maximum inspiratory mouth occlusion pressure (PImax) as a therapeutic target and surrogate marker. For patients on beta-blocker (BBL), prognostic data allowing this extrapolation do not exist. Furthermore, the effects of BBL, mainstay of modern chronic heart failure therapy, on respiratory muscle function remain controversial. Finally, no proper separate cutoff according to treatment exists. Prospective, observational inclusion of patients with stable systolic chronic heart failure and recording of 1 year and all-time mortality for endpoint analysis. In 686 patients, 81% men, 494 patients on BBL, PImax was measured along with clinical evaluation. The median follow-up was 50 months (interquartile range: 26-75 months). Patients with or without BBL did not differ significantly for PImax, percentage of predicted PImax or other marker of disease severity. PImax was a significant (hazard ratio: 0.925; 95% confidence interval: 0.879-0.975; chi(2): 8.62) marker of adverse outcome, independent of BBL-status or aetiology. Percentage of predicted PImax was not independent of PImax. The cutoff identified through receiver-operated characteristics for 1-year mortality was 4.14 kPa for patients on BBL and 7.29 kPa for patients not on BBL. When separated accordingly, 1-year mortality was 8.5 versus 21.4%, P=0.02, for patients not on BBL and 4.3 versus 16.2%, P<0.001, for patients on BBL. This study fills the gap between trials targeting respiratory muscle on a functional basis and the resultant prognostic information with regard to BBL. BBL lowered the optimal PImax cutoff values for risk stratification without changing the measured values of PImax. This should be considered at inclusion and evaluation of trials and interpretation of exercise parameters.

  12. Seizure Severity Is Correlated With Severity of Hypoxic-Ischemic Injury in Abusive Head Trauma.

    Science.gov (United States)

    Dingman, Andra L; Stence, Nicholas V; O'Neill, Brent R; Sillau, Stefan H; Chapman, Kevin E

    2017-12-12

    The objective of this study was to characterize hypoxic-ischemic injury and seizures in abusive head trauma. We performed a retrospective study of 58 children with moderate or severe traumatic brain injury due to abusive head trauma. Continuous electroencephalograms and magnetic resonance images were scored. Electrographic seizures (51.2%) and hypoxic-ischemic injury (77.4%) were common in our cohort. Younger age was associated with electrographic seizures (no seizures: median age 13.5 months, interquartile range five to 25 months, versus seizures: 4.5 months, interquartile range 3 to 9.5 months; P = 0.001). Severity of hypoxic-ischemic injury was also associated with seizures (no seizures: median injury score 1.0, interquartile range 0 to 3, versus seizures: 4.5, interquartile range 3 to 8; P = 0.01), but traumatic injury severity was not associated with seizures (no seizures: mean injury score 3.78 ± 1.68 versus seizures: mean injury score 3.83 ± 0.95, P = 0.89). There was a correlation between hypoxic-ischemic injury severity and seizure burden when controlling for patient age (r s =0.61, P interquartile range 0 to 0.23 on magnetic resonance imaging done within two days versus median restricted diffusion ratio 0.13, interquartile range 0.01 to 0.43 on magnetic resonance imaging done after two days, P = 0.03). Electrographic seizures are common in children with moderate to severe traumatic brain injury from abusive head trauma, and therefore children with suspected abusive head trauma should be monitored with continuous electroencephalogram. Severity of hypoxic-ischemic brain injury is correlated with severity of seizures, and evidence of hypoxic-ischemic injury on magnetic resonance imaging may evolve over time. Therefore children with a high seizure burden should be reimaged to evaluate for evolving hypoxic-ischemic injury. Published by Elsevier Inc.

  13. Extracorporeal membrane oxygenation in near-drowning patients with cardiac or pulmonary failure.

    Science.gov (United States)

    Kim, Kun Il; Lee, Won Yong; Kim, Hyoung Soo; Jeong, Jae Han; Ko, Ho Hyun

    2014-12-12

    The aim of this study was to determine the early outcomes of using extracorporeal membrane oxygenation (ECMO) in near-drowning patients with cardiac or pulmonary failure. This study was based on data from 9 patients including 2 children (mean age 33; 8 males, 1 female) who received ECMO after near-drowning between 2008 and 2013. Veno-arterial or veno-arteriovenous ECMO was used in 2 patients with sustained cardiac arrest and veno-venous ECMO was used in 7 patients with severe acute respiratory distress syndrome (ARDS). The means of the partial arterial oxygen pressure (PaO2), Murray score, sequential organ failure assessment (SOFA) score, and simplified acute physiology score II (SAPS-II) prior to ECMO were 59.7 ± 9.9 mmHg on 100% oxygen, 3.5 ± 0.6, 11.4 ± 1.9, and 73.0 ± 9.2, respectively. The PaO2 mean improved to 182 ± 152 mmHg within 2 h post-ECMO. The mean of SOFA score and SAPS-II decreased significantly to 8.6 ± 3.2 (p = 0.013) and 46.4 ± 5.1 (p = 0.008), respectively, at 24 h post-ECMO with mean flow rate of 3.9 ± 0.8 l/min. ECMO was weaned at a mean duration of 188 (range, 43-672) h in all patients. Seven patients were discharged home without neurological sequelae, while 2 patients who had hypoxic brain damage died after further referral. The overall survival with favourable neurological outcomes at 3 months was 77.8%. There were no complications related to ECMO. ECMO was safe and effective for patients with ongoing cardiac arrest or ARDS after a near-drowning incident and can be used as a resuscitative strategy in near-drowning patients with cardiac or pulmonary failure resistant to conventional ventilator therapy.

  14. CHANGES IN THE GLUTATHIONE SYSTEM IN P19 EMBRYONAL CARCINOMA CELLS UNDER HYPOXIC CONDITIONS

    Directory of Open Access Journals (Sweden)

    D. S. Orlov

    2015-01-01

    Full Text Available Introduction. According to modern perceptions, tumor growth, along with oxidative stress formation, is accompanied by hypoxia. Nowadays studying the regulation of cellular molecular system functioning by conformational changes in proteins appears to be a topical issue. Research goal was to evaluate the state of the glutathione system and the level of protein glutathionylation in P19 embryonal carcinoma (EC cells under hypoxic conditions.Material and methods. P19 EC cells (mouse embryonal carcinoma cultured under normoxic and hypox-ic conditions served the research material.The concentration of total, oxidized, reduced and protein-bound glutathione, the reduced to oxidized thiol ratio as well as glutathione peroxidase and glutathione reductase activity were determined by spectropho-tometry.Results. Glutathione imbalance was accompanied by a decrease in P19 EC cell redox status under hypox-ic conditions against the backdrop of a rise in protein-bound glutathione.Conclusions. As a result of the conducted study oxidative stress formation was identified when modeling hypoxia in P19 embryonal carcinoma cells. The rise in the concentration of protein-bound glutathione may indicate the role of protein glutathionylation in regulation of P19 cell metabolism and functions un-der hypoxia. 

  15. Efficacy of Noninvasive Ventilation in a Patient with Hypercapnic Respiratory Failure Complicating Eisenmenger’s Syndrome

    Directory of Open Access Journals (Sweden)

    Ana Jaureguizar Oriol

    2017-08-01

    Full Text Available Eisenmenger’s syndrome is a severe type of congenital heart disease characterized by severe pulmonary arterial hypertension. In the cases that the pressure in pulmonary circulation exceeds the systemic pressure, there appears a right-to-left shunting of blood. Consequently, the syndrome exists hypoxemia and cyanosis. Hypercapnia is not common in these patients; however, it might coexist with hypoxemic failure if there are other restrictive pathologies associated. Meanwhile, it has been described high prevalence of sleep disorders in Down syndrome. There is no evidence about the role of noninvasive ventilation in the management of these patients. We present a 39-year-old man, suffering of Down and Eisenmenger’s syndrome with multiple cardiac decompensations and obstructive sleep apnea (OSA, who was admitted to hospital due to severe somnolence, edema, and dyspnea. We observed a hypercapnic respiratory acidosis that ameliorated with noninvasive ventilation (NIV. The patient returned home with nocturnal NIV as a new treatment, and no further admission to hospital was seen in the following two years. To our knowledge, this is the first report about the utility of NIV in Eisenmenger’s and Down syndrome patients.

  16. Nondiabetic ketoacidosis in a pregnant woman due to acute starvation with concomitant influenza A (H1N1) and respiratory failure.

    Science.gov (United States)

    Skalley, G; Rodríguez-Villar, S

    2018-02-28

    Threatening refractory metabolic acidosis due to short-term starvation nondiabetic ketoacidosis is rarely reported. Severe ketoacidosis due to starvation itself is a rare occurrence, and more so in pregnancy with a concomitant stressful clinical situation. This case report presents a nondiabetic woman admitted in intensive care for respiratory failure type 1 during the third trimester of pregnancy with a severe metabolic acidosis refractory to medical treatment. We diagnosed the patient with acute starvation ketoacidosis based on her history and the absence of other causes of high anion gap metabolic acidosis after doing a rigorous analysis of her acid-base disorder. Crown Copyright © 2018. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. ACTIVE CYCLE BREATHING TECHNIQUES IN HEART FAILURE ...

    African Journals Online (AJOL)

    RICHY

    Pulmonary Function Responses to Active Cycle. Breathing ... Key Words: Heart Failure, Active Cycle of Breathing ... cough, fatigue, reduced respiratory muscle mass, and. [5] ... an amount of exercise which is said to lower disease. [9].

  18. Evaluation of the Usefulness of the Respiratory Guidance System in the Respiratory Gating Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yeong Cheol; Kim, Sun Myung; Do, Gyeong Min; Park, Geun Yong; Kim, Gun Oh; Kim, Young Bum [Dept. of Radiation Oncology, Guro Hospital, Korea Univeristy, Seoul (Korea, Republic of)

    2012-09-15

    The respiration is one of the most important factors in respiratory gating radiation therapy (RGRT). We have developed an unique respiratory guidance system using an audio-visual system in order to support and stabilize individual patient's respiration and evaluated the usefulness of this system. Seven patients received the RGRT at our clinic from June 2011 to April 2012. After breathing exercise standard deviations by the superficial contents of respiratory cycles and functions, and analyzed them to examine changes in their breathing before and with the audio-visual system, we measured their spontaneous respiration and their respiration with the audio-visual system respectively. With the measured data, we yielded after the therapy. The PTP (peak to peak) of the standard deviations of the free breathing, the audio guidance system, and the respiratory guidance system were 0.343, 0.148, and 0.078 respectively. The respiratory cycles were 0.645, 0.345, and 0.171 respectively and the superficial contents of the respiratory functions were 2.591, 1.008, and 0.877 respectively. The average values of the differences in the standard deviations among the whole patients at the CT room and therapy room were 0.425 for the PTP, 1.566 for the respiratory cycles, and 3.671 for the respiratory superficial contents. As for the standard deviations before and after the application of the PTP respiratory guidance system, that of the PTP was 0.265, that of the respiratory cycles was 0.474, and that of the respiratory superficial contents. The results of t-test of the values before and after free breathing and the audio-visual guidance system showed that the P-value of the PTP was 0.035, that of the cycles 0.009, and that of the respiratory superficial contents 0.010. The respiratory control could be one of the most important factors in the RGRT which determines the success or failure of a treatment. We were able to get more stable breathing with the audio-visual respiratory

  19. Evaluation of the Usefulness of the Respiratory Guidance System in the Respiratory Gating Radiation Therapy

    International Nuclear Information System (INIS)

    Lee, Yeong Cheol; Kim, Sun Myung; Do, Gyeong Min; Park, Geun Yong; Kim, Gun Oh; Kim, Young Bum

    2012-01-01

    The respiration is one of the most important factors in respiratory gating radiation therapy (RGRT). We have developed an unique respiratory guidance system using an audio-visual system in order to support and stabilize individual patient's respiration and evaluated the usefulness of this system. Seven patients received the RGRT at our clinic from June 2011 to April 2012. After breathing exercise standard deviations by the superficial contents of respiratory cycles and functions, and analyzed them to examine changes in their breathing before and with the audio-visual system, we measured their spontaneous respiration and their respiration with the audio-visual system respectively. With the measured data, we yielded after the therapy. The PTP (peak to peak) of the standard deviations of the free breathing, the audio guidance system, and the respiratory guidance system were 0.343, 0.148, and 0.078 respectively. The respiratory cycles were 0.645, 0.345, and 0.171 respectively and the superficial contents of the respiratory functions were 2.591, 1.008, and 0.877 respectively. The average values of the differences in the standard deviations among the whole patients at the CT room and therapy room were 0.425 for the PTP, 1.566 for the respiratory cycles, and 3.671 for the respiratory superficial contents. As for the standard deviations before and after the application of the PTP respiratory guidance system, that of the PTP was 0.265, that of the respiratory cycles was 0.474, and that of the respiratory superficial contents. The results of t-test of the values before and after free breathing and the audio-visual guidance system showed that the P-value of the PTP was 0.035, that of the cycles 0.009, and that of the respiratory superficial contents 0.010. The respiratory control could be one of the most important factors in the RGRT which determines the success or failure of a treatment. We were able to get more stable breathing with the audio-visual respiratory guidance

  20. Interstitial administration of perfluorochemical emulsions for reoxygenation of hypoxic tumor cells

    International Nuclear Information System (INIS)

    Woo, D.V.; Seegenschmiedt, H.; Schweighardt, F.K.; Emrich, J.; McGarvey, K.; Caridi, M.; Brady, L.W.

    1987-01-01

    Microparticulate perfluorochemical (PFC) emulsions have the capacity to solubilize significant quantities of oxygen compared to water. Although systemic administration of such emulsions may enhance oxygen delivery to some tissues, hypoxic tumor cells have marginal vascular supplies. The authors report studies which directly attempt to oxygenate hypoxic tumor cells by interstitial administration of oxygenated PFC emulsions followed by radiation therapy. Fortner MMI malignant melanomas (21 day old) grown in Syrian Golden hamsters were injected directly with either oxygenated PFC emulsions or Ringers solution. The volume of test substance administered was equal to 50% of the tumor volume. The tumors were immediately irradiated with 25 Gy of 10 MeV photons (Clinac 18). The tumor dimensions were measured daily post irradiation and the tumor doubling time determined. The results suggest that interstitial administration of oxygenated PFC emulsions directly into tumors followed by radiation therapy may increase the likelihood of killing hypoxic tumor cells

  1. Hypoxic stress up-regulates Kir2.1 expression and facilitates cell proliferation in brain capillary endothelial cells

    International Nuclear Information System (INIS)

    Yamamura, Hideto; Suzuki, Yoshiaki; Yamamura, Hisao; Asai, Kiyofumi; Imaizumi, Yuji

    2016-01-01

    The blood-brain barrier (BBB) is mainly composed of brain capillary endothelial cells (BCECs), astrocytes and pericytes. Brain ischemia causes hypoxic encephalopathy and damages BBB. However, it remains still unclear how hypoxia affects BCECs. In the present study, t-BBEC117 cells, an immortalized bovine brain endothelial cell line, were cultured under hypoxic conditions at 4–5% oxygen for 72 h. This hypoxic stress caused hyperpolarization of resting membrane potential. Patch-clamp recordings revealed a marked increase in Ba 2+ -sensitive inward rectifier K + current in t-BBEC117 cells after hypoxic culture. Western blot and real-time PCR analyses showed that Kir2.1 expression was significantly up-regulated at protein level but not at mRNA level after the hypoxic culture. Ca 2+ imaging study revealed that the hypoxic stress enhanced store-operated Ca 2+ (SOC) entry, which was significantly reduced in the presence of 100 μM Ba 2+ . On the other hand, the expression of SOC channels such as Orai1, Orai2, and transient receptor potential channels was not affected by hypoxic stress. MTT assay showed that the hypoxic stress significantly enhanced t-BBEC117 cell proliferation, which was inhibited by approximately 60% in the presence of 100 μM Ba 2+ . We first show here that moderate cellular stress by cultivation under hypoxic conditions hyperpolarizes membrane potential via the up-regulation of functional Kir2.1 expression and presumably enhances Ca 2+ entry, resulting in the facilitation of BCEC proliferation. These findings suggest potential roles of Kir2.1 expression in functional changes of BCECs in BBB following ischemia. -- Highlights: •Hypoxic culture of brain endothelial cells (BEC) caused membrane hyperpolarization. •This hyperpolarization was due to the increased expression of Kir2.1 channels. •Hypoxia enhanced store-operated Ca 2+ (SOC) entry via Kir2.1 up-regulation. •Expression levels of putative SOC channels were not affected by hypoxia.

  2. Quantification of structural changes in the corpus callosumin children with profound hypoxic-ischaemic brain injury

    Energy Technology Data Exchange (ETDEWEB)

    Stivaros, Stavros M. [Manchester Academic Health Science Centre, Academic Unit of Paediatric Radiology, Royal Manchester Children' s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester (United Kingdom); University of Manchester, Centre for Imaging Sciences, Institute of Population Health, Manchester (United Kingdom); Radon, Mark R. [The Walton Centre NHS Foundation Trust, Department of Neuroradiology, Liverpool (United Kingdom); Mileva, Reneta; Gledson, Ann; Keane, John A. [University of Manchester, School of Computer Science, Manchester (United Kingdom); Connolly, Daniel J.A.; Batty, Ruth [Sheffield Children' s Hospital NHS Foundation Trust, Department of Neuroradiology, Sheffield (United Kingdom); Cowell, Patricia E. [University of Sheffield, Department of Human Communication Sciences, Sheffield (United Kingdom); Hoggard, Nigel; Griffiths, Paul D. [University of Sheffield, Academic Unit of Radiology, Sheffield (United Kingdom); Wright, Neville B.; Tang, Vivian [Manchester Academic Health Science Centre, Academic Unit of Paediatric Radiology, Royal Manchester Children' s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester (United Kingdom)

    2016-01-15

    Birth-related acute profound hypoxic-ischaemic brain injury has specific patterns of damage including the paracentral lobules. To test the hypothesis that there is anatomically coherent regional volume loss of the corpus callosum as a result of this hemispheric abnormality. Study subjects included 13 children with proven acute profound hypoxic-ischaemic brain injury and 13 children with developmental delay but no brain abnormalities. A computerised system divided the corpus callosum into 100 segments, measuring each width. Principal component analysis grouped the widths into contiguous anatomical regions. We conducted analysis of variance of corpus callosum widths as well as support vector machine stratification into patient groups. There was statistically significant narrowing of the mid-posterior body and genu of the corpus callosum in children with hypoxic-ischaemic brain injury. Support vector machine analysis yielded over 95% accuracy in patient group stratification using the corpus callosum centile widths. Focal volume loss is seen in the corpus callosum of children with hypoxic-ischaemic brain injury secondary to loss of commissural fibres arising in the paracentral lobules. Support vector machine stratification into the hypoxic-ischaemic brain injury group or the control group on the basis of corpus callosum width is highly accurate and points towards rapid clinical translation of this technique as a potential biomarker of hypoxic-ischaemic brain injury. (orig.)

  3. Hypoxic preconditioning protects photoreceptors against light damage independently of hypoxia inducible transcription factors in rods.

    Science.gov (United States)

    Kast, Brigitte; Schori, Christian; Grimm, Christian

    2016-05-01

    Hypoxic preconditioning protects photoreceptors against light-induced degeneration preserving retinal morphology and function. Although hypoxia inducible transcription factors 1 and 2 (HIF1, HIF2) are the main regulators of the hypoxic response, photoreceptor protection does not depend on HIF1 in rods. Here we used rod-specific Hif2a single and Hif1a;Hif2a double knockout mice to investigate the potential involvement of HIF2 in rods for protection after hypoxic preconditioning. To identify potential HIF2 target genes in rods we determined the retinal transcriptome of hypoxic control and rod-specific Hif2a knockouts by RNA sequencing. We show that rods do not need HIF2 for hypoxia-induced increased survival after light exposure. The transcriptomic analysis revealed a number of genes that are potentially regulated by HIF2 in rods; among those were Htra1, Timp3 and Hmox1, candidates that are interesting due to their connection to human degenerative diseases of the retina. We conclude that neither HIF1 nor HIF2 are required in photoreceptors for protection by hypoxic preconditioning. We hypothesize that HIF transcription factors may be needed in other cells to produce protective factors acting in a paracrine fashion on photoreceptor cells. Alternatively, hypoxic preconditioning induces a rod-intrinsic response that is independent of HIF transcription factors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Quantification of structural changes in the corpus callosumin children with profound hypoxic-ischaemic brain injury

    International Nuclear Information System (INIS)

    Stivaros, Stavros M.; Radon, Mark R.; Mileva, Reneta; Gledson, Ann; Keane, John A.; Connolly, Daniel J.A.; Batty, Ruth; Cowell, Patricia E.; Hoggard, Nigel; Griffiths, Paul D.; Wright, Neville B.; Tang, Vivian

    2016-01-01

    Birth-related acute profound hypoxic-ischaemic brain injury has specific patterns of damage including the paracentral lobules. To test the hypothesis that there is anatomically coherent regional volume loss of the corpus callosum as a result of this hemispheric abnormality. Study subjects included 13 children with proven acute profound hypoxic-ischaemic brain injury and 13 children with developmental delay but no brain abnormalities. A computerised system divided the corpus callosum into 100 segments, measuring each width. Principal component analysis grouped the widths into contiguous anatomical regions. We conducted analysis of variance of corpus callosum widths as well as support vector machine stratification into patient groups. There was statistically significant narrowing of the mid-posterior body and genu of the corpus callosum in children with hypoxic-ischaemic brain injury. Support vector machine analysis yielded over 95% accuracy in patient group stratification using the corpus callosum centile widths. Focal volume loss is seen in the corpus callosum of children with hypoxic-ischaemic brain injury secondary to loss of commissural fibres arising in the paracentral lobules. Support vector machine stratification into the hypoxic-ischaemic brain injury group or the control group on the basis of corpus callosum width is highly accurate and points towards rapid clinical translation of this technique as a potential biomarker of hypoxic-ischaemic brain injury. (orig.)

  5. Bubble CPAP for respiratory distress syndrome in preterm infants.

    Science.gov (United States)

    Koti, Jagdish; Murki, Srinivas; Gaddam, Pramod; Reddy, Anupama; Reddy, M Dasaradha Rami

    2010-02-01

    To ascertain the immediate outcome of preterm infants with respiratory distress syndrome (RDS) on Bubble CPAP and identify risk factors associated with its failure. Prospective analytical study. Inborn preterm infants (gestation 28 to 34 weeks) admitted to the NICU with respiratory distress and chest X ray suggestive of RDS. Bubble CPAP with bi-nasal prongs. CPAP failures infants requiring ventilation in the first one week. 56 neonates were enrolled in the study. 14 (25%) babies failed CPAP. The predictors of failure were; no or only partial exposure to antenatal steroids, white-out on the chest X-ray, patent ductus arteriosus, sepsis/pneumonia and Downes score > 7 or FiO2 > or = 50% after 15-20 minutes of CPAP. Other maternal and neonatal variables did not influence the need for ventilation. Rates of mortality and duration of oxygen requirement was significantly higher in babies who failed CPAP. Only two infants developed pneumothorax. No baby had chronic lung disease. Infants with no or partial exposure to antenatal steroids, white-out chest X-ray, patent ductus arteriosus, sepsis/pneumonia and those with higher FiO2 requirement after initial stabilization on CPAP are at high risk of CPAP failure (needing mechanical ventilation). Bubble CPAP is safe for preterm infants with RDS.

  6. Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI)

    Science.gov (United States)

    2012-01-01

    Background Despite progresses in neonatal care, the mortality and the incidence of neuro-motor disability after perinatal asphyxia have failed to show substantial improvements. In countries with a high level of perinatal care, the incidence of asphyxia responsible for moderate or severe encephalopathy is still 2–3 per 1000 term newborns. Recent trials have demonstrated that moderate hypothermia, started within 6 hours after birth and protracted for 72 hours, can significantly improve survival and reduce neurologic impairment in neonates with hypoxic-ischemic encephalopathy. It is not currently known whether neuroprotective drugs can further improve the beneficial effects of hypothermia. Topiramate has been proven to reduce brain injury in animal models of neonatal hypoxic ischemic encephalopathy. However, the association of mild hypothermia and topiramate treatment has never been studied in human newborns. The objective of this research project is to evaluate, through a multicenter randomized controlled trial, whether the efficacy of moderate hypothermia can be increased by concomitant topiramate treatment. Methods/Design Term newborns (gestational age ≥ 36 weeks and birth weight ≥ 1800 g) with precocious metabolic, clinical and electroencephalographic (EEG) signs of hypoxic-ischemic encephalopathy will be randomized, according to their EEG pattern, to receive topiramate added to standard treatment with moderate hypothermia or standard treatment alone. Topiramate will be administered at 10 mg/kg once a day for the first 3 days of life. Topiramate concentrations will be measured on serial dried blood spots. 64 participants will be recruited in the study. To evaluate the safety of topiramate administration, cardiac and respiratory parameters will be continuously monitored. Blood samplings will be performed to check renal, liver and metabolic balance. To evaluate the efficacy of topiramate, the neurologic outcome of enrolled newborns will be evaluated by serial

  7. Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI

    Directory of Open Access Journals (Sweden)

    Filippi Luca

    2012-09-01

    Full Text Available Abstract Background Despite progresses in neonatal care, the mortality and the incidence of neuro-motor disability after perinatal asphyxia have failed to show substantial improvements. In countries with a high level of perinatal care, the incidence of asphyxia responsible for moderate or severe encephalopathy is still 2–3 per 1000 term newborns. Recent trials have demonstrated that moderate hypothermia, started within 6 hours after birth and protracted for 72 hours, can significantly improve survival and reduce neurologic impairment in neonates with hypoxic-ischemic encephalopathy. It is not currently known whether neuroprotective drugs can further improve the beneficial effects of hypothermia. Topiramate has been proven to reduce brain injury in animal models of neonatal hypoxic ischemic encephalopathy. However, the association of mild hypothermia and topiramate treatment has never been studied in human newborns. The objective of this research project is to evaluate, through a multicenter randomized controlled trial, whether the efficacy of moderate hypothermia can be increased by concomitant topiramate treatment. Methods/Design Term newborns (gestational age ≥ 36 weeks and birth weight ≥ 1800 g with precocious metabolic, clinical and electroencephalographic (EEG signs of hypoxic-ischemic encephalopathy will be randomized, according to their EEG pattern, to receive topiramate added to standard treatment with moderate hypothermia or standard treatment alone. Topiramate will be administered at 10 mg/kg once a day for the first 3 days of life. Topiramate concentrations will be measured on serial dried blood spots. 64 participants will be recruited in the study. To evaluate the safety of topiramate administration, cardiac and respiratory parameters will be continuously monitored. Blood samplings will be performed to check renal, liver and metabolic balance. To evaluate the efficacy of topiramate, the neurologic outcome of enrolled newborns

  8. Mechanisms of Hypoxic Up-Regulation of Versican Gene Expression in Macrophages.

    Directory of Open Access Journals (Sweden)

    Fattah Sotoodehnejadnematalahi

    Full Text Available Hypoxia is a hallmark of many pathological tissues. Macrophages accumulate in hypoxic sites and up-regulate a range of hypoxia-inducible genes. The matrix proteoglycan versican has been identified as one such gene, but the mechanisms responsible for hypoxic induction are not fully characterised. Here we investigate the up-regulation of versican by hypoxia in primary human monocyte-derived macrophages (HMDM, and, intriguingly, show that versican mRNA is up-regulated much more highly (>600 fold by long term hypoxia (5 days than by 1 day of hypoxia (48 fold. We report that versican mRNA decay rates are not affected by hypoxia, demonstrating that hypoxic induction of versican mRNA is mediated by increased transcription. Deletion analysis of the promoter identified two regions required for high level promoter activity of luciferase reporter constructs in human macrophages. The hypoxia-inducible transcription factor HIF-1 has previously been implicated as a key potential regulator of versican expression in hypoxia, however our data suggest that HIF-1 up-regulation is unlikely to be principally responsible for the high levels of induction observed in HMDM. Treatment of HMDM with two distinct specific inhibitors of Phosphoinositide 3-kinase (PI3K, LY290042 and wortmannin, significantly reduced induction of versican mRNA by hypoxia and provides evidence of a role for PI3K in hypoxic up-regulation of versican expression.

  9. Current Theory on the Cerebral Mechanisms of Hypoxic PRE- and Postconditioning.

    Science.gov (United States)

    Rybnikova, E A; Samoilov, M O

    2016-01-01

    An exposure of the organism to several episodes of mild hypoxia results in the development of brain hypoxic/ischemic tolerance, as well as cross-tolerance to the stressful factors of psychoemotional nature. Such kind of preconditioning by mild hypoxia functions as “alarm signalization” by I.P. Pavlov, preparing the organism and, in particularly, brain to the forthcoming harmful event. Dose-dependent action of hypoxia on the brain can be considered as one particular case of the general phenomenon termed hormesis, or neurohormesis. Endogenous defense processes launched by the hypoxic preconditioning and leading to the development of cerebral tolerance are associated with activation of intracellular signal cascades, transcriptional factors, regulatory proteins and expression of pro-adaptive genes and their products in the susceptible brain regions. Important mechanism of systemic adaptation induced by hypoxic preconditioning includes modifications of pituitary-adrenal axis aimed at enhancement of its adaptive resources. All these components are involved in the neuroprotective processes in three sequential phases - initiation, induction, and expression. Important role belongs also to epigenetic mechanisms controlling the activity of pro-adaptive genes. In contrast to the preconditioning, hypoxic postconditioning is comparatively novel phenomenon and therefore its mechanisms are less studied. The involvement of hypoxia-inducible factor HIF-1, and non-specific protective processes as up-regulation of anti-apoptotic factors and neurotrophines.

  10. Hypoxic challenge test applied to healthy children

    DEFF Research Database (Denmark)

    Kobbernagel, Helene Elgaard; Nielsen, Kim Gjerum; Hanel, Birgitte

    2013-01-01

    BACKGROUND: Commercial aircraft are pressurised to ~2438 m (8000 ft) above sea level that equates breathing 15% oxygen at sea level. A preflight hypoxic challenge test (HCT) is therefore recommended for children with cystic fibrosis or other chronic lung diseases and inflight oxygen is advised if...

  11. Targeting hypoxic microenvironment of pancreatic xenografts with the hypoxia-activated prodrug TH-302.

    Science.gov (United States)

    Lohse, Ines; Rasowski, Joanna; Cao, Pinjiang; Pintilie, Melania; Do, Trevor; Tsao, Ming-Sound; Hill, Richard P; Hedley, David W

    2016-06-07

    Previous reports have suggested that the hypoxic microenvironment provides a niche that supports tumor stem cells, and that this might explain clinical observations linking hypoxia to metastasis. To test this, we examined the effects of a hypoxia-activated prodrug, TH-302, on the tumor-initiating cell (TIC) frequency of patient-derived pancreatic xenografts (PDX).The frequencies of TIC, measured by limiting dilution assay, varied widely in 11 PDX models, and were correlated with rapid growth but not with the levels of hypoxia. Treatment with either TH-302 or ionizing radiation (IR), to target hypoxic and well-oxygenated regions, respectively, reduced TIC frequency, and the combination of TH-302 and IR was much more effective in all models tested. The combination was also more effective than TH-302 or IR alone controlling tumor growth, particularly treating the more rapidly-growing/hypoxic models. These findings support the clinical utility of hypoxia targeting in combination with radiotherapy to treat pancreatic cancers, but do not provide strong evidence for a hypoxic stem cell niche.

  12. Respiratory function after selective respiratory motor neuron death from intrapleural CTB-saporin injections.

    Science.gov (United States)

    Nichols, Nicole L; Vinit, Stéphane; Bauernschmidt, Lorene; Mitchell, Gordon S

    2015-05-01

    Amyotrophic lateral sclerosis (ALS) causes progressive motor neuron degeneration, paralysis and death by ventilatory failure. In rodent ALS models: 1) breathing capacity is preserved until late in disease progression despite major respiratory motor neuron death, suggesting unknown forms of compensatory respiratory plasticity; and 2) spinal microglia become activated in association with motor neuron cell death. Here, we report a novel experimental model to study the impact of respiratory motor neuron death on compensatory responses without many complications attendant to spontaneous motor neuron disease. In specific, we used intrapleural injections of cholera toxin B fragment conjugated to saporin (CTB-SAP) to selectively kill motor neurons with access to the pleural space. Motor neuron survival, CD11b labeling (microglia), ventilatory capacity and phrenic motor output were assessed in rats 3-28days after intrapleural injections of: 1) CTB-SAP (25 and 50μg), or 2) unconjugated CTB and SAP (i.e. control; (CTB+SAP). CTB-SAP elicited dose-dependent phrenic and intercostal motor neuron death; 7days post-25μg CTB-SAP, motor neuron survival approximated that in end-stage ALS rats (phrenic: 36±7%; intercostal: 56±10% of controls; n=9; pneuron death and provides an opportunity to study compensation for respiratory motor neuron loss. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Extubating Extremely Preterm Infants: Predictors of Success and Outcomes following Failure.

    Science.gov (United States)

    Manley, Brett J; Doyle, Lex W; Owen, Louise S; Davis, Peter G

    2016-06-01

    To identify variables that predict extubation success in extremely preterm infants born successful or failed extubation. A secondary analysis of data from a randomized trial of postextubation respiratory support that included 174 extremely preterm infants. "Extubation success" was defined as not requiring reintubation within 7 days, and "extubation failure" the converse. Predictive variables that were different between groups were included in a multivariable logistic regression model. Sixty-eight percent of infants were successfully extubated. Compared with those infants who had extubation failure, they had a higher GA and birth weight, were extubated earlier, were more often exposed to prolonged ruptured membranes, more often avoided intubation in the delivery room, had a higher pre-extubation pH, and had lower mean pre-extubation fraction of inspired oxygen and partial pressure of carbon dioxide (PCO2). Only GA and PCO2 remained significant in the multivariable analysis (area under a receiver operating characteristic curve = 0.81). Extubation failure was associated with death, bronchopulmonary dysplasia, severe retinopathy of prematurity, patent ductus arteriosus ligation, and longer durations of respiratory support, oxygen supplementation, and hospitalization. When adjusted for allocated treatment in the randomized trial, GA, and birth weight z-score, extubation failure remained associated with death before discharge and prolonged respiratory support and hospitalization. In extremely preterm infants, higher GA and lower pre-extubation PCO2 predicted extubation success. Infants in whom extubation failed were more likely to die and have prolonged respiratory support and hospitalization. Australian New Zealand Clinical Trials Network: ACTRN12610000166077. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Digoxin Downregulates NDRG1 and VEGF through the Inhibition of HIF-1α under Hypoxic Conditions in Human Lung Adenocarcinoma A549 Cells

    Directory of Open Access Journals (Sweden)

    Dong Wei

    2013-04-01

    Full Text Available Digoxin, an inhibitor of Na+/K+ ATPase, has been used in the treatment of heart-related diseases (such as congestive heart failure and atrial arrhythmia for decades. Recently, it was reported that digoxin is also an effective HIF-1α inhibitor. We investigated whether digoxin could suppress tumor cell growth through HIF-1α in non-small cell lung cancer cells (A549 cells under hypoxic conditions. An MTT assay was used to measure cell viability. RT-PCR and western blotting were performed to analyze the mRNA and protein expression of VEGF, NDRG1, and HIF-1α. HIF-1α nuclear translocation was then determined by EMSA. Digoxin was found to inhibit the proliferation of A549 cells under hypoxic conditions. Our results showed that hypoxia led to the upregulation of VEGF, NDRG1, and HIF-1α both at the mRNA and protein levels. We also found that the hypoxia-induced overexpression of VEGF, NDRG1, and HIF-1α was suppressed by digoxin in a concentration-dependent manner. As expected, our EMSA results demonstrated that under hypoxic conditions HIF-1α nuclear translocation was also markedly reduced by digoxin in a concentration-dependent manner. Our results suggest that digoxin downregulated hypoxia-induced overexpression of VEGF and NDRG1 at the transcriptional level probably through the inhibition of HIF-1α synthesis in A549 cells.

  15. Increased betulinic acid induced cytotoxicity and radiosensitivity in glioma cells under hypoxic conditions

    International Nuclear Information System (INIS)

    Bache, Matthias; Taubert, Helge; Vordermark, Dirk; Zschornak, Martin P; Passin, Sarina; Keßler, Jacqueline; Wichmann, Henri; Kappler, Matthias; Paschke, Reinhard; Kaluđerović, Goran N; Kommera, Harish

    2011-01-01

    Betulinic acid (BA) is a novel antineoplastic agent under evaluation for tumor therapy. Because of the selective cytotoxic effects of BA in tumor cells (including gliomas), the combination of this agent with conservative therapies (such as radiotherapy and chemotherapy) may be useful. Previously, the combination of BA with irradiation under hypoxic conditions had never been studied. In this study, the effects of 3 to 30 μM BA on cytotoxicity, migration, the protein expression of PARP, survivin and HIF-1α, as well as radiosensitivity under normoxic and hypoxic conditions were analyzed in the human malignant glioma cell lines U251MG and U343MG. Cytotoxicity and radiosensitivity were analyzed with clonogenic survival assays, migration was analyzed with Boyden chamber assays (or scratch assays) and protein expression was examined with Western blot analyses. Under normoxic conditions, a half maximal inhibitory concentration (IC 50 ) of 23 μM was observed in U251MG cells and 24 μM was observed in U343MG cells. Under hypoxic conditions, 10 μM or 15 μM of BA showed a significantly increased cytotoxicity in U251MG cells (p = 0.004 and p = 0.01, respectively) and U343MG cells (p < 0.05 and p = 0.01, respectively). The combination of BA with radiotherapy resulted in an additive effect in the U343MG cell line under normoxic and hypoxic conditions. Weak radiation enhancement was observed in U251MG cell line after treatment with BA under normoxic conditions. Furthermore, under hypoxic conditions, the incubation with BA resulted in increased radiation enhancement. The enhancement factor, at an irradiation dose of 15 Gy after treatment with 10 or 15 μM BA, was 2.20 (p = 0.02) and 4.50 (p = 0.03), respectively. Incubation with BA led to decreased cell migration, cleavage of PARP and decreased expression levels of survivin in both cell lines. Additionally, BA treatment resulted in a reduction of HIF-1α protein under hypoxic conditions. Our results suggest that BA is capable

  16. On the use of mobile inflatable hypoxic marquees for sport-specific altitude training in team sports.

    Science.gov (United States)

    Girard, Olivier; Brocherie, Franck; Millet, Grégoire P

    2013-12-01

    With the evolving boundaries of sports science and greater understanding of the driving factors in the human performance physiology, one of the limiting factors has now become the technology. The growing scientific interest on the practical application of hypoxic training for intermittent activities such as team and racket sports legitimises the development of innovative technologies serving athletes in a sport-specific setting. Description of a new mobile inflatable simulated hypoxic equipment. The system comprises two inflatable units-that is, a tunnel and a rectangular design, each with a 215 m(3) volume and a hypoxic trailer generating over 3000 Lpm of hypoxic air with FiO₂ between 0.21 and 0.10 (a simulated altitude up to 5100 m). The inflatable units offer a 45 m running lane (width=1.8 m and height=2.5 m) as well as a 8 m × 10 m dome tent. FiO₂ is stable within a range of 0.1% in normal conditions inside the tunnel. The air supplied is very dry-typically 10-15% relative humidity. This mobile inflatable simulated hypoxic equipment is a promising technological advance within sport sciences. It offers an opportunity for team-sport players to train under hypoxic conditions, both for repeating sprints (tunnel configuration) or small-side games (rectangular configuration).

  17. Anti hypoxic and antioxidant activity of Hibiscus esculentus seeds

    Energy Technology Data Exchange (ETDEWEB)

    Ebrahimzadeh, M. A.; Nabavi, S. F.; Nabavi, S. M.; Eslami, B.

    2010-07-01

    The anti hypoxic and antioxidant activities of Hibiscus esculentus seeds were investigated employing eight in vitro assay systems. Anti hypoxic activity was investigated in two models, haemic and circulatory. The effects were pronounced in both models of hypoxia. The anti hypoxic effects were dose-dependent. The results indicated that the extracts have a protective effect against hypoxia induced lethality in mice. The extracts showed antioxidant activity in some models. IC{sub 5}0 for DPPH radical-scavenging activity was 234 {+-} 8.9 {mu}g ml{sup 1}. The extracts showed weak nitric oxide-scavenging activity between 0.1 and 1.6 mg ml{sup -}1. The extracts showed weak Fe{sup 2}+ chelating ability. IC{sub 5}0 were 150 {+-} 13 {mu}g ml{sup -}1. The extracts also exhibited low antioxidant activity in the linoleic acid model but were capable of scavenging hydrogen peroxide in a concentration dependent manner. The total amount of phenolic compounds in each extract was determined as gallic acid equivalents and total flavonoid contents were calculated as quercetin equivalents from a calibration curve. Pharmacological effects may be attributed, at least in part, to the presence of phenols and flavonoids in the extracts. (Author) 40 refs.

  18. Hypoxic Response of Tumor Tissues in a Microfluidic Environment

    Science.gov (United States)

    Morshed, Adnan; Dutta, Prashanta

    2017-11-01

    Inside a tumor tissue, cells growing further away from the blood vessel often suffer from low oxygen levels known as hypoxia. Cancer cells have shown prolonged survival in hostile hypoxic conditions by sharply changing the cellular metabolism. In this work, different stages of growth of the tumor tissue and the oxygen transport across the tissue are investigated. The tissue was modeled as a contiguous block of cells inside a microfluidic environment with nutrient transport through advection and diffusion. While oxygen uptake inside the tissue is through diffusion, ascorbate transport from the extracellular medium is addressed by a concentration dependent uptake model. By varying the experimentally observed oxygen consumption rate, different types of cancer cells and their normoxic and hypoxic stages were studied. Even when the oxygen supply in the channel is maintained at normoxic levels, our results show the onset of hypoxia within minutes inside the cellblock. Interestingly, modeled cell blocks with and without a structured basal layer showed less than 5% variation in hypoxic response in chronic hypoxia. Results also indicate that the balance of cell survival and growth are affected by the flow rate of nutrients and the oxygen consumption rate. This work was supported in part by the National Science Foundation under Grant No. DMS 1317671.

  19. Acute respiratory distress syndrome assessment after traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Shahrooz Kazemi

    2016-01-01

    Full Text Available Background: Acute respiratory distress syndrome (ARDS is one of the most important complications associated with traumatic brain injury (TBI. ARDS is caused by inflammation of the lungs and hypoxic damage with lung physiology abnormalities associated with acute respiratory distress syndrome. Aim of this study is to determine the epidemiology of ARDS and the prevalence of risk factors. Methods: This prospective study performed on patients with acute traumatic head injury hospitalization in the intensive care unit of the Shohaday-e Haftom-e-Tir Hospital (September 2012 to September 2013 done. About 12 months, the data were evaluated. Information including age, sex, education, employment, drug and alcohol addiction, were collected and analyzed. The inclusion criteria were head traumatic patients and exclusion was the patients with chest trauma. Questionnaire was designed with doctors supervision of neurosurgery. Then the collected data were analysis. Results: In this study, the incidence of ARDS was 23.8% and prevalence of metabolic acidosis was 31.4%. Most injury with metabolic acidosis was Subarachnoid hemorrhage (SAH 48 (60% and Subdural hemorrhage (SDH was Next Level with 39 (48% Correlation between Glasgow Coma Scale (GCS and Respiratory Distress Syndrome (ARDS were significantly decreased (P< 0.0001. The level of consciousness in patients with skull fractures significantly lower than those without fractures (P= 0.009 [(2.3±4.6 vs (4.02±7.07]. Prevalence of metabolic acidosis during hospitalization was 80 patients (31.4%. Conclusion: Acute respiratory distress syndrome is a common complication of traumatic brain injury. Management and treatment is essential to reduce the mortality. In this study it was found the age of patients with ARDS was higher than patients without complications. ARDS risk factor for high blood pressure was higher in men. Most victims were pedestrians. The most common injury associated with ARDS was SDH. Our analysis

  20. Extreme Hypoxic Conditions Induce Selective Molecular Responses and Metabolic Reset in Detached Apple Fruit

    Science.gov (United States)

    Cukrov, Dubravka; Zermiani, Monica; Brizzolara, Stefano; Cestaro, Alessandro; Licausi, Francesco; Luchinat, Claudio; Santucci, Claudio; Tenori, Leonardo; Van Veen, Hans; Zuccolo, Andrea; Ruperti, Benedetto; Tonutti, Pietro

    2016-01-01

    The ripening physiology of detached fruit is altered by low oxygen conditions with profound effects on quality parameters. To study hypoxia-related processes and regulatory mechanisms, apple (Malus domestica, cv Granny Smith) fruit, harvested at commercial ripening, were kept at 1°C under normoxic (control) and hypoxic (0.4 and 0.8 kPa oxygen) conditions for up to 60 days. NMR analyses of cortex tissue identified eight metabolites showing significantly different accumulations between samples, with ethanol and alanine displaying the most pronounced difference between hypoxic and normoxic treatments. A rapid up-regulation of alcohol dehydrogenase and pyruvate-related metabolism (lactate dehydrogenase, pyruvate decarboxylase, alanine aminotransferase) gene expression was detected under both hypoxic conditions with a more pronounced effect induced by the lowest (0.4 kPa) oxygen concentration. Both hypoxic conditions negatively affected ACC synthase and ACC oxidase transcript accumulation. Analysis of RNA-seq data of samples collected after 24 days of hypoxic treatment identified more than 1000 genes differentially expressed when comparing 0.4 vs. 0.8 kPa oxygen concentration samples. Genes involved in cell-wall, minor and major CHO, amino acid and secondary metabolisms, fermentation and glycolysis as well as genes involved in transport, defense responses, and oxidation-reduction appeared to be selectively affected by treatments. The lowest oxygen concentration induced a higher expression of transcription factors belonging to AUX/IAA, WRKY, HB, Zinc-finger families, while MADS box family genes were more expressed when apples were kept under 0.8 kPa oxygen. Out of the eight group VII ERF members present in apple genome, two genes showed a rapid up-regulation under hypoxia, and western blot analysis showed that apple MdRAP2.12 proteins were differentially accumulated in normoxic and hypoxic samples, with the highest level reached under 0.4 kPa oxygen. These data suggest

  1. Severe Chronic Obstructive Pulmonary Disease : assessment of respiratory muscle activity and the benefits of noninvasive ventilation

    NARCIS (Netherlands)

    Duiverman, Marieke Leontine

    2008-01-01

    This thesis deals with two main topics. First, we investigated respiratory muscle function in Chronic Obstructive Pulmonary Disease (COPD) by surface electromyography. Second, we focused on the benefits of noninvasive ventilation in patients with respiratory failure, both in restrictive pulmonary

  2. Extracellular nucleotide derivatives protect cardiomyctes against hypoxic stress

    DEFF Research Database (Denmark)

    Golan, O; Issan, Y; Isak, A

    2011-01-01

    assures cardioprotection. Treatment with extracellular nucleotides, or with tri/di-phosphate, administered under normoxic conditions or during hypoxic conditions, led to a decrease in reactive oxygen species production. CONCLUSIONS: Extracellular tri/di-phosphates are apparently the molecule responsible...

  3. Is lactic acidosis a cause of exercise induced hyperventilation at the respiratory compensation point?

    OpenAIRE

    Meyer, T; Faude, O; Scharhag, J; Urhausen, A; Kindermann, W

    2004-01-01

    Objectives: The respiratory compensation point (RCP) marks the onset of hyperventilation ("respiratory compensation") during incremental exercise. Its physiological meaning has not yet been definitely determined, but the most common explanation is a failure of the body's buffering mechanisms which leads to metabolic (lactic) acidosis. It was intended to test this experimentally.

  4. Hypoxic stress up-regulates Kir2.1 expression and facilitates cell proliferation in brain capillary endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Yamamura, Hideto; Suzuki, Yoshiaki; Yamamura, Hisao [Department of Molecular & Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan); Asai, Kiyofumi [Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Imaizumi, Yuji, E-mail: yimaizum@phar.nagoya-cu.ac.jp [Department of Molecular & Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan)

    2016-08-05

    The blood-brain barrier (BBB) is mainly composed of brain capillary endothelial cells (BCECs), astrocytes and pericytes. Brain ischemia causes hypoxic encephalopathy and damages BBB. However, it remains still unclear how hypoxia affects BCECs. In the present study, t-BBEC117 cells, an immortalized bovine brain endothelial cell line, were cultured under hypoxic conditions at 4–5% oxygen for 72 h. This hypoxic stress caused hyperpolarization of resting membrane potential. Patch-clamp recordings revealed a marked increase in Ba{sup 2+}-sensitive inward rectifier K{sup +} current in t-BBEC117 cells after hypoxic culture. Western blot and real-time PCR analyses showed that Kir2.1 expression was significantly up-regulated at protein level but not at mRNA level after the hypoxic culture. Ca{sup 2+} imaging study revealed that the hypoxic stress enhanced store-operated Ca{sup 2+} (SOC) entry, which was significantly reduced in the presence of 100 μM Ba{sup 2+}. On the other hand, the expression of SOC channels such as Orai1, Orai2, and transient receptor potential channels was not affected by hypoxic stress. MTT assay showed that the hypoxic stress significantly enhanced t-BBEC117 cell proliferation, which was inhibited by approximately 60% in the presence of 100 μM Ba{sup 2+}. We first show here that moderate cellular stress by cultivation under hypoxic conditions hyperpolarizes membrane potential via the up-regulation of functional Kir2.1 expression and presumably enhances Ca{sup 2+} entry, resulting in the facilitation of BCEC proliferation. These findings suggest potential roles of Kir2.1 expression in functional changes of BCECs in BBB following ischemia. -- Highlights: •Hypoxic culture of brain endothelial cells (BEC) caused membrane hyperpolarization. •This hyperpolarization was due to the increased expression of Kir2.1 channels. •Hypoxia enhanced store-operated Ca{sup 2+} (SOC) entry via Kir2.1 up-regulation. •Expression levels of putative SOC

  5. Differences in baseline factors and survival between normocapnia, compensated respiratory acidosis and decompensated respiratory acidosis in COPD exacerbation: A pilot study.

    Science.gov (United States)

    Lun, Chung-Tat; Tsui, Miranda S N; Cheng, Suet-Lai; Chan, Veronica L; Leung, Wah-Shing; Cheung, Alice P S; Chu, Chung-Ming

    2016-01-01

    Patients with chronic obstructive pulmonary disease (COPD) experiencing acute exacerbation (AE-COPD) with decompensated respiratory acidosis are known to have poor outcomes in terms of recurrent respiratory failure and death. However, the outcomes of AE-COPD patients with compensated respiratory acidosis are not known. We performed a 1-year prospective, single-centre, cohort study in patients surviving the index admission for AE-COPD to compare baseline factors between groups with normocapnia, compensated respiratory acidosis and decompensated respiratory acidosis. Survival analysis was done to examine time to readmissions, life-threatening events and death. A total of 250 patients fulfilling the inclusion and exclusion criteria were recruited and 245 patients were analysed. Compared with normocapnia, both compensated and decompensated respiratory acidosis are associated with lower FEV1 % (P respiratory acidosis, there was no difference in FEV1 (% predicted) (P = 0.15), GOLD stage (P = 0.091), BODE index (P = 0.158) or time to life-threatening events (P = 0.301). High PaCO2 level (P = 0.002) and previous use of non-invasive ventilation (NIV) in acute setting (P respiratory acidosis are associated with poorer lung function and higher risk of future life-threatening events. High PaCO2 level and past history of NIV use in acute settings were predictive factors for future life-threatening events. Compensated respiratory acidosis warrants special attention and optimization of medical therapy as it poses risk of life-threatening events. © 2015 Asian Pacific Society of Respirology.

  6. Quantifying metabolic heterogeneity in head and neck tumors in real time: 2-DG uptake is highest in hypoxic tumor regions.

    Directory of Open Access Journals (Sweden)

    Erica C Nakajima

    Full Text Available Intratumoral metabolic heterogeneity may increase the likelihood of treatment failure due to the presence of a subset of resistant tumor cells. Using a head and neck squamous cell carcinoma (HNSCC xenograft model and a real-time fluorescence imaging approach, we tested the hypothesis that tumors are metabolically heterogeneous, and that tumor hypoxia alters patterns of glucose uptake within the tumor.Cal33 cells were grown as xenograft tumors (n = 16 in nude mice after identification of this cell line's metabolic response to hypoxia. Tumor uptake of fluorescent markers identifying hypoxia, glucose import, or vascularity was imaged simultaneously using fluorescent molecular tomography. The variability of intratumoral 2-deoxyglucose (IR800-2-DG concentration was used to assess tumor metabolic heterogeneity, which was further investigated using immunohistochemistry for expression of key metabolic enzymes. HNSCC tumors in patients were assessed for intratumoral variability of (18F-fluorodeoxyglucose ((18F-FDG uptake in clinical PET scans.IR800-2-DG uptake in hypoxic regions of Cal33 tumors was 2.04 times higher compared to the whole tumor (p = 0.0001. IR800-2-DG uptake in tumors containing hypoxic regions was more heterogeneous as compared to tumors lacking a hypoxic signal. Immunohistochemistry staining for HIF-1α, carbonic anhydrase 9, and ATP synthase subunit 5β confirmed xenograft metabolic heterogeneity. We detected heterogeneous (18F-FDG uptake within patient HNSCC tumors, and the degree of heterogeneity varied amongst tumors.Hypoxia is associated with increased intratumoral metabolic heterogeneity. (18F-FDG PET scans may be used to stratify patients according to the metabolic heterogeneity within their tumors, which could be an indicator of prognosis.

  7. Cell-cycle distributions and radiation responses of Chinese hamster cells cultured continuously under hypoxic conditions

    International Nuclear Information System (INIS)

    Tokita, N.; Carpenter, S.G.; Raju, M.R.

    1984-01-01

    Cell-cycle distributions were measured by flow cytometry for Chinese hamster (CHO) cells cultured continuously under hypoxic conditions. DNA histograms showed an accumulation of cells in the early S phase followed by a traverse delay through the S phase, and a G 2 block. During hypoxic culturing, cell viability decreased rapidly to less than 0.1% at 120 h. Radiation responses for cells cultured under these conditions showed an extreme radioresistance at 72 h. Results suggest that hypoxia induces a condition similar to cell synchrony which itself changes the radioresistance of hypoxic cells. (author)

  8. January 2017 pulmonary case of the month

    Directory of Open Access Journals (Sweden)

    Bering J

    2017-01-01

    Full Text Available No abstract available. Article truncated at 150 words. History of Present Illness: The patient is a 53-year-old woman transferred for acute respiratory failure and hemoptysis. She has a prior history of antiphospholipid syndrome and recurrent diffuse alveolar hemorrhage (DAH. She was admitted to another hospital about 2 weeks prior to transfer with hypoxic respiratory failure which ultimately required intubation. Bronchoscopy revealed a bloody aspirate raising concerns for recurrent DAH. She was started on high-dose solumedrol and extubated after 4 days. One week later, her respiratory status decompensated and her chest x-ray showed worsening diffuse bilateral opacities concerning for recurrent DAH. She was transferred to the Mayo Clinic Arizona for further evaluation. Upon arrival, she required 50% FiO2 by face mask to maintain adequate oxygenation and was started on broad-spectrum antibiotics. Her corticosteroids were tapered to 20 mg prednisone daily. Past Medical History, Social History and Family History: She has a history of a mitral valve replacement with a …

  9. OUTCOMES in CHILDHOOD FOLLOWING THERAPEUTIC HYPOTHERMIA for NEONATAL HYPOXIC-ISCHEMIC ENCEPHALOPATHY (HIE)

    Science.gov (United States)

    Natarajan, Girija; Pappas, Athina; Shankaran, Seetha

    2017-01-01

    In this chapter we review the childhood outcomes of neonates with birth depression and/or hypoxic-ischemic encephalopathy. The outcomes of these children prior to the era of hypothermia for neuroprotection will first be summarized, followed by discussion of results from randomized controlled trials of therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy. The predictors of outcome in childhood following neonatal HIE using clinical and imaging biomarkers following hypothermia therapy will be described. PMID:27863707

  10. Hypoxic exosomes facilitate bladder tumor growth and development through transferring long non-coding RNA-UCA1.

    Science.gov (United States)

    Xue, Mei; Chen, Wei; Xiang, An; Wang, Ruiqi; Chen, He; Pan, Jingjing; Pang, Huan; An, Hongli; Wang, Xiang; Hou, Huilian; Li, Xu

    2017-08-25

    To overcome the hostile hypoxic microenvironment of solid tumors, tumor cells secrete a large number of non-coding RNA-containing exosomes that facilitate tumor development and metastasis. However, the precise mechanisms of tumor cell-derived exosomes during hypoxia are unknown. Here, we aim to clarify whether hypoxia affects tumor growth and progression by transferring long non-coding RNA-urothelial cancer-associated 1 (lncRNA-UCA1) enriched exosomes secreted from bladder cancer cells. We used bladder cancer 5637 cells with high expression of lncRNA-UCA1 as exosome-generating cells and bladder cancer UMUC2 cells with low expression of lncRNA-UCA1 as recipient cells. Exosomes derived from 5637 cells cultured under normoxic or hypoxic conditions were isolated and identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting analysis. These exosomes were co-cultured with UMUC2 cells to evaluate cell proliferation, migration and invasion. We further investigated the roles of exosomal lncRNA-UCA1 derived from hypoxic 5637 cells by xenograft models. The availability of lncRNA-UCA1 in serum-derived exosomes as a biomarker for bladder cancer was also assessed. We found that hypoxic exosomes derived from 5637 cells promoted cell proliferation, migration and invasion, and hypoxic exosomal RNAs could be internalized by three bladder cancer cell lines. Importantly, lncRNA-UCA1 was secreted in hypoxic 5637 cell-derived exosomes. Compared with normoxic exosomes, hypoxic exosomes derived from 5637 cells showed the higher expression levels of lncRNA-UCA1. Moreover, Hypoxic exosomal lncRNA-UCA1 could promote tumor growth and progression though epithelial-mesenchymal transition, in vitro and in vivo. In addition, the expression levels of lncRNA-UCA1 in the human serum-derived exosomes of bladder cancer patients were higher than that in the healthy controls. Together, our results demonstrate that hypoxic bladder cancer cells remodel tumor

  11. [Successful microvascular decompression of the medulla oblongata for a case with respiratory failure: case report].

    Science.gov (United States)

    Koguchi, Motofumi; Nakahara, Yukiko; Kawashima, Masatou; Takase, Yukinori; Matsushima, Toshio

    2011-11-01

    We report a case of the medulla oblongata syndrome successfully treated by microvascular decompression surgery. The patient was a 75-year-old woman and had been suffering from gradual progressive dyspnea since July, 2009. Two month later, intubation and medial ventilator treatments were began because of severe respiratory problems. The central respiratory problems were considered in extensive testing by the physician. The head MR imaging showed that the left vertebral artery had markedly compressed the medulla oblongata. We thought that her respiratory problems were associated with this vertebral artery compression of the medulla oblongata. We performed the microvascular decompression surgery by left trans-condylar fossa approach. Her hypoventilation graduately improved after the surgery and she needed neither ventilator nor oxygen in several months. She is able to perform daily activities by herself. We report the case, and discuss the cause of respiratory problems especially by compression of the medulla oblongata.

  12. Keynote address: cellular reduction of nitroimidazole drugs: potential for selective chemotherapy and diagnosis of hypoxic cells

    International Nuclear Information System (INIS)

    Chapman, J.D.; Lee, J.; Meeker, B.E.

    1989-01-01

    Nitroimidazole drugs were initially developed as selective radiosensitizers of hypoxic cells and, consequently, as adjuvants to improve the local control probabilities of current radiotherapies. Misonidazole (MISO), the prototype radiosensitizing drug, was found in Phase I clinical studies to cause dose-limiting neurotoxicities (mainly peripheral neuropathies). MISO was also found to be cytotoxic in the absence of radiation and to covalently bind to cellular molecules, both processes demonstrating rates much higher in hypoxic compared with oxygenated cells. It is likely that neurotoxicity, cellular cytotoxicity and adduct formation results from reactions between reduction intermediates of MISO and cellular target molecules. Spin-offs from radiosensitizer research include the synthesis and characterization of more potent hypoxic cytotoxins and the exploitation of sensitizer-adducts as probes for measuring cellular and tissue oxygen levels. Current developments in hypoxic cell cytotoxin and hypoxic cell marker research are reviewed with specific examples from studies which characterize the cellular reduction of TF-MISO, (1-(2-nitro-1-imidazolyl)-3[2,2,2-trifluoroethoxy]-2-propanol). 45 references

  13. Radioprotection of normal tissues of the mouse by hypoxic breathing

    International Nuclear Information System (INIS)

    Stevens, G.N.; Joiner, B.; Denekamp, J.

    1989-01-01

    Hypoxic breathing during irradiation has been advocated as a therapeutic modality, to increase the efficacy of radiotherapy. In this form of treatment, the total and daily X-ray dose is increased by a factor of 1.25, on the assumption that all normal tissues in the beam will be protected to a similar extent by breathing gas containing a reduced oxygen concentration (usually 10%). To test this concept, we have determined the effect of varying the inspired oxygen tension on the radiosensitivity of 3 normal tissues in the mouse (kidney, jejunum and skin), and have compared these results with data from the literature for mouse lung. Reduction of the inspired oxygen tension from 21% (air) to 7-8% led to much greater radioprotection of skin (protection factor 1.37) than of lung (1.09). Protection factors for jejunum and kidney were 1.16 and 1.36 respectively. The results show that the extent of radioprotection afforded by hypoxic breathing is tissue dependent, and that great care must be taken clinically in choosing the increased radiation dose to be used in conjunction with hypoxic breathing

  14. Management of Mechanical Ventilation in Decompensated Heart Failure

    Directory of Open Access Journals (Sweden)

    Brooks T. Kuhn

    2016-12-01

    Full Text Available Mechanical ventilation (MV is a life-saving intervention for respiratory failure, including decompensated congestive heart failure. MV can reduce ventricular preload and afterload, decrease extra-vascular lung water, and decrease the work of breathing in heart failure. The advantages of positive pressure ventilation must be balanced with potential harm from MV: volutrauma, hyperoxia-induced injury, and difficulty assessing readiness for liberation. In this review, we will focus on cardiac, pulmonary, and broader effects of MV on patients with decompensated HF, focusing on practical considerations for management and supporting evidence.

  15. Retinal neuroprotection by hypoxic preconditioning is independent of hypoxia-inducible factor-1 alpha expression in photoreceptors.

    Science.gov (United States)

    Thiersch, Markus; Lange, Christina; Joly, Sandrine; Heynen, Severin; Le, Yun Zheng; Samardzija, Marijana; Grimm, Christian

    2009-06-01

    Hypoxic preconditioning stabilizes hypoxia-inducible factor (HIF) 1 alpha in the retina and protects photoreceptors against light-induced cell death. HIF-1 alpha is one of the major transcription factors responding to low oxygen tension and can differentially regulate a large number of target genes. To analyse whether photoreceptor-specific expression of HIF-1 alpha is essential to protect photoreceptors by hypoxic preconditioning, we knocked down expression of HIF-1 alpha specifically in photoreceptor cells, using the cyclization recombinase (Cre)-lox system. The Cre-mediated knockdown caused a 20-fold reduced expression of Hif-1 alpha in the photoreceptor cell layer. In the total retina, RNA expression was reduced by 65%, and hypoxic preconditioning led to only a small increase in HIF-1 alpha protein levels. Accordingly, HIF-1 target gene expression after hypoxia was significantly diminished. Retinas of Hif-1 alpha knockdown animals did not show any pathological alterations, and tolerated hypoxic exposure in a comparable way to wild-type retinas. Importantly, the strong neuroprotective effect of hypoxic preconditioning against light-induced photoreceptor degeneration persisted in knockdown mice, suggesting that hypoxia-mediated survival of light exposure does not depend on an autocrine action of HIF-1 alpha in photoreceptor cells. Hypoxia-mediated stabilization of HIF-2 alpha and phosphorylation of signal transducer and activator of transcription 3 (STAT 3) were not affected in the retinas of Hif-1 alpha knockdown mice. Thus, these factors are candidates for regulating the resistance of photoreceptors to light damage after hypoxic preconditioning, along with several potentially neuroprotective genes that were similarly induced in hypoxic knockdown and control mice.

  16. The Clinical Utilisation of Respiratory Elastance Software (CURE Soft): a bedside software for real-time respiratory mechanics monitoring and mechanical ventilation management.

    Science.gov (United States)

    Szlavecz, Akos; Chiew, Yeong Shiong; Redmond, Daniel; Beatson, Alex; Glassenbury, Daniel; Corbett, Simon; Major, Vincent; Pretty, Christopher; Shaw, Geoffrey M; Benyo, Balazs; Desaive, Thomas; Chase, J Geoffrey

    2014-09-30

    Real-time patient respiratory mechanics estimation can be used to guide mechanical ventilation settings, particularly, positive end-expiratory pressure (PEEP). This work presents a software, Clinical Utilisation of Respiratory Elastance (CURE Soft), using a time-varying respiratory elastance model to offer this ability to aid in mechanical ventilation treatment. CURE Soft is a desktop application developed in JAVA. It has two modes of operation, 1) Online real-time monitoring decision support and, 2) Offline for user education purposes, auditing, or reviewing patient care. The CURE Soft has been tested in mechanically ventilated patients with respiratory failure. The clinical protocol, software testing and use of the data were approved by the New Zealand Southern Regional Ethics Committee. Using CURE Soft, patient's respiratory mechanics response to treatment and clinical protocol were monitored. Results showed that the patient's respiratory elastance (Stiffness) changed with the use of muscle relaxants, and responded differently to ventilator settings. This information can be used to guide mechanical ventilation therapy and titrate optimal ventilator PEEP. CURE Soft enables real-time calculation of model-based respiratory mechanics for mechanically ventilated patients. Results showed that the system is able to provide detailed, previously unavailable information on patient-specific respiratory mechanics and response to therapy in real-time. The additional insight available to clinicians provides the potential for improved decision-making, and thus improved patient care and outcomes.

  17. Respiratory function after selective respiratory motor neuron death from intrapleural CTB–saporin injections

    Science.gov (United States)

    Nichols, Nicole L.; Vinit, Stéphane; Bauernschmidt, Lorene; Mitchell, Gordon S.

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) causes progressive motor neuron degeneration, paralysis and death by ventilatory failure. In rodent ALS models: 1) breathing capacity is preserved until late in disease progression despite major respiratory motor neuron death, suggesting unknown forms of compensatory respiratory plasticity; and 2) spinal microglia become activated in association with motor neuron cell death. Here, we report a novel experimental model to study the impact of respiratory motor neuron death on compensatory responses without many complications attendant to spontaneous motor neuron disease. In specific, we used intrapleural injections of cholera toxin B fragment conjugated to saporin (CTB–SAP) to selectively kill motor neurons with access to the pleural space. Motor neuron survival, CD11b labeling (microglia), ventilatory capacity and phrenic motor output were assessed in rats 3–28 days after intrapleural injections of: 1) CTB–SAP (25 and 50 μg), or 2) unconjugated CTB and SAP (i.e. control; (CTB + SAP). CTB–SAP elicited dose-dependent phrenic and intercostal motor neuron death; 7 days post-25 μg CTB–SAP, motor neuron survival approximated that in end-stage ALS rats (phrenic: 36 ± 7%; intercostal: 56 ± 10% of controls; n = 9; p phrenic motor nucleus, indicating microglial activation; 2) decreased breathing during maximal chemoreceptor stimulation; and 3) diminished phrenic motor output in anesthetized rats (7 days post-25 μg, CTB–SAP: 0.3 ± 0.07 V; CTB + SAP: 1.5 ± 0.3; n = 9; p < 0.05). Intrapleural CTB–SAP represents a novel, inducible model of respiratory motor neuron death and provides an opportunity to study compensation for respiratory motor neuron loss. PMID:25476493

  18. Reoxygenation of hypoxic cells by tumor shrinkage during irradiation. A computer simulation

    International Nuclear Information System (INIS)

    Kocher, M.; Treuer, H.

    1995-01-01

    A 3-dimensional computer simulation was developed in order to estimate the impact of tumor shrinkage on reoxygenation of chronic hypoxic tumor cells during a full course of fractionated irradiation. The growth of a small tumor situated in a vascularized stroma with 350 capillary cross-sections/mm 3 which were displaced by the growing tumor was simulated. Tumors contained 10 4 cells when irradiation started, intrinsic radiosensitivity was set to either low (α=0.3 Gy -1 , β=0.03 Gy -2 ) or high (α=0.4 Gy -1 , β=0.04 Gy -2 ) values. Oxygen enhancement ratio was 3.0, potential tumor doubling time T pot =1, 2 or 5 days. A simulated fractionated radiotherapy was carried out with daily fractions of 2.0 Gy, total dose 50 to 70 Gy. The presence or absence of factors preventing tumor cord shrinkage was also included. During the growth phase, all tumors developed a necrotic core with a hypoxic cell fraction of 25% under these conditions. During irradiation, the slower growing tumors (T pot =2 to 5 days) showed complete reoxygenation of the hypoxic cells after 30 to 40 Gy independent from radiosensitivity, undisturbed tumor shrinkage provided. If shrinkage was prevented, the hypoxic fraction rose to 100% after 30 to 50 Gy. Local tumor control, defined as the destruction of all clonogenic and hypoxic tumor cells increased by 20 to 100% due to reoxygenation and 50 Gy were enough in order to sterilize the tumors in these cases. In the fast growing tumors (T pot =1 day), reoxygenation was only observed in the case of high radiosensitivity and undisturbed tumor shrinkage. In these tumors reoxygenation increased the control rates by up to 60%. (orig./MG) [de

  19. Bubble–CPAP vs. Ventilatory–CPAP in Preterm Infants with Respiratory Distress

    OpenAIRE

    Mohammad-Reza Baneshi; Pedram Niknafs; Arash Malekiyan; Bahareh Bahman-Bijari

    2011-01-01

    Objective:Application of Continuous Positive Airway Pressure (CPAP) in neonate with respiratory distress is associated with reduction of respiratory failure, reduced complications and mortality. Bubble CPAP (B-CPAP) and ventilator-derived CPAP (V-CPAP) are two most popular CPAP modes. We aimed to determine whether B-CPAP and V-CPAP would have different survival rate and possible complications. Methods: This prospective clinical trial was performed on 50 preterm neonates weighing 1000-2000 gr ...

  20. Depressed Hypoxic and Hypercapnic Ventilatory Responses at Early Stage of Lethal Avian Influenza A Virus Infection in Mice.

    Directory of Open Access Journals (Sweden)

    Jianguo Zhuang

    Full Text Available H5N1 virus infection results in ~60% mortality in patients primarily due to respiratory failure, but the underlying causes of mortality are unclear. The goal of this study is to reveal respiratory disorders occurring at the early stage of infection that may be responsible for subsequent respiratory failure and death. BALB/c mice were intranasally infected with one of two H5N1 virus strains: HK483 (lethal or HK486 (non-lethal virus. Pulmonary ventilation and the responses to hypoxia (HVR; 7% O2 for 3 min and hypercapnia (HCVR; 7% CO2 for 5 min were measured daily at 2 days prior and 1, 2, and 3 days postinfection (dpi and compared to mortality typically by 8 dpi. At 1, 2, and 3 dpi, immunoreactivities (IR of substance P (SP-IR in the nodose ganglion or tyrosine hydroxylase (TH-IR in the carotid body coupled with the nucleoprotein of influenza A (NP-IR was examined in some mice, while arterial blood was collected in others. Our results showed that at 2 and 3 dpi: 1 both viral infections failed to alter body temperature and weight, [Formula: see text], or induce viremia while producing similarly high lung viral titers; 2 HK483, but not HK486, virus induced tachypnea and depressed HVR and HCVR without changes in arterial blood pH and gases; and 3 only HK483 virus led to NP-IR in vagal SP-IR neurons, but not in the carotid body, and increased density of vagal SP-IR neurons. In addition, all HK483, rather than HK486, mice died at 6 to 8 dpi and the earlier death was correlated with more severe depression of HVR and HCVR. Our data suggest that tachypnea and depressed HVR/HCVR occur at the early stage of lethal H5N1 viral infection associated with viral replication and increased SP-IR density in vagal neurons, which may contribute to the respiratory failure and death.

  1. Hypoxic-ischemic encefalopathy: Clinical course and prognosis

    Directory of Open Access Journals (Sweden)

    Ćosić-Cerovac Nataša

    2003-01-01

    Full Text Available Background. Establishing the value of neurological examination, and additional diagnostic methods (ultrasonography and magnetic resonance imaging of the brain in the diagnosis and prognosis of hypoxic-ischemic encephalopathy and its treatment, tracking the clinical course, and making the prognosis of neurological development in newborn infants with hypoxic-ischemic encefalopathy. Methods. The group of 40 term newborn infants with suspected intrauterine asphyxia was examined. All the infants were prospectivelly followed untill the 3rd year of age at the Clinic for Neurology and Psychiatry for Children and Youth in order to estimate their neurological development and to diagnose the occurence of persistent neurological disorders. All the infants were analyzed by their gestational age and Apgar score in the 1st and the 5th minute of life. They were all examined neurologically and by ultrasonography in the first week of life and, repeatedly, at the age of 1, 3, 6, 9, 12, 18, as well as in the 24th month of life. They were treated by the standard methods for this disease. Finally, all the infants were examined neurologically and by magnetic resonance imaging of the brain in their 3rd year of age. On the basis of neurological finding infants were devided into 3 groups: infants with normal neurological finding, infants with mild neurological symptomatology, and infants with severe neurological disorders. Results. It was shown that neurological finding, ultrasonography and magnetic resonance imaging of the brain positively correlated with the later neurological development of the infants with hypoxic-ischemic encephalopathy. Conclusion. Only the combined use of these techniques had full diagnostic and prognostic significance emphasizing that the integrative approach was very important in the diagnosis of brain lesions in infants.

  2. [Hypoxic brain injuries notified to the Danish Patient Insurance Association during 1992-2004. Secondary publication

    DEFF Research Database (Denmark)

    Bock, J.; Christoffersen, J.K.; Hedegaard, M.

    2008-01-01

    We investigated the files of the Danish Patient Insurance Association for newborns suffering from hypoxic brain injuries. From 1992 to 2004, a total of 127 approved claims concerning peripartum hypoxic injury were registered. Thirty-eight newborns died and the majority of the 89 surviving children...

  3. Intensity cut-points for the Respiratory Distress Observation Scale

    Science.gov (United States)

    Campbell, Margaret L; Templin, Thomas N

    2015-01-01

    Background The Respiratory Distress Observation Scale© is an innovative solution to assessment when a dyspnea report cannot be elicited. The Respiratory Distress Observation Scale has acceptable reliability and validity psychometrics. Aim To identify distress-intensity cut-points of the Respiratory Distress Observation Scale. Design Receiver operating characteristic curve analysis was conducted with inpatients stratified by four levels of respiratory distress—none, mild, moderate, or severe. Patients provided three self-report measures of dyspnea: dichotomous (yes/no); a ranking of none, mild, moderate, or severe; and a numerical rating scale. Respiratory distress was assessed using the Respiratory Distress Observation Scale instrument. Setting/participants Participants were 136 adult inpatients, mean age 61.8 years (standard deviation = 13.18 years), 89.7% African American, and 56.6% female, who were recruited from an urban, tertiary care hospital in the Midwest of the United States. Results In all, 47% (n = 64) self-reported dyspnea (yes/no). Ranking was distributed as follows: none = 36, mild = 35, moderate = 40, and severe = 25. Numerical rating scale scores ranged from 0 to 10, mean = 4.99 (standard deviation = 2.9). Respiratory Distress Observation Scale scores ranged from 0 to 7, median (interquartile range) = 2 (1–3). Receiver operating characteristic curve analysis–determined Respiratory Distress Observation Scale score of 0–2 suggests little or no respiratory distress; score ≥3 signified moderate to severe distress. Conclusion A Respiratory Distress Observation Scale score ≥3 signifies a patient’s need for palliation of respiratory distress. An end-point for identifying responsiveness to treatment, in other words, respiratory comfort, is Respiratory Distress Observation Scale <3. Because patients with imminent respiratory failure, as typified by dying patients, were not represented yielding lower than expected Respiratory Distress

  4. Interleukin-17 limits hypoxia-inducible factor 1α and development of hypoxic granulomas during tuberculosis.

    Science.gov (United States)

    Domingo-Gonzalez, Racquel; Das, Shibali; Griffiths, Kristin L; Ahmed, Mushtaq; Bambouskova, Monika; Gopal, Radha; Gondi, Suhas; Muñoz-Torrico, Marcela; Salazar-Lezama, Miguel A; Cruz-Lagunas, Alfredo; Jiménez-Álvarez, Luis; Ramirez-Martinez, Gustavo; Espinosa-Soto, Ramón; Sultana, Tamanna; Lyons-Weiler, James; Reinhart, Todd A; Arcos, Jesus; de la Luz Garcia-Hernandez, Maria; Mastrangelo, Michael A; Al-Hammadi, Noor; Townsend, Reid; Balada-Llasat, Joan-Miquel; Torrelles, Jordi B; Kaplan, Gilla; Horne, William; Kolls, Jay K; Artyomov, Maxim N; Rangel-Moreno, Javier; Zúñiga, Joaquín; Khader, Shabaana A

    2017-10-05

    Mycobacterium tuberculosis (Mtb) is a global health threat, compounded by the emergence of drug-resistant strains. A hallmark of pulmonary tuberculosis (TB) is the formation of hypoxic necrotic granulomas, which upon disintegration, release infectious Mtb. Furthermore, hypoxic necrotic granulomas are associated with increased disease severity and provide a niche for drug-resistant Mtb. However, the host immune responses that promote the development of hypoxic TB granulomas are not well described. Using a necrotic Mtb mouse model, we show that loss of Mtb virulence factors, such as phenolic glycolipids, decreases the production of the proinflammatory cytokine IL-17 (also referred to as IL-17A). IL-17 production negatively regulates the development of hypoxic TB granulomas by limiting the expression of the transcription factor hypoxia-inducible factor 1α (HIF1α). In human TB patients, HIF1α mRNA expression is increased. Through genotyping and association analyses in human samples, we identified a link between the single nucleotide polymorphism rs2275913 in the IL-17 promoter (-197G/G), which is associated with decreased IL-17 production upon stimulation with Mtb cell wall. Together, our data highlight a potentially novel role for IL-17 in limiting the development of hypoxic necrotic granulomas and reducing disease severity in TB.

  5. Vasotrophic Regulation of Age-Dependent Hypoxic Cerebrovascular Remodeling

    Science.gov (United States)

    Silpanisong, Jinjutha; Pearce, William J.

    2015-01-01

    Hypoxia can induce functional and structural vascular remodeling by changing the expression of trophic factors to promote homeostasis. While most experimental approaches have been focused on functional remodeling, structural remodeling can reflect changes in the abundance and organization of vascular proteins that determine functional remodeling. Better understanding of age-dependent hypoxic macrovascular remodeling processes of the cerebral vasculature and its clinical implications require knowledge of the vasotrophic factors that influence arterial structure and function. Hypoxia can affect the expression of transcription factors, classical receptor tyrosine kinase factors, non-classical G-protein coupled factors, catecholamines, and purines. Hypoxia’s remodeling effects can be mediated by Hypoxia Inducible Factor (HIF) upregulation in most vascular beds, but alterations in the expression of growth factors can also be independent of HIF. PPARγ is another transcription factor involved in hypoxic remodeling. Expression of classical receptor tyrosine kinase ligands, including vascular endothelial growth factor, platelet derived growth factor, fibroblast growth factor and angiopoietins, can be altered by hypoxia which can act simultaneously to affect remodeling. Tyrosine kinase-independent factors, such as transforming growth factor, nitric oxide, endothelin, angiotensin II, catecholamines, and purines also participate in the remodeling process. This adaptation to hypoxic stress can fundamentally change with age, resulting in different responses between fetuses and adults. Overall, these mechanisms integrate to assure that blood flow and metabolic demand are closely matched in all vascular beds and emphasize the view that the vascular wall is a highly dynamic and heterogeneous tissue with multiple cell types undergoing regular phenotypic transformation. PMID:24063376

  6. High phenobarbital clearance during continuous renal replacement therapy: a case report and pharmacokinetic analysis.

    Science.gov (United States)

    Rosenborg, Staffan; Saraste, Lars; Wide, Katarina

    2014-08-01

    Phenobarbital is an old antiepileptic drug used in severe epilepsy. Despite this, little is written about the need for dose adjustments in renal replacement therapy. Most sources recommend a moderately increased dose guided by therapeutic drug monitoring.A 14 year old boy with nonketotic hyperglycinemia, a rare inborn error of metabolism, characterized by high levels of glycine, epilepsy, spasticity, and cognitive impairment, was admitted to the emergency department with respiratory failure after a few days of fever and cough. The boy was unconscious at admittance and had acute renal and hepatic failure.Due to the acute respiratory infection, hypoxic hepatic and renal failure occurred and the patient had a status epilepticus.The patient was intubated and mechanically ventilated. Continuous renal replacement therapy was initiated. Despite increased phenobarbital doses, therapeutic levels were not reached until the dose was increased to 500 mg twice daily. Therapeutic drug monitoring was performed in plasma and dialysate. Calculations revealed that phenobarbital was almost freely dialyzed.Correct dosing of drugs in patients on renal replacement therapy may need a multidisciplinary approach and guidance by therapeutic drug monitoring.

  7. Outcomes in childhood following therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE).

    Science.gov (United States)

    Natarajan, Girija; Pappas, Athina; Shankaran, Seetha

    2016-12-01

    In this article, we review the childhood outcomes of neonates with birth depression and/or hypoxic-ischemic encephalopathy. The outcomes of these children prior to the era of hypothermia for neuroprotection will first be summarized, followed by discussion of results from randomized controlled trials of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy. The predictors of outcome in childhood following neonatal HIE using clinical and imaging biomarkers following hypothermia therapy will be described. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Is Overall Mortality the Right Composite Endpoint in Clinical Trials of Acute Respiratory Distress Syndrome?

    Science.gov (United States)

    Villar, Jesús; Martínez, Domingo; Mosteiro, Fernando; Ambrós, Alfonso; Añón, José M; Ferrando, Carlos; Soler, Juan A; Montiel, Raquel; Vidal, Anxela; Conesa-Cayuela, Luís A; Blanco, Jesús; Arrojo, Regina; Solano, Rosario; Capilla, Lucía; Del Campo, Rafael; Civantos, Belén; Fernández, María Mar; Aldecoa, César; Parra, Laura; Gutiérrez, Andrea; Martínez-Jiménez, Chanel; González-Martín, Jesús M; Fernández, Rosa L; Kacmarek, Robert M

    2018-06-01

    Overall mortality in patients with acute respiratory distress syndrome is a composite endpoint because it includes death from multiple causes. In most acute respiratory distress syndrome trials, it is unknown whether reported deaths are due to acute respiratory distress syndrome or the underlying disease, unrelated to the specific intervention tested. We investigated the causes of death after contracting acute respiratory distress syndrome in a large cohort. A secondary analysis from three prospective, multicenter, observational studies. A network of multidisciplinary ICUs. We studied 778 patients with moderate-to-severe acute respiratory distress syndrome treated with lung-protective ventilation. None. We examined death in the ICU from individual causes. Overall ICU mortality was 38.8% (95% CI, 35.4-42.3). Causes of acute respiratory distress syndrome modified the risk of death. Twenty-three percent of deaths occurred from refractory hypoxemia due to nonresolving acute respiratory distress syndrome. Most patients died from causes unrelated to acute respiratory distress syndrome: 48.7% of nonsurvivors died from multisystem organ failure, and cancer or brain injury was involved in 37.1% of deaths. When quantifying the true burden of acute respiratory distress syndrome outcome, we identified 506 patients (65.0%) with one or more exclusion criteria for enrollment into current interventional trials. Overall ICU mortality of the "trial cohort" (21.3%) was markedly lower than the parent cohort (relative risk, 0.55; 95% CI, 0.43-0.70; p respiratory distress syndrome patients are not directly related to lung damage but to extrapulmonary multisystem organ failure. It would be challenging to prove that specific lung-directed therapies have an effect on overall survival.

  9. Patterns of neonatal hypoxic-ischaemic brain injury

    International Nuclear Information System (INIS)

    Vries, Linda S. de; Groenendaal, Floris

    2010-01-01

    Enormous progress has been made in assessing the neonatal brain, using magnetic resonance imaging (MRI). In this review, we will describe the use of MRI and proton magnetic resonance spectroscopy in detecting different patterns of brain injury in (full-term) human neonates following hypoxic-ischaemic brain injury and indicate the relevance of these findings in predicting neurodevelopmental outcome. (orig.)

  10. Patterns of neonatal hypoxic-ischaemic brain injury

    Energy Technology Data Exchange (ETDEWEB)

    Vries, Linda S. de [University Medical Centre, Department of Neonatology, Wilhelmina Children' s Hospital, Utrecht (Netherlands); Wilhelmina Children' s Hospital, University Medical Centre, Department of Neonatology, KE 04.123.1, P.O. Box 85090, Utrecht (Netherlands); Groenendaal, Floris [University Medical Centre, Department of Neonatology, Wilhelmina Children' s Hospital, Utrecht (Netherlands)

    2010-06-15

    Enormous progress has been made in assessing the neonatal brain, using magnetic resonance imaging (MRI). In this review, we will describe the use of MRI and proton magnetic resonance spectroscopy in detecting different patterns of brain injury in (full-term) human neonates following hypoxic-ischaemic brain injury and indicate the relevance of these findings in predicting neurodevelopmental outcome. (orig.)

  11. Melatonin rescues cardiovascular dysfunction during hypoxic development in the chick embryo.

    Science.gov (United States)

    Itani, Nozomi; Skeffington, Katie L; Beck, Christian; Niu, Youguo; Giussani, Dino A

    2016-01-01

    There is a search for rescue therapy against fetal origins of cardiovascular disease in pregnancy complicated by chronic fetal hypoxia, particularly following clinical diagnosis of fetal growth restriction (FGR). Melatonin protects the placenta in adverse pregnancy; however, whether melatonin protects the fetal heart and vasculature in hypoxic pregnancy independent of effects on the placenta is unknown. Whether melatonin can rescue fetal cardiovascular dysfunction when treatment commences following FGR diagnosis is also unknown. We isolated the effects of melatonin on the developing cardiovascular system of the chick embryo during hypoxic incubation. We tested the hypothesis that melatonin directly protects the fetal cardiovascular system in adverse development and that it can rescue dysfunction following FGR diagnosis. Chick embryos were incubated under normoxia or hypoxia (14% O2) from day 1 ± melatonin treatment (1 mg/kg/day) from day 13 of incubation (term ~21 days). Melatonin in hypoxic chick embryos rescued cardiac systolic dysfunction, impaired cardiac contractility and relaxability, increased cardiac sympathetic dominance, and endothelial dysfunction in peripheral circulations. The mechanisms involved included reduced oxidative stress, enhanced antioxidant capacity and restored vascular endothelial growth factor expression, and NO bioavailability. Melatonin treatment of the chick embryo starting at day 13 of incubation, equivalent to ca. 25 wk of gestation in human pregnancy, rescues early origins of cardiovascular dysfunction during hypoxic development. Melatonin may be a suitable antioxidant candidate for translation to human therapy to protect the fetal cardiovascular system in adverse pregnancy. © 2015 The Authors. Journal of Pineal Research. Published by John Wiley & Sons Ltd.

  12. INTERMITTENT HYPOBARIC HYPOXIC STIMULATION IN TREATMENT OF CHILDREN WITH BRONCHIAL ASTHMA AT THE PERIOD OF REHABILITATION

    Directory of Open Access Journals (Sweden)

    G.D. Alemanova

    2009-01-01

    Full Text Available Bronchial asthma is one of the widespread chronic diseases of lungs. Immune mechanisms of disorder are one of the causes which lead to pathologic changes in lungs. The aim: to determine the clinical and immunologic effectiveness of pressure adaptation to the periodical hypobaric hypoxic stimulation of treatment of children with bronchial asthma of prepubertal and pubertal periods. In the present work there were observed the clinical and immunologic parameters of 129 children with the verified atopic bronchial asthma of different degree at the remission period before and after the course of pressure adaptation to the periodical hypobaric hypoxic stimulation in conditions of the medical hypobaric pressure chamber with many seats «Ural'1». Clinic effectiveness of hypobaric hypoxic stimulation revealed in continuation of remissions and diminishing of total numerical score of asthma degree. The positive dynamic indexes of cytokine profile was observed. It revealed in reduction of IL 1_, IL 4, IL 5, IL 18 levels and stimulated production of IFN - in blood serum. The course of hypobaric hypoxic stimulation has the positive impact on the named indexes of the patients with bronchial asthma and its intensity depends on the degree of disease and of the age of the child' patient. Thus the use of pressure adaptation to the periodical hypobaric hypoxic stimulation in treatment of children's with bronchial asthma led to the immunologic positive dynamics, especially of the children of prepubertal period. Determination of the immunologic indexes and the level of the cytokines can be used as the additional tests for the evaluation of the effectiveness of pressure adaptation to the periodical hypobaric hypoxic stimulation of children.Key words: bronchial asthma, periodical hypobaric hypoxic stimulation, cytokines, children.

  13. New strategy of cancer therapy by targeting the hypoxic circumstances

    International Nuclear Information System (INIS)

    Yasui, Hironobu; Yamamori, Tohru; Meike, Shunsuke; Eitaki, Masato; Kuwabara, Mikinori; Inanami, Osamu; Iizuka, Daisuke

    2010-01-01

    Described are studies on the sensitization of tumor cells in hypoxic circumstances (known as radio-resistant cells) by authors' recent molecular targeting to adaptive response as well as by the usual agents like nitro-imidazole compounds, and on the intermittent hypoxia, a new topic in this field. The hypoxia-inducible factor-1 (HIF-1) is a transcriptional factor and has been known to activate its many downstream genes to cause adoptive response of hypoxic cells. Authors have studied the anti-tumor and radiation sensitizing effects of ethynyl-cytidine (EC) which is found to suppress RNA synthesis through cytidine kinase (CK) inhibition, and the compound is of specificity to tumor cells as they have 5-10 times higher CK activity than normal cells. Authors have also found that EC is of the sensitizing efficacy to normoxic and hypoxic cells by enhancing the radiation-induced apoptosis essentially through inhibition of HIF-1 expression. Intermittent hypoxia in the tumor which has characteristic abnormal vascular morphology and function, occurs by the transient reduction of blood flow and occlusion of vessels in the tissue within minute to hour time cycles. Little is known about the regional hypoxic region and its distribution in the tumor due to difficulty of their detection and quantification. For this, authors have measured the temporal changes of oxygen levels in the mouse tumor with triaryl methyl radical, an oxygen-sensitive contrast compound continuously injected, by microwave-pulsed electron spin resonance imaging (EPRI). By superimposing the EPRI and T2-weighted MRI, the oxymetric imaging is possible in the tumor, which reveals the difference of oxygen level variation depending on the cell type and tissue size. Findings in the field are expected to give important information for more effective cancer therapy and its prognostic prediction in future. (T.T.)

  14. Hypoxic Vasospasm Mediated by cIMP: When Soluble Guanylyl Cyclase Turns Bad.

    Science.gov (United States)

    Gao, Yuansheng; Chen, Zhengju; Leung, Susan W S; Vanhoutte, Paul M

    2015-06-01

    In a number of isolated blood vessel types, hypoxia causes an acute contraction that is dependent on the presence of nitric oxide and activation of soluble guanylyl cyclase. It is more pronounced when the preparations are constricted and is therefore termed hypoxic augmentation of vasoconstriction. This hypoxic response is accompanied by increases in the intracellular level of inosine 5'-triphosphate and in the synthesis of inosine 3',5'-cyclic monophosphate (cIMP) by soluble guanylyl cyclase. The administration of exogenous cIMP or inosine 5'-triphosphate causes augmented vasoconstriction to hypoxia. Furthermore, the vasoconstriction evoked by hypoxia and cIMP is associated with increased activity of Rho kinase (ROCK), indicating that cIMP may mediate the hypoxic effect by sensitizing the myofilaments to Ca through ROCK. Hypoxia is implicated in exaggerated vasoconstriction in the pathogenesis of coronary artery disease, myocardial infarction, hypertension, and stroke. The newly found role of cIMP may help to identify unique therapeutic targets for certain cardiovascular disorders.

  15. Technical-Induced Hemolysis in Patients with Respiratory Failure Supported with Veno-Venous ECMO - Prevalence and Risk Factors.

    Science.gov (United States)

    Lehle, Karla; Philipp, Alois; Zeman, Florian; Lunz, Dirk; Lubnow, Matthias; Wendel, Hans-Peter; Göbölös, Laszlo; Schmid, Christof; Müller, Thomas

    2015-01-01

    The aim of the study was to explore the prevalence and risk factors for technical-induced hemolysis in adults supported with veno-venous extracorporeal membrane oxygenation (vvECMO) and to analyze the effect of hemolytic episodes on outcome. This was a retrospective, single-center study that included 318 adult patients (Regensburg ECMO Registry, 2009-2014) with acute respiratory failure treated with different modern miniaturized ECMO systems. Free plasma hemoglobin (fHb) was used as indicator for hemolysis. Throughout a cumulative support duration of 4,142 days on ECMO only 1.7% of the fHb levels were above a critical value of 500 mg/l. A grave rise in fHb indicated pumphead thrombosis (n = 8), while acute oxygenator thrombosis (n = 15) did not affect fHb. Replacement of the pumphead normalized fHb within two days. Neither pump or cannula type nor duration on the first system was associated with hemolysis. Multiple trauma, need for kidney replacement therapy, increased daily red blood cell transfusion requirements, and high blood flow (3.0-4.5 L/min) through small-sized cannulas significantly resulted in augmented blood cell trauma. Survivors were characterized by lower peak levels of fHb [90 (60, 142) mg/l] in comparison to non-survivors [148 (91, 256) mg/l, p≤0.001]. In conclusion, marked hemolysis is not common in vvECMO with modern devices. Clinically obvious hemolysis often is caused by pumphead thrombosis. High flow velocity through small cannulas may also cause technical-induced hemolysis. In patients who developed lung failure due to trauma, fHb was elevated independantly of ECMO. In our cohort, the occurance of hemolysis was associated with increased mortality.

  16. Respiratory muscle dysfunction in congestive heart failure: clinical correlation and prognostic significance.

    Science.gov (United States)

    Meyer, F J; Borst, M M; Zugck, C; Kirschke, A; Schellberg, D; Kübler, W; Haass, M

    2001-05-01

    In congestive heart failure (CHF), the prognostic significance of impaired respiratory muscle strength has not been established. Maximal inspiratory pressure (Pi(max)) was prospectively determined in 244 consecutive patients (207 men) with CHF (ischemic, n=75; idiopathic dilated cardiomyopathy, n=169; age, 54+/-11 years; left ventricular ejection fraction [LVEF], 22+/-10%). Pi(max) was lower in the 244 patients with CHF than in 25 control subjects (7.6+/-3.3 versus 10.5+/-3.7 kPa; P=0.001). The 57 patients (23%) who died during follow-up (23+/-16 months; range, 1 to 48 months) had an even more reduced Pi(max) (6.3+/-3.2 versus 8.1+/-3.2 kPa in survivors; P=0.001). Kaplan-Meier survival curves differentiated between patients subdivided according to quartiles for Pi(max) (P=0.014). Pi(max) was a strong risk predictor in both univariate (P=0.001) and multivariate Cox proportional hazard analyses (P=0.03); multivariate analyses also included NYHA functional class, LVEF, peak oxygen consumption (peak VO(2)), and norepinephrine plasma concentration. The areas under the receiver-operating characteristic curves for prediction of 1-year survival were comparable for Pi(max) and peak VO(2) (area under the curve [AUC], 0.68 versus 0.73; P=0.28), and they improved with the triple combination of Pi(max), peak VO(2), and LVEF (AUC, 0.82; P=0.004 compared with AUC of Pi(max)). In patients with CHF, inspiratory muscle strength is reduced and emerges as a novel, independent predictor of prognosis. Because testing for Pi(max) is simple in clinical practice, it might serve as an additional factor to improve risk stratification and patient selection for cardiac transplantation.

  17. Nitrofurantoin-induced acute respiratory distress syndrome during pregnancy: A case report

    Directory of Open Access Journals (Sweden)

    Sherif S. Wahba

    2014-01-01

    Full Text Available Acute respiratory distress syndrome (ARDS is a rarely seen complication with nitrfurantoin. We report improvement of a parturient who was admitted to our hospital’s obstetrical unit with life threatening nitrofurantoin-induced acute respiratory failure. She had been taking nitrofurantoin for one week for urinary tract infection (UTI. Her chest radiography showed bilateral parenchymal infiltrates of the lung. The patient responded well to nitrofurantoin discontinuation and methylprednisolone infusion 1 mg/kg/day.

  18. A pilot survey on the quality of life in respiratory rehabilitation carried out in COPD patients with severe respiratory failure: preliminary data of a novel Inpatient Respiratory Rehabilitation Questionnaire (IRRQ

    Directory of Open Access Journals (Sweden)

    Pasqua Franco

    2012-11-01

    Full Text Available Abstract Background Measuring the state of health is a method for quantifying the impact of an illness on the day-to-day life, health and wellbeing of a patient, providing a quantitative measure of an individual’s quality of life (QoL. QoL expresses patient point of view by a subjective dimension and can express the results of medical intervention. Pulmonary rehabilitation is an essential component in the management of COPD patients, and measuring QoL has become a central focus in the study of this disease. Although nowadays several questionnaires for measuring the QoL in COPD patients are available, there are no questionnaires specifically developed for evaluating QoL in COPD patients undergoing respiratory rehabilitation. The aim of this study was to develop a novel questionnaire for the QoL quantification in COPD patients undergoing in-patient pulmonary rehabilitation program. Methods The questionnaire, administered to COPD patients undergoing long-term oxygen therapy into a respiratory rehabilitation ward, was developed by a simple and graphic layout to be administered to elderly patients. It included one form for admission and another for discharge. It included only tips related to the subjective components of QoL that would be relevant for patient, although likely not strictly related to the respiratory function. A descriptive analysis was performed for the socio-demographic characteristics and both the non-parametric Wilcoxon T-test and the Cronbach’s alpha index were calculated for evaluating the sensitivity of the questionnaire to the effects of respiratory rehabilitation and for identifying its consistency. Results The physical and psychological condition of the 34 COPD patients improved after the rehabilitative treatment and this finding was detected by the questionnaire (overall improvement: 14.2±2.5%, as confirmed by the non-parametric Wilcoxon test (p Conclusions This proposed questionnaire represents a substantial innovation

  19. Impact of perinatal systemic hypoxic-ischemic injury on the brain of male offspring rats: an improved model of neonatal hypoxic-ischemic encephalopathy in early preterm newborns.

    Directory of Open Access Journals (Sweden)

    Yuejun Huang

    Full Text Available In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions.

  20. Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Kuzmanić Šamija, R. [Department of Pediatrics, University Hospital Split, Split (Croatia); Primorac, D. [School of Medicine Split, University of Split, Split (Croatia); Department of Pediatrics, School of Medicine, University of Osijek, Osijek (Croatia); Eberly College of Science, Penn State University, University Park, PA (United States); St. Catherine Speciality Hospital, Zabok (Croatia); Rešić, B. [School of Medicine Split, University of Split, Split (Croatia); Pavlov, V. [Department of Neonatology, University Hospital Split, Split (Croatia); Čapkun, V. [Department of Nuclear Medicine, University Hospital Split, Split (Croatia); Punda, H. [School of Medicine Split, University of Split, Split (Croatia); Lozić, B. [Department of Pediatrics, University Hospital Split, Split (Croatia); Zemunik, T. [Department of Medical Biology, School of Medicine Split, University of Split, Split (Croatia)

    2014-08-15

    The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.

  1. Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

    International Nuclear Information System (INIS)

    Kuzmanić Šamija, R.; Primorac, D.; Rešić, B.; Pavlov, V.; Čapkun, V.; Punda, H.; Lozić, B.; Zemunik, T.

    2014-01-01

    The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children

  2. Cerebral circulation and prognosis of the patients with hypoxic encephalopathy

    International Nuclear Information System (INIS)

    Nogami, Kenichiro; Fujii, Masami; Kashiwagi, Shiro; Sadamitsu Daikai; Maekawa, Tsuyoshi

    2000-01-01

    Recent progress in cardiopulmonary resuscitation techniques improved the survival rate of patients with acute cardiopulmonary disturbances. However, severe cerebral complications remained frequently in patients who survived the acute stage. Early prediction of cerebral prognosis is important to optimize the management of these patients. We examined the relations between radiological findings (Xe-CT and MRI) and cerebral prognosis. Patients included in this study were selected from all patients with hypoxic encephalopathy admitted to our hospital. There were 11 men and 10 women. Causes of hypoxic encephalopathy were heart disease (11 cases), suffocation (4 cases), CO intoxication (2 cases), asthma (1 case), pneumothorax (1 case), anaphyraxy shock (1 case) and electric shock (1 case). Xe-CT and MRI were carried out 3 weeks after the onset. Cerebral blood flow (CBF) of the patients was measured at rest and 15 minutes after intravenous administration of acetazolamide (1 g). The prognosis was evaluated 3 months after the onset in accordance with Glasgow Outcome Scale (GOS). Low hemispheric CBF (30 ml/100 g/min), poor reactivity of acetazolamide challenge test (10 ml/100 g/min), presence of hyperintensity areas in the basal ganglia in T1 weighted images (T1WI) and T2 weighted images (T2WI) are the factors associated with poor outcome in hypoxic encephalopathy. (author)

  3. Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) and acute lung injury in children and adults

    DEFF Research Database (Denmark)

    Afshari, Arash; Brok, Jesper; Møller, Ann

    2010-01-01

    Acute hypoxaemic respiratory failure (AHRF), defined as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), are critical conditions. AHRF results from a number of systemic conditions and is associated with high mortality and morbidity in all ages. Inhaled nitric oxide (INO) has...

  4. Incidence and Outcome of CPAP Failure in Preterm Infants.

    Science.gov (United States)

    Dargaville, Peter A; Gerber, Angela; Johansson, Stefan; De Paoli, Antonio G; Kamlin, C Omar F; Orsini, Francesca; Davis, Peter G

    2016-07-01

    Data from clinical trials support the use of continuous positive airway pressure (CPAP) for initial respiratory management in preterm infants, but there is concern regarding the potential failure of CPAP support. We aimed to examine the incidence and explore the outcomes of CPAP failure in Australian and New Zealand Neonatal Network data from 2007 to 2013. Data from inborn preterm infants managed on CPAP from the outset were analyzed in 2 gestational age ranges (25-28 and 29-32 completed weeks). Outcomes after CPAP failure (need for intubation CPAP using adjusted odds ratios (AORs). Within the cohort of 19 103 infants, 11 684 were initially managed on CPAP. Failure of CPAP occurred in 863 (43%) of 1989 infants commencing on CPAP at 25-28 weeks' gestation and 2061 (21%) of 9695 at 29-32 weeks. CPAP failure was associated with a substantially higher rate of pneumothorax, and a heightened risk of death, bronchopulmonary dysplasia (BPD) and other morbidities compared with those managed successfully on CPAP. The incidence of death or BPD was also increased: (25-28 weeks: 39% vs 20%, AOR 2.30, 99% confidence interval 1.71-3.10; 29-32 weeks: 12% vs 3.1%, AOR 3.62 [2.76-4.74]). The CPAP failure group had longer durations of respiratory support and hospitalization. CPAP failure in preterm infants is associated with increased risk of mortality and major morbidities, including BPD. Strategies to promote successful CPAP application should be pursued vigorously. Copyright © 2016 by the American Academy of Pediatrics.

  5. Hypoxic activation of the unfolded protein response (UPR) induces expression of the metastasis-associated gene LAMP3

    International Nuclear Information System (INIS)

    Mujcic, Hilda; Rzymski, Tomasz; Rouschop, Kasper M.A.; Koritzinsky, Marianne; Milani, Manuela; Harris, Adrian L.; Wouters, Bradly G.

    2009-01-01

    Background and purpose: Tumour hypoxia contributes to failure of cancer treatment through its ability to protect against therapy and adversely influence tumour biology. In particular, several studies suggest that hypoxia promotes metastasis. Hypoxia-induced cellular changes are mediated by oxygen-sensitive signaling pathways that activate downstream transcription factors. We have investigated the induction and transcriptional regulation of a novel metastasis-associated gene, LAMP3 during hypoxia. Materials and methods: Microarray, quantitative PCR, Western blot analysis and immunohistochemistry were used to investigate hypoxic regulation of LAMP3. The mechanism for LAMP3 induction was investigated using transient RNAi and stable shRNA targeting components of the hypoxic response. Endoplasmic reticulum stress inducing agents, including proteasome inhibitors were assessed for their ability to regulate LAMP3. Results: LAMP3 is strongly induced by hypoxia at both the mRNA and protein levels in a large panel of human tumour cell lines. Induction of LAMP3 occurs as a consequence of the activation of the PERK/eIF2α/ATF4 arm of the unfolded protein response (UPR) and is independent of HIF-1α. LAMP3 is expressed heterogeneously within the microenvironment of tumours, overexpressed in breast cancer, and increases in tumours treated with avastin. Conclusions: These data identify LAMP3 as a novel hypoxia-inducible gene regulated by the UPR. LAMP3 is a new candidate biomarker of UPR activation by hypoxia in tumours and is a potential mediator of hypoxia-induced metastasis.

  6. Sevoflurane postconditioning improves myocardial mitochondrial respiratory function and reduces myocardial ischemia-reperfusion injury by up-regulating HIF-1.

    Science.gov (United States)

    Yang, Long; Xie, Peng; Wu, Jianjiang; Yu, Jin; Yu, Tian; Wang, Haiying; Wang, Jiang; Xia, Zhengyuan; Zheng, Hong

    2016-01-01

    Sevoflurane postconditioning (SPostC) can exert myocardial protective effects similar to ischemic preconditioning. However, the exact myocardial protection mechanism by SPostC is unclear. Studies indicate that hypoxia-inducible factor-1 (HIF-1) maintains cellular respiration homeostasis by regulating mitochondrial respiratory chain enzyme activity under hypoxic conditions. This study investigated whether SPostC could regulate the expression of myocardial HIF-1α and to improve mitochondrial respiratory function, thereby relieving myocardial ischemia-reperfusion injury in rats. The myocardial ischemia-reperfusion rat model was established using the Langendorff isolated heart perfusion apparatus. Additionally, postconditioning was performed using sevoflurane alone or in combination with the HIF-1α inhibitor 2-methoxyestradiol (2ME2). The changes in hemodynamic parameters, HIF-1α protein expression levels, mitochondrial respiratory function and enzyme activity, mitochondrial reactive oxygen species (ROS) production rates, and mitochondrial ultrastructure were measured or observed. Compared to the ischemia-reperfusion (I/R) group, HIF-1α expression in the SPostC group was significantly up-regulated. Additionally, cardiac function indicators, mitochondrial state 3 respiratory rate, respiratory control ratio (RCR), cytochrome C oxidase (C c O), NADH oxidase (NADHO), and succinate oxidase (SUCO) activities, mitochondrial ROS production rate, and mitochondrial ultrastructure were significantly better than those in the I/R group. However, these advantages were completely reversed by the HIF-1α specific inhibitor 2ME2 ( P <0.05). The myocardial protective function of SPostC might be associated with the improvement of mitochondrial respiratory function after up-regulation of HIF-1α expression.

  7. Respiratory guiding system for respiratory motion management in respiratory gated radiotherapy

    International Nuclear Information System (INIS)

    Kang, Seong Hee; Kim, Dong Su; Kim, Tae Ho; Suh, Tae Suk

    2013-01-01

    Respiratory guiding systems have been shown to improve the respiratory regularity. This, in turn, improves the efficiency of synchronized moving aperture radiation therapy, and it reduces the artifacts caused by irregular breathing in imaging techniques such as four-dimensional computed tomography (4D CT), which is used for treatment planning in RGRT. We have previously developed a respiratory guiding system that incorporates an individual-specific guiding waveform, which is easy to follow for each volunteer, to improve the respiratory regularity. The present study evaluates the application of this system to improve the respiratory regularity for respiratory-gated radiation therapy (RGRT). In this study, we evaluated the effectiveness of an in-house-developed respiratory guiding system incorporating an individual specific guiding waveform to improve the respiratory regularity for RGRT. Most volunteers showed significantly less residual motion at each phase during guided breathing owing to the improvement in respiratory regularity. Therefore, the respiratory guiding system can clearly reduce the residual, or respiratory, motion in each phase. From the result, the CTV and the PTV margins during RGRT can be reduced by using the respiratory guiding system, which reduces the residual motions, thus improving the accuracy of RGRT

  8. Functional connectivity and information flow of the respiratory neural network in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Yu, Lianchun; De Mazancourt, Marine; Hess, Agathe; Ashadi, Fakhrul R; Klein, Isabelle; Mal, Hervé; Courbage, Maurice; Mangin, Laurence

    2016-08-01

    Breathing involves a complex interplay between the brainstem automatic network and cortical voluntary command. How these brain regions communicate at rest or during inspiratory loading is unknown. This issue is crucial for several reasons: (i) increased respiratory loading is a major feature of several respiratory diseases, (ii) failure of the voluntary motor and cortical sensory processing drives is among the mechanisms that precede acute respiratory failure, (iii) several cerebral structures involved in responding to inspiratory loading participate in the perception of dyspnea, a distressing symptom in many disease. We studied functional connectivity and Granger causality of the respiratory network in controls and patients with chronic obstructive pulmonary disease (COPD), at rest and during inspiratory loading. Compared with those of controls, the motor cortex area of patients exhibited decreased connectivity with their contralateral counterparts and no connectivity with the brainstem. In the patients, the information flow was reversed at rest with the source of the network shifted from the medulla towards the motor cortex. During inspiratory loading, the system was overwhelmed and the motor cortex became the sink of the network. This major finding may help to understand why some patients with COPD are prone to acute respiratory failure. Network connectivity and causality were related to lung function and illness severity. We validated our connectivity and causality results with a mathematical model of neural network. Our findings suggest a new therapeutic strategy involving the modulation of brain activity to increase motor cortex functional connectivity and improve respiratory muscles performance in patients. Hum Brain Mapp 37:2736-2754, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  9. CD44 Interacts with HIF-2α to Modulate the Hypoxic Phenotype of Perinecrotic and Perivascular Glioma Cells

    DEFF Research Database (Denmark)

    Johansson, Elinn; Grassi, Elisa S.; Pantazopoulou, Vasiliki

    2017-01-01

    Hypoxia-inducible factors enhance glioma stemness, and glioma stem cells have an amplified hypoxic response despite residing within a perivascular niche. Still, little is known about differential HIF regulation in stem versus bulk glioma cells. We show that the intracellular domain of stem cell...... marker CD44 (CD44ICD) is released at hypoxia, binds HIF-2α (but not HIF-1α), enhances HIF target gene activation, and is required for hypoxia-induced stemness in glioma. In a glioma mouse model, CD44 was restricted to hypoxic and perivascular tumor regions, and in human glioma, a hypoxia signature...... correlated with CD44. The CD44ICD was sufficient to induce hypoxic signaling at perivascular oxygen tensions, and blocking CD44 cleavage decreased HIF-2α stabilization in CD44-expressing cells. Our data indicate that the stem cell marker CD44 modulates the hypoxic response of glioma cells and that the pseudo-hypoxic...

  10. Acute kidney injury in children with heart failure: any relationship to ...

    African Journals Online (AJOL)

    Materials and Method : Prospective study of cohort of children with heart failure were studied. Heart failure was defined using heart rate for age, respiratory rate for age and tender hepatomegaly. Acute kidney injury was based on absolute serum creatinine level > 0.5 mg/dl on admission. Age, gender, and out come we r e ...

  11. Risk factor for hypoxic ischemic encephalopathy in children

    International Nuclear Information System (INIS)

    Butt, T.K.; Farooqui, R.; Khan, U.; Farooqui, R.

    2008-01-01

    To determine underlying risk factors in neonates with hypoxic ischemic encephalopathy. All neonates (153) with the diagnosis of Hypoxic Ischemic Encephalopathy (HIE) were included in the study. Controls (187) were selected from admissions on the same day. Possible risk factors such as maternal age, parity, antenatal monitoring, place of delivery, prolonged second stage of labour, type of delivery, type of attendant at delivery and the gestational age were noted and compared. Sixty one (39.9%) mothers of asphyxiated babies reported no antenatal visits compared to 24.1% in the control group (OR 2.1, 95% CI 1.3-3.2; p=0.002). Only 6.5% of cases were born in government hospitals (teaching and district) in comparison to 20.9% of controls (OR 3.8, 95% CI 1.9-7.6; p=0.001). In 28.1% of cases, mothers had history of prolonged 2nd stage of labour in comparison to 5.9% of controls (OR 6.3, 95% CI 3.3-11.9; p<0.001). Fifty five cases (35.9%) were delivered by unskilled birth attendants compared to 28 (14.9%) controls (OR 3.2, 95% CI 1.9-5.3; p<0.001). No significant difference was found in maternal age, maternal parity, gestational age and the mode of delivery between the two groups. Delivery by unskilled birth attendant, prolonged second stage of labour, birth in a non-government hospital setup and absence of antenatal care were significant risk factors for hypoxic ischemic encephalopathy in neonates. Improvement in antenatal and intrapartum care may be helpful in decreasing the frequency of this problem. (author)

  12. Sirtuin 6 protects the heart from hypoxic damage

    International Nuclear Information System (INIS)

    Maksin-Matveev, Anna; Kanfi, Yariv; Hochhauser, Edith; Isak, Ahuva; Cohen, Haim Y.; Shainberg, Asher

    2015-01-01

    Sirtuin 6 (SIRT6) is a protein associated with prolonged life expectancy. We investigated whether life extension is associated with cardioprotection against hypoxia. The proposed study is to develop approaches to reduce hypoxic damage through the use of the sirtuin pathway and to elucidate the mechanism involved. For that purpose we subjected cardiomyocytes from transgenic mice (TG) with over-expression of SIRT6, to hypoxic stress in cell cultures. We hypothesized that cardiomyocytes from transgenic mice subjected to prolonged hypoxia may release survival factors or fewer damage markers to protect them from hypoxic stress compared with wild type (WT) mice. Lactate dehydrogenase (LDH) and creatine kinase (CK) released to the medium and propidium iodide (PI) binding, were markedly decreased following hypoxia in TG cardiomyocytes. The protective mechanism of SIRT6 over-expression includes the activation of pAMPKα pathway, the increased protein level of B-cell lymphoma 2 (Bcl2), the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), the decrease of reactive oxygen species (ROS) and the reduction in the protein level of phospho-protein kinase B (pAkt) during hypoxia. Together, all these processes impede the necrosis/apoptosis pathways leading to the improved survival of cardiomyocytes following hypoxia, which might explain life extension. - Highlights: • Sirtuin 6 is a protein associated with prolonged life expectancy. • Over-expression of sirtuin 6 protects cardiocytes from hypoxia and oxidative stress. • Over-expression of sirtuin 6 activates the pAMPKα pathway and the Bcl2 expression. • Over-expression of sirtuin 6 decreases ROS formation and pAkt level during hypoxia. • These pathways protect cardiocytes from hypoxia and might explain lifespan extension

  13. Sirtuin 6 protects the heart from hypoxic damage

    Energy Technology Data Exchange (ETDEWEB)

    Maksin-Matveev, Anna; Kanfi, Yariv [The Mina and Everard Goodman, Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900 (Israel); Hochhauser, Edith [The Laboratory of the Department of Cardiothoracic Surgery, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva (Israel); Isak, Ahuva; Cohen, Haim Y. [The Mina and Everard Goodman, Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900 (Israel); Shainberg, Asher, E-mail: asher.shainberg@gmail.com [The Mina and Everard Goodman, Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900 (Israel)

    2015-01-01

    Sirtuin 6 (SIRT6) is a protein associated with prolonged life expectancy. We investigated whether life extension is associated with cardioprotection against hypoxia. The proposed study is to develop approaches to reduce hypoxic damage through the use of the sirtuin pathway and to elucidate the mechanism involved. For that purpose we subjected cardiomyocytes from transgenic mice (TG) with over-expression of SIRT6, to hypoxic stress in cell cultures. We hypothesized that cardiomyocytes from transgenic mice subjected to prolonged hypoxia may release survival factors or fewer damage markers to protect them from hypoxic stress compared with wild type (WT) mice. Lactate dehydrogenase (LDH) and creatine kinase (CK) released to the medium and propidium iodide (PI) binding, were markedly decreased following hypoxia in TG cardiomyocytes. The protective mechanism of SIRT6 over-expression includes the activation of pAMPKα pathway, the increased protein level of B-cell lymphoma 2 (Bcl2), the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), the decrease of reactive oxygen species (ROS) and the reduction in the protein level of phospho-protein kinase B (pAkt) during hypoxia. Together, all these processes impede the necrosis/apoptosis pathways leading to the improved survival of cardiomyocytes following hypoxia, which might explain life extension. - Highlights: • Sirtuin 6 is a protein associated with prolonged life expectancy. • Over-expression of sirtuin 6 protects cardiocytes from hypoxia and oxidative stress. • Over-expression of sirtuin 6 activates the pAMPKα pathway and the Bcl2 expression. • Over-expression of sirtuin 6 decreases ROS formation and pAkt level during hypoxia. • These pathways protect cardiocytes from hypoxia and might explain lifespan extension.

  14. [Congenital diaphragmatic hernia: respiratory and vascular outcomes].

    Science.gov (United States)

    Pennaforte, T; Rakza, T; Sfeir, R; Aubry, E; Bonnevalle, M; Fayoux, P; Deschildre, A; Thumerelle, C; de Lagausie, P; Benachi, A; Storme, L

    2012-02-01

    Congenital diaphragmatic hernia (CDH) is a life-threatening anomaly associated with a variable degree of pulmonary hypoplasia (PH) and persistent pulmonary hypertension (PPH). Despite remarkable advances in neonatal resuscitation and intensive care, and new postnatal treatment strategies, the rates of mortality and morbidity in the newborn with CDH remain high as the result of severe respiratory failure secondary to PH and PPH. Later, lung function assessments show obstructive and restrictive impairments due to altered lung structure and lung damage due to prolonged ventilatory support. The long-term consequences of pulmonary hypertension are unknown. Other problems include chronic pulmonary aspiration caused by gastro-oesophageal reflux and respiratory manifestations of allergy such as asthma or rhinitis. Finally, failure to thrive may be caused by increased caloric requirements due to pulmonary morbidity. Follow-up studies that systematically assess long-term sequelae are needed. Based on such studies, a more focused approach for routine multidisciplinary follow-up programs could be established. It is the goal of the French Collaborative Network to promote exchange of knowledge, future research and development of treatment protocols. Copyright © 2012. Published by Elsevier Masson SAS.

  15. Genetic control of yeast cell radiosensitivity modification by oxygen and hypoxic sensitizers

    International Nuclear Information System (INIS)

    Zhuranovskaya, G.P.; Petin, V.G.

    1984-01-01

    Diploid yeast cells Saccharomyces cerevisiae ''of the wild type'', individual mutants, homozygous in rad 2 and rad 54 and double mutants, containing both these loci in homozygous state are considered to prove genetic determination of radiosensitivity modification of hypoxic cells by oxygen and electron acceptor compounds previously demonstrated on yeast cells of other genotypes. It is shown that both ''oxygen effect'' and the effect of hypoxic sensitizers depend on the activity of repair systems. The possible mechanism of participation of post-radiation restoration processes in the modification of cell radiosensitivity, is discussed

  16. Milrinone attenuates thromboxane receptor-mediated hyperresponsiveness in hypoxic pulmonary arterial myocytes.

    Science.gov (United States)

    Santhosh, K T; Elkhateeb, O; Nolette, N; Outbih, O; Halayko, A J; Dakshinamurti, S

    2011-07-01

    Neonatal pulmonary hypertension (PPHN) is characterized by pulmonary vasoconstriction, due in part to dysregulation of the thromboxane prostanoid (TP) receptor. Hypoxia induces TP receptor-mediated hyperresponsiveness, whereas serine phosphorylation mediates desensitization of TP receptors. We hypothesized that prostacyclin (IP) receptor activity induces TP receptor phosphorylation and decreases ligand affinity; that TP receptor sensitization in hypoxic myocytes is due to IP receptor inactivation; and that this would be reversible by the cAMP-specific phosphodiesterase inhibitor milrinone. We examined functional regulation of TP receptors by serine phosphorylation and effects of IP receptor stimulation and protein kinase A (PKA) activity on TP receptor sensitivity in myocytes from neonatal porcine resistance pulmonary arteries after 72 h hypoxia in vitro. Ca(2+) response curves to U46619 (TP receptor agonist) were determined in hypoxic and normoxic myocytes incubated with or without iloprost (IP receptor agonist), forskolin (adenylyl cyclase activator), H8 (PKA inhibitor) or milrinone. TP and IP receptor saturation binding kinetics were measured in presence of iloprost or 8-bromo-cAMP. Ligand affinity for TP receptors was normalized in vitro by IP receptor signalling intermediates. However, IP receptor affinity was compromised in hypoxic myocytes, decreasing cAMP production. Milrinone normalized TP receptor sensitivity in hypoxic myocytes by restoring PKA-mediated regulatory TP receptor phosphorylation. TP receptor sensitivity and EC(50) for TP receptor agonists was regulated by PKA, as TP receptor serine phosphorylation by PKA down-regulated Ca(2+) mobilization. Hypoxia decreased IP receptor activity and cAMP generation, inducing TP receptor hyperresponsiveness, which was reversed by milrinone. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  17. Review of supplemental oxygen and respiratory support for paediatric emergency care in sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    Andreas Hansmann

    Full Text Available Introduction: In African countries, respiratory infections and severe sepsis are common causes of respiratory failure and mortality in children under five years of age. Mortality and morbidity in these children could be reduced with adequate respiratory support in the emergency care setting. The purpose of this review is to describe management priorities in the emergency care of critically ill children presenting with respiratory problems. Basic and advanced respiratory support measures are described for implementation according to available resources, work load and skill-levels. Methods: We did a focused search of respiratory support for critically ill children in resource-limited settings over the past ten years, using the search tools PubMed and Google Scholar, the latest WHO guidelines, international ‘Advanced Paediatric Life Support’ guidelines and paediatric critical care textbooks. Results: The implementation of triage and rapid recognition of respiratory distress and hypoxia with pulse oximetry is important to correctly identify critically ill children with increased risk of mortality in all health facilities in resource constrained settings. Basic, effective airway management and respiratory support are essential elements of emergency care. Correct provision of supplemental oxygen is safe and its application alone can significantly improve the outcome of critically ill children. Non-invasive ventilatory support is cost-effective and feasible, with the potential to improve emergency care packages for children with respiratory failure and other organ dysfunctions. Non-invasive ventilation is particularly important in severely under-resourced regions unable to provide intubation and invasive mechanical ventilation support. Malnutrition and HIV-infection are important co-morbid conditions, associated with increased mortality in children with respiratory dysfunction. Discussion: A multi-disciplinary approach is required to optimise

  18. Synthesis and radiolabelling of novel nitrogen mustards for the imaging of hypoxic tissue

    International Nuclear Information System (INIS)

    Falzon, C.; Ackermann, U.; Tochon-Danguy, H.J.; O'Keefe, G.J.; White, J.; Spratt, N.; Howells, D.; Scott, A.M.

    2005-01-01

    Hypoxic tissue is of great significance in stroke and oncology. Among the radiotracers currently used to detect hypoxia, derivatives based on the 2-nitro-imidazole ring such as FMISO or FAZA have received considerable attention in medical imaging. Unfortunately, due to slow clearance of these tracers from normoxic tissue a waiting period of two hours is required between tracer injection and the scanning of the patient. In addition the target to background ratio is low and the quality of the image is therefore poor. Nitrogen mustards are another class of compounds that have great affinity to hypoxic tissue. Derivatives of these compounds labelled with a positron emitting radionuclide, such as [ 18 F], may allow for the imaging of hypoxic regions in the ischemic penumbra. It therefore, may be a useful diagnostic tool in stroke. Radiolabeled N-(2-[ 18 F]-fluoroethyl)-N-(2-chloroethyl)-4-methylsulfinylaniline was successfully synthesised using a potassium fluoride kryptofix complex, giving the desired product in 40% radiochemical yield (10 min at 100 Degrees C). In vitro analysis to determine the stability of the radiotracer in plasma and saline indicated no defluorination. Biological evaluation studies of the radiotracer were undertaken using a rat stroke model (Middle cerebral Arterial Occlusion (MCAO)) to determine whether the ischemic penumbra can be imaged using PET. 150//Ci (5.5MBq) of the radiotracer was injected into the tail vein of the rat immediately after the MCAO. The rat was sacrificed 2 hours post injection and ex-vivo autoradiography was performed. Uptake of the radiotracer was observed in hypoxic regions of the brain (n=6). Dynamic PET images revealed that the ischemic penumbra can be imaged 15 minutes post injection of this tracer. With these promising results, we are now synthesizing other analogues to determine their relationship between selectivity for hypoxic tissue and brain uptake

  19. Effects of bleomycin and irradiation on euoxic and hypoxic cells

    International Nuclear Information System (INIS)

    Shrieve, D.C.; Harris, J.W.

    1979-01-01

    EMT6 cells in vitro were exposed to bleomycin (BLM), either alone (under euoxic or hypoxic conditions) or in conjunction with x-radiation. Hypoxic and euoxic cells were equally sensitive to the drug in both of the systems used to induce hypoxia (ampules or chambers). Exposure to BLM immediately before x-irradiation altered the shape of the radiation survival curve decreasing the D 0 by a factor of 1.3. Simultaneous exposure to x-ray and BLM resulted in lower survivals than when radiation was given either before or after drug treatment. Cells recovered quickly from BLM damage if trypsinization was delayed. The results indicate that BLM and x-rays interact to lower cell survival but that cells recover from this effect if trypsinization is delayed

  20. Gene editing as a promising approach for respiratory diseases.

    Science.gov (United States)

    Bai, Yichun; Liu, Yang; Su, Zhenlei; Ma, Yana; Ren, Chonghua; Zhao, Runzhen; Ji, Hong-Long

    2018-03-01

    Respiratory diseases, which are leading causes of mortality and morbidity in the world, are dysfunctions of the nasopharynx, the trachea, the bronchus, the lung and the pleural cavity. Symptoms of chronic respiratory diseases, such as cough, sneezing and difficulty breathing, may seriously affect the productivity, sleep quality and physical and mental well-being of patients, and patients with acute respiratory diseases may have difficulty breathing, anoxia and even life-threatening respiratory failure. Respiratory diseases are generally heterogeneous, with multifaceted causes including smoking, ageing, air pollution, infection and gene mutations. Clinically, a single pulmonary disease can exhibit more than one phenotype or coexist with multiple organ disorders. To correct abnormal function or repair injured respiratory tissues, one of the most promising techniques is to correct mutated genes by gene editing, as some gene mutations have been clearly demonstrated to be associated with genetic or heterogeneous respiratory diseases. Zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN) and clustered regulatory interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) systems are three innovative gene editing technologies developed recently. In this short review, we have summarised the structure and operating principles of the ZFNs, TALENs and CRISPR/Cas9 systems and their preclinical and clinical applications in respiratory diseases. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.