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Sample records for acute severe hypoxia

  1. Muscle Activation During Exercise in Severe Acute Hypoxia: Role of Absolute and Relative Intensity

    PubMed Central

    Torres-Peralta, Rafael; Losa-Reyna, José; González-Izal, Miriam; Perez-Suarez, Ismael; Calle-Herrero, Jaime; Izquierdo, Mikel

    2014-01-01

    Abstract Torres-Peralta, Rafael, José Losa-Reyna, Miriam González-Izal, Ismael Perez-Suarez, Jaime Calle-Herrero, Mikel Izquierdo, and José A.L. Calbet. Muscle activation during exercise in severe acute hypoxia: Role of absolute and relative intensity. High Alt Med Biol 15:472–482, 2014.—The aim of this study was to determine the influence of severe acute hypoxia on muscle activation during whole body dynamic exercise. Eleven young men performed four incremental cycle ergometer tests to exhaustion breathing normoxic (FIo2=0.21, two tests) or hypoxic gas (FIo2=0.108, two tests). Surface electromyography (EMG) activities of rectus femoris (RF), vastus medialis (VL), vastus lateralis (VL), and biceps femoris (BF) were recorded. The two normoxic and the two hypoxic tests were averaged to reduce EMG variability. Peak Vo2 was 34% lower in hypoxia than in normoxia (p<0.05). The EMG root mean square (RMS) increased with exercise intensity in all muscles (p<0.05), with greater effect in hypoxia than in normoxia in the RF and VM (p<0.05), and a similar trend in VL (p=0.10). At the same relative intensity, the RMS was greater in normoxia than in hypoxia in RF, VL, and BF (p<0.05), with a similar trend in VM (p=0.08). Median frequency increased with exercise intensity (p<0.05), and was higher in hypoxia than in normoxia in VL (p<0.05). Muscle contraction burst duration increased with exercise intensity in VM and VL (p<0.05), without clear effects of FIo2. No significant FIo2 effects on frequency domain indices were observed when compared at the same relative intensity. In conclusion, muscle activation during whole body exercise increases almost linearly with exercise intensity, following a muscle-specific pattern, which is adjusted depending on the FIo2 and the relative intensity of exercise. Both VL and VM are increasingly involved in power output generation with the increase of intensity and the reduction in FIo2. PMID:25225839

  2. Increased oxidative stress and anaerobic energy release, but blunted Thr172-AMPKα phosphorylation, in response to sprint exercise in severe acute hypoxia in humans.

    PubMed

    Morales-Alamo, David; Ponce-González, Jesús Gustavo; Guadalupe-Grau, Amelia; Rodríguez-García, Lorena; Santana, Alfredo; Cusso, Maria Roser; Guerrero, Mario; Guerra, Borja; Dorado, Cecilia; Calbet, José A L

    2012-09-01

    AMP-activated protein kinase (AMPK) is a major mediator of the exercise response and a molecular target to improve insulin sensitivity. To determine if the anaerobic component of the exercise response, which is exaggerated when sprint is performed in severe acute hypoxia, influences sprint exercise-elicited Thr(172)-AMPKα phosphorylation, 10 volunteers performed a single 30-s sprint (Wingate test) in normoxia and in severe acute hypoxia (inspired Po(2): 75 mmHg). Vastus lateralis muscle biopsies were obtained before and immediately after 30 and 120 min postsprint. Mean power output and O(2) consumption were 6% and 37%, respectively, lower in hypoxia than in normoxia. O(2) deficit and muscle lactate accumulation were greater in hypoxia than in normoxia. Carbonylated skeletal muscle and plasma proteins were increased after the sprint in hypoxia. Thr(172)-AMPKα phosphorylation was increased by 3.1-fold 30 min after the sprint in normoxia. This effect was prevented by hypoxia. The NAD(+)-to-NADH.H(+) ratio was reduced (by 24-fold) after the sprints, with a greater reduction in hypoxia than in normoxia (P < 0.05), concomitant with 53% lower sirtuin 1 (SIRT1) protein levels after the sprint in hypoxia (P < 0.05). This could have led to lower liver kinase B1 (LKB1) activation by SIRT1 and, hence, blunted Thr(172)-AMPKα phosphorylation. Ser(485)-AMPKα(1)/Ser(491)-AMPKα(2) phosphorylation, a known negative regulating mechanism of Thr(172)-AMPKα phosphorylation, was increased by 60% immediately after the sprint in hypoxia, coincident with increased Thr(308)-Akt phosphorylation. Collectively, our results indicate that the signaling response to sprint exercise in human skeletal muscle is altered in severe acute hypoxia, which abrogated Thr(172)-AMPKα phosphorylation, likely due to lower LKB1 activation by SIRT1.

  3. Severe acute intermittent hypoxia elicits phrenic long-term facilitation by a novel adenosine-dependent mechanism

    PubMed Central

    Nichols, Nicole L.; Dale, Erica A.

    2012-01-01

    Acute intermittent hypoxia [AIH; 3, 5-min episodes; 35–45 mmHg arterial Po2 (PaO2)] elicits serotonin-dependent phrenic long-term facilitation (pLTF), a form of phrenic motor facilitation (pMF) initiated by Gq protein-coupled metabotropic 5-HT2 receptors. An alternate pathway to pMF is induced by Gs protein-coupled metabotropic receptors, including adenosine A2A receptors. AIH-induced pLTF is dominated by the serotonin-dependent pathway and is actually restrained via inhibition from the adenosine-dependent pathway. Here, we hypothesized that severe AIH shifts pLTF from a serotonin-dependent to an adenosine-dependent form of pMF. pLTF induced by severe (25–30 mmHg PaO2) and moderate (45–55 mmHg PaO2) AIH were compared in anesthetized rats, with and without intrathecal (C4) spinal A2A (MSX-3, 130 ng/kg, 12 μl) or 5-HT receptor antagonist (methysergide, 300 μg/kg, 15 μl) injections. During severe, but not moderate AIH, progressive augmentation of the phrenic response during hypoxic episodes was observed. Severe AIH (78% ± 8% 90 min post-AIH, n = 6) elicited greater pLTF vs. moderate AIH (41% ± 12%, n = 8; P < 0.05). MSX-3 (28% ± 6%; n = 6; P < 0.05) attenuated pLTF following severe AIH, but enhanced pLTF following moderate AIH (86% ± 26%; n = 8; P < 0.05). Methysergide abolished pLTF after moderate AIH (12% ± 5%; n = 6; P = 0.035), but had no effect after severe AIH (66 ± 13%; n = 5; P > 0.05). Thus severe AIH shifts pLTF from a serotonin-dependent to an adenosine-dependent mechanism; the adenosinergic pathway inhibits the serotonergic pathway following moderate AIH. Here we demonstrate a novel adenosine-dependent pathway to pLTF following severe AIH. Shifts in the mechanisms of respiratory plasticity provide the ventilatory control system greater flexibility as challenges that differ in severity are confronted. PMID:22403346

  4. Mammalian target of rapamycin is required for phrenic long-term facilitation following severe but not moderate acute intermittent hypoxia

    PubMed Central

    Dougherty, Brendan J.; Fields, Daryl P.

    2015-01-01

    Phrenic long-term facilitation (pLTF) is a persistent increase in phrenic nerve activity after acute intermittent hypoxia (AIH). Distinct cell-signaling cascades give rise to pLTF depending on the severity of hypoxemia within hypoxic episodes. Moderate AIH (mAIH; three 5-min episodes, PaO2 ∼35–55 mmHG) elicits pLTF by a serotonin (5-HT)-dependent mechanism that requires new synthesis of brain-derived neurotrophic factor (BDNF), activation of its high-affinity receptor (TrkB), and ERK MAPK signaling. In contrast, severe AIH (sAIH; three 5-min episodes, PaO2 ∼25–30 mmHG) elicits pLTF by an adenosine-dependent mechanism that requires new TrkB synthesis and Akt signaling. Although both mechanisms require spinal protein synthesis, the newly synthesized proteins are distinct, as are the neurochemicals inducing plasticity (serotonin vs. adenosine). In many forms of neuroplasticity, new protein synthesis requires translational regulation via mammalian target of rapamycin (mTOR) signaling. Since Akt regulates mTOR activity, we hypothesized that mTOR activity is necessary for sAIH- but not mAIH-induced pLTF. Phrenic nerve activity in anesthetized, paralyzed, and ventilated rats was recorded before, during, and 60 min after mAIH or sAIH. Rats were pretreated with intrathecal injections of 20% DMSO (vehicle controls) or rapamycin (0.1 mM, 12 μl), a selective mTOR complex 1 inhibitor. Consistent with our hypothesis, rapamycin blocked sAIH- but not mAIH-induced pLTF. Thus spinal mTOR activity is required for adenosine-dependent (sAIH) but not serotonin-dependent (mAIH) pLTF, suggesting that distinct mechanisms regulate new protein synthesis in these forms of spinal neuroplasticity. PMID:26224775

  5. Acute hypoxia produces a superoxide burst in cells.

    PubMed

    Hernansanz-Agustín, Pablo; Izquierdo-Álvarez, Alicia; Sánchez-Gómez, Francisco J; Ramos, Elena; Villa-Piña, Tamara; Lamas, Santiago; Bogdanova, Anna; Martínez-Ruiz, Antonio

    2014-06-01

    Oxygen is a key molecule for cell metabolism. Eukaryotic cells sense the reduction in oxygen availability (hypoxia) and trigger a series of cellular and systemic responses to adapt to hypoxia, including the optimization of oxygen consumption. Many of these responses are mediated by a genetic program induced by the hypoxia-inducible transcription factors (HIFs), regulated by a family of prolyl hydroxylases (PHD or EGLN) that use oxygen as a substrate producing HIF hydroxylation. In parallel to these oxygen sensors modulating gene expression within hours, acute modulation of protein function in response to hypoxia is known to occur within minutes. Free radicals acting as second messengers, and oxidative posttranslational modifications, have been implied in both groups of responses. Localization and speciation of the paradoxical increase in reactive oxygen species production in hypoxia remain debatable. We have observed that several cell types respond to acute hypoxia with a transient increase in superoxide production for about 10 min, probably originating in the mitochondria. This may explain in part the apparently divergent results found by various groups that have not taken into account the time frame of hypoxic ROS production. We propose that this acute and transient hypoxia-induced superoxide burst may be translated into oxidative signals contributing to hypoxic adaptation and preconditioning.

  6. Sympathoadrenal responses to acute and chronic hypoxia in the rat.

    PubMed Central

    Johnson, T S; Young, J B; Landsberg, L

    1983-01-01

    The sympathoadrenal responses to acute and chronic hypoxic exposure at 10.5 and 7.5% oxygen were determined in the rat. Cardiac norepinephrine (NE) turnover was used to assess sympathetic nervous system (SNS) activity, and urinary excretion of epinephrine (E) was measured as an index of adrenal medullary activity. The responses of the adrenal medulla and SNS were distinct and dependent upon the degree and duration of hypoxic exposure. Chronic hypoxia at 10.5% oxygen increased cardiac NE turnover by 130% after 3, 7, and 14 d of hypoxic exposure. Urinary excretion of NE was similarly increased over this time interval, while urinary E excretion was marginally elevated. In contrast, acute exposure to moderate hypoxia at 10.5% oxygen was not associated with an increase in SNS activity; in fact, decreased SNS activity was suggested by diminished cardiac NE turnover and urinary NE excretion over the first 12 h of hypoxic exposure, and by a rebound increase in NE turnover after reexposure to normal oxygen tension. Adrenal medullary activity, on the other hand, increased substantially during acute exposure to moderate hypoxia (2-fold increase in urinary E excretion) and severe hypoxia (greater than 10-fold). In distinction to the lack of effect of acute hypoxic exposure (10.5% oxygen), the SNS was markedly stimulated during the first day of hypoxia exposure at 7.5% oxygen, an increase that was sustained throughout at least 7 d at 7.5% oxygen. These results demonstrate that chronic exposure to moderate and severe hypoxia increases the activity of the SNS and adrenal medulla, the effect being greater in severe hypoxic exposure. The response to acute hypoxic exposure is more complicated; during the first 12 h of exposure at 10.5% oxygen, the SNS is not stimulated and appears to be restrained, while adrenal medullary activity is enhanced. Acute exposure to a more severe degree of hypoxia (7.5% oxygen), however, is associated with stimulation of both the SNS and adrenal medulla

  7. Approximate Simulation of Acute Hypobaric Hypoxia with Normobaric Hypoxia

    NASA Technical Reports Server (NTRS)

    Conkin, J.; Wessel, J. H., III

    2011-01-01

    INTRODUCTION. Some manufacturers of reduced oxygen (O2) breathing devices claim a comparable hypobaric hypoxia (HH) training experience by providing F(sub I) O2 < 0.209 at or near sea level pressure to match the ambient O2 partial pressure (iso-pO2) of the target altitude. METHODS. Literature from investigators and manufacturers indicate that these devices may not properly account for the 47 mmHg of water vapor partial pressure that reduces the inspired partial pressure of O2 (P(sub I) O2). Nor do they account for the complex reality of alveolar gas composition as defined by the Alveolar Gas Equation. In essence, by providing iso-pO2 conditions for normobaric hypoxia (NH) as for HH exposures the devices ignore P(sub A)O2 and P(sub A)CO2 as more direct agents to induce signs and symptoms of hypoxia during acute training exposures. RESULTS. There is not a sufficient integrated physiological understanding of the determinants of P(sub A)O2 and P(sub A)CO2 under acute NH and HH given the same hypoxic pO2 to claim a device that provides isohypoxia. Isohypoxia is defined as the same distribution of hypoxia signs and symptoms under any circumstances of equivalent hypoxic dose, and hypoxic pO2 is an incomplete hypoxic dose. Some devices that claim an equivalent HH experience under NH conditions significantly overestimate the HH condition, especially when simulating altitudes above 10,000 feet (3,048 m). CONCLUSIONS. At best, the claim should be that the devices provide an approximate HH experience since they only duplicate the ambient pO2 at sea level as at altitude (iso-pO2 machines). An approach to reduce the overestimation is to at least provide machines that create the same P(sub I)O2 (iso-P(sub I)O2 machines) conditions at sea level as at the target altitude, a simple software upgrade.

  8. Melatonin modulates the fetal cardiovascular defense response to acute hypoxia.

    PubMed

    Thakor, Avnesh S; Allison, Beth J; Niu, Youguo; Botting, Kimberley J; Serón-Ferré, Maria; Herrera, Emilio A; Giussani, Dino A

    2015-08-01

    Experimental studies in animal models supporting protective effects on the fetus of melatonin in adverse pregnancy have prompted clinical trials in human pregnancy complicated by fetal growth restriction. However, the effects of melatonin on the fetal defense to acute hypoxia, such as that which may occur during labor, remain unknown. This translational study tested the hypothesis, in vivo, that melatonin modulates the fetal cardiometabolic defense responses to acute hypoxia in chronically instrumented late gestation fetal sheep via alterations in fetal nitric oxide (NO) bioavailability. Under anesthesia, 6 fetal sheep at 0.85 gestation were instrumented with vascular catheters and a Transonic flow probe around a femoral artery. Five days later, fetuses were exposed to acute hypoxia with or without melatonin treatment. Fetal blood was taken to determine blood gas and metabolic status and plasma catecholamine concentrations. Hypoxia during melatonin treatment was repeated during in vivo NO blockade with the NO clamp. This technique permits blockade of de novo synthesis of NO while compensating for the tonic production of the gas, thereby maintaining basal cardiovascular function. Melatonin suppressed the redistribution of blood flow away from peripheral circulations and the glycemic and plasma catecholamine responses to acute hypoxia. These are important components of the fetal brain sparing response to acute hypoxia. The effects of melatonin involved NO-dependent mechanisms as the responses were reverted by fetal treatment with the NO clamp. Melatonin modulates the in vivo fetal cardiometabolic responses to acute hypoxia by increasing NO bioavailability.

  9. Arterial to end-tidal Pco2 difference during exercise in normoxia and severe acute hypoxia: importance of blood temperature correction

    PubMed Central

    Losa-Reyna, José; Torres-Peralta, Rafael; Henriquez, Juan José González; Calbet, José A L

    2015-01-01

    Negative arterial to end-tidal Pco2 differences ((a-ET)Pco2) have been reported in normoxia. To determine the influence of blood temperature on (a-ET)Pco2, 11 volunteers (21 ± 2 years) performed incremental exercise to exhaustion in normoxia (Nx, PIo2: 143 mmHg) and hypoxia (Hyp, PIo2: 73 mmHg), while arterial blood gases and temperature (ABT) were simultaneously measured together with end-tidal Pco2 (PETco2). After accounting for blood temperature, the (a-ET) Pco2 was reduced (in absolute values) from −4.2 ± 1.6 to −1.1 ± 1.5 mmHg in normoxia and from −1.7 ± 1.6 to 0.9 ± 0.9 mmHg in hypoxia (both P < 0.05). The temperature corrected (a-ET)Pco2 was linearly related with absolute and relative exercise intensity, VO2, VCO2, and respiratory rate (RR) in normoxia and hypoxia (R2: 0.52–0.59). Exercise CO2 production and PETco2 values were lower in hypoxia than normoxia, likely explaining the greater (less negative) (a-ET)Pco2 difference in hypoxia than normoxia (P < 0.05). At near-maximal exercise intensity the (a-ET)Pco2 lies close to 0 mmHg, that is, the mean Paco2 and the mean PETco2 are similar. The mean exercise (a-ET)Pco2 difference is closely related to the mean A-aDO2 difference (r = 0.90, P < 0.001), as would be expected if similar mechanisms perturb the gas exchange of O2 and CO2 during exercise. In summary, most of the negative (a-ET)Pco2 values observed in previous studies are due to lack of correction of Paco2 for blood temperature. The absolute magnitude of the (a-ET)Pco2 difference is lower during exercise in hypoxia than normoxia. PMID:26508736

  10. Sildenafil does not Improve Exercise Capacity under Acute Hypoxia Exposure.

    PubMed

    Toro-Salinas, A H; Fort, N; Torrella, J R; Pagès, T; Javierre, C; Viscor, G

    2016-09-01

    The increase in pulmonary arterial pressure (PAP) due to hypoxic pulmonary vasoconstriction (HPV) could be a limiting factor for physical performance during hypoxic exposure. Sildenafil has been shown to reduce PAP in situations of moderate or severe hypoxia, and consequently its role as an ergogenic aid and even a possible doping substance must be considered. We performed a double-blind crossover study to determine the effects of sildenafil on cardiovascular, respiratory and metabolic parameters in normoxia and during acute exposure to hypobaric hypoxia (4 000 m) at rest and during maximal and submaximal (60% VO2 max) exercise tests. One hour before testing started, sildenafil (100 mg) or a placebo was orally administered to 11 volunteers. In normoxic conditions, sildenafil did not affect performance. Similarly, no significant differences were found in cardiovascular and respiratory parameters in hypoxic conditions at rest or during exercise. The use of sildenafil to improve physical performance in non-acclimatized subjects is not supported by our data. PMID:27414159

  11. Acute mountain sickness: medical problems associated with acute and subacute exposure to hypobaric hypoxia

    PubMed Central

    Clarke, C

    2006-01-01

    This article summarises the medical problems of travel to altitudes above 3000 m. These are caused by chronic hypoxia. Acute mountain sickness (AMS), a self limiting common illness is almost part of normal acclimatisation—a transient condition lasting for several days. However, in <2% of people staying above 4000 m, serious illnesses related to hypoxia develop – high altitude pulmonary oedema and cerebral oedema. These are potentially fatal but can be largely avoided by gradual ascent. Short vacations, pressure from travel companies and peer groups often encourage ascent to 4000 m more rapidly than is prudent. Sensible guidelines for ascent are outlined, clinical features, management and treatment of these conditions. PMID:17099095

  12. Two long-lasting central respiratory responses following acute hypoxia in glomectomized cats.

    PubMed

    Gallman, E A; Millhorn, D E

    1988-01-01

    1. Central respiratory response to acute (10 min) hypoxia, as measured by phrenic nerve activity, was determined in peripheral chemo-denervated cats. 2. Hypoxia was induced by ventilating cats for 10 min at reduced inspired oxygen levels (inspired O2 fraction, FI,O2 = 0.06-0.15). The degree of hypoxaemia was determined from an arterial blood sample and ranged from 'severe' (arterial O2 pressure, Pa,O2 less than 26 Torr) to 'mild' (Pa,O2 greater than 35 Torr). The respiratory response was monitored for 1 h following return to ventilation with 100% oxygen. 3. The results confirmed the finding of prolonged (greater than 60 min) inhibition of respiration upon return to hyperoxic conditions following severe hypoxia, as reported previously (Millhorn, Eldridge, Kiley & Waldrop, 1984). A new finding was a long-lasting (greater than 60 min) facilitation of respiration following exposure to less severe (Pa,O2 greater than 35 Torr) hypoxia. 4. Medullary extracellular fluid pH was measured in six cats. Changes in pH could not explain either the prolonged inhibition following severe hypoxia or the long-lasting facilitation observed following mild hypoxia. 5. Ablation studies were performed in order to determine the locations of the neuronal substrates for the inhibitory and facilitatory mechanisms. The results of this series of experiments indicate that the mesencephalon is necessary for activation of the inhibitory mechanism, while the facilitatory mechanism requires the presence of higher brain structures, notably the diencephalon. 6. Following removal of the diencephalon, the inhibitory response was seen following even mild hypoxic insults, i.e. those shown to produce facilitation in animals with intact brains. In the absence of the mesencephalon, neither prolonged inhibition nor prolonged facilitation could be produced following hypoxia. 7. It is proposed that there are two centrally mediated long-lasting responses to acute hypoxia. Facilitation is seen following mild

  13. Acute and chronic hypoxia: implications for cerebral function and exercise tolerance

    PubMed Central

    Goodall, Stuart; Twomey, Rosie; Amann, Markus

    2015-01-01

    Purpose To outline how hypoxia profoundly affects neuronal functionality and thus compromise exercise-performance. Methods Investigations using electroencephalography (EEG) and transcranial magnetic stimulation (TMS) detecting neuronal changes at rest and those studying fatiguing effects on whole-body exercise performance in acute (AH) and chronic hypoxia (CH) were evaluated. Results At rest during very early hypoxia (<1-h), slowing of cerebral neuronal activity is evident despite no change in corticospinal excitability. As time in hypoxia progresses (3-h), increased corticospinal excitability becomes evident; however, changes in neuronal activity are unknown. Prolonged exposure (3–5 d) causes a respiratory alkalosis which modulates Na+ channels, potentially explaining reduced neuronal excitability. Locomotor exercise in AH exacerbates the development of peripheral-fatigue; as the severity of hypoxia increases, mechanisms of peripheral-fatigue become less dominant and CNS hypoxia becomes the predominant factor. The greatest central-fatigue in AH occurs when SaO2 is ≤75%, a level that coincides with increasing impairments in neuronal activity. CH does not improve the level of peripheral-fatigue observed in AH; however, it attenuates the development of central-fatigue paralleling increases in cerebral O2 availability and corticospinal excitability. Conclusions The attenuated development of central-fatigue in CH might explain, the improvements in locomotor exercise-performance commonly observed after acclimatisation to high altitude. PMID:25593787

  14. Restraint Stress Intensifies Interstitial K+ Accumulation during Severe Hypoxia

    PubMed Central

    Schnell, Christian; Janc, Oliwia A.; Kempkes, Belinda; Callis, Carolina Araya; Flügge, Gabriele; Hülsmann, Swen; Müller, Michael

    2012-01-01

    Chronic stress affects neuronal networks by inducing dendritic retraction, modifying neuronal excitability and plasticity, and modulating glial cells. To elucidate the functional consequences of chronic stress for the hippocampal network, we submitted adult rats to daily restraint stress for 3 weeks (6 h/day). In acute hippocampal tissue slices of stressed rats, basal synaptic function and short-term plasticity at Schaffer collateral/CA1 neuron synapses were unchanged while long-term potentiation was markedly impaired. The spatiotemporal propagation pattern of hypoxia-induced spreading depression episodes was indistinguishable among control and stress slices. However, the duration of the extracellular direct current potential shift was shortened after stress. Moreover, K+ fluxes early during hypoxia were more intense, and the postsynaptic recoveries of interstitial K+ levels and synaptic function were slower. Morphometric analysis of immunohistochemically stained sections suggested hippocampal shrinkage in stressed rats, and the number of cells that are immunoreactive for glial fibrillary acidic protein was increased in the CA1 subfield indicating activation of astrocytes. Western blots showed a marked downregulation of the inwardly rectifying K+ channel Kir4.1 in stressed rats. Yet, resting membrane potentials, input resistance, and K+-induced inward currents in CA1 astrocytes were indistinguishable from controls. These data indicate an intensified interstitial K+ accumulation during hypoxia in the hippocampus of chronically stressed rats which seems to arise from a reduced interstitial volume fraction rather than impaired glial K+ buffering. One may speculate that chronic stress aggravates hypoxia-induced pathophysiological processes in the hippocampal network and that this has implications for the ischemic brain. PMID:22470344

  15. Effect of Acute Exposure to Moderate Altitude on Muscle Power: Hypobaric Hypoxia vs. Normobaric Hypoxia

    PubMed Central

    Feriche, Belén; García-Ramos, Amador; Calderón-Soto, Carmen; Drobnic, Franchek; Bonitch- Góngora, Juan G.; Galilea, Pedro A.; Riera, Joan; Padial, Paulino

    2014-01-01

    When ascending to a higher altitude, changes in air density and oxygen levels affect the way in which explosive actions are executed. This study was designed to compare the effects of acute exposure to real or simulated moderate hypoxia on the dynamics of the force-velocity relationship observed in bench press exercise. Twenty-eight combat sports athletes were assigned to two groups and assessed on two separate occasions: G1 (n = 17) in conditions of normoxia (N1) and hypobaric hypoxia (HH) and G2 (n = 11) in conditions of normoxia (N2) and normobaric hypoxia (NH). Individual and complete force-velocity relationships in bench press were determined on each assessment day. For each exercise repetition, we obtained the mean and peak velocity and power shown by the athletes. Maximum power (Pmax) was recorded as the highest Pmean obtained across the complete force-velocity curve. Our findings indicate a significantly higher absolute load linked to Pmax (∼3%) and maximal strength (1RM) (∼6%) in G1 attributable to the climb to altitude (P<0.05). We also observed a stimulating effect of natural hypoxia on Pmean and Ppeak in the middle-high part of the curve (≥60 kg; P<0.01) and a 7.8% mean increase in barbell displacement velocity (P<0.001). No changes in any of the variables examined were observed in G2. According to these data, we can state that acute exposure to natural moderate altitude as opposed to simulated normobaric hypoxia leads to gains in 1RM, movement velocity and power during the execution of a force-velocity curve in bench press. PMID:25474104

  16. Effect of acute exposure to moderate altitude on muscle power: hypobaric hypoxia vs. normobaric hypoxia.

    PubMed

    Feriche, Belén; García-Ramos, Amador; Calderón-Soto, Carmen; Drobnic, Franchek; Bonitch-Góngora, Juan G; Galilea, Pedro A; Riera, Joan; Padial, Paulino

    2014-01-01

    When ascending to a higher altitude, changes in air density and oxygen levels affect the way in which explosive actions are executed. This study was designed to compare the effects of acute exposure to real or simulated moderate hypoxia on the dynamics of the force-velocity relationship observed in bench press exercise. Twenty-eight combat sports athletes were assigned to two groups and assessed on two separate occasions: G1 (n = 17) in conditions of normoxia (N1) and hypobaric hypoxia (HH) and G2 (n = 11) in conditions of normoxia (N2) and normobaric hypoxia (NH). Individual and complete force-velocity relationships in bench press were determined on each assessment day. For each exercise repetition, we obtained the mean and peak velocity and power shown by the athletes. Maximum power (Pmax) was recorded as the highest P(mean) obtained across the complete force-velocity curve. Our findings indicate a significantly higher absolute load linked to P(max) (∼ 3%) and maximal strength (1 RM) (∼ 6%) in G1 attributable to the climb to altitude (P<0.05). We also observed a stimulating effect of natural hypoxia on P(mean) and P(peak) in the middle-high part of the curve (≥ 60 kg; P<0.01) and a 7.8% mean increase in barbell displacement velocity (P<0.001). No changes in any of the variables examined were observed in G2. According to these data, we can state that acute exposure to natural moderate altitude as opposed to simulated normobaric hypoxia leads to gains in 1 RM, movement velocity and power during the execution of a force-velocity curve in bench press.

  17. Acute normobaric hypoxia reduces body temperature in humans.

    PubMed

    DiPasquale, Dana M; Kolkhorst, Fred W; Buono, Michael J

    2015-03-01

    Anapyrexia is the regulated decrease in body temperature during acute exposure to hypoxia. This study examined resting rectal temperature (Trec) in adult humans during acute normobaric hypoxia (NH). Ten subjects breathed air consisting of 21% (NN), 14% (NH14), and 12% oxygen (NH12) for 30 min each in thermoneutral conditions while Trec and blood oxygen saturation (Spo2) were measured. Linear regression indicated that Spo2 was progressively lower in NH14 (p=0.0001) and NH12 (p=0.0001) compared to NN, and that Spo2 in NH14 was different than NH12 (p=0.00001). Trec was progressively lower during NH14 (p=0.014) and in NH12 (p=0.0001) compared to NN. The difference in Trec between NH14 and NH12 was also significant (p=0.0287). Spo2 was a significant predictor of Trec such that for every 1% decrease in Spo2, Trec decreased by 0.15°C (p=0.0001). The present study confirmed that, similar to many other species, human adults respond to acute hypoxia exposure by lowering rectal temperature.

  18. The effects of acute intermittent hypoxia on cardiovascular parameters in normotensive and chronic hypobaric hypoxia-induced hypertensive rabbits.

    PubMed

    Yaman, Muhittin O; Guner, Ibrahim; Uzun, Hafize; Sahin, Gulderen; Yelmen, Nermin

    2014-01-01

    The effects of both chronic hypoxia and acute intermittent hypoxia (AIH) on cardiovascular system are unclear. We designed this study to develop a rabbit model of hypertension by exposure to chronic hypobaric hypoxia (CHH) and to investigate the effects of AIH on hypertensive rabbits. Present study was performed in 13 albino rabbits that divided into CHH and control groups. To develop hypertension, the rabbits were placed in a hypobaric chamber (390 mmHg; 22 hours/day, 30 days). Afterwards, AIH protocol was applied (8% FIO2 (Fraction of Inspired Oxygen) 1 min + 5 min normoxia, 20 cycles, 2 hours) to rabbits anesthetized with urethane and alpha-chloralose. Mean arterial pressure (MAP), heart rate (HR) and hematocrit values have been determined. Also asymmetric dimethylarginine (ADMA), endothelial nitric oxide synthase (eNOS), endothelin-1 and norepinephrine values have been analyzed in blood. We developed a model of hypertension in rabbits via exposure to severe CHH and we believe that ADMA is an important parameter in the development and permanence of CHH-induced hypertension. The main finding of this sudy was the depressor effect of AIH on blood pressure and heart rate in CHH- induced hypertension model. Finally, we believe that AIH protocol may be applicable for prevention and treatment of hypertension if properly developed. PMID:24448370

  19. Baroreflex sensitivity in acute hypoxia and carbohydrate loading.

    PubMed

    Klemenc, Matjaž; Golja, Petra

    2011-10-01

    Hypoxia decreases baroreflex sensitivity (BRS) and can be a sufficient cause for syncope in healthy individuals. Carbohydrate loading enhances efferent sympathetic activity, which affects cardiac contractility, heart rate and vascular resistance, the main determinants of blood pressure. Thus, in both normoxia and hypoxia, carbohydrate loading may be more than simply metabolically beneficial, as it may affect blood pressure regulation. We hypothesised that carbohydrate loading will, in both normoxia and hypoxia, alter the regulation of blood pressure, as reflected in a change in baroreflex sensitivity. Fourteen subjects participated in two experiments, composed of a 15-min normoxic period, after which the subjects ingested water or an equal amount of water with carbohydrates. A 30-min rest period was then followed by a 10-min second normoxic and a 30-min hypoxic period. Blood pressure and heart rate were monitored continuously during the experiment to determine BRS. Despite an increased sympathetic activation, reflected in increased heart rate (P < 0.001) BRS was lower (P < 0.01) after carbohydrate loading, as compared to the water experiment, in both normoxic [23.7 (12.4) versus 28.8 (13.8) ms/mmHg] and hypoxic [16.8 (11.0) versus 24.3 (12.3) ms/mmHg] phases of the present study. As BRS was decreased in acute hypoxic exposure, the results confirm that hypoxia interferes with blood pressure regulation. However, although oral carbohydrate loading induced sympathoexcitation, it did not improve blood pressure regulation in hypoxia, as evident from the BRS data. Baroreflex effects of other forms of carbohydrate loading, not causing postprandial blood shifts to digestive system, should therefore be investigated. PMID:21360202

  20. Baroreflex sensitivity in acute hypoxia and carbohydrate loading.

    PubMed

    Klemenc, Matjaž; Golja, Petra

    2011-10-01

    Hypoxia decreases baroreflex sensitivity (BRS) and can be a sufficient cause for syncope in healthy individuals. Carbohydrate loading enhances efferent sympathetic activity, which affects cardiac contractility, heart rate and vascular resistance, the main determinants of blood pressure. Thus, in both normoxia and hypoxia, carbohydrate loading may be more than simply metabolically beneficial, as it may affect blood pressure regulation. We hypothesised that carbohydrate loading will, in both normoxia and hypoxia, alter the regulation of blood pressure, as reflected in a change in baroreflex sensitivity. Fourteen subjects participated in two experiments, composed of a 15-min normoxic period, after which the subjects ingested water or an equal amount of water with carbohydrates. A 30-min rest period was then followed by a 10-min second normoxic and a 30-min hypoxic period. Blood pressure and heart rate were monitored continuously during the experiment to determine BRS. Despite an increased sympathetic activation, reflected in increased heart rate (P < 0.001) BRS was lower (P < 0.01) after carbohydrate loading, as compared to the water experiment, in both normoxic [23.7 (12.4) versus 28.8 (13.8) ms/mmHg] and hypoxic [16.8 (11.0) versus 24.3 (12.3) ms/mmHg] phases of the present study. As BRS was decreased in acute hypoxic exposure, the results confirm that hypoxia interferes with blood pressure regulation. However, although oral carbohydrate loading induced sympathoexcitation, it did not improve blood pressure regulation in hypoxia, as evident from the BRS data. Baroreflex effects of other forms of carbohydrate loading, not causing postprandial blood shifts to digestive system, should therefore be investigated.

  1. Chronic intermittent hypoxia alters ventilatory and metabolic responses to acute hypoxia in rats.

    PubMed

    Morgan, Barbara J; Adrian, Russell; Wang, Zun-Yi; Bates, Melissa L; Dopp, John M

    2016-05-15

    We determined the effects of chronic exposure to intermittent hypoxia (CIH) on chemoreflex control of ventilation in conscious animals. Adult male Sprague-Dawley rats were exposed to CIH [nadir oxygen saturation (SpO2), 75%; 15 events/h; 10 h/day] or normoxia (NORM) for 21 days. We assessed the following responses to acute, graded hypoxia before and after exposures: ventilation (V̇e, via barometric plethysmography), V̇o2 and V̇co2 (analysis of expired air), heart rate (HR), and SpO2 (pulse oximetry via neck collar). We quantified hypoxia-induced chemoreceptor sensitivity by calculating the stimulus-response relationship between SpO2 and the ventilatory equivalent for V̇co2 (linear regression). An additional aim was to determine whether CIH causes proliferation of carotid body glomus cells (using bromodeoxyuridine). CIH exposure increased the slope of the V̇e/V̇co2/SpO2 relationship and caused hyperventilation in normoxia. Bromodeoxyuridine staining was comparable in CIH and NORM. Thus our CIH paradigm augmented hypoxic chemosensitivity without causing glomus cell proliferation. PMID:26917692

  2. [Tomodensitometry of severe acute pancreatitis].

    PubMed

    Frija, J; Abanou, A; Viandier, A; Laval-Jeantet, M

    1983-01-01

    90 computed tomographic examinations were performed to 57 patients referred at Hospital Saint-Louis for an acute pancreatitis. 32 patients were operated or autopsied. Among these 32 patients, 19 patients had 21 examinations before surgery or autopsy; the other 13 patients had their computed tomographic examinations after one or more surgical procedures. During a severe acute pancreatitis the pancreas is always large either locally or diffusely. A pancreatic reaction is visible around and possibly at distance of the pancreas. When extraluminal gas is visible (3/5) it signifies gangrenous pancreatitis but it is necessary to eliminate a digestive fistulous tract and/or a communication between a pseudocyst and the digestive tract. Except gangrenous it is not possible to precise the nature of pancreatic reaction. The diagnosis of pseudocyst was easy 9/10, difficult 1/10; we did a false positive diagnosis of pseudocyst. Computed tomography and ultrasounds were compared in ten patients for the search of gallbladder lithiasis. Computed tomography can show large and small (2/4) biliary calculus in the gallbladder that cannot be shown by ultrasounds. A normal pancreas in a normal retroperitoneal space exclude the diagnosis of a severe acute pancreatitis. CT aspects of acute pancreatitis must be considered as a good diagnostic test of an acute pancreatitis.

  3. Severe acute pancreatitis and pregnancy.

    PubMed

    Robertson, K W; Stewart, I S; Imrie, C W

    2006-01-01

    For most patients with pregnancy-associated pancreatitis there is little maternal survival threat and only occasionally are there foetal deaths. We describe 4 young women with pregnancy-associated severe acute pancreatitis who each had gallstones. Their ages were 17, 18, 20 and 24 years. Each was a tertiary referral to our unit in Glasgow and each pursued a life-threatening course with hospital stays ranging from 37 to 90 days. One patient required pancreatic necrosectomy for infected necrosis, another had percutaneous management of a pancreatic abscess and 2 had cystogastrostomy as treatment for pancreatic pseudocyst. All underwent early endoscopic sphincterotomy and later cholecystectomy. It is important to be aware that pregnancy-associated acute pancreatitis may be severe, posing a survival threat even in the youngest patients. Gallstones, as we reported almost 20 years ago, are the most common aetiological factor in such patients.

  4. Acute physical exercise under hypoxia improves sleep, mood and reaction time.

    PubMed

    de Aquino-Lemos, Valdir; Santos, Ronaldo Vagner T; Antunes, Hanna Karen Moreira; Lira, Fabio S; Luz Bittar, Irene G; Caris, Aline V; Tufik, Sergio; de Mello, Marco Tulio

    2016-02-01

    This study aimed to assess the effect of two sessions of acute physical exercise at 50% VO2peak performed under hypoxia (equivalent to an altitude of 4500 m for 28 h) on sleep, mood and reaction time. Forty healthy men were randomized into 4 groups: Normoxia (NG) (n = 10); Hypoxia (HG) (n = 10); Exercise under Normoxia (ENG) (n = 10); and Exercise under Hypoxia (EHG) (n = 10). All mood and reaction time assessments were performed 40 min after awakening. Sleep was reassessed on the first day at 14 h after the initiation of hypoxia; mood and reaction time were measured 28 h later. Two sessions of acute physical exercise at 50% VO2peak were performed for 60 min on the first and second days after 3 and 27 h, respectively, after starting to hypoxia. Improved sleep efficiency, stage N3 and REM sleep and reduced wake after sleep onset were observed under hypoxia after acute physical exercise. Tension, anger, depressed mood, vigor and reaction time scores improved after exercise under hypoxia. We conclude that hypoxia impairs sleep, reaction time and mood. Acute physical exercise at 50% VO2peak under hypoxia improves sleep efficiency, reversing the aspects that had been adversely affected under hypoxia, possibly contributing to improved mood and reaction time.

  5. Microenvironmental oxygen partial pressure in acute myeloid leukemia: Is there really a role for hypoxia?

    PubMed

    Rieger, Christina T; Fiegl, Michael

    2016-07-01

    Reduced oxygen partial pressure (pO2) has been recognized as being relevant in hematopoiesis and the pathophysiology of malignant diseases. Although hypoxic (meaning insufficient supply of oxygen) and anoxic areas are present and of pathophysiologic importance (by hypoxia-induced pathways such as HiF1α) in solid tumors, this may not be true for (malignant) hematologic cells. Hematopoiesis occurs in the stem cell niche, which is characterized, among other things, by extremely low pO2. However, in contrast to solid tumors, in this context, the low pO2 is physiological and this feature, among others, is shared by the malignant stem cell niche harboring leukemia-initiating cells. Upon differentiation, hematopoietic cells are constantly exposed to changes in pO2 as they travel throughout the human body and encounter arterial and venous blood and migrate into oxygen-carrier-free tissue with low pO2. Hematologic malignancies such as acute myeloid leukemia (AML) make little difference in this respect and, whereas low oxygen is the usual environment of AML cells, recent evidence suggests no role for real hypoxia. Although there is no evidence that AML pathophysiology is related to hypoxia, leukemic blasts still show several distinct biological features when exposed to reduced pO2: they down- or upregulate membrane receptors such as CXCR4 or FLT3, activate or inhibit intracellular signaling pathways such as PI3K, and specifically secrete cytokines (IL-8). In summary, reduced pO2 should not be mistaken for hypoxia (nor should it be so called), and it does not automatically induce hypoxia-response mechanisms; therefore, a strict distinction should be made between physiologically low pO2 (physoxia) and hypoxia. PMID:27118044

  6. Predicting severity of acute pancreatitis.

    PubMed

    Rau, Bettina M

    2007-04-01

    Severity stratification is a critical issue in acute pancreatitis that strongly influences diagnostic and therapeutic decision making. According to the widely used Atlanta classification, "severe" disease comprises various local and systemic complications that are associated with an increased risk of mortality. However, results from recent clinical studies indicate that these complications vary in their effect on outcome, and many are not necessarily life threatening on their own. Therefore, "severe," as defined by Atlanta, must be distinguished from "prognostic," aiming at nonsurvival. In the first week after disease onset, pancreatitis-related organ failure is the preferred variable for predicting severity and prognosis because it outweighs morphologic complications. Contrast-enhanced CT and MRI allow for accurate stratification of local severity beyond the first week after symptom onset. Among the biochemical markers, C-reactive protein is still the parameter of choice to assess attack severity, although prognostic estimation is not possible. Other markers, including pancreatic protease activation peptides, interleukins-6 and -8, and polymorphonuclear elastase are useful early indicators of severity. Procalcitonin is one of the most promising single markers for assessment of major complications and prognosis throughout the disease course.

  7. Hepatic metabolism of ibuprofen in rats under acute hypobaric hypoxia.

    PubMed

    Gola, Shefali; Keshri, Gaurav Km; Gupta, Asheesh

    2013-09-01

    Hypobaric hypoxia induced at high altitude causes a subnormal oxygen concentration in cells which affects the drug metabolic and pharmacokinetic (PK) capacity of the body. The metabolism and PK of drugs like ibuprofen may be impaired under hypoxia and may require a different than usual therapeutic dose regimen to ensure safe therapy. The present investigation was undertaken to evaluate the effect of acute hypobaric hypoxia (AHH) on hepatic metabolism and PK of ibuprofen in rats. Animals were exposed to simulated altitude of 7620 m (∼25,000 ft) for AHH exposure (6 and 24 h) in a decompression chamber and were administrated with single dose of ibuprofen (80 mg/kg body weight, p.o.). The results showed that GST activity was significantly reduced at 6 h (15%) and 24 h (23%) (p<0.05) in hypoxic group as compared to normoxic. A significant increase by 20-24% (p<0.05) in AST level was observed after AHH exposure. LDH activity also exhibited significant increase (p<0.05) after 24h of AHH. A significant down-regulated CYP2C9 level and mild histopathological changes were observed after 24h of AHH. Furthermore, PK variables viz. elimination half-life (T½) and mean residence time (MRT) of ibuprofen exhibited significant increase by 42% and 51% (p<0.05) respectively after 24h of AHH. Thus, results suggest that AHH exposure of 24h significantly affects phase II conjugation pathway, CYP2C9 level, AST level, liver histology and PK parameters. This asserts that AHH can impair disposition of ibuprofen however, it requires further investigation under chronic hypobaric hypoxic conditions.

  8. Severe acute malnutrition and infection

    PubMed Central

    Jones, Kelsey D J; Berkley, James A

    2014-01-01

    Severe acute malnutrition (SAM) is associated with increased severity of common infectious diseases, and death amongst children with SAM is almost always as a result of infection. The diagnosis and management of infection are often different in malnourished versus well-nourished children. The objectives of this brief are to outline the evidence underpinning important practical questions relating to the management of infectious diseases in children with SAM and to highlight research gaps. Overall, the evidence base for many aspects covered in this brief is very poor. The brief addresses antimicrobials; antipyretics; tuberculosis; HIV; malaria; pneumonia; diarrhoea; sepsis; measles; urinary tract infection; nosocomial Infections; soil transmitted helminths; skin infections and pharmacology in the context of SAM. The brief is structured into sets of clinical questions, which we hope will maximise the relevance to contemporary practice. PMID:25475887

  9. Ventilatory response to acute hypoxia in transgenic mice over-expressing erythropoietin: effect of acclimation to 3-week hypobaric hypoxia.

    PubMed

    Villafuerte, Francisco C; Cárdenas-Alayza, Rosa; Macarlupú, José Luis; Monge-C, Carlos; León-Velarde, Fabiola

    2007-09-30

    We used transgenic mice constitutively over-expressing erythropoietin ("tg6" mice) and wild-type (wt) mice to investigate whether the high hematocrit (hct), consequence of Epo over-expression affected: (1) the normoxic ventilation (V (E)) and the acute hypoxic ventilatory response (HVR) and decline (HVD), (2) the increase in ventilation observed after chronic exposure to hypobaric hypoxia (430mmHg for 21 days), (3) the respiratory "blunting", and (4) the erythrocythemic response induced by chronic hypoxia exposure. V (E) was found to be similar in tg6 and wt mice in normoxia (FIO2=0.21). Post-acclimation V (E) was significantly elevated in every time point in wt mice at FIO2=0.10 when compared to pre-acclimation values. In contrast, tg6 mice exhibited a non-significant increase in V (E) throughout acute hypoxia exposure. Changes in V (E) are associated with adjustments in tidal volume (V(T)). HVR and HVD were independent of EE in tg6 and wt mice before chornic hypoxia exposure. HVR was significantly greater in wt than in tg6 mice after chronic hypoxia. After acclimation, HVD decreased in tg6 mice. Chronic hypoxia exposure caused hct to increase significantly in wt mice, while only a marginal increase occurred in the tg6 group. Although pre-existent EE does not appear to have an effect on HVR, the observation of alterations on V(T) suggests that it may contribute to time-dependent changes in ventilation and in the acute HVR during exposure to chronic hypoxia. In addition, our results suggest that EE may lead to an early "blunting" of the ventilatory response.

  10. Treating severe acute malnutrition seriously

    PubMed Central

    Collins, Steve

    2007-01-01

    Severe acute malnutrition (SAM) affects approximately 13 million children under the age of 5 and is associated with 1–2 million preventable child deaths each year. In most developing countries, case fatality rates (CFRs) in hospitals treating SAM remain at 20–30% and few of those requiring care actually access treatment. Recently, community‐based therapeutic care (CTC) programmes treating most cases of SAM solely as outpatients have dramatically reduced CFRs and increased the numbers receiving care. CTC uses ready‐to‐use therapeutic foods and aims to increase access to services, promoting early presentation and compliance, thereby increasing coverage and recovery rates. Initial data indicate that this combination of centre‐based and community‐based care is cost effective and should be integrated into mainstream child survival programmes. PMID:17449529

  11. Effect of acute nitrate supplementation on neurovascular coupling and cognitive performance in hypoxia.

    PubMed

    Lefferts, Wesley K; Hughes, William E; White, Corey N; Brutsaert, Tom D; Heffernan, Kevin S

    2016-02-01

    The matching of oxygen supply to neural demand (i.e., neurovascular coupling (NVC)) is an important determinant of cognitive performance. The impact of hypoxia on NVC remains poorly characterized. NVC is partially modulated by nitric oxide (NO), which may initially decrease in hypoxia. This study investigated the effect of acute NO-donor (nitrate) supplementation on NVC and cognitive function in hypoxia. Twenty healthy men participated in this randomized, double-blind, crossover design study. Following normoxic cognitive/NVC testing, participants consumed either nitrate (NIT) or a NIT-depleted placebo (PLA). Participants then underwent 120 min of hypoxia (11.6% ± 0.1% O2) and all cognitive/NVC testing was repeated. NVC was assessed as change in middle cerebral artery (MCA) blood flow during a cognitive task (incongruent Stroop) using transcranial Doppler. Additional computerized cognitive testing was conducted separately to assess memory, executive function, attention, sensorimotor, and social cognition domains. Salivary nitrite significantly increased following supplementation in hypoxia for NIT (+2.6 ± 1.0 arbitrary units (AU)) compared with PLA (+0.2 ± 0.3 AU; p < 0.05). Memory performance (-6 ± 13 correct) significantly decreased (p < 0.05) in hypoxia while all other cognitive domains were unchanged in hypoxia for both PLA and NIT conditions (p > 0.05). MCA flow increased during Stroop similarly in normoxia (PLA +5 ± 6 cm·s(-1), NIT +7 ± 7 cm·s(-1)) and hypoxia (PLA +5 ± 9 cm·s(-1), NIT +6 ± 7 cm·s(-1)) (p < 0.05) and this increase was not altered by PLA or NIT (p > 0.05). In conclusion, acute hypoxia resulted in significant reductions in memory concomitant with preservation of executive function, attention, and sensorimotor function. Hypoxia had no effect on NVC. Acute NIT supplementation had no effect on NVC or cognitive performance in hypoxia. PMID:26751937

  12. Effect of acute nitrate supplementation on neurovascular coupling and cognitive performance in hypoxia.

    PubMed

    Lefferts, Wesley K; Hughes, William E; White, Corey N; Brutsaert, Tom D; Heffernan, Kevin S

    2016-02-01

    The matching of oxygen supply to neural demand (i.e., neurovascular coupling (NVC)) is an important determinant of cognitive performance. The impact of hypoxia on NVC remains poorly characterized. NVC is partially modulated by nitric oxide (NO), which may initially decrease in hypoxia. This study investigated the effect of acute NO-donor (nitrate) supplementation on NVC and cognitive function in hypoxia. Twenty healthy men participated in this randomized, double-blind, crossover design study. Following normoxic cognitive/NVC testing, participants consumed either nitrate (NIT) or a NIT-depleted placebo (PLA). Participants then underwent 120 min of hypoxia (11.6% ± 0.1% O2) and all cognitive/NVC testing was repeated. NVC was assessed as change in middle cerebral artery (MCA) blood flow during a cognitive task (incongruent Stroop) using transcranial Doppler. Additional computerized cognitive testing was conducted separately to assess memory, executive function, attention, sensorimotor, and social cognition domains. Salivary nitrite significantly increased following supplementation in hypoxia for NIT (+2.6 ± 1.0 arbitrary units (AU)) compared with PLA (+0.2 ± 0.3 AU; p < 0.05). Memory performance (-6 ± 13 correct) significantly decreased (p < 0.05) in hypoxia while all other cognitive domains were unchanged in hypoxia for both PLA and NIT conditions (p > 0.05). MCA flow increased during Stroop similarly in normoxia (PLA +5 ± 6 cm·s(-1), NIT +7 ± 7 cm·s(-1)) and hypoxia (PLA +5 ± 9 cm·s(-1), NIT +6 ± 7 cm·s(-1)) (p < 0.05) and this increase was not altered by PLA or NIT (p > 0.05). In conclusion, acute hypoxia resulted in significant reductions in memory concomitant with preservation of executive function, attention, and sensorimotor function. Hypoxia had no effect on NVC. Acute NIT supplementation had no effect on NVC or cognitive performance in hypoxia.

  13. Severe hypoxia and malnutrition collectively contribute to scar fibroblast inhibition and cell apoptosis.

    PubMed

    Lynam, Emily C; Xie, Yan; Dawson, Rebecca; Mcgovern, Jacqui; Upton, Zee; Wang, XiQiao

    2015-09-01

    This study aims to investigate whether severe hypoxia and malnutrition in scar tissue play key roles to induce hypertrophic scar regression. And scar-derived fibroblasts were treated with moderate/severe hypoxia and malnutrition to model condition of proliferative and regressive scar (5%O2 +5%FCS and 0.5%O2  + 0.5%FCS), and normoxia with well nutrition as control (10%O2  + 10%FCS). Our results demonstrated that severe hypoxia and malnutrition resulted in significantly reduced cell viability and collagen production, as well as HIF-1, VEGF, TGF-β1, and Bcl-2 protein expression when compared with control, and cell apoptosis occurred. Therefore, the severe hypoxia and malnutrition in scar tissue contribute to fibroblast inhibition and cell apoptosis, which is correlated with scar regression.

  14. [Prediction and monitoring of severe acute pancreatitis].

    PubMed

    Gürlich, R; Maruna, P; Spicák, J

    2006-01-01

    Twenty to thirty percent patients with acute pancreatitis develop severe acute pancreatitis with high mortality and morbidity rate. Markers of severity of acute pancreatitis are clinically important for the early diagnosis of complications. We reviewed the literature for markers of acute pancreatitis. On their relevance for prediction of severe pancreatitis are given. Several markers can predict severe cases of acute pancreatitis with a different positive and negative predictive value. Useful predictors of severity may include serum procalcitonin and urinary trypsinogen activation peptide at the admission, serum interleukins-6 and -8 at 24 h, and serum C-reactive protein (CRP) in 48 hours interval. The valuable marker for daily monitoring appears to be serum procalcitonin.

  15. Modification by Beta-Adrenergic Blockade of the Circulatory Responses to Acute Hypoxia in Man*

    PubMed Central

    Richardson, David W.; Kontos, Hermes A.; Raper, A. Jarrell; Patterson, John L.

    1967-01-01

    In 17 healthy men, beta-adrenergic blockade reduced significantly the tachycardia and the elevation of cardiac output associated with inhalation of 7.5% oxygen for 7 to 10 minutes. Hypoxia did not increase plasma concentrations of epinephrine or norepinephrine in six subjects. Furthermore, blockade of alpha and beta receptors in the forearm did not modify the vasodilation in the forearm induced by hypoxia, providing pharmacologic evidence that hypoxia of the degree and duration used was not associated with an increase in the concentrations of circulating catecholamines in man. Part of the increase in cardiac output and heart rate during acute hypoxia in man is produced by stimulation of beta-adrenergic receptors, probably by cardiac sympathetic nerves. The mechanism of the vasodilation in the forearm during hypoxia remains uncertain. PMID:4381183

  16. Hypoxia is a modifier of SMN2 splicing and disease severity in a severe SMA mouse model

    PubMed Central

    Bebee, Thomas W.; Dominguez, Catherine E.; Samadzadeh-Tarighat, Somayeh; Akehurst, Kristi L.; Chandler, Dawn S.

    2012-01-01

    Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease associated with low levels of the essential survival motor neuron (SMN) protein. Reduced levels of SMN is due to the loss of the SMN1 gene and inefficient splicing of the SMN2 gene caused by a C>T mutation in exon 7. Global analysis of the severe SMNΔ7 SMA mouse model revealed altered splicing and increased levels of the hypoxia-inducible transcript, Hif3alpha, at late stages of disease progression. Severe SMA patients also develop respiratory deficiency during disease progression. We sought to evaluate whether hypoxia was capable of altering SMN2 exon 7 splicing and whether increased oxygenation could modulate disease in a severe SMA mouse model. Hypoxia treatment in cell culture increased SMN2 exon 7 skipping and reduced SMN protein levels. Concordantly, the treatment of SMNΔ7 mice with hyperoxia treatment increased the inclusion of SMN2 exon 7 in skeletal muscles and resulted in improved motor function. Transfection splicing assays of SMN minigenes under hypoxia revealed that hypoxia-induced skipping is dependent on poor exon definition due to the SMN2 C>T mutation and suboptimal 5′ splice site. Hypoxia treatment in cell culture led to increased hnRNP A1 and Sam68 levels. Mutation of hnRNP A1-binding sites prevented hypoxia-induced skipping of SMN exon 7 and was found to bind both hnRNP A1 and Sam68. These results implicate hypoxic stress as a modulator of SMN2 exon 7 splicing in disease progression and a coordinated regulation by hnRNP A1 and Sam68 as modifiers of hypoxia-induced skipping of SMN exon 7. PMID:22763238

  17. Severe hypoxia during incremental exercise to exhaustion provokes negative post-exercise affects.

    PubMed

    Keramidas, Michail E; Stavrou, Nektarios A M; Kounalakis, Stylianos N; Eiken, Ola; Mekjavic, Igor B

    2016-03-15

    The post-exercise emotional response is mainly dependent on the intensity of the exercise performed; moderate exercise causes positive feelings, whereas maximal exercise may prompt negative affects. Acute hypoxia impairs peak O2 uptake (V̇O2peak), resulting in a shift to a lower absolute intensity at the point of exhaustion. Hence, the purpose of the study was to examine whether a severe hypoxic stimulus would influence the post-exercise affective state in healthy lowlanders performing an incremental exercise to exhaustion. Thirty-six male lowlanders performed, in a counter-balanced order and separated by a 48-h interval, two incremental exercise trials to exhaustion to determine their V̇O2peak, while they were breathing either room air (AIR; FiO2: 0.21), or a hypoxic gas mixture (HYPO; FiO2: 0.12). Before and immediately after each trial, subjects were requested to complete two questionnaires, based on how they felt at that particular moment: (i) the Profile of Mood States-Short Form, and (ii) the Activation Deactivation Adjective Check List. During the post-exercise phase, they also completed the Multidimensional Fatigue Inventory. V̇O2peak was significantly lower in the HYPO than the AIR trial (~15%; p<0.001). Still, after the HYPO trial, energy, calmness and motivation were markedly impaired, whereas tension, confusion, and perception of physical and general fatigue were exaggerated (p≤0.05). Accordingly, present findings suggest that an incremental exercise to exhaustion performed in severe hypoxia provokes negative post-exercise emotions, induces higher levels of perceived fatigue and decreases motivation; the affective responses coincide with the comparatively lower V̇O2peak than that achieved in normoxic conditions.

  18. [Serum lactate level as a indicator of tissue hypoxia in severely ill patients].

    PubMed

    Bakker, J; Schieveld, S J; Brinkert, W

    2000-04-15

    Adequate oxygen supply to the tissues is of vital importance to survive critical illness and trauma. Shock can be defined as an imbalance between oxygen demand and oxygen supply. Clinical features of shock, like hypotension, tachycardia, cold clammy skin et cetera, are poorly correlated with presence of tissue hypoxia. A high lactate level is an early sign of tissue hypoxia. In severely ill patients tissue hypoxia is the most important cause of increased lactate levels. Increased blood lactate levels are related to increased mortality. Optimizing oxygen supply by fluid resuscitation is the intervention of first choice. PMID:10812440

  19. Locomotory fatigue during moderate and severe hypoxia and hypercapnia in the Atlantic blue crab, Callinectes sapidus.

    PubMed

    Stover, Kristin K; Burnett, Karen G; McElroy, Eric J; Burnett, Louis E

    2013-04-01

    The Atlantic blue crab, Callinectes sapidus (Rathbun), is a highly mobile crustacean that must locomote to find food, evade predators, find mates, and avoid adverse conditions such as hypoxia. In this study we tested the effects of two levels of hypoxia (10.4 kPa, 50% air saturation = moderate hypoxia; 4 kPa, 20% air saturation = severe hypoxia) and hypercapnic hypoxia (50% air saturation O(2) with Pco(2) = 2 kPa) on fatigue during sustained continuous exercise. Fatigue was induced by an exercise trial that entailed continuous sideways hexapedal walking on an underwater treadmill. Fatigue was quantified using two methods: (1) a pull force test that measures the holding strength of the legs, and (2) the number of fatigue-resisting behaviors (180° turns and stopping). Fatigue was defined as a pull force of 67% or less of the initial pre-exercise pull force and was reached after 6.12 h of walking for crabs in well-aerated normoxic seawater, 4 h in 50% air saturation, 2.07 h in 20% air saturation, and 4.58 h in 50% air saturation and hypercapnia. The number of fatigue-resisting behaviors increased with walking time in all treatments. Performance decreased in hypoxia, with fatigue being reached more quickly as the level of hypoxia intensified. Hypercapnia in moderate hypoxia did not have a deleterious influence on behavior and lengthened slightly the time it took crabs to fatigue. In addition, severe hypoxia exacerbated changes in gait kinematics as crabs became fatigued, by significantly increasing stride length and decreasing stride frequency.

  20. Tolerance of acute hypoxia while performing operator activity and after a prolonged period under altered gas environment conditions

    NASA Technical Reports Server (NTRS)

    Bloshchinskiy, P.; Golets, L.; Agadzhanyan, N. A.; Sergiyenko, A. V.

    1974-01-01

    Human and animal studies on physiological factors in resistance to acute hypoxia are elaborated. Results show that tolerance of acute hypoxia depends on gas composition and temperature in a sealed cabin, on the length of the stay and motive regime, and on the kind of operator and professional activity. After preliminary adaptation to hypoxia, resistance of the body increases not only to insufficiency of oxygen in inspired air, but also to the effects of other extremum factors of manned space flight.

  1. Acute effects of head-down tilt and hypoxia on modulators of fluid homeostasis

    NASA Technical Reports Server (NTRS)

    Whitson, P. A.; Cintron, N. M.; Pietrzyk, R. A.; Scotto, P.; Loeppky, J. A.

    1994-01-01

    In an effort to understand the interaction between acute postural fluid shifts and hypoxia on hormonal regulation of fluid homeostasis, the authors measured the responses to head-down tilt with and without acute exposure to normobaric hypoxia. Plasma atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP), plasma aldosterone (ALD), and plasma renin activity (PRA) were measured in six healthy male volunteers who were exposed to a head-down tilt protocol during normoxia and hypoxia. The tilt protocol consisted of a 17 degrees head-up phase (30 minutes), a 28 degrees head-down phase (1 hour), and a 17 degrees head-up recovery period (2 hours, with the last hour normoxic in both experiments). Altitude equivalent to 14,828 ft was simulated by having the subjects breathe an inspired gas mixture with 13.9% oxygen. The results indicate that the postural fluid redistribution associated with a 60-minute head-down tilt induces the release of ANP and cGMP during both hypoxia and normoxia. Hypoxia increased cGMP, cAMP, ALD, and PRA throughout the protocol and significantly potentiated the increase in cGMP during head-down tilt. Hypoxia had no overall effect on the release of ANP, but appeared to attenuate the increase with head-down tilt. This study describes the acute effects of hypoxia on the endocrine response during fluid redistribution and suggests that the magnitude, but not the direction, of these changes with posture is affected by hypoxia.

  2. Repeated acute hypoxia temporarily attenuates the ventilatory respiratory response to hypoxia in conscious newborn rats.

    PubMed

    Matsuoka, T; Yoda, T; Ushikubo, S; Matsuzawa, S; Sasano, T; Komiyama, A

    1999-07-01

    We asked whether repeated hypoxic exposures during the early neonatal periods could affect the ventilatory control, such as the lung volume-dependent ventilatory inhibition (HBR), pulmonary ventilation (VE), and CO2 production (VCO2). Within each litter of rats, one group of pups (experimental group H) was exposed to 6% O2 (30-min duration twice a day from postnatal d 1 to 4). The other group (control group C) was exposed to air. At 5 d after birth, the HBR was triggered by lung inflation via negative body surface pressure (10 cm H2O). Measurements of VE and VCO2 were done by plethysmography and the inflow-outflow CO2 difference, respectively. At 2 wk of age, VE and VCO2 measurements were repeated by the barometric technique and the inflow-outflow CO2 difference, respectively. Each conscious pup was breathing normoxia (21% O2) and then hypoxia (10% O2). Results were as follows: 1) during normoxia, HBR was stronger and both VE and VCO2 were higher in H pups than in C pups; 2) during hypoxia, the HBR of C was as in normoxia, whereas that of H was increased above the normoxic value; 3) during hypoxia, C maintained VE, whereas H decreased it; 4) in hypoxia, VCO2 was reduced significantly in both groups; 5) at 2 wk of age, VE and VCO2 did not differ between H and C during normoxia or in response to 10% hypoxia. We conclude that in rat pups, repeated hypoxic episodes can modify the HBR and, at least temporarily, reduce the VE response to hypoxia with a decrease in VCO2. The findings are in agreement with the view that repeated hypoxic exposures in the neonatal period could interfere with the development of respiratory control and could possibly be involved in the mechanisms of neonatal apnea or sudden infant death syndrome. PMID:10400145

  3. [Severe acute pancreatitis associated with gallbladder gangrene].

    PubMed

    Arroyo-Sánchez, Abel S; Aguirre-Mejía, Rosa Y; Echenique-Martínez, Sergio E

    2014-01-01

    We present a diabetic patient who developed severe acute pancreatitis associated to gallbladder gangrene, in this case we assessed the applicability of classification criteria and management of the pathways for acute pancreatitis and also we suggest some topics that could be investigated in the future.

  4. Carotid sinus nerve section and the increase in plasma cortisol during acute hypoxia in fetal sheep.

    PubMed Central

    Giussani, D A; McGarrigle, H H; Moore, P J; Bennet, L; Spencer, J A; Hanson, M A

    1994-01-01

    1. We studied the effects of acute isocapnic hypoxia on plasma concentrations of adrenocorticotrophic hormone (ACTH) and cortisol in sixteen sheep fetuses at 118-125 days of gestation (term is 147 days). Eight fetuses had their carotid sinus nerves cut (denervation); the remaining eight had these nerves left intact. 2. There were no differences in the plasma concentrations of ACTH or cortisol between intact and denervated fetuses during normoxia. 3. Whilst plasma cortisol increased in early (after 15 min) and late (after 45 min) hypoxia in intact fetuses, the rise in cortisol in denervated fetuses was delayed, increasing significantly only by late hypoxia. 4. In contrast, plasma ACTH concentrations were increased in early and late hypoxia in both intact and denervated fetuses. The rise was smaller in denervated fetuses, but was not significantly different from that in intact fetuses. 5. Our results indicate that, in the sheep fetus, carotid sinus nerve section delays the rise in plasma cortisol in response to acute hypoxia without affecting the ACTH response. Further work is needed to establish the mechanism underlying this effect of denervation. PMID:8071889

  5. The protective role of 5-hydroxymethyl-2-furfural (5-HMF) against acute hypobaric hypoxia.

    PubMed

    Li, Ming-Ming; Wu, Li-Ying; Zhao, Tong; Wu, Kui-Wu; Xiong, Lei; Zhu, Ling-Ling; Fan, Ming

    2011-09-01

    Our previous study showed that pretreatment with 5-hydroxymethyl-2-furfural (5-HMF) led to protection against hypoxic injury via a p-ERK-mediated pathway in vitro. Whether the protection of 5-HMF against hypoxia is effective in vivo is unknown. The present study is aimed to verify the role of 5-HMF in acute hypobaric hypoxia using Kunming mice as an in vivo model and further investigate the underlying mechanisms. Mice pretreated with or without 5-HMF for 1 h were exposed to acute hypobaric hypoxic condition for 6 h and then the survival time, the survival rate, the permeability of blood-brain barrier (BBB), the histological analysis in hippocampus and cortex, and the phosphorylation level of mitogen-activated protein kinases (ERK, JNK, and p38) were investigated. The results showed that 5-HMF significantly increased the survival time and the survival rate of mice. Accordingly, pretreatment with 5-HMF markedly attenuated acute hypobaric hypoxia-induced permeability of BBB (P < 0.01). In addition, the cellular damage extent of the hippocampus and the cortex induced by hypoxia for 6 h was also attenuated by pretreatment with 5-HMF, especially in the hippocampus CA1 region. Furthermore, the activation of ERK rather than JNK and p38 was involved in the protection of 5-HMF against acute hypobaric hypoxia. In summary, 5-HMF enhanced the survival capability of mice and decreased acute hypoxic damage to the brain, which may be associated with the effects on BBB and p-ERK. PMID:21494793

  6. Consensus guidelines on severe acute pancreatitis.

    PubMed

    Pezzilli, Raffaele; Zerbi, Alessandro; Campra, Donata; Capurso, Gabriele; Golfieri, Rita; Arcidiacono, Paolo G; Billi, Paola; Butturini, Giovanni; Calculli, Lucia; Cannizzaro, Renato; Carrara, Silvia; Crippa, Stefano; De Gaudio, Raffaele; De Rai, Paolo; Frulloni, Luca; Mazza, Ernesto; Mutignani, Massimiliano; Pagano, Nico; Rabitti, Piergiorgio; Balzano, Gianpaolo

    2015-07-01

    This Position Paper contains clinically oriented guidelines by the Italian Association for the Study of the Pancreas (AISP) for the diagnosis and treatment of severe acute pancreatitis. The statements were formulated by three working groups of experts who searched and analysed the most recent literature; a consensus process was then performed using a modified Delphi procedure. The statements provide recommendations on the most appropriate definition of the complications of severe acute pancreatitis, the diagnostic approach and the timing of conservative as well as interventional endoscopic, radiological and surgical treatments.

  7. [Pharmacotherapy in acute tinnitis. The special role of hypoxia and ischemia in the pathogenesis of tinnitis].

    PubMed

    Mazurek, B; Haupt, H; Gross, J

    2006-01-01

    Hypoxia/ischemia may play an important role in the pathogenesis of sensorineural tinnitus due to the characteristics of the cochlear blood supply. In addition, hypoxia modulates molecular processes both in the acute and chronic forms of tinnitus. Transcription factor HIF-1 (hypoxia-inducible factor) may play a key role in the cells' adaptation to hypoxia and ischemia, while under hypoxic/ischemic conditions, HIF-1 induces changes in the gene expression which may contribute to the remodeling of particular structures within the cochlea. Disturbances in the cochlear blood supply may result in membrane changes, perineural edema, inflammation, disturbances in ion homeostasis and in the formation of reactive oxygen species. Thus, the pharmacotherapy of acute tinnitus may be aimed at the improvement of cochlear blood supply and the prevention of acute processes leading to cell damage. Pharmacotherapies with colloidal plasma substitutes, vasodilators, calcium antagonists, procaine, and cortisone have been described in the literature and are discussed here. Many of the pharmacological treatments have not been validated in double blind studies. Although it is impossible to deduce the cause of tinnitus from a drug's efficiency, there is some evidence that it can be effectively suppressed by improving blood supply, at least at certain stages. The aim is to achieve an improved pharmacotherapy by means of sophisticated diagnostic instruments for classifying particular types of tinnitus. PMID:16132881

  8. Maximum Running Speed of Captive Bar-Headed Geese Is Unaffected by Severe Hypoxia

    PubMed Central

    Hawkes, Lucy A.; Butler, Patrick J.; Frappell, Peter B.; Meir, Jessica U.; Milsom, William K.; Scott, Graham R.; Bishop, Charles M.

    2014-01-01

    While bar-headed geese are renowned for migration at high altitude over the Himalayas, previous work on captive birds suggested that these geese are unable to maintain rates of oxygen consumption while running in severely hypoxic conditions. To investigate this paradox, we re-examined the running performance and heart rates of bar-headed geese and barnacle geese (a low altitude species) during exercise in hypoxia. Bar-headed geese (n = 7) were able to run at maximum speeds (determined in normoxia) for 15 minutes in severe hypoxia (7% O2; simulating the hypoxia at 8500 m) with mean heart rates of 466±8 beats min−1. Barnacle geese (n = 10), on the other hand, were unable to complete similar trials in severe hypoxia and their mean heart rate (316 beats.min−1) was significantly lower than bar-headed geese. In bar-headed geese, partial pressures of oxygen and carbon dioxide in both arterial and mixed venous blood were significantly lower during hypoxia than normoxia, both at rest and while running. However, measurements of blood lactate in bar-headed geese suggested that anaerobic metabolism was not a major energy source during running in hypoxia. We combined these data with values taken from the literature to estimate (i) oxygen supply, using the Fick equation and (ii) oxygen demand using aerodynamic theory for bar-headed geese flying aerobically, and under their own power, at altitude. This analysis predicts that the maximum altitude at which geese can transport enough oxygen to fly without environmental assistance ranges from 6,800 m to 8,900 m altitude, depending on the parameters used in the model but that such flights should be rare. PMID:24710001

  9. Maximum running speed of captive bar-headed geese is unaffected by severe hypoxia.

    PubMed

    Hawkes, Lucy A; Butler, Patrick J; Frappell, Peter B; Meir, Jessica U; Milsom, William K; Scott, Graham R; Bishop, Charles M

    2014-01-01

    While bar-headed geese are renowned for migration at high altitude over the Himalayas, previous work on captive birds suggested that these geese are unable to maintain rates of oxygen consumption while running in severely hypoxic conditions. To investigate this paradox, we re-examined the running performance and heart rates of bar-headed geese and barnacle geese (a low altitude species) during exercise in hypoxia. Bar-headed geese (n = 7) were able to run at maximum speeds (determined in normoxia) for 15 minutes in severe hypoxia (7% O2; simulating the hypoxia at 8500 m) with mean heart rates of 466±8 beats min-1. Barnacle geese (n = 10), on the other hand, were unable to complete similar trials in severe hypoxia and their mean heart rate (316 beats.min-1) was significantly lower than bar-headed geese. In bar-headed geese, partial pressures of oxygen and carbon dioxide in both arterial and mixed venous blood were significantly lower during hypoxia than normoxia, both at rest and while running. However, measurements of blood lactate in bar-headed geese suggested that anaerobic metabolism was not a major energy source during running in hypoxia. We combined these data with values taken from the literature to estimate (i) oxygen supply, using the Fick equation and (ii) oxygen demand using aerodynamic theory for bar-headed geese flying aerobically, and under their own power, at altitude. This analysis predicts that the maximum altitude at which geese can transport enough oxygen to fly without environmental assistance ranges from 6,800 m to 8,900 m altitude, depending on the parameters used in the model but that such flights should be rare.

  10. [Evaluation of severity in acute pancreatitis].

    PubMed

    Ryu, Ji Kon

    2009-10-01

    Acute pancreatitis has a variable etiology and natural history, and some patients have severe complications with a significant risk of death. The prediction of severe disease should be achieved by careful ongoing clinical assessment coupled with the use of a multiple factor scoring system and imaging studies. Over the past 30 years several scoring systems have been developed to predict the severity of acute pancreatitis. However, there are no complete scoring index with high sensitivity and specificity till now. The interest in new biological markers and predictive models for identifying severe acute pancreatitis testifies to the continued clinical importance of early severity prediction. Among them, IL-6, IL-10, procalcitonin, and trypsinogen activation peptide are most likely to be used in clinical practice as predictors of severity. Even if contrast-enhanced CT has been considered the gold standard for diagnosing pancreatic necrosis, early scanning for the prediction of severity is limited because the full extent of pancreatic necrosis may not develop within the first 48 hour of presentation.

  11. Drug induced acute pancreatitis: incidence and severity.

    PubMed Central

    Lankisch, P G; Dröge, M; Gottesleben, F

    1995-01-01

    To determine the incidence and severity of drug induced acute pancreatitis, data from 45 German centres of gastroenterology were evaluated. Among 1613 patients treated for acute pancreatitis in 1993, drug induced acute pancreatitis was diagnosed in 22 patients (incidence 1.4%). Drugs held responsible were azathioprine, mesalazine/sulfasalazine, 2',3'-dideoxyinosine (ddI), oestrogens, frusemide, hydrochlorothiazide, and rifampicin. Pancreatic necrosis not exceeding 33% of the organ was found on ultrasonography or computed tomography, or both, in three patients (14%). Pancreatic pseudocysts did not occur. A decrease of arterial PO2 reflecting respiratory insufficiency, and an increase of serum creatinine, reflecting renal insufficiency as complications of acute pancreatitis were seen in two (9%) and four (18%) patients, respectively. Artificial ventilation was not needed, and dialysis was necessary in only one (5%) case. Two patients (9%) died of AIDS and tuberculosis, respectively; pancreatitis did not seem to have contributed materially to their death. In conclusion, drugs rarely cause acute pancreatitis, and drug induced acute pancreatitis usually runs a benign course. PMID:7489946

  12. Inspiratory muscle work in acute hypoxia influences locomotor muscle fatigue and exercise performance of healthy humans.

    PubMed

    Amann, Markus; Pegelow, David F; Jacques, Anthony J; Dempsey, Jerome A

    2007-11-01

    Our aim was to isolate the independent effects of 1) inspiratory muscle work (W(b)) and 2) arterial hypoxemia during heavy-intensity exercise in acute hypoxia on locomotor muscle fatigue. Eight cyclists exercised to exhaustion in hypoxia [inspired O(2) fraction (Fi(O(2))) = 0.15, arterial hemoglobin saturation (Sa(O(2))) = 81 +/- 1%; 8.6 +/- 0.5 min, 273 +/- 6 W; Hypoxia-control (Ctrl)] and at the same work rate and duration in normoxia (Sa(O(2)) = 95 +/- 1%; Normoxia-Ctrl). These trials were repeated, but with a 35-80% reduction in W(b) achieved via proportional assist ventilation (PAV). Quadriceps twitch force was assessed via magnetic femoral nerve stimulation before and 2 min after exercise. The isolated effects of W(b) in hypoxia on quadriceps fatigue, independent of reductions in Sa(O(2)), were revealed by comparing Hypoxia-Ctrl and Hypoxia-PAV at equal levels of Sa(O(2)) (P = 0.10). Immediately after hypoxic exercise potentiated twitch force of the quadriceps (Q(tw,pot)) decreased by 30 +/- 3% below preexercise baseline, and this reduction was attenuated by about one-third after PAV exercise (21 +/- 4%; P = 0.0007). This effect of W(b) on quadriceps fatigue occurred at exercise work rates during which, in normoxia, reducing W(b) had no significant effect on fatigue. The isolated effects of reduced Sa(O(2)) on quadriceps fatigue, independent of changes in W(b), were revealed by comparing Hypoxia-PAV and Normoxia-PAV at equal levels of W(b). Q(tw,pot) decreased by 15 +/- 2% below preexercise baseline after Normoxia-PAV, and this reduction was exacerbated by about one-third after Hypoxia-PAV (-22 +/- 3%; P = 0.034). We conclude that both arterial hypoxemia and W(b) contribute significantly to the rate of development of locomotor muscle fatigue during exercise in acute hypoxia; this occurs at work rates during which, in normoxia, W(b) has no effect on peripheral fatigue.

  13. Tolerance of human placental tissue to severe hypoxia and its relevance for dual ex vivo perfusion.

    PubMed

    Schneider, H

    2009-03-01

    In the dual ex vivo perfusion of an isolated human placental cotyledon it takes on average 20-30 min to set up stable perfusion circuits for the maternal and fetal vascular compartments. In vivo placental tissue of all species maintains a highly active metabolism and it continues to puzzle investigators how this tissue can survive 30 min of ischemia with more or less complete anoxia following expulsion of the organ from the uterus and do so without severe damage. There seem to be parallels between "depressed metabolism" seen in the fetus and the immature neonate in the peripartum period and survival strategies described in mammals with increased tolerance of severe hypoxia like hibernators in the state of torpor or deep sea diving turtles. Increased tolerance of hypoxia in both is explained by "partial metabolic arrest" in the sense of a temporary suspension of Kleiber's rule. Furthermore the fetus can react to major changes in surrounding oxygen tension by decreasing or increasing the rate of specific basal metabolism, providing protection against severe hypoxia as well as oxidative stress. There is some evidence that adaptive mechanisms allowing increased tolerance of severe hypoxia in the fetus or immature neonate can also be found in placental tissue, of which at least the villous portion is of fetal origin. A better understanding of the molecular details of reprogramming of fetal and placental tissues in late pregnancy may be of clinical relevance for an improved risk assessment of the individual fetus during the critical transition from intrauterine life to the outside and for the development of potential prophylactic measures against severe ante- or intrapartum hypoxia. Responses of the tissue to reperfusion deserve intensive study, since they may provide a rational basis for preventive measures against reperfusion injury and related oxidative stress. Modification of the handling of placental tissue during postpartum ischemia, and adaptation of the

  14. Pazopanib-Induced Severe Acute Pancreatitis.

    PubMed

    Kawakubo, Kazumichi; Hata, Hiroo; Kawakami, Hiroshi; Kuwatani, Masaki; Kawahata, Shuhei; Kubo, Kimitoshi; Imafuku, Keisuke; Kitamura, Shinya; Sakamoto, Naoya

    2015-01-01

    Pazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptors, platelet-derived growth factor receptors, and c-Kit approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Nonselective kinase inhibitors, such as sunitinib and sorafenib, are known to be associated with acute pancreatitis. There are few case reports of severe acute pancreatitis induced by pazopanib treatment. We present a case of severe acute pancreatitis caused by pazopanib treatment for cutaneous angiosarcoma. The patient was an 82-year-old female diagnosed with cutaneous angiosarcoma. She had been refractory to docetaxel treatment and began pazopanib therapy. Three months after pazopanib treatment, CT imaging of the abdomen showed the swelling of the pancreas and surrounding soft tissue inflammation without abdominal pain. After she continued pazopanib treatment for 2 months, she presented with nausea and appetite loss. Abdominal CT showed the worsening of the surrounding soft tissue inflammation of the pancreas. Serum amylase and lipase levels were 296 and 177 IU/l, respectively. She was diagnosed with acute pancreatitis induced by pazopanib treatment and was managed conservatively with discontinuation of pazopanib, but the symptoms did not improve. Subsequently, an abdominal CT scan demonstrated the appearance of a pancreatic pseudocyst. She underwent endoscopic ultrasound-guided pseudocyst drainage using a flared-end fully covered self-expandable metallic stent. Then, the symptoms resolved without recurrence. Due to the remarkable progress of molecular targeted therapy, the oncologist should know that acute pancreatitis was recognized as a potential adverse event of pazopanib treatment and could proceed to severe acute pancreatitis. PMID:26464570

  15. Ionoregulatory Aspects of the Osmorespiratory Compromise during Acute Environmental Hypoxia in 12 Tropical and Temperate Teleosts.

    PubMed

    Robertson, Lisa M; Val, Adalberto Luis; Almeida-Val, Vera F; Wood, Chris M

    2015-01-01

    In the traditional osmorespiratory compromise, as seen in the hypoxia-intolerant freshwater rainbow trout (Oncorhynchus mykiss), the branchial modifications that occur to improve O2 uptake during hypoxia result in unfavorable increases in the fluxes of ions and water. However, at least one hypoxia-tolerant freshwater species, the Amazonian oscar (Astronotus ocellatus), shows exactly the opposite: decreased branchial flux rates of ions, water, and nitrogenous wastes during acute hypoxia. In order to find out whether the two strategies were widespread, we used a standard 2-h normoxia, 2-h hypoxia (20%-30% saturation), 2-h normoxic recovery protocol to survey 10 other phylogenetically diverse tropical and temperate species. Unidirectional influx and efflux rates of Na(+) and net flux rates of K(+), ammonia, and urea-N were measured. The flux reduction strategy was seen only in one additional species, the Amazonian tambaqui (Colossoma macropomum), which is similarly hypoxia tolerant and lives in the same ion-poor waters as the oscar. However, five other species exhibited evidence of the increased flux rates typical of the traditional osmorespiratory compromise in the trout: the rosaceu tetra (Hyphessobrycon bentosi rosaceus), the moenkhausia tetra (Moenkhausia diktyota), the bluegill sunfish (Lepomis macrochirus), the zebra fish (Danio rerio), and the goldfish (Carassius auratus). Four other species exhibited no marked flux changes during hypoxia: the cardinal tetra (Paracheirodon axelrodi), the hemigrammus tetra (Hemigrammus rhodostomus), the pumpkinseed sunfish (Lepomis gibbosus), and the Atlantic killifish (Fundulus heteroclitus). Overall, a diversity of strategies exist; we speculate that these may be linked to differences in habitat and/or lifestyle. PMID:26052633

  16. Investigating the complexity of respiratory patterns during recovery from severe hypoxia

    NASA Astrophysics Data System (ADS)

    Akay, Metin; Sekine, Noriko

    2004-03-01

    Progressive hypoxemia in anesthetized, peripherally chemodenervated piglets results in initial depression of the phrenic neurogram (PN) culminating in phrenic silence and, eventually, gasping. These changes reverse after the 30 min reoxygenation (recovery) period. To determine if changes in the PN patterns correspond to changes in temporal patterning, we have used the approximate entropy (ApEn) method to examine the effects of maturation on the complexity of breathing patterns in chemodenervated, vagotomized and decerebrated piglets during severe hypoxia and reoxygenation. The phrenic neurogram in piglets was recorded during eupnea (normal breathing), severe hypoxia (gasping) and recovery from severe hypoxia in 31 piglets (2 35 days). Nonlinear dynamical analysis of the phrenic neurogram was performed using the ApEn method. The mean ApEn values for a recording of five consecutive breaths during eupnea, a few phrenic neurogram signals during gasping, the beginning of the recovery period, and five consecutive breaths at every 5 min interval for the 30 min recovery period were calculated. Our data suggest that gasping resulted in reduced duration of the phrenic neurogram, and the gasp-like patterns exist at the beginning of the recovery. But, the durations of phrenic neurograms during recovery were increased after 10 min postreoxygenation, but were restored 30 min post recovery. The ApEn (complexity) values of the phrenic neurogram during eupnea were higher than those of gasping and the early (the onset of) recovery from severe hypoxia (p < 0.01), but were not statistically different than 5 min post recovery regardless of the maturation stages. These results suggest that hypoxia results in a reversible reconfiguration of the central respiratory pattern generator.

  17. Air exposure behavior of the semiterrestrial crab Neohelice granulata allows tolerance to severe hypoxia but not prevent oxidative damage due to hypoxia-reoxygenation cycle.

    PubMed

    de Lima, Tábata Martins; Geihs, Márcio Alberto; Nery, Luiz Eduardo Maia; Maciel, Fábio Everton

    2015-11-01

    The air exposure behavior of the semi-terrestrial crab Neohelice granulata during severe hypoxia was studied. This study also verified whether this behavior mitigates possible oxidative damage, namely lipoperoxidation, caused by hypoxia and reoxygenation cycles. The lethal time for 50% of the crabs subjected to severe hypoxia (0.5 mgO2 · L(-1)) with free access to air was compared to that of crabs subjected to severe hypoxia without access to air. Crabs were placed in aquaria divided into three zones: water (when the animal was fully submersed), land (when the animal was completely emerged) and intermediate (when the animal was in contact with both environments) zones. Then the crabs were held in this condition for 270 min, and the time spent in each zone was recorded. Lipid peroxidation (LPO) damage to the walking leg muscles was determined for the following four experimental conditions: a--normoxic water with free access to air; b--hypoxic water without access to air; c--hypoxic water followed by normoxic water without air access; and d--hypoxic water with free access to air. When exposed to hypoxic water, N. granulata spent significantly more time on land, 135.3 ± 17.7 min, whereas control animals (exposed to normoxic water) spent more time submerged, 187.4 ± 20.2 min. By this behavior, N. granulata was able to maintain a 100% survival rate when exposed to severe hypoxia. However, N. granulata must still return to water after periods of air exposure (~ 14 min), causing a sequence of hypoxia/reoxygenation events. Despite increasing the survival rate, hypoxia with air access does not decrease the lipid peroxidation damage caused by the hypoxia and reoxygenation cycle experienced by these crabs.

  18. [The modification of nitric oxide production by exogenous substrates of Krebs cycle during acute hypoxia].

    PubMed

    Kurhaliuk, N M; Kotsiuruba, A V; Sahach, V F

    2005-01-01

    Hypoxia causes the disruption of mitochondria electron respiratory chain, production of active oxygen forms and the unoxidative protection. In experiments on Wistar rats the influence of sodium succinate (50 mg/kg) and 6-ketoglutarate (200 mg/kg) on NO2-, NO3-, urea and polyamines contents in blood and liver under acute hypoxia (7% O2 in N2, 30 min) was investigated. Nitrite and nitrate content decreased in erythrocytes and liver but not in plasma under acute hypoxia. The exogenous succinate (SK) stimulated production of nitric oxide in erythrocytes and liver while 6-ketoglutarate (KG) only in liver. The switch from more intensive SK oxidation that reveals adrenomimetic influence and causes the synthesis and release of NO from erythrocyte, to less intensive KG correlates with well-known decrease of tissue respiration under the activation of the cholinergic system due to urea cycle activation particularly in liver. The activation of the SK oxidation takes place mainly under the different stress conditions and causes NO production in the blood cells. These conditions of the intensive and fast action under acute hypoxia are accompanied on the one hand by the increase of oxygen input ratio and on the other hand by activation of the free radical oxidation. The protective effect of the natural Krebs cycle intermediates--SK and KG in particular, is related to the regulation of NO synthesis and its metabolism in the main organs. These results proved the existence not only metabolite control of NO system by Krebs cycle intermediates, but the existence of the systemic mechanism for the support of the functional state of mitochondria under hypoxia.

  19. Effects of preconditioning on the resistance to acute hypobaric hypoxia and their correction with selective antagonists of nicotinic receptors.

    PubMed

    Zakharova, E I; Dudchenko, A M; Germanova, E L

    2011-06-01

    Hypobaric hypoxic preconditioning increased the resistance of low resistant and highly resistant rats to acute hypobaric hypoxia at a critical height. Intergroup differences in the resistance of rats to acute hypobaric hypoxia were not observed after hypobaric hypoxia and one variational series with a wide range of resistance (4.5-24.5 min) appeared. Methyllycaconitine, an antagonist of subtype α(7) nicotinic cholinergic receptors, abolished the influence of hypobaric hypoxia on low resistant rats, but had no effect on highly resistant animals. Mecamylamine, a preferential antagonist of subtype α(4)β(2) and α(3)-containing cholinergic receptors, did not modulate the effect of hypobaric hypoxia. By contrast, hypobaric hypoxia abolished the effect of mecamylamine on the resistance of rats that were not trained under conditions of hypobaric hypoxia (low resistant and highly resistant animals with low sensitivity to hypobaric hypoxia). We conclude that the same effect of hypobaric hypoxia is mediated by various mechanisms, which involve different nicotinic cholinergic receptors. They differ from the resistance mechanisms in non-trained rats. PMID:22238744

  20. Aminophylline influences cerebral hyperperfusion after severe birth hypoxia.

    PubMed

    Robel-Tillig, E; Vogtmann, C

    2000-08-01

    Doppler sonographic investigations have presented cerebral hyperperfusion in neonates after severe asphyxia. Neonates with disturbed cerebral blood flow velocity (CBFV) tend to have poor outcomes. The purpose of this clinical study was to examine the influence of aminophylline on cerebral hyperperfusion. An intravenous bolus of 4 mg/kg aminophylline was given to nine neonates with Doppler sonographic signs of cerebral hyperperfusion. CBFV was determined before, 5 min, 60 min and 120 min after aminophylline administration and on the following day. After aminophylline the mean systolic (56.5 vs. 41.6 cm/s) and end diastolic (21.0 vs. 12.3 cm/s) blood flow velocity decreased and the mean pulsatility index (0.83 vs. 1.1) increased significantly. Repeated measurements showed a decrease in blood flow velocities and an increase in pulsatility index on the following days. Heart rate, mean arterial blood pressure and pCO2 were not significantly changed. We conclude that aminophylline influences cerebral hyperperfusion in neonates with disturbed autoregulation.

  1. Protective effects of thoracic epidural anesthesia on hypoxia-induced acute lung injury in rabbits

    PubMed Central

    WANG, LIJUN; CANG, JING; XUE, ZHANGGANG

    2016-01-01

    The mechanism underlying the effect of thoracic epidural anesthesia (TEA) on hypoxia-induced acute lung injury (ALI) is currently unknown. In the present study, a rabbit acute lung injury model was established to investigate the effects of TEA on inflammatory factors, pulmonary surfactant and ultrastructure. A total of 56 rabbits were randomly assigned to four groups (n=14 per group): Control group (Group C), hypoxia group (Group H), sevoflurane group (Group S) and combined sevoflurane-epidural anesthesia group (Group ES). The ALI model was considered to have been successfully induced when the ratio of arterial oxygen partial pressure to fractional inspired oxygen was <300. The correct placement of a catheter for TEA was confirmed using epidurography. ALI was maintained for 3 h. Arterial blood samples were collected from all groups during spontaneous breathing (T0) and at 3 h after ALI induction (T5) in order to evaluate the serum levels of interleukin (IL)-6, IL-8 and IL-10. Bronchoalveolar lavage fluid was harvested to determine the total phospholipid, saturated phosphatidylcholine and total protein levels. Furthermore, the dry/wet weight ratio and the mRNA expression levels of IL-6, IL-8 and IL-10 in the lung tissue were determined using ELISA. In addition, light and transmission electron microscopy and histological techniques were used to examine the morphology of alveolar type II cells in the rat lung tissue. The results indicate that changes of serum IL-6, IL-8 and IL-10 levels following ALI were consistent with the changes in the mRNA expression levels of IL-6, IL-8 and IL-10 in the lung tissue. TEA attenuated these changes and thus reduced the severity of the ALI. In addition, TEA improved the alveolar structure, reduced the number of polymorphonuclear cells and mitigated the damage of lamellar bodies. In summary, the results of the present study indicate that TEA reduces lung tissue damage by inhibiting systemic and local inflammation, decreasing the

  2. Adipogenesis, lipogenesis and lipolysis is stimulated by mild but not severe hypoxia in 3T3-L1 cells.

    PubMed

    Weiszenstein, Martin; Musutova, Martina; Plihalova, Andrea; Westlake, Katerina; Elkalaf, Moustafa; Koc, Michal; Prochazka, Antonin; Pala, Jan; Gulati, Sumeet; Trnka, Jan; Polak, Jan

    2016-09-16

    In-vitro investigation of the effects of hypoxia is limited by physical laws of gas diffusion and cellular O2 consumption, making prolonged exposures to stable O2 concentrations impossible. Using a gas-permeable cultureware, chronic effects of mild and severe hypoxia on triglyceride accumulation, lipid droplet size distribution, spontaneous lipolysis and gene expression of adipocyte-specific markers were assessed. 3T3-L1 cells were differentiated under 20%, 4% or 1% O2 using a gas-permeable cultureware. Triglyceride accumulation, expression of genes characteristic for advanced adipocyte differentiation and involvement of key lipogenesis enzymes were assessed after exposures. Lipogenesis increased by 375% under mild hypoxia, but dropped by 43% in severe hypoxia. Mild, but not severe, hypoxia increased formation of large lipid droplets 6.4 fold and strongly induced gene expression of adipocyte-specific markers. Spontaneous lipolysis increased by 488% in mild, but only by 135% in severe hypoxia. Inhibition of ATP-dependent citrate lyase suppressed hypoxia-induced lipogenesis by 81% and 85%. Activation of HIF inhibited lipogenesis by 59%. Mild, but not severe, hypoxia stimulates lipolysis and promotes adipocyte differentiation, probably through excess of acetyl-CoA originating from tricarboxylic acid cycle independently of HIF activation.

  3. Adipogenesis, lipogenesis and lipolysis is stimulated by mild but not severe hypoxia in 3T3-L1 cells.

    PubMed

    Weiszenstein, Martin; Musutova, Martina; Plihalova, Andrea; Westlake, Katerina; Elkalaf, Moustafa; Koc, Michal; Prochazka, Antonin; Pala, Jan; Gulati, Sumeet; Trnka, Jan; Polak, Jan

    2016-09-16

    In-vitro investigation of the effects of hypoxia is limited by physical laws of gas diffusion and cellular O2 consumption, making prolonged exposures to stable O2 concentrations impossible. Using a gas-permeable cultureware, chronic effects of mild and severe hypoxia on triglyceride accumulation, lipid droplet size distribution, spontaneous lipolysis and gene expression of adipocyte-specific markers were assessed. 3T3-L1 cells were differentiated under 20%, 4% or 1% O2 using a gas-permeable cultureware. Triglyceride accumulation, expression of genes characteristic for advanced adipocyte differentiation and involvement of key lipogenesis enzymes were assessed after exposures. Lipogenesis increased by 375% under mild hypoxia, but dropped by 43% in severe hypoxia. Mild, but not severe, hypoxia increased formation of large lipid droplets 6.4 fold and strongly induced gene expression of adipocyte-specific markers. Spontaneous lipolysis increased by 488% in mild, but only by 135% in severe hypoxia. Inhibition of ATP-dependent citrate lyase suppressed hypoxia-induced lipogenesis by 81% and 85%. Activation of HIF inhibited lipogenesis by 59%. Mild, but not severe, hypoxia stimulates lipolysis and promotes adipocyte differentiation, probably through excess of acetyl-CoA originating from tricarboxylic acid cycle independently of HIF activation. PMID:27498031

  4. Acute hypoxia up-regulates HIF-1α and VEGF mRNA levels in Amazon hypoxia-tolerant Oscar (Astronotus ocellatus).

    PubMed

    Baptista, R B; Souza-Castro, N; Almeida-Val, V M F

    2016-10-01

    Amazon fish maintain oxygen uptake through a variety of strategies considered evolutionary and adaptive responses to the low water oxygen saturation, commonly found in Amazon waters. Oscar (Astronotus ocellatus) is among the most hypoxia-tolerant fish in Amazon, considering its intriguing anaerobic capacity and ability to depress oxidative metabolism. Previous studies in hypoxia-tolerant and non-tolerant fish have shown that hypoxia-inducible factor-1α (HIF-1α) gene expression is positively regulated during low oxygen exposure, affecting vascular endothelial growth factor (VEGF) transcription and fish development or tolerance in different manners. However, whether similar isoforms exists in tolerant Amazon fish and whether they are affected similarly to others physiological responses to improve hypoxia tolerance remain unknown. Here we evaluate the hepatic HIF-1α and VEGF mRNA levels after 3 h of acute hypoxia exposure (0.5 mgO2/l) and 3 h of post-hypoxia recovery. Additionally, hematological parameters and oxidative enzyme activities of citrate synthase (CS) and malate dehydrogenase (MDH) were analyzed in muscle and liver tissues. Overall, three sets of responses were detected: (1) as expected, hematocrit, hemoglobin concentration, red blood cells, and blood glucose increased, improving oxygen carrying capacity and glycolysis potential; (2) oxidative enzymes from liver decreased, corroborating the tendency to a widespread metabolic suppression; and (3) HIF-1α and VEGF increased mRNA levels in liver, revealing their role in the oxygen homeostasis through, respectively, activation of target genes and vascularization. This is the first study to investigate a hypoxia-related transcription factor in a representative Amazon hypoxia-tolerant fish and suggests that HIF-1α and VEGF mRNA regulation have an important role in enhancing hypoxia tolerance in extreme tolerant species. PMID:26994906

  5. Acute hypoxia up-regulates HIF-1α and VEGF mRNA levels in Amazon hypoxia-tolerant Oscar (Astronotus ocellatus).

    PubMed

    Baptista, R B; Souza-Castro, N; Almeida-Val, V M F

    2016-10-01

    Amazon fish maintain oxygen uptake through a variety of strategies considered evolutionary and adaptive responses to the low water oxygen saturation, commonly found in Amazon waters. Oscar (Astronotus ocellatus) is among the most hypoxia-tolerant fish in Amazon, considering its intriguing anaerobic capacity and ability to depress oxidative metabolism. Previous studies in hypoxia-tolerant and non-tolerant fish have shown that hypoxia-inducible factor-1α (HIF-1α) gene expression is positively regulated during low oxygen exposure, affecting vascular endothelial growth factor (VEGF) transcription and fish development or tolerance in different manners. However, whether similar isoforms exists in tolerant Amazon fish and whether they are affected similarly to others physiological responses to improve hypoxia tolerance remain unknown. Here we evaluate the hepatic HIF-1α and VEGF mRNA levels after 3 h of acute hypoxia exposure (0.5 mgO2/l) and 3 h of post-hypoxia recovery. Additionally, hematological parameters and oxidative enzyme activities of citrate synthase (CS) and malate dehydrogenase (MDH) were analyzed in muscle and liver tissues. Overall, three sets of responses were detected: (1) as expected, hematocrit, hemoglobin concentration, red blood cells, and blood glucose increased, improving oxygen carrying capacity and glycolysis potential; (2) oxidative enzymes from liver decreased, corroborating the tendency to a widespread metabolic suppression; and (3) HIF-1α and VEGF increased mRNA levels in liver, revealing their role in the oxygen homeostasis through, respectively, activation of target genes and vascularization. This is the first study to investigate a hypoxia-related transcription factor in a representative Amazon hypoxia-tolerant fish and suggests that HIF-1α and VEGF mRNA regulation have an important role in enhancing hypoxia tolerance in extreme tolerant species.

  6. Acute respiratory failure following severe arsenic poisoning.

    PubMed

    Greenberg, C; Davies, S; McGowan, T; Schorer, A; Drage, C

    1979-11-01

    A 47-year-old man had an episode of severe respiratory failure after acute intoxication with arsenic. Features of the initial clinical presentation included nausea, vomiting, and diarrhea, acute psychosis, diffuse skin rash, and marked pancytopenia. A peripheral neuropathy then developed which resulted in severe weakness of all muscles of the limbs, the shoulder and pelvis girdles, and the trunk. The neuropathy continued to progress despite treatment with dimercaprol (BAL in oil). Five weeks after the initial exposure, the patient was no longer able to maintain adquate ventilation and required mechanical ventilatory support. Improvement in the patient's neuromuscular status permitted successful weaning from the ventilator after one month of mechanical ventilation. Long-term follow-up revealed no further respiratory difficulty and slow improvement in the strength of the peripheral muscles.

  7. Tissue factor in predicted severe acute pancreatitis

    PubMed Central

    Andersson, Ellen; Axelsson, Jakob; Eckerwall, Gunilla; Ansari, Daniel; Andersson, Roland

    2010-01-01

    AIM: To study tissue factor (TF) in acute pancreatitis and evaluate the role of TF as a predictive marker of severity. METHODS: Forty-nine consecutive patients admitted to Lund University Hospital, fulfilling the criteria of predicted severe acute pancreatitis (AP), were recruited prospectively between 2002 and 2004. Blood samples for TF analyses were drawn at inclusion in the study and 12 h, 1 d and 3 d later. RESULTS: Twenty-seven patients developed mild AP, and 22 patients severe AP. At inclusion in the study, the groups were comparable with respect to gender, aetiology, Acute Physiology and Chronic Health Evaluation II score, and duration of pain. At inclusion in the study and at 12 h, TF was higher in the severe AP group (P = 0.035 and P = 0.049, respectively). After 1 and 3 d, no differences in TF levels were noted. Interleukin (IL)-6 was significantly higher in the severe AP group at all of the studied time points. C-reactive protein (CRP) was significantly higher in the AP group at 1 and 3 d. In receiver operating characteristic-curves, the area under the curve (AUC) for TF was 0.679 (P = 0.035) at inclusion in the study, and a cut off level for TF of 40 pg/mL showed a sensitivity of 71% and a specificity of 67%, whereas corresponding AUC for IL-6 was 0.775, P = 0.001, and for CRP was 0.653. IL-6 showed better AUC-values than TF at all time points studied. CONCLUSION: TF-levels are raised early in severe AP. TF as an early predictive marker of severe AP is superior to CRP, but inferior to IL-6. PMID:21182229

  8. Therapeutic Strategies for Severe Acute Lung Injury

    PubMed Central

    Diaz, Janet. V.; Brower, Roy; Calfee, Carolyn S.; Matthay, Michael A.

    2015-01-01

    Objective In the management of patients with severe Acute Lung Injury and the Acute Respiratory Distress Syndrome (ALI/ARDS), clinicians are sometimes challenged to maintain acceptable gas exchange while avoiding harmful mechanical ventilation practices. In some of these patients, physicians may consider the use of “rescue therapies” to sustain life. Our goal is to provide a practical, evidence-based review to assist critical care physicians’ care for patients with severe ALI/ARDS. Data Sources and Study Selection We searched the Pub Med database for clinical trials examining the use of the following therapies in ALI/ARDS: recruitment maneuvers, high positive end expiratory pressure, prone position, high frequency oscillatory ventilation, glucocorticoids, inhaled nitric oxide, buffer therapy and extracorporeal life support. Study selection All clinical trials that included patients with severe ALI/ARDS were included in the review. Data Synthesis The primary author reviewed the aforementioned trials in depth and then disputed findings and conclusions with other authors until consensus was achieved. Conclusions This article is designed to: a) provide clinicians with a simple, bedside definition for the diagnosis of severe ARDS; b) describe several therapies that can be used in severe ARDS with an emphasis on the potential risks as well as the indications and benefits; and c) to offer practical guidelines for implementation of these therapies. PMID:20562704

  9. Chapter 14: Acute severe asthma (status asthmaticus).

    PubMed

    Shah, Rachna; Saltoun, Carol A

    2012-01-01

    Acute severe asthma, formerly known as status asthmaticus, is defined as severe asthma unresponsive to repeated courses of beta-agonist therapy such as inhaled albuterol, levalbuterol, or subcutaneous epinephrine. It is a medical emergency that requires immediate recognition and treatment. Oral or parenteral corticosteroids should be administered to all patients with acute severe asthma as early as possible because clinical benefits may not occur for a minimum of 6-12 hours. Approximately 50% of episodes are attributable to upper respiratory infections, and other causes include medical nonadherence, nonsteroidal anti-inflammatory exposure in aspirin-allergic patients, allergen exposure (especially pets) in severely atopic individuals, irritant inhalation (smoke, paint, etc.), exercise, and insufficient use of inhaled or oral corticosteroids. The patient history should be focused on acute severe asthma including current use of oral or inhaled corticosteroids, number of hospitalizations, emergency room visits, intensive-care unit admissions and intubations, the frequency of albuterol use, the presence of nighttime symptoms, exercise intolerance, current medications or illicit drug use, exposure to allergens, and other significant medical conditions. Severe airflow obstruction may be predicted by accessory muscle use, pulsus paradoxus, refusal to recline below 30°, a pulse >120 beats/min, and decreased breath sounds. Physicians' subjective assessments of airway obstruction are often inaccurate. More objective measures of airway obstruction via peak flow (or forced expiratory volume in 1 second) and pulse oximetry before oxygen administration usually are helpful. Pulse oximetry values >90% are less commonly associated with problems although CO(2) retention and a low Pao(2) may be missed. PMID:22794687

  10. Survival in acute and severe low o environment: use of a genetic model system.

    PubMed

    Azad, Priti; Haddad, Gabriel G

    2009-10-01

    Hypoxia whether present during physiologic states (e.g., embryogenesis) or during pathologic states (e.g., obstructive sleep apnea and sickle cell anemia), challenges the vertebrate or invertebrate organism. Clearly, hypoxia can lead to sublethal cell injury or death and consequently organ or systemic injury and failure, depending on severity. We discovered that the adult Drosophila melanogaster is tolerant to a low O(2) environment, withstanding approximately 3-4 hours of total O(2) deprivation or anoxia without showing any evidence of cell injury. This opened major avenues for us since the Drosophila has been used so effectively in so many relevant research areas. We investigated the changes in gene expression in D. melanogaster after severe (1% O(2)) intermittent or constant hypoxia treatment for 2.5 hours. Our microarray analysis has identified multiple gene families that are up- or downregulated in response to acute constant (CH) and intermittent hypoxia (IH). We observed that even for short-term the gene expression response to IH and CH varied not only in the number of genes but also type of gene families. Furthermore, by utilizing powerful Drosophila genetic tools we studied the role of single genes (up- or downregulated in arrays) in survival under either paradigm in adult flies. We observed significant increased adult survival (as compared to controls) of P-element lines for Hsp70 and Hsp23 genes during CH and Mdr49 and l (2)08717 genes during IH. This suggests that the increased transcript levels as observed in array data after either paradigm play an important role under severe hypoxia. Indeed, we found for example that over-expressing Hsp70 in vivo in specific fly organs (such as heart) significantly increased adult survival during CH as compared to controls. These data provide further clues about the mechanisms by which intermittent and constant hypoxia lead to cell injury and morbidity or adaptation and survival. PMID:19845605

  11. Hypoxia-Induced miR-210 Modulates Tissue Response to Acute Peripheral Ischemia

    PubMed Central

    Zaccagnini, Germana; Maimone, Biagina; Di Stefano, Valeria; Fasanaro, Pasquale; Greco, Simona; Perfetti, Alessandra; Capogrossi, Maurizio C.; Gaetano, Carlo

    2014-01-01

    Abstract Aims: Peripheral artery disease is caused by the restriction or occlusion of arteries supplying the leg. Better understanding of the molecular mechanisms underpinning tissue response to ischemia is urgently needed to improve therapeutic options. The aim of this study is to investigate hypoxia-induced miR-210 regulation and its role in a mouse model of hindlimb ischemia. Results: miR-210 expression was induced by femoral artery dissection. To study the role of miR-210, its function was inhibited by the systemic administration of a miR-210 complementary locked nucleic acid (LNA)-oligonucleotide (anti-miR-210). In the ischemic skeletal muscle, anti-miR-210 caused a marked decrease of miR-210 compared with LNA-scramble control, while miR-210 target expression increased accordingly. Histological evaluation of acute tissue damage showed that miR-210 inhibition increased both apoptosis at 1 day and necrosis at 3 days. Capillary density decrease caused by ischemia was significantly more pronounced in anti-miR-210-treated mice; residual limb perfusion decreased accordingly. To investigate the molecular mechanisms underpinning the increased damage triggered by miR-210 blockade, we tested the impact of anti-miR-210 treatment on the transcriptome. Gene expression analysis highlighted the deregulation of mitochondrial function and redox balance. Accordingly, oxidative damage was more severe in the ischemic limb of anti-miR-210-treated mice and miR-210 inhibition increased oxidative metabolism. Further, oxidative-stress resistant p66Shc-null mice displayed decreased tissue damage following ischemia. Innovation: This study identifies miR-210 as a crucial element in the adaptive mechanisms to acute peripheral ischemia. Conclusions: The physiopathological significance of miR-210 is context dependent. In the ischemic skeletal muscle it seems to be cytoprotective, regulating oxidative metabolism and oxidative stress. Antioxid. Redox Signal. 21, 1177–1188. PMID:23931770

  12. Acute Effects of Normobaric Hypoxia on Hand-Temperature Responses During and After Local Cold Stress

    PubMed Central

    Kölegård, Roger; Mekjavic, Igor B.; Eiken, Ola

    2014-01-01

    Abstract Keramidas, Michail E, Roger Kölegård, Igor B. Mekjavic, and Ola Eiken. Acute effects of normobaric hypoxia on hand-temperature responses during and after local cold stress. High Alt Med Biol. 15:183–191, 2014.—The purpose was to investigate acute effects of normobaric hypoxia on hand-temperature responses during and after a cold-water hand immersion test. Fifteen males performed two right-hand immersion tests in 8°C water, during which they were inspiring either room air (Fio2: 0.21; AIR), or a hypoxic gas mixture (Fio2: 0.14; HYPO). The tests were conducted in a counterbalanced order and separated by a 1-hour interval. Throughout the 30-min cold-water immersion (CWI) and the 15-min spontaneous rewarming (RW) phases, finger-skin temperatures were measured continuously with thermocouple probes; infrared thermography was also employed during the RW phase to map all segments of the hand. During the CWI phase, the average skin temperature (Tavg) of the fingers did not differ between the conditions (AIR: 10.2±0.5°C, HYPO: 10.0±0.5°C; p=0.67). However, Tavg was lower in the HYPO than the AIR RW phase (AIR: 24.5±3.4°C; HYPO: 22.0±3.8°C; p=0.002); a response that was alike in all regions of the immersed hand. Accordingly, present findings suggest that acute exposure to normobaric hypoxia does not aggravate the cold-induced drop in hand temperature of normothermic males. Still, hypoxia markedly impairs the rewarming responses of the hand. PMID:24666109

  13. CO2-O2 interactions in extension of tolerance to acute hypoxia

    NASA Technical Reports Server (NTRS)

    Lambertsen, C. J.

    1995-01-01

    Objectives and results of experimental projects a re summarized. The scope of information desired included (1) physiological and performance consequences of exposures to simulated microgravity, in rest and graded physical activity, (2) separate influences of graded degrees of atmospheric hypercapnia and hypoxia, and (3) composite effects of hypoxia and hypercapnia. The research objectives were selected for close relevance to existing quantitative information concerning interactions of hypercapnia and hypoxia on respiratory and brain circulatory control. They include: (1) to determine influences of normoxic immersion on interrelations of pulmonary ventilation, arterial PCO2 and PO2, and brain blood flow, in rest and physical work; (2) to determine influence of normoxic immersion on respiratory reactivity to atmospheric hypercapnia at rest; (3) to determine influence of atmospheric hypoxia on respiratory reactivity to hypercapnia at rest and in work; and (4) to provide physiological baselines of data concerning adaptations in acute exposures to aid in investigation of rates of adaptation or deteriorations in physiological or performance capability during subsequent multi-day exposures. A list of publications related to the present grant period is included along with an appendix describing the Performance Measurement System (human perceptual, cognitive and psychomotor functions).

  14. Laboratory markers predicting severity of acute pancreatitis.

    PubMed

    Staubli, Sebastian Manuel; Oertli, Daniel; Nebiker, Christian Andreas

    2015-01-01

    Acute pancreatitis (AP) is an inflammatory disease of highly variable severity, ranging from mild cases with low mortality to severe cases with high mortality. Numerous biomarkers have been studied as potential early predictors of the severity of this disease so that treatment can be optimally tailored to prevent complications. We aim to present and discuss the most relevant biomarkers for early severity assessment in AP that have been studied to date. We review the current literature on biomarkers that have been used to predict the severity in AP. C-reactive protein (CRP) is still considered to be the gold standard, with a cut-off value of 150 mg/ml 48 h after disease onset. Other markers, including procalcitonin (PCT) and interleukin 6 (IL-6) have been implemented in some hospitals, but are not used on a routine basis. Most other markers, including acute phase proteins (LBP, SAA, PTX3), cytokines (Il-8, TNF-a, MIF), activation peptides of pancreatic proteases (TAP, CAPAP, PLAP), antiproteases (AAT, a2M), adhesion molecules (ICAM-1, selectins, E-cadherin) and leukocyte-derived enzymes (PA2, PMN-E) have shown some promising results but have not been routinely implemented. Furthermore, new and interesting biomarkers (Copeptin, TRX-1, Ang-2, E-2) have shown good results, but more research is needed to determine if they could play a role in the future. Various reasons why new markers for disease severity have not been adopted in daily routine include low accuracy, cumbersome laboratory techniques and high cost. Despite these difficulties, research is still very active in finding new markers to predict the severity of AP.

  15. [Principles of acute management of the severe diving accident].

    PubMed

    Lampl, L; Frey, G; Dietze, T; Bock, K H

    1989-10-01

    The basics of the acute management of severe diving accidents are outlined by means of 25 patients (20 patients presented with decompression sickness, 5 suffered from a barotrauma of the lungs with consecutive air embolism) treated at our facilities. Contrary to widespread notion, disturbed vital functions have to be treated by intensive care measures, prior to the definite recompression therapy. These are: (1) Treatment of generalized or localized tissue hypoxia secondary to bubble-generation; (2) puncture of a (valvular-) pneumothorax after a pulmonary barotrauma; (3) haemodynamic stabilization when cardiac or spinal shock is present; (4) improvement of the rheological situation. When vital functions are unstable or endangered, these patients must not be transported in a monoplace chamber. This type of chamber does not leave any access to the patient in case of a deteriorating status. Since the severe diving accident mostly turns out to be a problem of intensive care medicine in close combination with the recompression therapy, the continuous integration of the recompression protocol with a comprehensive intensive care therapy is considered crucial. PMID:2817326

  16. Severe acute pancreatitis: Clinical course and management.

    PubMed

    Beger, Hans G; Rau, Bettina M

    2007-10-14

    Severe acute pancreatitis (SAP) develops in about 25% of patients with acute pancreatitis (AP). Severity of AP is linked to the presence of systemic organ dysfunctions and/or necrotizing pancreatitis pathomorphologically. Risk factors determining independently the outcome of SAP are early multi-organ failure, infection of necrosis and extended necrosis (>50%). Up to one third of patients with necrotizing pancreatitis develop in the late course infection of necroses. Morbidity of SAP is biphasic, in the first week strongly related to early and persistence of organ or multi-organ dysfunction. Clinical sepsis caused by infected necrosis leading to multi-organ failure syndrome (MOFS) occurs in the later course after the first week. To predict sepsis, MOFS or deaths in the first 48-72 h, the highest predictive accuracy has been objectified for procalcitonin and IL-8; the Sepsis-Related Organ Failure Assessment (SOFA)-score predicts the outcome in the first 48 h, and provides a daily assessment of treatment response with a high positive predictive value. Contrast-enhanced CT provides the highest diagnostic accuracy for necrotizing pancreatitis when performed after the first week of disease. Patients who suffer early organ dysfunctions or at risk of developing a severe disease require early intensive care treatment. Early vigorous intravenous fluid replacement is of foremost importance. The goal is to decrease the hematocrit or restore normal cardiocirculatory functions. Antibiotic prophylaxis has not been shown as an effective preventive treatment. Early enteral feeding is based on a high level of evidence, resulting in a reduction of local and systemic infection. Patients suffering infected necrosis causing clinical sepsis, pancreatic abscess or surgical acute abdomen are candidates for early intervention. Hospital mortality of SAP after interventional or surgical debridement has decreased in high volume centers to below 20%.

  17. Dynamic regulation of metabolic efficiency explains tolerance to acute hypoxia in humans.

    PubMed

    Schiffer, Tomas A; Ekblom, Björn; Lundberg, Jon O; Weitzberg, Eddie; Larsen, Filip J

    2014-10-01

    The maximum power principle dictates that open biological systems tend to self-organize to a level of efficiency that allows maximal power production. Applying this principle to cellular energetics and whole-body physiology would suggest that for every metabolic challenge, an optimal efficiency exists that maximizes power production. On exposure to hypoxia, it would be favorable if metabolic efficiency would rapidly adjust so as to better preserve work performance. We tested this idea in humans by measuring metabolic efficiency and exercise tolerance under normoxic (Fio2=20.9%) and hypoxic (Fio2=16%) conditions, where Fio2 is fraction of inhaled oxygen. The results were compared with respirometric analyses of skeletal muscle mitochondria from the same individuals. We found that among healthy trained subjects (n=14) with a wide range of metabolic efficiency (ME), those with a high ME during normoxic exercise were able to better maintain exercise capacity (Wmax) in hypoxia. On hypoxic exposure, these subjects acutely decreased their efficiency from 19.2 to 17.4%, thereby likely shifting it closer to a degree of efficiency where maximal power production is achieved. In addition, mitochondria from these subjects had a lower intrinsic respiration compared to subjects that showed a large drop in Wmax in hypoxia An acute shift in efficiency was also demonstrated in isolated mitochondria exposed to physiological levels of hypoxia as P/O ratio increased from 0.9 to 1.3 with hypoxic exposure. These findings suggest the existence of a physiological adaptive response by which metabolic efficiency is dynamically optimized to maximize power production.

  18. [Concept of SIRS and severe acute pancreatitis].

    PubMed

    Hirota, Masahiko; Sugita, Hiroki; Maeda, Keisuke; Ichibara, Atsushi; Ogawa, Michio

    2004-11-01

    Acute pancreatitis is a potentially fatal disease, the severity of which ranges from a mild edematous form to a severe necrotizing form. Most patients develop systemic inflammatory response syndrome (SIRS), which is induced by proinflammatory cytokines. The cytokine production can be induced by activation of Toll-like receptor. The breakdown products of the pancreatic and peripancreatic tissues by proteases might be the agonists. Cytokines are supposed to be produced as a biological defense system. However, cytokines may often evoke organ failure and/or immunosuppressive state, if they would be produced excessively. To express this complicated pathologic condition, Ogawa proposed a concept of LISIS(local inflammation-induced systemic immunosuppression syndrome). We have to pay attention to such aspects in the management of this disease. PMID:15552899

  19. Slow channel inhibitor effects on brain function: tolerance to severe hypoxia in the rat.

    PubMed Central

    Cartheuser, C. F.

    1988-01-01

    1. The protective effects of ten slow channel inhibitor drugs against severe progressive hypoxia were investigated in rats breathing spontaneously during light anaesthesia. Respiration, heart rate, electrocorticogram (ECoG) and/or electroencephalogram (EEG) were recorded. 2. Tolerance times were monitored from hypoxia onset until cessation of respiration, ECoG, EEG synchronization, and 'background-EEG'. Drugs were administered i.v. 5 min before the onset of hypoxia. 3. Verapamil, gallopamil, and nimodipine resulted in a significant increase of tolerance times; fendiline and bepridil showed a small increase (not significant); bencyclan and prenylamine were ineffective; cinnarizine and diltiazem slightly reduced tolerance times as did flunarizine at low doses. 4. At protective doses, verapamil, gallopamil, and nimodipine significantly raised the respiration rate but had little or no cardiac depressor effects. Bencyclan showed ventilatory drive but cardiocirculatory depression. A clear-cut ventilatory drive did not occur with the other ineffective slow channel inhibitors. 5. It is suggested that the protective actions observed were not due to slow channel inhibition per se, nor to spasmolytic potency or increased cerebral blood flow. Ventilatory drive associated with other cardiopulmonary actions which secondarily raise the brain oxygen supply are likely to be responsible for this effect. PMID:3264735

  20. Exhaled nitric oxide decreases upon acute exposure to high-altitude hypoxia.

    PubMed

    Brown, Daniel E; Beall, Cynthia M; Strohl, Kingman P; Mills, Phoebe S

    2006-01-01

    Nitric oxide (NO) is a vasodilator that plays a role in blood flow and oxygen delivery. Acute hypoxia down regulates NO synthesis, a response that may exacerbate hypoxic stress by decreasing blood flow. This study was designed to test the hypotheses that pulmonary NO decreases upon acute exposure to high-altitude hypoxia and that relatively low levels of NO at altitude are associated with greater stress as reflected in more symptoms of acute mountain sickness (AMS). A sample of 47 healthy, adult, nonsmoking, sea-level residents provided measurements at sea level, at 2,800 m, and at 0-, 2-, and 3-h exposure times at 4,200 m altitude on Mauna Kea, Hawaii. Measurements were made of exhaled NO, oxygen saturation of hemoglobin, heart rate, and reported symptoms of AMS. The partial pressure of NO concentration in exhaled breath decreased significantly from a sea level mean of 4.2 nmHg to 3.8 nmHg at 2,800 m and 3.4 nmHg at 4,200 m. NO concentration in exhaled breath did not change significantly over a 3-h exposure at 4,200 m and recovered to pre-exposure baseline upon return to sea level. There was no significant association between the level of NO exhaled and the number of self-reported symptoms of AMS during this brief exposure. PMID:16493632

  1. Cerebral perfusion pressure and risk of brain hypoxia in severe head injury: a prospective observational study

    PubMed Central

    Marín-Caballos, Antonio J; Murillo-Cabezas, Francisco; Cayuela-Domínguez, Aurelio; Domínguez-Roldán, Jose M; Rincón-Ferrari, M Dolores; Valencia-Anguita, Julio; Flores-Cordero, Juan M; Muñoz-Sánchez, M Angeles

    2005-01-01

    Introduction Higher and lower cerebral perfusion pressure (CPP) thresholds have been proposed to improve brain tissue oxygen pressure (PtiO2) and outcome. We study the distribution of hypoxic PtiO2 samples at different CPP thresholds, using prospective multimodality monitoring in patients with severe traumatic brain injury. Methods This is a prospective observational study of 22 severely head injured patients admitted to a neurosurgical critical care unit from whom multimodality data was collected during standard management directed at improving intracranial pressure, CPP and PtiO2. Local PtiO2 was continuously measured in uninjured areas and snapshot samples were collected hourly and analyzed in relation to simultaneous CPP. Other variables that influence tissue oxygen availability, mainly arterial oxygen saturation, end tidal carbon dioxide, body temperature and effective hemoglobin, were also monitored to keep them stable in order to avoid non-ischemic hypoxia. Results Our main results indicate that half of PtiO2 samples were at risk of hypoxia (defined by a PtiO2 equal to or less than 15 mmHg) when CPP was below 60 mmHg, and that this percentage decreased to 25% and 10% when CPP was between 60 and 70 mmHg and above 70 mmHg, respectively (p < 0.01). Conclusion Our study indicates that the risk of brain tissue hypoxia in severely head injured patients could be really high when CPP is below the normally recommended threshold of 60 mmHg, is still elevated when CPP is slightly over it, but decreases at CPP values above it. PMID:16356218

  2. [The influence of acute hypoxia on motility of rats in the open field test under the conditions of an altered photoperiod].

    PubMed

    Sopova, I Iu

    2014-01-01

    The influence of acute hypoxia on the motility of rats under the conditions of an altered photoperiod in the open field test was studied. Thus, keeping the animals in constant darkness after the modeling of acute hypoxia leads to the depression of locomotive and exploratory components of the behavior. At the same time the animals that were kept under the conditions of constant light show a change in the correlation between the components of motility after the action of hypoxia.

  3. Changes in phosphorylation of connexin43 in rats during acute myocardial hypoxia and effects of antiarrhythmic peptide on the phosphorylation.

    PubMed

    Wang, Rong; Zhang, Cuntai; Ruan, Yanfei; Liu, Nian; Wang, Lin

    2007-06-01

    In order to confirm the hypothesis that during acute hypoxia, the antiarrhythmic peptide (AAP10) could improve conductance by changing the phosphorylation state of connexin43 (Cx43), isolated perfused rat hearts were randomly divided into three groups: control, hypoxia and AAP10 (n=9 in each group). The change in Cx43 phosphorylation was tested by Western-blot; the distribution of Cx43 was observed by confocal immunofluorescence microscopy. Western-blot analysis revealed that the expression of total Cx43 protein was significantly decreased during acute hypoxia, while nonphosphorylated Cx43 (NP-Cx43) was unchanged. AAP10 could increase the expression of total Cx43 protein, but had no effects on the NP-Cx43 protein. Immunofluorescence study showed that during acute hypoxia, both total Cx43 and NP-Cx43 proteins were greatly decreased, while AAP10 only increased the expression of total Cx43 protein, but had no effect of the NP-Cx43 protein expression. These findings suggested that the decrease of intercellular communication may be associated with the reduction of phosphorylated Cx43 (p-Cx43) and translocation of NP-Cx43 from the surface of gap junction into intracellular pools during acute hypoxia. AAP10 can improve intercellular communication by enhancing phosphorylation of Cx43.

  4. The antioxidative effect of a novel free radical scavenger 4'-hydroxyl-2-substituted phenylnitronyl nitroxide in acute high-altitude hypoxia mice.

    PubMed

    Fan, Peng-Cheng; Ma, Hui-Ping; Jing, Lin-lin; Li, Lin; Jia, Zheng-Ping

    2013-01-01

    Acute mountain sickness is caused by sub-acute hypoxia in healthy individuals going rapidly to altitude. Both tissue hypoxia in vitro and whole-body hypoxia in vivo have been found to promote the release of reactive oxygen species. Nitronyl nitroxide can trap free radicals such as ·NO or ·OH, and may therefore be efficient protective agents. This study assessed the ability of nitronyl nitroxide to against acute mountain sickness as a free radical scavenger in acute high-altitude hypoxia mice model. Normobaric hypoxia and hypobaric hypoxia model were used to estimate the protect effects of nitronyl nitroxide against acute mountain sickness. Low pressure oxygen compartment system was used to stimulate high-altitude hypobaric hypoxia environment. Mice in nitronyl nitroxide groups survived longer than acetazolamide group in normobaric hypoxia test. Hydrogen peroxide (H2O2) and malondialdehyde (MDA) increased in both cerebrum and myocardium in vehicle group. The results indicated more radicals were generated during high-altitude hypobaric hypoxia environment. In therapeutic groups H2O2 and MDA were significantly reduced while the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were similar to normal group. These results demonstrated that nitronyl nitroxide was an efficient tissue radical scavenger and a potential protective agent for acute mountain sickness.

  5. Phase I/II study of the hypoxia-activated prodrug PR104 in refractory/relapsed acute myeloid leukemia and acute lymphoblastic leukemia

    PubMed Central

    Konopleva, Marina; Thall, Peter F.; Yi, Cecilia Arana; Borthakur, Gautam; Coveler, Andrew; Bueso-Ramos, Carlos; Benito, Juliana; Konoplev, Sergej; Gu, Yongchuan; Ravandi, Farhad; Jabbour, Elias; Faderl, Stefan; Thomas, Deborah; Cortes, Jorge; Kadia, Tapan; Kornblau, Steven; Daver, Naval; Pemmaraju, Naveen; Nguyen, Hoang Q.; Feliu, Jennie; Lu, Hongbo; Wei, Caimiao; Wilson, William R.; Melink, Teresa J.; Gutheil, John C.; Andreeff, Michael; Estey, Elihu H.; Kantarjian, Hagop

    2015-01-01

    We previously demonstrated vast expansion of hypoxic areas in the leukemic microenvironment and provided a rationale for using hypoxia-activated prodrugs. PR104 is a phosphate ester that is rapidly hydrolyzed in vivo to the corresponding alcohol PR-104A and further reduced to the amine and hydroxyl-amine nitrogen mustards that induce DNA cross-linking in hypoxic cells under low oxygen concentrations. In this phase I/II study, patients with relapsed/refractory acute myeloid leukemia (n=40) after 1 or 2 prior treatments or acute lymphoblastic leukemia (n=10) after any number of prior treatments received PR104; dose ranged from 1.1 to 4 g/m2. The most common treatment-related grade 3/4 adverse events were myelosuppression (anemia 62%, neutropenia 50%, thrombocytopenia 46%), febrile neutropenia (40%), infection (24%), and enterocolitis (14%). Ten of 31 patients with acute myeloid leukemia (32%) and 2 of 10 patients with acute lymphoblastic leukemia (20%) who received 3 g/m2 or 4 g/m2 had a response (complete response, n=1; complete response without platelet recovery, n=5; morphological leukemia-free state, n=6). The extent of hypoxia was evaluated by the hypoxia tracer pimonidazole administered prior to a bone marrow biopsy and by immunohistochemical assessments of hypoxia-inducible factor alpha and carbonic anhydrase IX. A high fraction of leukemic cells expressed these markers, and PR104 administration resulted in measurable decrease of the proportions of hypoxic cells. These findings indicate that hypoxia is a prevalent feature of the leukemic microenvironment and that targeting hypoxia with hypoxia-activated prodrugs warrants further evaluation in acute leukemia. The trial is registered at clinicaltrials.gov identifier: 01037556. PMID:25682597

  6. Acute hypoxia increases the cerebral metabolic rate – a magnetic resonance imaging study

    PubMed Central

    Lindberg, Ulrich; Aachmann-Andersen, Niels Jacob; Lisbjerg, Kristian; Christensen, Søren Just; Law, Ian; Rasmussen, Peter; Olsen, Niels V; Larsson, Henrik BW

    2015-01-01

    The aim of the present study was to examine changes in cerebral metabolism by magnetic resonance imaging of healthy subjects during inhalation of 10% O2 hypoxic air. Hypoxic exposure elevates cerebral perfusion, but its effect on energy metabolism has been less investigated. Magnetic resonance imaging techniques were used to measure global cerebral blood flow and the venous oxygen saturation in the sagittal sinus. Global cerebral metabolic rate of oxygen was quantified from cerebral blood flow and arteriovenous oxygen saturation difference. Concentrations of lactate, glutamate, N-acetylaspartate, creatine and phosphocreatine were measured in the visual cortex by magnetic resonance spectroscopy. Twenty-three young healthy males were scanned for 60 min during normoxia, followed by 40 min of breathing hypoxic air. Inhalation of hypoxic air resulted in an increase in cerebral blood flow of 15.5% (p = 0.058), and an increase in cerebral metabolic rate of oxygen of 8.5% (p = 0.035). Cerebral lactate concentration increased by 180.3% (p<10-6), glutamate increased by 4.7% (p<10-4) and creatine and phosphocreatine decreased by 15.2% (p<10-3). The N-acetylaspartate concentration was unchanged (p = 0.36). In conclusion, acute hypoxia in healthy subjects increased perfusion and metabolic rate, which could represent an increase in neuronal activity. We conclude that marked changes in brain homeostasis occur in the healthy human brain during exposure to acute hypoxia. PMID:26661163

  7. [Acute altitude sickness and ventilatory function in subjects intermittently exposed to hypobaric hypoxia].

    PubMed

    Saldías, F; Beroíza, T; Lisboa, C

    1995-01-01

    Aiming to assess the magnitude of acute mountain sickness symptoms and ventilatory function in subjects intermittently exposed to hypobaric hypoxia, we studied 48 healthy men aged 32.6 +/- 8.2 years old who worked in a gold mine at a altitude of 4600 m, using a schedule of 8-12 days of work at the mine followed by 4 days of rest at the sea level. Studies were performed at the sea level (A), during the first two days of ascension (B) and after three or four days of stay at 4600 m (C). Mountain sickness symptoms were evaluated with a questionnaire devised in the 1991 International Hypoxia Symposium and respiratory function was assessed with a Collins Eagle II respirometer, following American Thoracic Society recommendations. Subjects reported mild to moderate symptoms during the first 24 hours of ascending (mean score of 6.4 +/- 3.1 for a maximum of 15). Forced vital capacity fell significantly in period B and returned to normal in period C and forced expiratory volume in 1 s did not change in any period. However, maximal expiratory flow and maximal midexpiratory flow rate significantly increased and remained elevated during the four days stay at the mine. No correlation was found between acute mountain sickness symptoms and changes in ventilatory function.

  8. Severe hypoxia affects exercise performance independently of afferent feedback and peripheral fatigue.

    PubMed

    Millet, Guillaume Y; Muthalib, Makii; Jubeau, Marc; Laursen, Paul B; Nosaka, Kazunori

    2012-04-01

    To test the hypothesis that hypoxia centrally affects performance independently of afferent feedback and peripheral fatigue, we conducted two experiments under complete vascular occlusion of the exercising muscle under different systemic O(2) environmental conditions. In experiment 1, 12 subjects performed repeated submaximal isometric contractions of the elbow flexor to exhaustion (RCTE) with inspired O(2) fraction fixed at 9% (severe hypoxia, SevHyp), 14% (moderate hypoxia, ModHyp), 21% (normoxia, Norm), or 30% (hyperoxia, Hyper). The number of contractions (performance), muscle (biceps brachii), and prefrontal near-infrared spectroscopy (NIRS) parameters and high-frequency paired-pulse (PS100) evoked responses to electrical muscle stimulation were monitored. In experiment 2, 10 subjects performed another RCTE in SevHyp and Norm conditions in which the number of contractions, biceps brachii electromyography responses to electrical nerve stimulation (M wave), and transcranial magnetic stimulation responses (motor-evoked potentials, MEP, and cortical silent period, CSP) were recorded. Performance during RCTE was significantly reduced by 10-15% in SevHyp (arterial O(2) saturation, SpO(2) = ∼75%) compared with ModHyp (SpO(2) = ∼90%) or Norm/Hyper (SpO(2) > 97%). Performance reduction in SevHyp occurred despite similar 1) metabolic (muscle NIRS parameters) and functional (changes in PS100 and M wave) muscle states and 2) MEP and CSP responses, suggesting comparable corticospinal excitability and spinal and cortical inhibition between SevHyp and Norm. It is concluded that, in SevHyp, performance and central drive can be altered independently of afferent feedback and peripheral fatigue. It is concluded that submaximal performance in SevHyp is partly reduced by a mechanism related directly to brain oxygenation. PMID:22323647

  9. Medical emergencies: pulmonary embolism and acute severe asthma.

    PubMed

    Somasundaram, K; Ball, J

    2013-01-01

    In this, the second of two articles covering specific medical emergencies, we discuss the definitions, epidemiology, pathophysiology, acute and chronic management of pulmonary embolus and acute severe asthma. PMID:23210560

  10. Pterostilbene as treatment for severe acute pancreatitis.

    PubMed

    Lin, Y J; Ding, Y; Wu, J; Ning, B T

    2016-01-01

    Acute pancreatitis (AP) has a fast onset and progression, which lead to an unfavorable prognosis. Therefore, the development of novel drugs for its treatment is critical. As a homologous derivative of resveratrol, pterostilbene exerts a variety of effects including anti-inflammatory, antioxidant, and antitumor effects. This study investigated the potential of pterostilbene for treatment of severe AP (SAP) and related mechanisms. Effects of pterostilbene were evaluated in a Wistar rat model of AP. Serum levels of amylase (AMY), creatinine (Cr), and alanine aminotransferase (ALT) were quantified. Furthermore, serum levels of tumor necrosis factor (TNF)-a and interleukin (IL)-1b were quantified using enzyme-linked immunosorbent assay. Nuclear factor (NF)-kB expression in pancreatic tissues was quantified by real-time PCR and western blotting. The production of reactive oxygen species (ROS) was determined using a spectrometer, while superoxide dismutase (SOD) activity was assayed. In the AP rat model, the expression of inflammatory markers TNF-a and IL-1b, expression of NF-kB, and serum indices (AMY, Cr, and ALT) increased compared to the corresponding levels in the control group (P < 0.05). Pterostilbene reduced serum levels of TNF-a and IL-1b; decreased NF-kB gene expression, serum indices, and ROS generation; and increased SOD activity in a dose-dependent manner. In conclusion, pterostilbene can alleviate SAP-induced tissue damage by decreasing the inflammatory response and by promoting antioxidation leading to the protection of pancreatic tissues. PMID:27525946

  11. The effect of acute and chronic hypoxia on thoracic gas volume in anaesthetized rats.

    PubMed Central

    Barer, G R; Herget, J; Sloan, P J; Suggett, A J

    1978-01-01

    1. Thoracic gas volume at end expiration (functional residual capacity, FRC) was measured in chronically and acutely hypoxic anaesthetized rats by a plethysmograph method. 2. FRC, measured during air breathing, was 34-62% larger in rats which had been kept in an environmental chamber in 8, 10 or 12% O2 for 3 weeks than in littermate controls. FRC returned to normal after the rats had returned to air for 9 days. There was no constant difference in the pattern of breathing between control and chronically hypoxic rats. 3. Pressure-volume curves measured post mortem showed no difference in the volume of the lung at 25 cm H2O pressure or in the compliance of the lung between chronically hypoxic and control rats. Thus there was no gross mechanical change in the lung to account for the increase in FRC. 4. Acute hypoxia caused by breathing 12% O2 increased FRC in control but not in chronically hypoxic rats. The increase in FRC in control rats was abolished by combined blockade of the vagus nerves and carotid bodies (with procaine) but not by vagal blockade alone. 5. The combined vagal and carotid body blockade reduced FRC significantly in rats which had been in 10% O2 for 3 days but not in those which had been in 10% O2 for 21 days. 6. Lung area measured from radiographs was not reduced by a muscle relaxant in chronically hypoxic rats. Electromyograms from anterior intercostal muscles and the diaphragm showed no electrical activity in expiration in chronically hypoxic rats which might indicate an active muscular basis for their increased FRC. However when FRC was raised by acute hypoxia in control animals there was also no increase in electrical activity in expiration which could have explained their increase in lung volume. 7. We concluded that the increase in FRC during acute hypoxia in control rats was probably due to a reflex from the carotid body. The increase in FRC in chronically hypoxic rats, which was present while they breathed air, may have had an active

  12. Effects of copper, hypoxia and acute temperature shifts on mitochondrial oxidation in rainbow trout (Oncorhynchus mykiss) acclimated to warm temperature.

    PubMed

    Sappal, Ravinder; Fast, Mark; Stevens, Don; Kibenge, Fred; Siah, Ahmed; Kamunde, Collins

    2015-12-01

    Temperature fluctuations, hypoxia and metals pollution frequently occur simultaneously or sequentially in aquatic systems and their interactions may confound interpretation of their biological impacts. With a focus on energy homeostasis, the present study examined how warm acclimation influences the responses and interactions of acute temperature shift, hypoxia and copper (Cu) exposure in fish. Rainbow trout (Oncorhynchus mykiss) were acclimated to cold (11°C; control) and warm (20°C) temperature for 3 weeks followed by exposure to environmentally realistic levels of Cu and hypoxia for 24h. Subsequently, mitochondrial electron transport system (ETS) respiratory activity supported by complexes I-IV (CI-IV), plasma metabolites and condition indices were measured. Warm acclimation reduced fish condition, induced aerobic metabolism and altered the responses of fish to acute temperature shift, hypoxia and Cu. Whereas warm acclimation decelerated the ETS and increased the sensitivity of maximal oxidation rates of the proximal (CI and II) complexes to acute temperature shift, it reduced the thermal sensitivity of state 4 (proton leak). Effects of Cu with and without hypoxia were variable depending on the acclimation status and functional index. Notably, Cu stimulated respiratory activity in the proximal ETS segments, while hypoxia was mostly inhibitory and minimized the stimulatory effect of Cu. The effects of Cu and hypoxia were modified by temperature and showed reciprocal antagonistic interaction on the ETS and plasma metabolites, with modest additive actions limited to CII and IV state 4. Overall, our results indicate that warm acclimation came at a cost of reduced ETS efficiency and increased sensitivity to added stressors. PMID:26513222

  13. Effects of copper, hypoxia and acute temperature shifts on mitochondrial oxidation in rainbow trout (Oncorhynchus mykiss) acclimated to warm temperature.

    PubMed

    Sappal, Ravinder; Fast, Mark; Stevens, Don; Kibenge, Fred; Siah, Ahmed; Kamunde, Collins

    2015-12-01

    Temperature fluctuations, hypoxia and metals pollution frequently occur simultaneously or sequentially in aquatic systems and their interactions may confound interpretation of their biological impacts. With a focus on energy homeostasis, the present study examined how warm acclimation influences the responses and interactions of acute temperature shift, hypoxia and copper (Cu) exposure in fish. Rainbow trout (Oncorhynchus mykiss) were acclimated to cold (11°C; control) and warm (20°C) temperature for 3 weeks followed by exposure to environmentally realistic levels of Cu and hypoxia for 24h. Subsequently, mitochondrial electron transport system (ETS) respiratory activity supported by complexes I-IV (CI-IV), plasma metabolites and condition indices were measured. Warm acclimation reduced fish condition, induced aerobic metabolism and altered the responses of fish to acute temperature shift, hypoxia and Cu. Whereas warm acclimation decelerated the ETS and increased the sensitivity of maximal oxidation rates of the proximal (CI and II) complexes to acute temperature shift, it reduced the thermal sensitivity of state 4 (proton leak). Effects of Cu with and without hypoxia were variable depending on the acclimation status and functional index. Notably, Cu stimulated respiratory activity in the proximal ETS segments, while hypoxia was mostly inhibitory and minimized the stimulatory effect of Cu. The effects of Cu and hypoxia were modified by temperature and showed reciprocal antagonistic interaction on the ETS and plasma metabolites, with modest additive actions limited to CII and IV state 4. Overall, our results indicate that warm acclimation came at a cost of reduced ETS efficiency and increased sensitivity to added stressors.

  14. Theoretical simulation of tumour oxygenation and results from acute and chronic hypoxia

    NASA Astrophysics Data System (ADS)

    Dasu, Alexandru; Toma-Dasu, Iuliana; Karlsson, Mikael

    2003-09-01

    The tumour microenvironment is considered to be responsible for the outcome of cancer treatment and therefore it is extremely important to characterize and quantify it. Unfortunately, most of the experimental techniques available now are invasive and generally it is not known how this influences the results. Non-invasive methods on the other hand have a geometrical resolution that is not always suited for the modelling of the tumour response. Theoretical simulation of the microenvironment may be an alternative method that can provide quantitative data for accurately describing tumour tissues. This paper presents a computerized model that allows the simulation of the tumour oxygenation. The model simulates numerically the fundamental physical processes of oxygen diffusion and consumption in a two-dimensional geometry in order to study the influence of the different parameters describing the tissue geometry. The paper also presents a novel method to simulate the effects of diffusion-limited (chronic) hypoxia and perfusion-limited (acute) hypoxia. The results show that all the parameters describing tissue vasculature are important for describing tissue oxygenation. Assuming that vascular structure is described by a distribution of inter-vessel distances, both the average and the width of the distribution are needed in order to fully characterize the tissue oxygenation. Incomplete data, such as distributions measured in a non-representative region of the tissue, may not give relevant tissue oxygenation. Theoretical modelling of tumour oxygenation also allows the separation between acutely and chronically hypoxic cells, a distinction that cannot always be seen with other methods. It was observed that the fraction of acutely hypoxic cells depends not only on the fraction of collapsed blood vessels at any particular moment, but also on the distribution of vessels in space as well. All these suggest that theoretical modelling of tissue oxygenation starting from the basic

  15. [The role of adenosine Al receptors and mitochondrial K+ATP channels in the mechanism of increasing the resistance to acute hypoxia in the combined effects of hypoxia and hypercapnia].

    PubMed

    Tregub, P P; Kulikov, V P; Stepanova, L A; Zabrodina, A S; Nagibaeva, M E

    2014-01-01

    We studied the role of the role of mitoK+ATp channels and Al-adenosine receptor in the mechanism of increasing the resistance to acute hypoxia after hypoxic, hypercapnic and hypercapnic-hypoxic preconditioning. It is shown that mitochondrial ATP-sensitive potassium channels and Al-adenosine receptors, an important mechanism of preconditioning have a high value to increase the resistance to acute hypoxia/ischemia in the combined effect of hypoxia and hypercapnia. However, with regard to the adenosine receptor, this mechanism is realized without the participation hypercapnic component, which apparently starts neuroprotection without activation of the adenosine Al receptors. PMID:25980226

  16. Nitric oxide synthase and NADPH-diaphorase after acute hypobaric hypoxia in the rat caudate putamen.

    PubMed

    Encinas, Juan Manuel; Fernández, Ana Patricia; Salas, Eduardo; Castro-Blanco, Susana; Muñoz, Priscila; Rodrigo, José; Serrano, Julia

    2004-03-01

    Changes in the production system of nitric oxide (NO), a multifunctional biological messenger known to participate in blood-flow regulation, neuromodulation, and neuroprotection or neurotoxicity, were investigated in the caudate putamen of adult rats submitted to hypobaric hypoxia. Employing immunohistochemistry, Western blotting, enzymatic assay, and NADPH-diaphorase staining, we demonstrate that neuronal nitric oxide synthase (nNOS) expression and constitutive nitric oxide synthase (cNOS) activity were transiently activated by 7 h of exposure to a simulated altitude of 8325 m (27,000 ft). In addition, endothelial nitric oxide synthase (eNOS) immunoreactivity and blood vessel NADPH-diaphorase staining peaked immediately after the hypoxic stimulus, whereas inducible nitric oxide synthase (iNOS) expression and activity remained unaltered. Nitrotyrosine formation, a marker of protein nitration, was evaluated by immunohistochemistry and Western blotting, and was found to increase parallel to nitric oxide synthesis. We conclude that the nitric oxide system undergoes significant transient alterations in the caudate putamen of adult rats submitted to acute hypobaric hypoxia.

  17. Down regulation of Kv3.4 channels by chronic hypoxia increases acute oxygen sensitivity in rabbit carotid body

    PubMed Central

    Kääb, Stefan; Miguel-Velado, Eduardo; López-López, José Ramón; Pérez-García, M Teresa

    2005-01-01

    The carotid body (CB) chemoreceptors participate in the ventilatory responses to acute and chronic hypoxia (CH). Arterial hypoxaemia increases breathing within seconds, and CB chemoreceptors are the principal contributors to this reflex hyperventilatory response. Acute hypoxia induces depolarization of CB chemoreceptors by inhibiting certain K+ channels, but the role of these channels in CH, as in high-altitude acclimatization, is less known. Here we explored the effects of prolonged (24–48 h) hypoxic exposure of rabbit CB chemoreceptor cells in primary cultures on the voltage-dependent K+ currents and on their response to acute hypoxia. We found that CH induces a decrease in the amplitude of outward K+ currents due to a reduction in a fast-inactivating BDS- and highly TEA-sensitive component of the current. In spite of this effect, acute hypoxic inhibition of K+ currents is increased in CH cultures, as well as hypoxia-induced depolarization. These data suggest that downregulation of this component (that does not contribute to the oxygen-sensitive K+ current (IKO2)) participates in the hypoxic sensitization. Pharmacological, immunocytochemical and quantitative PCR (qPCR) experiments demonstrate that CH-induced decrease in outward K+ currents is due to a downregulation of the expression of Kv3.4 channels. Taken together, our results suggest that CH sensitization in rabbit CB could be achieved by an increase in the relative contribution of IKO2 to the outward K+ current as a consequence of the decreased expression of the oxygen-insensitive component of the current. We conclude that acute and chronic hypoxia can exert their effects acting on different molecular targets. PMID:15890707

  18. Clinical value of severity markers in acute pancreatitis.

    PubMed

    Lempinen, M; Puolakkainen, P; Kemppainen, E

    2005-01-01

    Acute pancreatitis is a common digestive disease of which the severity may vary from mild, edematous to severe, necrotizing disease. An improved outcome in the severe form of the disease is based on early identification of disease severity and subsequent focused management of these high-risk patients. However, the ability of clinicians to predict, upon presentation, which patient will have mild or severe acute pancreatitis is not accurate. Prospective systems using clinical criteria have been used to determine severity in patients with acute pancreatitis, such as the Ranson's prognostic signs, Glasgow score, and the acute physiology and chronic health evaluation II score (APACHE II). Their application in clinical practise has been limited by the time delay of at least 48 h to judge all parameters in the former two and by being cumbersome and time-consuming in the latter. Contrast-enhanced computed tomography is presently the most accurate non-invasive single method to evaluate the severity of acute pancreatitis. It cannot, however, be performed to all patients with acute pancreatitis. Therefore, considerable interest has grown in the development of reliable biochemical markers that reflect the severity of acute pancreatitis. In this article we critically appraise current and new severity markers of acute pancreatitis in their ability to distinguish between mild and severe disease and their clinical utility.

  19. Cardiopulmonary responses to acute hypoxia, head-down tilt and fluid loading in anesthetized dogs

    NASA Technical Reports Server (NTRS)

    Loeppky, J. A.; Scotto, P.; Riedel, C.; Avasthi, P.; Koshukosky, V.; Chick, T. W.

    1991-01-01

    Cardiopulmonary responses to acute hypoxia (HY), fluid loading by saline infusion (FL), and head-down tilt (HD) of mechanically ventilated anesthetized dogs were investigated by measuring thermodynamics and pulmonary gas exchange. It was found that HD decreased the total respiratory compliance both during HY and normoxia (NO) and that the reduction in compliance by FL was twice as large as by HD. Superimposing HD on HY doubled the increase in vascular resistance due to HY alone. In the systemic circulation, HD lowered the resistance to below NO levels. There was a significant positive correlation between the changes in blood volume and in pulmonary artery pressure for experimental transitions, suggesting that a shift in blood volume from systemic to pulmonary circulations and changes in the total blood volume may contribute substantially to these apparent changes in resistance.

  20. Potential role of the glycolytic oscillator in acute hypoxia in tumors

    NASA Astrophysics Data System (ADS)

    Che Fru, Leonard; Adamson, Erin B.; Campos, David D.; Fain, Sean B.; Jacques, Steven L.; van der Kogel, Albert J.; Nickel, Kwang P.; Song, Chihwa; Kimple, Randall J.; Kissick, Michael W.

    2015-12-01

    Tumor acute hypoxia has a dynamic component that is also, at least partially, coherent. Using blood oxygen level dependent magnetic resonance imaging, we observed coherent oscillations in hemoglobin saturation dynamics in cell line xenograft models of head and neck squamous cell carcinoma. We posit a well-established biochemical nonlinear oscillatory mechanism called the glycolytic oscillator as a potential cause of the coherent oscillations in tumors. These data suggest that metabolic changes within individual tumor cells may affect the local tumor microenvironment including oxygen availability and therefore radiosensitivity. These individual cells can synchronize the oscillations in patches of similar intermediate glucose levels. These alterations have potentially important implications for radiation therapy and are a potential target for optimizing the cancer response to radiation.

  1. THE PANC 3 SCORE PREDICTING SEVERITY OF ACUTE PANCREATITIS

    PubMed Central

    BEDUSCHI, Murilo Gamba; MELLO, André Luiz Parizi; VON-MÜHLEN, Bruno; FRANZON, Orli

    2016-01-01

    Background : About 20% of cases of acute pancreatitis progress to a severe form, leading to high mortality rates. Several studies suggested methods to identify patients that will progress more severely. However, most studies present problems when used on daily practice. Objective : To assess the efficacy of the PANC 3 score to predict acute pancreatitis severity and its relation to clinical outcome. Methods : Acute pancreatitis patients were assessed as to sex, age, body mass index (BMI), etiology of pancreatitis, intensive care need, length of stay, length of stay in intensive care unit and mortality. The PANC 3 score was determined within the first 24 hours after diagnosis and compared to acute pancreatitis grade of the Revised Atlanta classification. Results : Out of 64 patients diagnosed with acute pancreatitis, 58 met the inclusion criteria. The PANC 3 score was positive in five cases (8.6%), pancreatitis progressed to a severe form in 10 cases (17.2%) and five patients (8.6%) died. Patients with a positive score and severe pancreatitis required intensive care more often, and stayed for a longer period in intensive care units. The PANC 3 score showed sensitivity of 50%, specificity of 100%, accuracy of 91.4%, positive predictive value of 100% and negative predictive value of 90.6% in prediction of severe acute pancreatitis. Conclusion : The PANC 3 score is useful to assess acute pancreatitis because it is easy and quick to use, has high specificity, high accuracy and high predictive value in prediction of severe acute pancreatitis. PMID:27120730

  2. Antibiotics as part of the management of severe acute malnutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Severe acute malnutrition contributes to 1 million deaths among children annually. Adding routine antibiotic agents to nutritional therapy may increase recovery rates and decrease mortality among children with severe acute malnutrition treated in the community. In this randomized, double-blind, plac...

  3. Different cyclical intermittent hypoxia severities have different effects on hippocampal microvasculature.

    PubMed

    Lim, Diane C; Brady, Daniel C; Soans, Rajath; Kim, Emily Y; Valverde, Laise; Keenan, Brendan T; Guo, Xiaofeng; Kim, Woo Young; Park, Min Jeong; Galante, Raymond; Shackleford, James A; Pack, Allan I

    2016-07-01

    Recent studies have shown an association between obstructive sleep apnea (OSA) and cognitive impairment. This study was done to investigate whether varied levels of cyclical intermittent hypoxia (CIH) differentially affect the microvasculature in the hippocampus, operating as a mechanistic link between OSA and cognitive impairment. We exposed C57BL/6 mice to sham [continuous air, arterial O2 saturation (SaO2 ) 97%], severe CIH to inspired O2 fraction (FiO2 ) = 0.10 (CIH10; SaO2 nadir of 61%), or very severe CIH to FiO2 = 0.05 (CIH5; SaO2 nadir of 37%) for 12 h/day for 2 wk. We quantified capillary length using neurostereology techniques in the dorsal hippocampus and utilized quantitative PCR methods to measure changes in sets of genes related to angiogenesis and to metabolism. Next, we employed immunohistochemistry semiquantification algorithms to quantitate GLUT1 protein on endothelial cells within hippocampal capillaries. Capillary length differed among CIH severity groups (P = 0.013) and demonstrated a linear relationship with CIH severity (P = 0.002). There was a strong association between CIH severity and changes in mRNA for VEGFA (P < 0.0001). Less strong, but nominally significant associations with CIH severity were also observed for ANGPT2 (PANOVA = 0.065, PTREND = 0.040), VEGFR2 (PANOVA = 0.032, PTREND = 0.429), and TIE-2 (PANOVA = 0.006, PTREND = 0.010). We found that the CIH5 group had increased GLUT1 protein relative to sham (P = 0.006) and CIH10 (P = 0.001). There was variation in GLUT1 protein along the microvasculature in different hippocampal subregions. An effect of CIH5 on GLUT1 mRNA was seen (PANOVA = 0.042, PTREND = 0.012). Thus CIH affects the microvasculature in the hippocampus, but consequences depend on CIH severity. PMID:27125850

  4. Methylprednisolone pulse therapy in severe acute asthma.

    PubMed

    Pedersen, B K; Laursen, L C; Lervang, H H; Stjernebjerg, T; Weeke, B

    1987-02-01

    In a group comparative double blind pilot study six asthmatic patients with an acute exacerbation of their disease were randomly treated with either methylprednisolone pulse therapy (MPPT) (1000 mg daily for 3 days) (n = 2) followed by placebo tablets, or standard doses of methylprednisolone (MP) (50 mg daily gradually decreased to zero over 3 weeks) (n = 4). The results showed that the effect of MPPT did not differ from that of standard doses of MP. MPPT has, however, the potential of being preferable to standard treatment with MP, because of easy administration and optimal patient compliance. PMID:3296841

  5. Determinants of frequency long-term facilitation following acute intermittent hypoxia in vagotomized rats

    PubMed Central

    Baker-Herman, Tracy L.; Mitchell, Gordon S.

    2008-01-01

    Acute intermittent (AIH), but not acute sustained hypoxia (ASH) elicits a form of respiratory plasticity known as long-term facilitation (LTF). In anesthetized rats, LTF is expressed as increased respiratory-related nerve burst amplitude, with variable effects on burst frequency. We analyzed a large data set from multiple investigators using the same experimental protocol to determine factors influencing frequency LTF. Our meta-analysis revealed that AIH elicits both phrenic amplitude and frequency LTF in anesthetized and vagotomized rats, but frequency LTF is small in comparison with amplitude LTF (12% versus 60%, respectively). ASH elicits a small, but significant frequency and amplitude LTF (8% and 10%, respectively) that is not significantly different than controls. Similar to all published reports, analysis of this large data set confirms that phrenic amplitude LTF following AIH is significantly greater than ASH. Multiple regression analysis revealed a strong correlation between baseline burst frequency and frequency LTF. Variations in baseline burst frequency may contribute to variation in frequency LTF and may underlie the apparent effects of some drug treatments. PMID:18450525

  6. Oxidative stress in severe acute illness.

    PubMed

    Bar-Or, David; Bar-Or, Raphael; Rael, Leonard T; Brody, Edward N

    2015-01-01

    The overall redox potential of a cell is primarily determined by oxidizable/reducible chemical pairs, including glutathione-glutathione disulfide, reduced thioredoxin-oxidized thioredoxin, and NAD(+)-NADH (and NADP-NADPH). Current methods for evaluating oxidative stress rely on detecting levels of individual byproducts of oxidative damage or by determining the total levels or activity of individual antioxidant enzymes. Oxidation-reduction potential (ORP), on the other hand, is an integrated, comprehensive measure of the balance between total (known and unknown) pro-oxidant and antioxidant components in a biological system. Much emphasis has been placed on the role of oxidative stress in chronic diseases, such as Alzheimer's disease and atherosclerosis. The role of oxidative stress in acute diseases often seen in the emergency room and intensive care unit is considerable. New tools for the rapid, inexpensive measurement of both redox potential and total redox capacity should aid in introducing a new body of literature on the role of oxidative stress in acute illness and how to screen and monitor for potentially beneficial pharmacologic agents.

  7. Acute ventilatory responses to hypoxia during voluntary and electrically induced leg exercise in man.

    PubMed Central

    Pandit, J J; Robbins, P A

    1994-01-01

    1. The acute ventilatory response to a brief period of hypoxia (AHVR) was measured in six subjects (a) at rest, (b) during electrically induced leg exercise (EEL), (c) during voluntary leg exercise at an external work rate matched to electrical exercise (EV1) and (d) during voluntary leg exercise at an internal work rate (i.e. metabolic rate) matched to electrical exercise (EV2). The end-tidal PO2 during hypoxia was 50 mmHg and the end-tidal PCO2 was held constant at 1-2 mmHg above resting values throughout each of these four protocols. 2. EEL was produced by surface electrode stimulation of the quadriceps muscles so as to cause the legs to extend at the knee and lift a set of weights via a pulley system. During EV1, each subject lifted the same weight through the same height and at the same frequency as during his EEL protocol. During EV2, the weight, the height through which it was lifted and the frequency of voluntary contractions were altered to produce a similar O2 consumption and CO2 production as during EEL. 3. In each subject, end-tidal PCO2 values showed no change between the four protocols, and in three subjects in whom they were measured, arterial PCO2 values were also similar between the protocols. Venous lactate levels did not increase after EEL or EV2. 4. The AHVR during EEL (14.1 +/- 1.42 l min-1; mean +/- S.E.M) was significantly increased (Student's paired t test) compared with rest (7.55 +/- 1.10 l min-1; P < 0.003).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8071883

  8. High Resolution ECG for Evaluation of QT Interval Variability during Exposure to Acute Hypoxia

    NASA Technical Reports Server (NTRS)

    Zupet, P.; Finderle, Z.; Schlegel, Todd T.; Starc, V.

    2010-01-01

    Ventricular repolarization instability as quantified by the index of QT interval variability (QTVI) is one of the best predictors for risk of malignant ventricular arrhythmias and sudden cardiac death. Because it is difficult to appropriately monitor early signs of organ dysfunction at high altitude, we investigated whether high resolution advanced ECG (HR-ECG) analysis might be helpful as a non-invasive and easy-to-use tool for evaluating the risk of cardiac arrhythmias during exposure to acute hypoxia. 19 non-acclimatized healthy trained alpinists (age 37, 8 plus or minus 4,7 years) participated in the study. Five-minute high-resolution 12-lead electrocardiograms (ECGs) were recorded (Cardiosoft) in each subject at rest in the supine position breathing room air and then after breathing 12.5% oxygen for 30 min. For beat-to-beat RR and QT variability, the program of Starc was utilized to derive standard time domain measures such as root mean square of the successive interval difference (rMSSD) of RRV and QTV, the corrected QT interval (QTc) and the QTVI in lead II. Changes were evaluated with paired-samples t-test with p-values less than 0.05 considered statistically significant. As expected, the RR interval and its variability both decreased with increasing altitude, with p = 0.000 and p = 0.005, respectively. Significant increases were found in both the rMSSDQT and the QTVI in lead II, with p = 0.002 and p = 0.003, respectively. There was no change in QTc interval length (p = non significant). QT variability parameters may be useful for evaluating changes in ventricular repolarization caused by hypoxia. These changes might be driven by increases in sympathetic nervous system activity at ventricular level.

  9. Effects of acute hypoxia/acidosis on intracellular pH in differentiating neural progenitor cells.

    PubMed

    Nordström, Tommy; Jansson, Linda C; Louhivuori, Lauri M; Akerman, Karl E O

    2012-06-21

    The response of differentiating mouse neural progenitor cells, migrating out from neurospheres, to conditions simulating ischemia (hypoxia and extracellular or intracellular acidosis) was studied. We show here, by using BCECF and single cell imaging to monitor intracellular pH (pH(i)), that two main populations can be distinguished by exposing migrating neural progenitor cells to low extracellular pH or by performing an acidifying ammonium prepulse. The cells dominating at the periphery of the neurosphere culture, which were positive for neuron specific markers MAP-2, calbindin and NeuN had lower initial resting pH(i) and could also easily be further acidified by lowering the extracellular pH. Moreover, in this population, a more profound acidification was seen when the cells were acidified using the ammonium prepulse technique. However, when the cell population was exposed to depolarizing potassium concentrations no alterations in pH(i) took place in this population. In contrast, depolarization caused an increase in pH(i) (by 0.5 pH units) in the cell population closer to the neurosphere body, which region was positive for the radial cell marker (GLAST). This cell population, having higher resting pH(i) (pH 6.9-7.1) also responded to acute hypoxia. During hypoxic treatment the resting pH(i) decreased by 0.1 pH units and recovered rapidly after reoxygenation. Our results show that migrating neural progenitor cells are highly sensitive to extracellular acidosis and that irreversible damage becomes evident at pH 6.2. Moreover, our results show that a response to acidosis clearly distinguishes two individual cell populations probably representing neuronal and radial cells.

  10. Severe Hypotension, Hypoxia, and Subcutaneous Erythema Induced by Indigo Carmine Administration during Open Prostatectomy

    PubMed Central

    Voelzke, Bryan B.

    2016-01-01

    Indigo carmine (also known as 5,5′-indigodisulfonic acid sodium salt or indigotine) is a blue dye that is administered intravenously to examine the urinary tract and usually is biologically safe and inert. Indigo carmine rarely may cause adverse reactions. We treated a 66-year-old man who had general anesthesia and radical retropubic prostatectomy for prostate cancer. He had a previous history of allergy to bee sting with nausea, vomiting, and dizziness. Within 1 minute after injection of indigo carmine for evaluation of the ureters, the patient developed hypotension to 40 mmHg, severe hypoxia (the value of SpO2 (peripheral capillary oxygen saturation) was 75% on 40% inspired oxygen concentration), poor air movement and bilateral diffuse wheezing on auscultation, and marked subcutaneous erythema at the upper extremities. After treatment with 100% oxygen, epinephrine (total, 1.5 mg), hydrocortisone (100 mg), diphenhydramine (50 mg), albuterol nebulizer (0.083%), and continuous infusion of epinephrine (0.15 μg/kg/min), the vital signs became stable, and he recovered completely. In summary, indigo carmine rarely may cause life-threatening anaphylactic or anaphylactoid reaction that may necessitate rapid treatment to stabilize cardiovascular, hemodynamic, and pulmonary function.

  11. Severe Hypotension, Hypoxia, and Subcutaneous Erythema Induced by Indigo Carmine Administration during Open Prostatectomy

    PubMed Central

    Voelzke, Bryan B.

    2016-01-01

    Indigo carmine (also known as 5,5′-indigodisulfonic acid sodium salt or indigotine) is a blue dye that is administered intravenously to examine the urinary tract and usually is biologically safe and inert. Indigo carmine rarely may cause adverse reactions. We treated a 66-year-old man who had general anesthesia and radical retropubic prostatectomy for prostate cancer. He had a previous history of allergy to bee sting with nausea, vomiting, and dizziness. Within 1 minute after injection of indigo carmine for evaluation of the ureters, the patient developed hypotension to 40 mmHg, severe hypoxia (the value of SpO2 (peripheral capillary oxygen saturation) was 75% on 40% inspired oxygen concentration), poor air movement and bilateral diffuse wheezing on auscultation, and marked subcutaneous erythema at the upper extremities. After treatment with 100% oxygen, epinephrine (total, 1.5 mg), hydrocortisone (100 mg), diphenhydramine (50 mg), albuterol nebulizer (0.083%), and continuous infusion of epinephrine (0.15 μg/kg/min), the vital signs became stable, and he recovered completely. In summary, indigo carmine rarely may cause life-threatening anaphylactic or anaphylactoid reaction that may necessitate rapid treatment to stabilize cardiovascular, hemodynamic, and pulmonary function. PMID:27610263

  12. Severe Hypotension, Hypoxia, and Subcutaneous Erythema Induced by Indigo Carmine Administration during Open Prostatectomy.

    PubMed

    Nandate, Koichiro; Voelzke, Bryan B

    2016-01-01

    Indigo carmine (also known as 5,5'-indigodisulfonic acid sodium salt or indigotine) is a blue dye that is administered intravenously to examine the urinary tract and usually is biologically safe and inert. Indigo carmine rarely may cause adverse reactions. We treated a 66-year-old man who had general anesthesia and radical retropubic prostatectomy for prostate cancer. He had a previous history of allergy to bee sting with nausea, vomiting, and dizziness. Within 1 minute after injection of indigo carmine for evaluation of the ureters, the patient developed hypotension to 40 mmHg, severe hypoxia (the value of SpO2 (peripheral capillary oxygen saturation) was 75% on 40% inspired oxygen concentration), poor air movement and bilateral diffuse wheezing on auscultation, and marked subcutaneous erythema at the upper extremities. After treatment with 100% oxygen, epinephrine (total, 1.5 mg), hydrocortisone (100 mg), diphenhydramine (50 mg), albuterol nebulizer (0.083%), and continuous infusion of epinephrine (0.15 μg/kg/min), the vital signs became stable, and he recovered completely. In summary, indigo carmine rarely may cause life-threatening anaphylactic or anaphylactoid reaction that may necessitate rapid treatment to stabilize cardiovascular, hemodynamic, and pulmonary function. PMID:27610263

  13. Severe Plasmodium falciparum infection mimicking acute myocardial infarction.

    PubMed

    Sulaiman, Helmi; Ismail, Muhammad Dzafir; Jalalonmuhali, Maisarah; Atiya, Nadia; Ponnampalavanar, Sasheela

    2014-08-30

    This case report describes a case of presumed acute myocardial infarction in a returned traveler who was later diagnosed to have severe malaria. Emergency coronary angiography was normal and subsequent peripheral blood film was positive for Plasmodium falciparum.

  14. Survival from acute renal failure after severe burns.

    PubMed

    Sawada, Y; Momma, S; Takamizawa, A; Nishida, S

    1984-12-01

    We describe a patient with 50 per cent, third degree flame burns who had a history of paint thinner inhalation for over 10 years. Moreover, chlorpromazine had been administered for the treatment of insomnia caused by chronic thinner intoxication. He developed oliguric acute renal failure soon after the burn injury, although adequate resuscitation therapy was given, and survived following frequent haemodialysis. Although survival from acute renal failure after severe burns is rare, once the diagnosis of acute renal failure has been made, haemodialysis should be instituted as early as possible. Furthermore, in a severely burnt patient with episodes of chronic and acute intoxication from organic chemicals or drugs which may have caused renal damage, acute renal failure may occur, so that careful observation is advised. PMID:6525538

  15. [PREVENTION AND CORRECTION OF PULMONARY COMPLICATIONS FOR SEVERE ACUTE PANCREATITIS].

    PubMed

    Fedorkiv, M B

    2015-06-01

    Increased of proinflammatory cytokines levels, including interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) on severe acute pancreatitis causes vasodilatation, increased permeability of the wall, accumulation of fluid in lung tissue and pleural sinuses. Transudate from acute parapancreatyc clusters of hot liquid and abdomen falls into the chest cavity through microscopic defects in the diaphragm due to the formation of pathological pleural-peritoneal connections or the relevant pressure gradient between the abdominal and pleural cavities. Remediation and removal of acute parapancreatyc clusters combined with the use of a multicomponent drug infusion therapy Cytoflavin provide a reduction in the frequency of pulmonary complications of acute pancreatitis from 48.3 to 31.0%. Use of the drug Cytoflavin reduces the severity of endogenous intoxication and mortality from acute lung injury from 12.9 to 6.1%. PMID:26521460

  16. CO2-O2 Interactions in Extension of Tolerance to Acute Hypoxia

    NASA Technical Reports Server (NTRS)

    Lambertsen, C. J.; Gelfand, R.

    1996-01-01

    Advantageous and/or detrimental influences associated with purposeful deviations from atmospheric levels of O2 and CO2 are studied. Specific goals have been directed to simulating situations of emergency or accidental exposure to hypoxic (10% O2) environments. They included establishing dynamic effects of hypoxia with and without CO2 (rate of acute adaptation), and stable-state (equilibrium) effects on blood and brain oxygenation. They also included effects on the physiological parameters of respiration and blood gas composition which underlie brain oxygenation. For 10% O2, a complete experiment consisted of three identical rest-exercise phases of 32 minutes duration. Following a five minute air control period, each inspired gas was administered over the next 27 minutes. The test gases were room air control, 10% +/- 0.1% O2 with 4% +/- 0.1% CO2, and 10% +/- 0.1% O2. A minimum of 45 minutes separated each phase. Relative to inspiration of 10% O2, brain oxygenation is enhanced by addition of 4% CO2. This is accomplished by increasing the rate at which O2 in arterial blood is supplied to the brain circulation (well above even the normoxic level), and on relative improvement in the arterial pressure of O2.

  17. Effects of acute intermittent hypoxia on energy balance and hypothalamic feeding pathways.

    PubMed

    Moreau, J M; Ciriello, J

    2013-12-01

    This study was done to investigate the effects of acute intermittent hypoxia (IH) on metabolic factors associated with energy balance and body weight, and on hypothalamic satiety-inducing pathways. Adult male Sprague-Dawley rats were exposed to either 8h IH or normoxic control conditions. Food intake, locomotion and body weights were examined after IH. Additionally, plasma levels of leptin, adiponectin corticosterone, insulin and blood glucose were measured following exposure to IH. Furthermore, adipose tissue was removed and analyzed for leptin and adiponectin content. Finally, the hypothalamic arcuate nucleus (ARC) was assessed for alterations in protein signaling associated with satiety. IH reduced body weight, food intake and active cycle locomotion without altering adipose tissue mass. Leptin protein content was reduced while adiponectin content was elevated in adipose tissue after IH. Plasma concentration of leptin was significantly increased while adiponectin decreased after IH. No changes were found in plasma corticosterone, insulin and blood glucose. In ARC, phosphorylation of signal transducer and activator of transcription-3 and pro-opiomelanocortin (POMC) expression were elevated. In addition, POMC-expressing neurons were activated as determined by immediate early gene FRA-1/2 expression. Finally, ERK1/2 and its phosphorylation were reduced in response to IH. These data suggest that IH induces significant alterations to body energy balance through changes in the secretion of leptin which exert effects on satiety-inducing pathways within the hypothalamus.

  18. Severe acute ulcerative colitis: the pediatric perspective.

    PubMed

    Turner, Dan

    2009-01-01

    Many features of pediatric ulcerative colitis (UC) are similar to adult-onset disease, but the rate of extensive disease is doubled in children. It is, therefore, not surprising that the admission rate for severe UC is higher in childhood-onset UC, reaching 28% by the age of 16 years. Approximately 30-40% of children will fail corticosteroids and require second-line medical therapy or colectomy. A pediatric UC activity index (PUCAI) score of >65 indicates severe disease and the index can assist in determining the need and timing of second-line medical therapy or colectomy early during the admission. A PUCAI score of >45 points on day 3 identify patients likely to fail corticosteroids (negative predictive value 90-95%), and a score >70 points on day 5 identify patients who will require short-term treatment escalation (positive predicting value 95-100%). Data in children are limited, but it seems that cyclosporine, tacrolimus and infliximab achieve a similar short-term response rate, in the range of 60-80%. Infliximab has the advantage that it may be given for a prolonged period of time while calcineurin inhibitors should not be used for more than 3-4 months, bridging to a thiopurine regimen. Colectomy is indicated in toxic megacolon or in cases refractory to one salvage therapy. The choice of colectomy in other cases should carefully consider its effect on the patient's quality of life, its impact on the physical and emotional development at a critical age of personality development, and its association with a high infertility rate in females undergoing pouch procedure before childbearing age.

  19. Liver transplantation for acute liver failure accompanied by severe acute pancreatitis.

    PubMed

    Kirino, Izumi; Fujimoto, Yasuhiro; Hata, Koichiro; Uemoto, Shinji

    2016-01-01

    The role of liver transplantation (LT) in acute liver failure (ALF) complicated by severe acute pancreatitis is still unclear. We here report a case of deceased-donor LT for idiopathic ALF accompanied by severe acute pancreatitis. A 58-year-old man with no history of liver disease presented with idiopathic ALF and acute pancreatitis. After careful consideration, he received a liver from a deceased donor. Following surgery, the patient's liver function rapidly reverted to normal level and the acute pancreatitis simultaneously subsided. The patient later developed a pancreatic pseudocyst, which was treated successfully with combination interventional radiology. LT can be considered for ALF associated with severe acute pancreatitis if there is no clinical evidence of an absolute contraindication for organ transplantation, such as systemic or local infection. Moreover, we recommend a close follow-up by ultrasonography to allow early detection and treatment of pancreatic pseudocysts following surgery. PMID:27600056

  20. Upregulation of Steroidogenic Acute Regulatory Protein by Hypoxia Stimulates Aldosterone Synthesis in Pulmonary Artery Endothelial Cells to Promote Pulmonary Vascular Fibrosis

    PubMed Central

    Maron, Bradley A.; Oldham, William M.; Chan, Stephen Y.; Vargas, Sara O.; Arons, Elena; Zhang, Ying-Yi; Loscalzo, Joseph; Leopold, Jane A.

    2014-01-01

    Background The molecular mechanism(s) regulating hypoxia-induced vascular fibrosis are unresolved. Hyperaldosteronism correlates positively with vascular remodeling in pulmonary arterial hypertension (PAH), suggesting that aldosterone may contribute to the pulmonary vasculopathy of hypoxia. The hypoxia-sensitive transcription factors c-Fos/c-Jun regulate steroidogenic acute regulatory protein (StAR), which facilitates the rate-limiting step of aldosterone steroidogenesis. We hypothesized that c-Fos/c-Jun upregulation by hypoxia activates StAR-dependent aldosterone synthesis in human pulmonary artery endothelial cells (HPAECs) to promote vascular fibrosis in PAH. Methods and Results Patients with PAH, rats with Sugen/hypoxia-PAH, and mice exposed to chronic hypoxia expressed increased StAR in remodeled pulmonary arterioles, providing a basis for investigating hypoxia-StAR signaling in HPAECs. Hypoxia (2.0% FiO2) increased aldosterone levels selectively in HPAECs, which was confirmed by liquid chromatography-mass spectrometry. Increased aldosterone by hypoxia resulted from enhanced c-Fos/c-Jun binding to the proximal activator protein (AP-1) site of the StAR promoter in HPAECs, which increased StAR expression and activity. In HPAECs transfected with StAR-siRNA or treated with the AP-1 inhibitor, SR-11302, hypoxia failed to increase aldosterone, confirming that aldosterone biosynthesis required StAR activation by c-Fos/c-Jun. The functional consequences of aldosterone were confirmed by pharmacological inhibition of the mineralocorticoid receptor with spironolactone or eplerenone, which attenuated hypoxia-induced upregulation of the fibrogenic protein connective tissue growth factor and collagen III in vitro, and decreased pulmonary vascular fibrosis to improve pulmonary hypertension in Conclusions Our findings identify autonomous aldosterone synthesis in HPAECs due to hypoxia-mediated upregulation of StAR as a novel molecular mechanism that promotes pulmonary vascular

  1. Cross Acclimation between Heat and Hypoxia: Heat Acclimation Improves Cellular Tolerance and Exercise Performance in Acute Normobaric Hypoxia

    PubMed Central

    Lee, Ben J.; Miller, Amanda; James, Rob S.; Thake, Charles D.

    2016-01-01

    Background: The potential for cross acclimation between environmental stressors is not well understood. Thus, the aim of this investigation was to determine the effect of fixed-workload heat or hypoxic acclimation on cellular, physiological, and performance responses during post acclimation hypoxic exercise in humans. Method: Twenty-one males (age 22 ± 5 years; stature 1.76 ± 0.07 m; mass 71.8 ± 7.9 kg; V˙O2 peak 51 ± 7 mL.kg−1.min−1) completed a cycling hypoxic stress test (HST) and self-paced 16.1 km time trial (TT) before (HST1, TT1), and after (HST2, TT2) a series of 10 daily 60 min training sessions (50% N V˙O2 peak) in control (CON, n = 7; 18°C, 35% RH), hypoxic (HYP, n = 7; fraction of inspired oxygen = 0.14, 18°C, 35% RH), or hot (HOT, n = 7; 40°C, 25% RH) conditions. Results: TT performance in hypoxia was improved following both acclimation treatments, HYP (−3:16 ± 3:10 min:s; p = 0.0006) and HOT (−2:02 ± 1:02 min:s; p = 0.005), but unchanged after CON (+0:31 ± 1:42 min:s). Resting monocyte heat shock protein 72 (mHSP72) increased prior to HST2 in HOT (62 ± 46%) and HYP (58 ± 52%), but was unchanged after CON (9 ± 46%), leading to an attenuated mHSP72 response to hypoxic exercise in HOT and HYP HST2 compared to HST1 (p < 0.01). Changes in extracellular hypoxia-inducible factor 1-α followed a similar pattern to those of mHSP72. Physiological strain index (PSI) was attenuated in HOT (HST1 = 4.12 ± 0.58, HST2 = 3.60 ± 0.42; p = 0.007) as a result of a reduced HR (HST1 = 140 ± 14 b.min−1; HST2 131 ± 9 b.min−1 p = 0.0006) and Trectal (HST1 = 37.55 ± 0.18°C; HST2 37.45 ± 0.14°C; p = 0.018) during exercise. Whereas PSI did not change in HYP (HST1 = 4.82 ± 0.64, HST2 4.83 ± 0.63). Conclusion: Heat acclimation improved cellular and systemic physiological tolerance to steady state exercise in moderate hypoxia. Additionally we show, for the first time, that heat acclimation improved cycling time trial performance to a magnitude

  2. The body weight loss during acute exposure to high-altitude hypoxia in sea level residents.

    PubMed

    Ge, Ri-Li; Wood, Helen; Yang, Hui-Huang; Liu, Yi-Ning; Wang, Xiu-Juan; Babb, Tony

    2010-12-25

    Weight loss is frequently observed after acute exposure to high altitude. However, the magnitude and rate of weight loss during acute exposure to high altitude has not been clarified in a controlled prospective study. The present study was performed to evaluate weight loss at high altitude. A group of 120 male subjects [aged (32±6) years] who worked on the construction of the Golmud-Lhasa Railway at Kunlun Mountain (altitude of 4 678 m) served as volunteer subjects for this study. Eighty-five workers normally resided at sea level (sea level group) and 35 normally resided at an altitude of 2 200 m (moderate altitude group). Body weight, body mass index (BMI), and waist circumference were measured in all subjects after a 7-day stay at Golmud (altitude of 2 800 m, baseline measurements). Measurements were repeated after 33-day working on Kunlun Mountain. In order to examine the daily rate of weight loss at high altitude, body weight was measured in 20 subjects from the sea level group (sea level subset group) each morning before breakfast for 33 d at Kunlun Mountain. According to guidelines established by the Lake Louise acute mountain sickness (AMS) consensus report, each subject completed an AMS self-report questionnaire two days after arriving at Kunlun Mountain. After 33-day stay at an altitude of 4 678 m, the average weight loss for the sea level group was 10.4% (range 6.5% to 29%), while the average for the moderate altitude group was 2.2% (-2% to 9.1%). The degree of weight loss (Δ weight loss) after a 33-day stay at an altitude of 4 678 m was significantly correlated with baseline body weight in the sea level group (r=0.677, P<0.01), while the correlation was absent in the moderate altitude group (r=0.296, P>0.05). In the sea level subset group, a significant weight loss was observed within 20 d, but the weight remained stable thereafter. AMS-score at high altitude was significantly higher in the sea level group (4.69±2.48) than that in the moderate

  3. Gene promoter of apoptosis inhibitory protein IAP2: identification of enhancer elements and activation by severe hypoxia.

    PubMed Central

    Dong, Zheng; Nishiyama, Junichiro; Yi, Xiaolan; Venkatachalam, Manjeri A; Denton, Michael; Gu, Sumin; Li, Senlin; Qiang, Mei

    2002-01-01

    Inhibitors of apoptosis (IAPs) antagonize cell death and regulate the cell cycle. One mechanism controlling IAP expression is translation initiation through the internal ribosome entry sites. Alternatively, IAP expression can be regulated at the transcription level. We showed recently the activation of IAP2 transcription by severe hypoxia. To pursue this regulation, we have cloned the full-length cDNA of rat IAP2, and have isolated and analysed the promoter regions of this gene. The cDNA encodes a protein of 589 amino acids, exhibiting structural features of IAP. In rat tissues, a major IAP2 transcript of approximately 3.5 kb was detected. We subsequently isolated 3.3 kb of the proximal 5'-flanking regions of this gene, which showed significant promoter activity. Of interest, 5' sequential deletion of the promoter sequence identified an enhancer of approximately 200 bp. Deletion of cAMP-response-element-binding protein (CREB) sites in the enhancer sequence diminished its activity. Finally, the IAP2 gene promoter was activated significantly by severe hypoxia and not by CoCl(2) or desferrioxamine, pharmacological inducers of hypoxia-inducible factor-1. In conclusion, in this study we have cloned the full-length cDNA of rat IAP2, and for the first time we have isolated and analysed promoter sequences of this gene, leading to the identification of enhancer elements. Moreover, we have demonstrated activation of the gene promoter by severe hypoxia, a condition shown to induce IAP2. These findings provide a basis for further investigation of gene regulation of IAP2, a protein with multiple functions. PMID:12023884

  4. Effect of sinusoidal modulated currents and acute hypoxia on corticosterone content and activity of certain dehydrogenases in tissues of different rat organs during hypokinesia

    NASA Technical Reports Server (NTRS)

    Melik-Aslanova, L. L.; Frenkel, I. D.

    1980-01-01

    The state of hypokinesia in rats was reproduced by keeping them for 30 days in special box cages that restricted their mobility in all directions. Results show the resistance to acute hypoxic hypoxia is increased. This is linked to the considerable rise in the reduced level of corticosterone in different organs and the succinate dehydrogenase activity in the liver and brain. The letter indicated the primary oxidation of succinate, which has great importance in the adaptation of the oxidative metabolism to acute oxygen insufficiency. The use of sinusoidal modulated currents in the period of hypokinesia promotes normalization of the indices for resistance of the rats to acute hypoxia.

  5. Serotonin in the dorsal periaqueductal gray inhibits panic-like defensive behaviors in rats exposed to acute hypoxia.

    PubMed

    Spiacci, A; Sergio, T de Oliveira; da Silva, G S F; Glass, M L; Schenberg, L C; Garcia-Cairasco, N; Zangrossi, H

    2015-10-29

    It has been proposed that spontaneous panic attacks are the outcome of the misfiring of an evolved suffocation alarm system. Evidence gathered in the last years is suggestive that the dorsal periaqueductal gray (dPAG) in the midbrain harbors a hypoxia-sensitive suffocation alarm system. We here investigated whether facilitation of 5-HT-mediated neurotransmission within the dPAG changes panic-like defensive reactions expressed by male Wistar rats submitted to a hypoxia challenge (7% O2), as observed in other animal models of panic. Intra-dPAG injection of 5-HT (20 nmol), (±)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT) (8 nmol), a 5-HT1A receptor agonist, or (±)-2,5-dimethoxy-4-iodo amphetamine hydrochloride (DOI) (16 nmol), a preferential 5-HT2A agonist, reduced the number of upward jumps directed to the border of the experimental chamber during hypoxia, interpreted as escape attempts, without affecting the rats' locomotion. These effects were similar to those caused by chronic, but not acute, intraperitoneal administration of the antidepressant fluoxetine (5-15 mg/kg), or acute systemic administration of the benzodiazepine receptor agonist alprazolam (1-4 mg/kg), both drugs clinically used in the treatment of panic disorder. Our findings strengthen the view that the dPAG is a key encephalic area involved in the defensive behaviors triggered by activation of the suffocation alarm system. They also support the use of hypoxia-evoked escape as a model of respiratory-type panic attacks. PMID:26319117

  6. On the mechanisms that limit oxygen uptake during exercise in acute and chronic hypoxia: role of muscle mass

    PubMed Central

    Calbet, José A L; Rådegran, Göran; Boushel, Robert; Saltin, Bengt

    2009-01-01

    Peak aerobic power in humans () is markedly affected by inspired O2 tension (). The question to be answered in this study is what factor plays a major role in the limitation of muscle peak in hypoxia: arterial O2 partial pressure () or O2 content ()? Thus, cardiac output (dye dilution with Cardio-green), leg blood flow (thermodilution), intra-arterial blood pressure and femoral arterial-to-venous differences in blood gases were determined in nine lowlanders studied during incremental exercise using a large (two-legged cycle ergometer exercise: Bike) and a small (one-legged knee extension exercise: Knee) muscle mass in normoxia, acute hypoxia (AH) () and after 9 weeks of residence at 5260 m (CH). Reducing the size of the active muscle mass blunted by 62% the effect of hypoxia on in AH and abolished completely the effect of hypoxia on after altitude acclimatization. Acclimatization improved Bike peak exercise from 34 ± 1 in AH to 45 ± 1 mmHg in CH (P < 0.05) and Knee from 38 ± 1 to 55 ± 2 mmHg (P < 0.05). Peak cardiac output and leg blood flow were reduced in hypoxia only during Bike. Acute hypoxia resulted in reduction of systemic O2 delivery (46 and 21%) and leg O2 delivery (47 and 26%) during Bike and Knee, respectively, almost matching the corresponding reduction in . Altitude acclimatization restored fully peak systemic and leg O2 delivery in CH (2.69 ± 0.27 and 1.28 ± 0.11 l min−1, respectively) to sea level values (2.65 ± 0.15 and 1.16 ± 0.11 l min−1, respectively) during Knee, but not during Bike. During Knee in CH, leg oxygen delivery was similar to normoxia and, therefore, also in spite of a of 55 mmHg. Reducing the size of the active muscle mass improves pulmonary gas exchange during hypoxic exercise, attenuates the Bohr effect on oxygen uploading at the lungs and preserves sea level convective O2 transport to the active muscles. Thus, the altitude-acclimatized human has potentially a similar exercising capacity as at sea level when the

  7. On the mechanisms that limit oxygen uptake during exercise in acute and chronic hypoxia: role of muscle mass.

    PubMed

    Calbet, José A L; Rådegran, Göran; Boushel, Robert; Saltin, Bengt

    2009-01-15

    Peak aerobic power in humans (VO2,peak) is markedly affected by inspired O2 tension (FIO2). The question to be answered in this study is what factor plays a major role in the limitation of muscle peak VO2 in hypoxia: arterial O2 partial pressure (Pa,O2) or O2 content (Ca,O2)? Thus, cardiac output (dye dilution with Cardio-green), leg blood flow (thermodilution), intra-arterial blood pressure and femoral arterial-to-venous differences in blood gases were determined in nine lowlanders studied during incremental exercise using a large (two-legged cycle ergometer exercise: Bike) and a small (one-legged knee extension exercise: Knee)muscle mass in normoxia, acute hypoxia (AH) (FIO2 = 0.105) and after 9 weeks of residence at 5260 m (CH). Reducing the size of the active muscle mass blunted by 62% the effect of hypoxia on VO2,peak in AH and abolished completely the effect of hypoxia on VO2,peak after altitude acclimatization. Acclimatization improved Bike peak exercise Pa,O2 from 34 +/- 1 in AH to 45 +/- 1 mmHg in CH(P <0.05) and Knee Pa,O2 from 38 +/- 1 to 55 +/- 2 mmHg(P <0.05). Peak cardiac output and leg blood flow were reduced in hypoxia only during Bike. Acute hypoxia resulted in reduction of systemic O2 delivery (46 and 21%) and leg O2 delivery (47 and 26%) during Bike and Knee, respectively, almost matching the corresponding reduction in VO2,peak. Altitude acclimatization restored fully peak systemic and leg O(2) delivery in CH (2.69 +/- 0.27 and 1.28 +/- 0.11 l min(-1), respectively) to sea level values (2.65 +/- 0.15 and 1.16 +/- 0.11 l min(-1), respectively) during Knee, but not during Bike. During Knee in CH, leg oxygen delivery was similar to normoxia and, therefore, also VO2,peak in spite of a Pa,O2 of 55 mmHg. Reducing the size of the active mass improves pulmonary gas exchange during hypoxic exercise, attenuates the Bohr effect on oxygen uploading at the lungs and preserves sea level convective O2 transport to the active muscles. Thus, the altitude

  8. Effects of hypoxia-induced neonatal seizures on acute hippocampal injury and later-life seizure susceptibility and anxiety-related behavior in mice.

    PubMed

    Rodriguez-Alvarez, Natalia; Jimenez-Mateos, Eva M; Dunleavy, Mark; Waddington, John L; Boylan, Geraldine B; Henshall, David C

    2015-11-01

    Seizures are common during the neonatal period, often due to hypoxic-ischemic encephalopathy and may contribute to acute brain injury and the subsequent development of cognitive deficits and childhood epilepsy. Here we explored short- and long-term consequences of neonatal hypoxia-induced seizures in 7 day old C57BL/6J mice. Seizure activity, molecular markers of hypoxia and histological injury were investigated acutely after hypoxia and response to chemoconvulsants and animal behaviour was explored at adulthood. Hypoxia was induced by exposing pups to 5% oxygen for 15 min (global hypoxia). Electrographically defined seizures with behavioral correlates occurred in 95% of these animals and seizures persisted for many minutes after restitution of normoxia. There was minimal morbidity or mortality. Pre- or post-hypoxia injection of phenobarbital (50mg/kg) had limited efficacy at suppressing seizures. The hippocampus from neonatal hypoxia-seizure mice displayed increased expression of vascular endothelial growth factor and the immediate early gene c-fos, minimal histological evidence of cell injury and activation of caspase-3 in scattered neurons. Behavioral analysis of mice five weeks after hypoxia-induced seizures detected novel anxiety-related and other behaviors, while performance in a spatial memory test was similar to controls. Seizure threshold tests with kainic acid at six weeks revealed that mice previously subject to neonatal hypoxia-induced seizures developed earlier, more frequent and longer-duration seizures. This study defines a set of electro-clinical, molecular, pharmacological and behavioral consequences of hypoxia-induced seizures that indicate short- and long-term deleterious outcomes and may be a useful model to investigate the pathophysiology and treatment of neonatal seizures in humans.

  9. Effects of hypoxia-induced neonatal seizures on acute hippocampal injury and later-life seizure susceptibility and anxiety-related behavior in mice.

    PubMed

    Rodriguez-Alvarez, Natalia; Jimenez-Mateos, Eva M; Dunleavy, Mark; Waddington, John L; Boylan, Geraldine B; Henshall, David C

    2015-11-01

    Seizures are common during the neonatal period, often due to hypoxic-ischemic encephalopathy and may contribute to acute brain injury and the subsequent development of cognitive deficits and childhood epilepsy. Here we explored short- and long-term consequences of neonatal hypoxia-induced seizures in 7 day old C57BL/6J mice. Seizure activity, molecular markers of hypoxia and histological injury were investigated acutely after hypoxia and response to chemoconvulsants and animal behaviour was explored at adulthood. Hypoxia was induced by exposing pups to 5% oxygen for 15 min (global hypoxia). Electrographically defined seizures with behavioral correlates occurred in 95% of these animals and seizures persisted for many minutes after restitution of normoxia. There was minimal morbidity or mortality. Pre- or post-hypoxia injection of phenobarbital (50mg/kg) had limited efficacy at suppressing seizures. The hippocampus from neonatal hypoxia-seizure mice displayed increased expression of vascular endothelial growth factor and the immediate early gene c-fos, minimal histological evidence of cell injury and activation of caspase-3 in scattered neurons. Behavioral analysis of mice five weeks after hypoxia-induced seizures detected novel anxiety-related and other behaviors, while performance in a spatial memory test was similar to controls. Seizure threshold tests with kainic acid at six weeks revealed that mice previously subject to neonatal hypoxia-induced seizures developed earlier, more frequent and longer-duration seizures. This study defines a set of electro-clinical, molecular, pharmacological and behavioral consequences of hypoxia-induced seizures that indicate short- and long-term deleterious outcomes and may be a useful model to investigate the pathophysiology and treatment of neonatal seizures in humans. PMID:26341542

  10. Hypoxia. 4. Hypoxia and ion channel function

    PubMed Central

    Polak, Jan

    2011-01-01

    The ability to sense and respond to oxygen deprivation is required for survival; thus, understanding the mechanisms by which changes in oxygen are linked to cell viability and function is of great importance. Ion channels play a critical role in regulating cell function in a wide variety of biological processes, including neuronal transmission, control of ventilation, cardiac contractility, and control of vasomotor tone. Since the 1988 discovery of oxygen-sensitive potassium channels in chemoreceptors, the effect of hypoxia on an assortment of ion channels has been studied in an array of cell types. In this review, we describe the effects of both acute and sustained hypoxia (continuous and intermittent) on mammalian ion channels in several tissues, the mode of action, and their contribution to diverse cellular processes. PMID:21178108

  11. Markers for predicting severity and progression of acute pancreatitis.

    PubMed

    Schütte, Kerstin; Malfertheiner, Peter

    2008-01-01

    Several tools have been developed for severity stratification in acute pancreatitis. They include single biochemical markers, imaging methods, and complex scoring systems, all of which aim at an early detection of severe acute pancreatitis to optimise monitoring and treatment of patients as early as possible. Among single biochemical markers, C-reactive protein (CRP) remains the most useful. Despite its delayed increase, peaking not earlier than 72 h after the onset of symptoms, it is accurate and widely available. Many other markers have been evaluated for their usefulness, and for some of them very promising data could be shown. Among them interleukin 6 seems to be the most promising parameter for use in clinical routine. For the detection of pancreatic infection, procalcitonin is the most sensitive, and can be used as an indicator for the need for fine-needle aspiration of pancreatic necrosis. Regarding imaging, contrast-enhanced computed tomography is still the reference method for the detection of necrotising acute pancreatitis. Pancreatitis-specific scoring systems have been shown to be of value for the prediction of severity and progression of acute pancreatitis, but cannot be applied any earlier than 48 h after admission to hospital. The APACHE-II score has not been developed specifically for acute pancreatitis and is rather complex to assess, but has been proven to be an early and reliable tool. Indication, timing and consequences of the methods applied need to be carefully considered and incorporated into clinical assessments to avoid costs and harm to the patient.

  12. Long-term facilitation of expiratory and sympathetic activities following acute intermittent hypoxia in rats

    PubMed Central

    Lemes, Eduardo V.; Aiko, Simone; Orbem, Caroline B.; Formentin, Cleiton; Bassi, Mirian; Colombari, Eduardo; Zoccal, Daniel B.

    2015-01-01

    Aim Acute intermittent hypoxia (AIH) promotes persistent increases in ventilation and sympathetic activity, referred as long-term facilitation (LTF). Augmented inspiratory activity is suggested as a major component of respiratory LTF. In the present study, we hypothesized that AIH also elicits a sustained increase in expiratory motor activity. We also investigated whether the expiratory LTF contributes to the development of sympathetic LTF after AIH. Methods Rats were exposed to AIH (10 × 6–7 % O2 for 45 s, every 5 min) and the cardiorespiratory parameters were evaluated during 60 min using in vivo and in situ approaches. Results In unanesthetized conditions (n=9), AIH elicited a modest but sustained increase in baseline mean arterial pressure (MAP, 104±2 vs 111±3 mmHg, P<0.05) associated with enhanced sympathetic and respiratory-related variabilities. In the in situ preparations (n=9), AIH evoked LTF in phrenic (33±12%), thoracic sympathetic (75±25%) and abdominal nerve activities (69±14%). The sympathetic overactivity after AIH was phase-locked with the emergence of bursts in abdominal activity during the late-expiratory phase. In anesthetized vagus-intact animals, AIH increased baseline MAP (113±3 vs 122±2 mmHg, P<0.05) and abdominal muscle activity (535±94%), which were eliminated after pharmacological inhibition of the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG). Conclusion These findings indicate that increased expiratory activity is also an important component of AIH-elicited respiratory LTF. Moreover, the development of sympathetic LTF after AIH is linked to the emergence of active expiratory pattern and depends on the integrity of the neurones of the RTN/pFRG. PMID:26910756

  13. [Principles of intensive care in severe acute pancreatitis in 2008].

    PubMed

    Darvas, Katalin; Futó, Judit; Okrös, Ilona; Gondos, Tibor; Csomós, Akos; Kupcsulik, Péter

    2008-11-23

    Acute pancreatitis is a dynamic, often progressive disease; 14-20% require intensive care in its severe form due to multiorgan dysfunction and/or failure. This review was created using systematic literature review of articles published on this subject in the last 5 years. The outcome of severe acute pancreatitis is determined by the inflammatory response and multiorgan dysfunction - the prognostic scores (Acute Physiology and Chronic Health Evaluation, Glasgow Prognostic Index, Sepsis-related Organ Failure Assessment, Multi Organ Dysfunction Syndrome Scale, Ranson Scale) can be used to determine outcome. Clinical signs (age, coexisting diseases, confusion, obesity) and biochemistry values (serum amylase, lipase, C-reactive protein, procalcitonin, creatinine, urea, calcium) have important prognostic roles as well. Early organ failure increases the risk of late abdominal complications and mortality. Intensive care can provide appropriate multi-function patient monitoring which helps in early recognition of complications and appropriate target-controlled treatment. Treatment of severe acute pancreatitis aims at reducing systemic inflammatory response and multiorgan dysfunction and, on the other side, at increasing the anti-inflammatory response. Oral starvation for 24-48 hours is effective in reducing the exocrine activity of the pancreas; the efficacy of protease inhibitors is questionable. Early intravascular volume resuscitation and stable haemodynamics improve microcirculation. Early oxygen therapy and mechanical ventilation provide adequate oxygenation. Electrolyte and acid-base control can be as important as tight glucose control. Adequate pain relief can be achieved by thoracic epidural catheterization. Early enteral nutrition with immunonutrition should be used. There is evidence that affecting the coagulation cascade by activated protein C can play a role in reducing the inflammatory response. The complex therapy of acute pancreatitis includes appropriate

  14. [Principles of intensive care in severe acute pancreatitis in 2008].

    PubMed

    Darvas, Katalin; Futó, Judit; Okrös, Ilona; Gondos, Tibor; Csomós, Akos; Kupcsulik, Péter

    2008-11-23

    Acute pancreatitis is a dynamic, often progressive disease; 14-20% require intensive care in its severe form due to multiorgan dysfunction and/or failure. This review was created using systematic literature review of articles published on this subject in the last 5 years. The outcome of severe acute pancreatitis is determined by the inflammatory response and multiorgan dysfunction - the prognostic scores (Acute Physiology and Chronic Health Evaluation, Glasgow Prognostic Index, Sepsis-related Organ Failure Assessment, Multi Organ Dysfunction Syndrome Scale, Ranson Scale) can be used to determine outcome. Clinical signs (age, coexisting diseases, confusion, obesity) and biochemistry values (serum amylase, lipase, C-reactive protein, procalcitonin, creatinine, urea, calcium) have important prognostic roles as well. Early organ failure increases the risk of late abdominal complications and mortality. Intensive care can provide appropriate multi-function patient monitoring which helps in early recognition of complications and appropriate target-controlled treatment. Treatment of severe acute pancreatitis aims at reducing systemic inflammatory response and multiorgan dysfunction and, on the other side, at increasing the anti-inflammatory response. Oral starvation for 24-48 hours is effective in reducing the exocrine activity of the pancreas; the efficacy of protease inhibitors is questionable. Early intravascular volume resuscitation and stable haemodynamics improve microcirculation. Early oxygen therapy and mechanical ventilation provide adequate oxygenation. Electrolyte and acid-base control can be as important as tight glucose control. Adequate pain relief can be achieved by thoracic epidural catheterization. Early enteral nutrition with immunonutrition should be used. There is evidence that affecting the coagulation cascade by activated protein C can play a role in reducing the inflammatory response. The complex therapy of acute pancreatitis includes appropriate

  15. Protein tyrosine kinase regulates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking induced by acute hypoxia in cultured brainstem neurons.

    PubMed

    Wang, H; Yu, L C; Li, Y C

    2016-01-01

    This study was performed to investigate the modulation effect of protein tyrosine kinase on postsynaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking induced by acute hypoxia in cultured brainstem neurons. The cultured neurons were exposed to 1% O2 and the expression of AMPA receptor subunit GluR2 on the cell surface was significantly increased, while total GluR2 was not markedly changed. Furthermore, the hypoxia-induced increase in GluR2 expression on the cell surface was partially blocked by the protein tyrosine kinase membrane-permeable inhibitor genistein. In contrast, both the protein tyrosine kinase agonist nerve growth factor and protein tyrosine phosphatase inhibitor vanadate promoted the hypoxia-induced increase of GluR2 expression on cell surface. Moreover, GluR2 could be phosphorylated by tyrosine under normoxia and hypoxia conditions in vitro on brainstem neurons, and tyrosine phosphorylation of GluR2 was significantly stronger under hypoxia conditions. Our results indicate that acute hypoxia induces the AMPA receptor subunit GluR2 to rapidly migrate to the cell membrane to modify the strength of the synapse. This study indicates that tyrosine phosphorylation of the receptor is an important pathway regulating the rapid migration of GluR2 in the postsynaptic domain induced by hypoxia. PMID:27525851

  16. Psychosocial Care and its Association with Severe Acute Malnutrition.

    PubMed

    Singh, Anurag; Agarwal, Sheesham

    2016-05-01

    This cross-sectional study compared 120 children having severe acute malnutrition with 120 healthy children for exposure to 40 behaviors, by measuring psychosocial care based on Home Observation for Measurement of the Environment (HOME) inventory. The mean (SD) psychosocial care score of cases and controls significantly differed [18.2 (2.2) vs 23.5 (2.1); P<0.001]. A score of less than 14 was significantly associated with severe acute malnutrition (OR 23.2; 95% CI 8.2, 50). PMID:27254059

  17. Management of patients after recovering from acute severe biliary pancreatitis

    PubMed Central

    Dedemadi, Georgia; Nikolopoulos, Manolis; Kalaitzopoulos, Ioannis; Sgourakis, George

    2016-01-01

    Cholelithiasis is the most common cause of acute pancreatitis, accounting 35%-60% of cases. Around 15%-20% of patients suffer a severe attack with high morbidity and mortality rates. As far as treatment is concerned, the optimum method of late management of patients with severe acute biliary pancreatitis is still contentious and the main question is over the correct timing of every intervention. Patients after recovering from an acute episode of severe biliary pancreatitis can be offered alternative options in their management, including cholecystectomy, endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy, or no definitive treatment. Delaying cholecystectomy until after resolution of the inflammatory process, usually not earlier than 6 wk after onset of acute pancreatitis, seems to be a safe policy. ERCP and sphincterotomy on index admission prevent recurrent episodes of pancreatitis until cholecystectomy is performed, but if used for definitive treatment, they can be a valuable tool for patients unfit for surgery. Some patients who survive severe biliary pancreatitis may develop pseudocysts or walled-off necrosis. Management of pseudocysts with minimally invasive techniques, if not therapeutic, can be used as a bridge to definitive operative treatment, which includes delayed cholecystectomy and concurrent pseudocyst drainage in some patients. A management algorithm has been developed for patients surviving severe biliary pancreatitis according to the currently published data in the literature. PMID:27678352

  18. Management of patients after recovering from acute severe biliary pancreatitis

    PubMed Central

    Dedemadi, Georgia; Nikolopoulos, Manolis; Kalaitzopoulos, Ioannis; Sgourakis, George

    2016-01-01

    Cholelithiasis is the most common cause of acute pancreatitis, accounting 35%-60% of cases. Around 15%-20% of patients suffer a severe attack with high morbidity and mortality rates. As far as treatment is concerned, the optimum method of late management of patients with severe acute biliary pancreatitis is still contentious and the main question is over the correct timing of every intervention. Patients after recovering from an acute episode of severe biliary pancreatitis can be offered alternative options in their management, including cholecystectomy, endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy, or no definitive treatment. Delaying cholecystectomy until after resolution of the inflammatory process, usually not earlier than 6 wk after onset of acute pancreatitis, seems to be a safe policy. ERCP and sphincterotomy on index admission prevent recurrent episodes of pancreatitis until cholecystectomy is performed, but if used for definitive treatment, they can be a valuable tool for patients unfit for surgery. Some patients who survive severe biliary pancreatitis may develop pseudocysts or walled-off necrosis. Management of pseudocysts with minimally invasive techniques, if not therapeutic, can be used as a bridge to definitive operative treatment, which includes delayed cholecystectomy and concurrent pseudocyst drainage in some patients. A management algorithm has been developed for patients surviving severe biliary pancreatitis according to the currently published data in the literature.

  19. Management of patients after recovering from acute severe biliary pancreatitis.

    PubMed

    Dedemadi, Georgia; Nikolopoulos, Manolis; Kalaitzopoulos, Ioannis; Sgourakis, George

    2016-09-14

    Cholelithiasis is the most common cause of acute pancreatitis, accounting 35%-60% of cases. Around 15%-20% of patients suffer a severe attack with high morbidity and mortality rates. As far as treatment is concerned, the optimum method of late management of patients with severe acute biliary pancreatitis is still contentious and the main question is over the correct timing of every intervention. Patients after recovering from an acute episode of severe biliary pancreatitis can be offered alternative options in their management, including cholecystectomy, endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy, or no definitive treatment. Delaying cholecystectomy until after resolution of the inflammatory process, usually not earlier than 6 wk after onset of acute pancreatitis, seems to be a safe policy. ERCP and sphincterotomy on index admission prevent recurrent episodes of pancreatitis until cholecystectomy is performed, but if used for definitive treatment, they can be a valuable tool for patients unfit for surgery. Some patients who survive severe biliary pancreatitis may develop pseudocysts or walled-off necrosis. Management of pseudocysts with minimally invasive techniques, if not therapeutic, can be used as a bridge to definitive operative treatment, which includes delayed cholecystectomy and concurrent pseudocyst drainage in some patients. A management algorithm has been developed for patients surviving severe biliary pancreatitis according to the currently published data in the literature. PMID:27678352

  20. Assessment of the fetal PO2 changes by cerebral and umbilical Doppler on lamb fetuses during acute hypoxia.

    PubMed

    Arbeille, P; Maulik, D; Fignon, A; Stale, H; Berson, M; Bodard, S; Locatelli, A

    1995-01-01

    The objective of the present study was to validate one or a combination of fetal Doppler parameters in order to assess acute fetal hypoxia in an ovine model. Acute hypoxia was induced by reducing umbilical, or maternal aortic flow (approx. 70%). A CW Doppler probe was fixed on the fetal cervical skin, facing the internal carotid artery and the fetal abdominal skin adjacent to the umbilical arteries. (The angle between Doppler beam and flow vector remained constant.) A "Doptek 3000" spectrum analyser was used to measure the maximal and mean Doppler frequencies. Heart rate (HR), umbilical blood flow (UBF), carotid blood flow (CBF), umbilical RI (URI), cerebral RI (CRI) and cerebroplacental ratio (CPR = CRI/URI) were calculated in real time. A catheter was inserted into the fetal femoral artery, for blood gas (PO2, PCO2 pH) and blood pressure (BP) measurements. After 1 min of aorta compression (70% aortic flow reduction), the URI increased by 10% (P < 0.05), and the UBF decreased by 10% (P < 0.05), but the CRI decreased by 20% (P < 0.02), and the CBF did not change significantly. Fetal PO2 and CPR fell down after 1 min (59% and 38%, respectively; P < 0.001), although strong fetal heart rate decelerations were observed. The blood pressure, PCO2 and pH did not change significantly during this test. Throughout the 12 min of cord compression (70% umbilical flow reduction) the URI increased (70% to 80% P < 0.001), and the UBF decreased (approx. 60%; P < 0.001), but the CRI decreased (approx. 25%; P < 0.01), and the CBF remained constant (+/- 5%; ns). Fetal PO2 and CPR all decreased during the compression (30% to 44% and 40% to 60%, respectively; P < 0.001). HR, pH and PCO2 did not change significantly. During cord compression the blood pressure did not change significantly. In both cases, the CPR decreased significantly (P < 0.001) with the PO2 in the same direction and with a comparable amplitude (-30% to -50%). Nevertheless, the drop in CPR was greater during cord

  1. NW Black Sea ecosystems recovery from former severe seasonal hypoxia and effect on macrofauna

    NASA Astrophysics Data System (ADS)

    Gomoiu, Marian-Traian; Begun, Tatiana; Teaca, Adrian

    2013-04-01

    The benthos researches carried out in the last decade on the NW Black Sea shelf established the transitional process of the bottom communities, from the severe disturbed state resulted from seasonal hypoxia of high eutrophication from 1970-2000 period towards a new state. The authors, with their expertise achieved in the framework of several national and EU FP6&7 projects (SESAME, HYPOX, PERSEUS), analyzing more than 600 quantitative samples, consider the benthic associations influenced mainly by the Danube River discharge being characterized as follows: • decrease in the specific diversity (e.g. Mollusca - from 170 species in the 1960s - 1970s to 70 species in the present in NW Black Sea); • loss or diminishing of some habitat areas (typical habitat with Zostera, Phyllophora, Cystoseira, Barnea, Donacilla etc.); • increase in the numeric abundance and biomass of some specific benthic populations (Melinna, Alitta, Dipolydora etc.); • loss or reduction of some specific populations (Abra prismatica, Spisula subtruncata, Chamelia gallina etc.); • replacement of some strong and quite large benthic populations by metapopulation of small extension; • diminution of the biofilter strength by reduction of the filter - feeder populations; • qualitative and quantitative worsening of benthic biological resources, especially molluscs - forms playing an important ecological part and with great economic importance (mussel Mytilus galloprovincialis, soft-shell clam Mya arenaria, veined rapa whelk Rapana venosa); • thriving of opportunistic forms (especially worms populations causing sediment bioturbation - Melinna palmata, Heteromastus filiformis) and, temporarily, some exotic species recently pervading Black Sea (Mya, Anadara, Rapana etc.); • great quantitative fluctuations of all benthic populations; • occurrence of some weak sing of ecosystem recovery. However, recovery of the benthic ecosystem appears to be less certain although an improvement on

  2. Oxidative stress response to acute hypobaric hypoxia and its association with indirect measurement of increased intracranial pressure: a field study

    PubMed Central

    Strapazzon, Giacomo; Malacrida, Sandro; Vezzoli, Alessandra; Dal Cappello, Tomas; Falla, Marika; Lochner, Piergiorgio; Moretti, Sarah; Procter, Emily; Brugger, Hermann; Mrakic-Sposta, Simona

    2016-01-01

    High altitude is the most intriguing natural laboratory to study human physiological response to hypoxic conditions. In this study, we investigated changes in reactive oxygen species (ROS) and oxidative stress biomarkers during exposure to hypobaric hypoxia in 16 lowlanders. Moreover, we looked at the potential relationship between ROS related cellular damage and optic nerve sheath diameter (ONSD) as an indirect measurement of intracranial pressure. Baseline measurement of clinical signs and symptoms, biological samples and ultrasonography were assessed at 262 m and after passive ascent to 3830 m (9, 24 and 72 h). After 24 h the imbalance between ROS production (+141%) and scavenging (−41%) reflected an increase in oxidative stress related damage of 50–85%. ONSD concurrently increased, but regression analysis did not infer a causal relationship between oxidative stress biomarkers and changes in ONSD. These results provide new insight regarding ROS homeostasis and potential pathophysiological mechanisms of acute exposure to hypobaric hypoxia, plus other disease states associated with oxidative-stress damage as a result of tissue hypoxia. PMID:27579527

  3. Oxidative stress response to acute hypobaric hypoxia and its association with indirect measurement of increased intracranial pressure: a field study.

    PubMed

    Strapazzon, Giacomo; Malacrida, Sandro; Vezzoli, Alessandra; Dal Cappello, Tomas; Falla, Marika; Lochner, Piergiorgio; Moretti, Sarah; Procter, Emily; Brugger, Hermann; Mrakic-Sposta, Simona

    2016-01-01

    High altitude is the most intriguing natural laboratory to study human physiological response to hypoxic conditions. In this study, we investigated changes in reactive oxygen species (ROS) and oxidative stress biomarkers during exposure to hypobaric hypoxia in 16 lowlanders. Moreover, we looked at the potential relationship between ROS related cellular damage and optic nerve sheath diameter (ONSD) as an indirect measurement of intracranial pressure. Baseline measurement of clinical signs and symptoms, biological samples and ultrasonography were assessed at 262 m and after passive ascent to 3830 m (9, 24 and 72 h). After 24 h the imbalance between ROS production (+141%) and scavenging (-41%) reflected an increase in oxidative stress related damage of 50-85%. ONSD concurrently increased, but regression analysis did not infer a causal relationship between oxidative stress biomarkers and changes in ONSD. These results provide new insight regarding ROS homeostasis and potential pathophysiological mechanisms of acute exposure to hypobaric hypoxia, plus other disease states associated with oxidative-stress damage as a result of tissue hypoxia. PMID:27579527

  4. Severe Acute Respiratory Syndrome (SARS) Prevention in Taiwan

    ERIC Educational Resources Information Center

    Liu, Hsueh-Erh

    2004-01-01

    Severe Acute Respiratory Syndrome (SARS) is a newly identified respiratory disease that threatened Taiwan between April 14 and July 5, 2003. Chang Gung University experienced various SARS-related episodes, such as the postponement of classes for 7 days, the reporting of probable SARS cases, and the isolation of students under Level A and B…

  5. Is ketamine a lifesaving agent in childhood acute severe asthma?

    PubMed Central

    Hendaus, Mohamed A; Jomha, Fatima A; Alhammadi, Ahmed H

    2016-01-01

    Children with acute severe asthma exacerbation are at risk of developing respiratory failure. Moreover, conventional aggressive management might be futile in acute severe asthma requiring intubation and invasive ventilation. The aim of this review is to detail evidence on the use of ketamine in childhood asthma exacerbations. A search of the MEDLINE, EMBASE, and Cochrane databases was performed, using different combinations of the following terms: ketamine, asthma, use, exacerbation, and childhood. In addition, we searched the references of the identified articles for additional articles. We then reviewed titles and included studies that were relevant to the topic of interest. Finally, the search was limited to studies published in English and Spanish from 1918 to June 2015. Due to the scarcity in the literature, we included all published articles. The literature reports conflicting results of ketamine use for acute severe asthma in children. Taking into consideration the relatively good safety profile of the drug, ketamine might be a reasonable option in the management of acute severe asthma in children who fail to respond to standard therapy. Furthermore, pediatricians and pediatric emergency clinicians administering ketamine should be knowledgeable about the unique actions of this drug and its potential side effects. PMID:26955277

  6. [Acute necrotizing esophagitis (black esophagus) with secondary severe stenosis].

    PubMed

    Gómez, Álvaro A; Guerrero, Diego; Hani, Albis C; Cañadas, Raúl

    2015-01-01

    We report the case of a 67 years old patient with a history of diabetes mellitus, atrial fibrillation and chronic renal failure, who developed diabetic ketoacidosis and severe sepsis, later presenting an acute necrotizing esophagitis, and then a esophageal stenosis requiring treatment with self-expanding esophageal prosthesis with good clinical results. PMID:26802889

  7. Daily acute intermittent hypoxia elicits functional recovery of diaphragm and inspiratory intercostal muscle activity after acute cervical spinal injury

    PubMed Central

    Navarrete-Opazo, A.; Vinit, S; Dougherty, B.J.; Mitchell, G.S.

    2015-01-01

    A major cause of mortality after spinal cord injury is respiratory failure. In normal rats, acute intermittent hypoxia (AIH) induces respiratory motor plasticity, expressed as diaphragm (Dia) and second external intercostal (T2 EIC) long-term facilitation (LTF). Dia (not T2 EIC) LTF is enhanced by systemic adenosine 2A (A2a) receptor inhibition in normal rats. We investigated the respective contributions of Dia and T2 EIC to daily AIH-induced functional recovery of breathing capacity with/without A2a receptor antagonist (KW6002, i.p.) following C2 hemisection (C2HS). Rats received daily AIH (dAIH: 10, 5-min episodes, 10.5% O2; 5-min normoxic intervals; 7 successive days beginning 7 days post-C2HS) or daily normoxia (dNx) with/without KW6002, followed by weekly (reminder) presentations for 8 weeks. Ventilation and EMGs from bilateral diaphragm and T2 EIC muscles were measured with room air breathing (21% O2) and maximum chemoreceptor stimulation (MCS: 7% CO2, 10.5% O2). dAIH increased tidal volume (Vt) in C2HS rats breathing room air (dAIH + vehicle: 0.47 ± 0.02, dNx + vehicle: 0.40 ± 0.01ml/100 g; p<0.05) and MCS (dAIH + vehicle: 0.83 ± 0.01, dNx + vehicle: 0.73 ± 0.01ml/100g; p<0.001); KW6002 had no significant effect. dAIH enhanced contralateral (uninjured) diaphragm EMG activity, an effect attenuated by KW6002, during room air breathing and MCS (p<0.05). Although dAIH enhanced contralateral T2 EIC EMG activity during room air breathing, KW6002 had no effect. dAIH had no statistically significant effects on diaphragm or T2 EIC EMG activity ipsilateral to injury. Thus, two weeks post-C2HS: 1) dAIH enhances breathing capacity by effects on contralateral diaphragm and T2 EIC activity; and 2) dAIH-induced recovery is A2a dependent in diaphragm, but not T2 EIC. Daily AIH may be a useful in promoting functional recovery of breathing capacity after cervical spinal injury, but A2a receptor antagonists (eg. caffeine) may undermine its effectiveness shortly after

  8. Meteorological parameters and severity of acute pulmonary embolism episodes.

    PubMed

    Staśkiewicz, Grzegorz; Czekajska-Chehab, Elżbieta; Przegaliński, Jerzy; Maciejewski, Marcin; Pachowicz, Marcin; Drop, Andrzej

    2011-01-01

    Frequency of acute pulmonary embolism episodes has been previously shown to correlate significantly with meteorological factors in the period preceding their occurrence. The purpose of the study was to analyze the relation of meteorological factors and the severity of acute pulmonary embolism, expressed by the CT-based pulmonary obstruction score. A retrospective analysis of medical data of 182 consecutive patients with acute pulmonary embolism diagnosed with CT pulmonary angiography was performed. Severity of pulmonary obstruction was assessed by analysis of CT pulmonary angiography examinations, and defined with pulmonary obstruction score by Qanadli et al. The study group was divided into low (L group, 95 patients) and high PE severity (H group, 87 patients), with a cutoff value of 50% of maximum pulmonary obstruction score. Meteorological data collected for the relevant time period were: air temperature, humidity, atmospheric pressure, visibility, wind speed and precipitation. No significant differences in seasonal distribution of pulmonary embolism episodes were observed. Episodes of more severe pulmonary embolism were preceded by periods of lower atmospheric pressure (1,016.35 hPA for group H, vs. 1,016.35 hPa for group L, p = 0.022). No significant relations between other meteorological factors and severity of PE were observed. The reported finding shows the need of further research on the nature of meteorological factors influence on the course of pulmonary embolism, which should be analyzed not ony regarding the frequency, but also severity of PE episodes.

  9. A microfluidic system for studying the behavior of zebrafish larvae under acute hypoxia.

    PubMed

    Erickstad, Michael; Hale, Laura A; Chalasani, Sreekanth H; Groisman, Alex

    2015-02-01

    Oxygen is essential for metabolism of animals and is a vital component of their natural habitats. Hypoxic conditions in tissue, when oxygen levels are lower than normal, change a variety of cellular processes, while environmental hypoxia can have physiological and behavioral effects on the whole animal. Larval zebrafish respond to oxygen deprivation with a characteristic set of physiological changes and motor behaviors, making them a convenient vertebrate model to study hypoxia responses. However, to date, hypoxia studies in zebrafish are limited by the existing experimental setups, which only impose hypoxia on a scale of minutes to hours. Here, we present a microfluidic system, which makes it possible to expose spatially confined unanesthetized zebrafish larvae to a broad range of hypoxic and normoxic conditions and to switch between different oxygen concentrations in the medium around the larvae on a 2 second timescale. We used the system to observe different behavioral responses of zebrafish larvae to three levels of rapidly imposed hypoxia. Larvae increased their rate of body movements in response to the strongest hypoxia and increased their rate of pectoral fin beats in response to all levels of hypoxia. Importantly, the behavior of the larvae changed within 15 seconds of the changes in the oxygen content of the medium. The proposed experimental system can be used to study the behavior of zebrafish larvae or other aquatic organisms exposed to other water-dissolved gasses or to different temporal patterns of oxygen concentration. This system can also potentially be used for testing the effects of genetic modifications and small molecule drugs and for probing neural mechanisms underlying various behaviors. PMID:25490410

  10. Extracorporeal life support for adults with severe acute respiratory failure.

    PubMed

    Del Sorbo, Lorenzo; Cypel, Marcelo; Fan, Eddy

    2014-02-01

    Extracorporeal life support (ECLS) is an artificial means of maintaining adequate oxygenation and carbon dioxide elimination to enable injured lungs to recover from underlying disease. Technological advances have made ECLS devices smaller, less invasive, and easier to use. ECLS might, therefore, represent an important step towards improved management and outcomes of patients with acute respiratory distress syndrome. Nevertheless, rigorous evidence of the ability of ECLS to improve short-term and long-term outcomes is needed before it can be widely implemented. Moreover, how to select patients and the timing and indications for ECLS in severe acute respiratory distress syndrome remain unclear. We describe the physiological principles, the putative risks and benefits, and the clinical evidence supporting the use of ECLS in patients with acute respiratory distress syndrome. Additionally, we discuss controversies and future directions, such as novel technologies and indications, mechanical ventilation of the native lung during ECLS, and ethics considerations. PMID:24503270

  11. Pharmacological stimulation of Hypoxia Inducible Factor-1α facilitates the corticosterone response to a mild acute stressor

    PubMed Central

    Harrell, Constance S.; Rowson, Sydney A.; Neigh, Gretchen N.

    2015-01-01

    While both glucocorticoids (the principal output of the hypothalamic-pituitary-adrenal axis) and oxidative stress have been implicated in outcomes due to an excessive or prolonged stress response, the precise mechanisms linking these two systems remain poorly elucidated. One potential mediator between the hypothalamic-pituitary-adrenal axis and oxidative stress is the Hypoxia Inducible Factor-1 (HIF-1) pathway. HIF-1 is an oxygen-responsive transcription factor with diverse effects including changes in cellular metabolism. The experiments in this manuscript sought to determine if pharmacological stimulation of HIF-1α via administration of dimethyloxalylglycine (DMOG) would facilitate the corticosterone response to a mild acute stressor. DMOG administration significantly increased plasma corticosterone five minutes after an acute airpuff without changing baseline plasma corticosterone or plasma corticosterone level two hours post-startle. DMOG administration also reduced hippocampal gene expression of the pro-translocation co-chaperone for the glucocorticoid receptor, FKBP4, two hours after airpuff startle. At this same two-hour time point, hippocampal expression of FKBP5, an anti-translocation co-chaperone of glucocorticoid receptor, in the DMOG-treated group was also positively correlated with plasma corticosterone levels. These data indicate that there is significant crosstalk between the hypothalamic-pituitary-axis and the HIF-1 pathway and extend the current knowledge of glucocorticoid and hypoxia interactions in an ethologically relevant stress model. PMID:26037418

  12. Early plasmapheresis in patients with severe hypertriglyceridemia induced acute pancreatitis.

    PubMed

    Nasa, Prashant; Alexander, George; Kulkarni, Amitabh; Juneja, Deven; Sehra, Sudhish; Agarwal, Rajesh; Koul, Kandy

    2015-08-01

    Hypertriglyceridemia can cause severe diseases such as acute pancreatitis (AP) and coronary artery disease. The routine management of hypertriglyceridemia is dietary restriction of fat and lipid-lowering medications to manage the secondary or precipitating causes of hypertriglyceridemia. However, in cases of AP with severe hypertriglyceridemia (SHTG) (triglycerides [TG] >1000 mg/dl) rapid reduction of TG levels to well below 1000 mg/dl can improve outcome and prevent further episodes of pancreatitis. Plasmapheresis is a therapeutic option in such medical emergencies. We discussed 2 cases of severe AP with SHTG where we used early plsmapheresis along with other supportive management. PMID:26321811

  13. Neuroanatomical correlates of severe cardiac arrhythmias in acute ischemic stroke.

    PubMed

    Seifert, Frank; Kallmünzer, Bernd; Gutjahr, Isabell; Breuer, Lorenz; Winder, Klemens; Kaschka, Iris; Kloska, Stephan; Doerfler, Arnd; Hilz, Max-Josef; Schwab, Stefan; Köhrmann, Martin

    2015-05-01

    Neurocardiological interactions can cause severe cardiac arrhythmias in patients with acute ischemic stroke. The relationship between the lesion location in the brain and the occurrence of cardiac arrhythmias is still discussed controversially. The aim of the present study was to correlate the lesion location with the occurrence of cardiac arrhythmias in patients with acute ischemic stroke. Cardiac arrhythmias were systematically assessed in patients with acute ischemic stroke during the first 72 h after admission to a monitored stroke unit. Voxel-based lesion-symptom mapping (VLSM) was used to correlate the lesion location with the occurrence of clinically relevant severe arrhythmias. Overall 150 patients, 56 with right-hemispheric and 94 patients with a left-hemispheric lesion, were eligible to be included in the VLSM study. Severe cardiac arrhythmias were present in 49 of these 150 patients (32.7%). We found a significant association (FDR correction, q < 0.05) between lesions in the right insular, right frontal and right parietal cortex as well as the right amygdala, basal ganglia and thalamus and the occurrence of cardiac arrhythmias. Because left- and right-hemispheric lesions were analyzed separately, the significant findings rely on the 56 patients with right-hemispheric lesions. The data indicate that these areas are involved in central autonomic processing and that right-hemispheric lesions located to these areas are associated with an elevated risk for severe cardiac arrhythmias.

  14. [Effect of acute hypoxia with hypercapnia on the content of monoamines in symmetrical brain structures of the BALB/c male mice].

    PubMed

    Karpova, I V; Mikheev, V V; Marysheva, V V; Bychkov, E R; Shabanov, P D

    2014-01-01

    The changes in activity of monoaminergic systems of both the right and the left brain hemispheres of the BALB/c male mice after an acute hypoxia with hypercapnia were studied. The concentrations of dopamine, serotonin and their metabolites dihydroxyphenylacetic, homovanilic and 5-hydroxyindolacetic acids were measured by HPLC in the brain cortex, hippocampus and striatum of the right and the left hemispheres. The more high concentration of serotonin was revealed only in the cortex of the left hemisphere in control mice without hypoxia with hypercapnia. The asymmetry in dopamine level was not registered in all structures studied. Acute hypoxia with hypercapnia decreased the dopamine level in the striatum and the serotonin level both in the hippocampus and the brain cortex. The dopamine metabolites level was reduced in the striatum and in the brain cortex of hypoxed mice: both metabolites in the right brain cortex and only dihydroxyphenylacetic acid in the left br ain cortex. Serotonin metabolism was decreased in all brain structures studied after hypoxia with hypercapnia in mice. Therefore, serotoninergic system of the brain is more sensitive to acute hypoxia with hypercapnia than dopaminergic system.

  15. Severe fever with thrombocytopenia syndrome presenting as acute hepatic failure

    PubMed Central

    Park, Jung Gil

    2015-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is characterized by fever, thrombocytopenia, leukopenia, and altered consciousness, which may also involve multi-organ failure. Initially SFTS mortality was as high as 30%, when diagnosis remained unclear. We present a case of a 53-year- old man with SFTS presenting with acute hepatic failure. On admission, he presented with confusion, elevated serum liver enzyme and ammonia levels, whose serum markers were negative for acute viral hepatitis. He was diagnosed with SFTS based on reverse transcription-polymerase chain reaction identification of the SFTS virus M segment. Percutaneous liver biopsy was performed to identify the degree and extent of necroinflammation and patient prognosis. After recovery, he was followed-up for 12 months with no SFTS-related sequelae. A discordance in severity between biopsy findings and clinical course could explain the rapid clinical improvement. Atypical presentations with multi-organ failure can delay timely diagnosis and management of infected patients. PMID:27752587

  16. Severe acute respiratory syndrome and its lesions in digestive system

    PubMed Central

    Zhang, Jian-Zhong

    2003-01-01

    Severe acute respiratory syndrome (SARS) is an infectious atypical pneumonia that has recently been recognized in the patients in 32 countries and regions. This brief review summarizes some of the initial etiologic findings, pathological description, and its lesions of digestive system caused by SARS virus. It is an attempt to draw gastroenterologists and hepatologists' attention to this fatal illness, especially when it manifests itself initially as digestive symptoms. PMID:12800212

  17. Control Measures for Severe Acute Respiratory Syndrome (SARS) in Taiwan

    PubMed Central

    Twu, Shiing-Jer; Chen, Tzay-Jinn; Chen, Chien-Jen; Olsen, Sonja J.; Lee, Long-Teng; Fisk, Tamara; Hsu, Kwo-Hsiung; Chang, Shan-Chwen; Chen, Kow-Tong; Chiang, I-Hsin; Wu, Yi-Chun; Wu, Jiunn-Shyan

    2003-01-01

    As of April 14, 2003, Taiwan had had 23 probable cases of severe acute respiratory syndrome (SARS), all imported. Taiwan isolated these first 23 patients with probable SARS in negative-pressure rooms; extensive personal protective equipment was used for healthcare workers and visitors. For the first 6 weeks of the SARS outbreak, recognized spread was limited to one healthcare worker and three household contacts. PMID:12781013

  18. Rapid regulation of blood parameters under acute hypoxia in the Amazonian fish Prochilodus nigricans.

    PubMed

    Val, Adalberto Luis; Gomes, Katia Regina Maruyama; de Almeida-Val, Vera Maria Fonseca

    2015-06-01

    Prochilodus nigricans, locally known as curimatã, is an Amazonian commercial fish that endures adverse environmental conditions, in particular low dissolved oxygen, during its migration. Poorer environmental conditions are expected in the near future. Prochilodus nigricans overcomes current seasonal and diurnal changes in dissolved oxygen by adjusting erythrocytic levels of ATP and GTP, modulators of Hb-O2 affinity. Will this fish species be endangered under more extreme environmental conditions as hypoxia and acidification tend to occur in a shorter period of time? As P. nigricans does not exhibit any apparent morphological alterations to exploit the air-water interface, it must rely on fast adjustments of blood properties. To investigate this aspect, basic hematology indices, pHe, pHi, plasma lactate, erythrocytic levels of ATP and GTP and functional properties of the hemolysate of P. nigricans were analyzed over a period of 6h in hypoxia and subsequent recovery in normoxia. The levels of erythrocytic GTP were four times higher than ATP and were reduced to ¼ of the original level after 3h under hypoxia. Erythrocytic levels of ATP were unaffected over the experimental period. All other analyzed blood parameters exhibited a time-course change in animals under hypoxia and returned to normoxic levels. Considering the hemolysate functional properties and the ability to regulate the above mentioned blood characteristics, P. nigricans is able to endure short-term changes in dissolved oxygen. PMID:25737030

  19. Aerobic fitness influences the response of maximal oxygen uptake and lactate threshold in acute hypobaric hypoxia.

    PubMed

    Koistinen, P; Takala, T; Martikkala, V; Leppäluoto, J

    1995-02-01

    We studied 12 highly trained athletes, 6 male ice-hockey players and 6 cross-country skiers (2 females, 4 males). All of them participated in a maximal electrically braked bicycle ergometer test in a hypobaric chamber at the simulated altitude of 3000m (520 mmHg) and in normobaric conditions two days apart in random order. The maximal oxygen uptake was 57.4 +/- 7.1 (SD) ml/kg/min in normobaria (VO2maxnorm) and 46.6 +/- 4.9 (SD) ml/kg/min in hypobaric hypoxia (VO2maxhyp). The decrease in maximal oxygen uptake (delta VO2max) at the simulated altitude of 3000m correlated significantly (p < 0.05, r = 0.61) to the maximal oxygen uptake in normobaric conditions (VO2maxnorm). The lactate threshold was 43.5 +/- 6.4 (SD) ml/kg/min in normobaria (VO2LTnorm) and 36.5 +/- 4.2 (SD) ml/kg/min in hypobaric hypoxia (VO2LThyp). The decrement (delta VO2LT) of lactate threshold in hypoxia correlated significantly (p < 0.01, r = 0.68) with the lactate threshold in normobaric conditions (VOLTnorm). Thus we observed the largest reduction of both maximal oxygen uptake and lactate threshold during exercise at hypobaric hypoxia in the most fit athletes. PMID:7751080

  20. Update: Outbreak of severe acute respiratory syndrome--worldwide, 2003.

    PubMed

    2003-03-28

    CDC continues to support the World Health Organization (WHO) in the investigation of a multicountry outbreak of unexplained atypical pneumonia referred to as severe acute respiratory syndrome (SARS). This report includes summaries of the epidemiologic investigations and public health responses in several affected locations where CDC is collaborating with international and national health authorities. This report also describes an unusual cluster of cases associated with a hotel in Hong Kong and identifies the potential etiologic agent of SARS. Epidemiologic and laboratory investigations of SAPS are ongoing. PMID:12680518

  1. Severe Raynaud's phenomenon-A streamlined approach to acute management.

    PubMed

    Lee, Regent; Lomas, Oliver; Handa, Ashok

    2011-01-01

    Raynaud's phenomenon is an exaggerated vasospastic response to cold or emotional stress which not only may cause the patient severe pain but also critical ischaemia and necrosis of the digits. We report the case of a 69-year-old woman who presented with rest pain, impending ulceration and necrosis of finger tips due to an episode of left-sided Raynaud's phenomenon. Intravenous prostacyclin was administered successfully as a bridge to endoscopic thoracic sympathectomy. Vascular surgery units are ideally positioned for the acute management of severe Raynaud's phenomenon to provide continuity of care to patients with profound digital ischaemia and impending tissue loss.

  2. Acute Beetroot Juice Supplementation Does Not Improve Cycling Performance in Normoxia or Moderate Hypoxia.

    PubMed

    MacLeod, Kristin E; Nugent, Sean F; Barr, Susan I; Koehle, Michael S; Sporer, Benjamin C; MacInnis, Martin J

    2015-08-01

    Beetroot juice (BR) has been shown to lower the oxygen cost of exercise in normoxia and may have similar effects in hypoxia. We investigated the effect of BR on steady-state exercise economy and 10-km time trial (TT) performance in normoxia and moderate hypoxia (simulated altitude: ~2500 m). Eleven trained male cyclists (VO 2peak ≥ 60 ml · kg(-1) · min(-1)) completed four exercise trials. Two hours before exercise, subjects consumed 70 mL BR (~6 mmol nitrate) or placebo (nitrate-depleted BR) in a randomized, double-blind manner. Subjects then completed a 15-min self-selected cycling warm-up, a 15-min steady-state exercise bout at 50% maximum power output, and a 10-km time trial (TT) in either normoxia or hypoxia. Environmental conditions were randomized and single-blind. BR supplementation increased plasma nitrate concentration and fraction of exhaled nitric oxide relative to PL (p < .05 for both comparisons). Economy at 50% power output was similar in hypoxic and normoxic conditions (p > .05), but mean power output was greater in the normoxic TT relative to the hypoxic TT (p < .05). BR did not affect economy, steady-state SpO2, mean power output, or 10-km TT completion time relative to placebo in either normoxia or hypoxia (p > .05 in all comparisons). In conclusion, BR did not lower the oxygen cost of steady-state exercise or improve exercise performance in normoxia or hypoxia in a small sample of well-trained male cyclists.

  3. Severe acute pancreatitis: Pathogenetic aspects and prognostic factors

    PubMed Central

    Mofleh, Ibrahim A Al

    2008-01-01

    Approximately 20% of patients with acute pancreatitis develop a severe disease associated with complications and high risk of mortality. The purpose of this study is to review pathogenesis and prognostic factors of severe acute pancreatitis (SAP). An extensive medline search was undertaken with focusing on pathogenesis, complications and prognostic evaluation of SAP. Cytokines and other inflammatory markers play a major role in the pathogenesis and course of SAP and can be used as prognostic markers in its early phase. Other markers such as simple prognostic scores have been found to be as effective as multifactorial scoring systems (MFSS) at 48 h with the advantage of simplicity, efficacy, low cost, accuracy and early prediction of SAP. Recently, several laboratory markers including hematocrit, blood urea nitrogen (BUN), creatinine, matrix metalloproteinase-9 (MMP-9) and serum amyloid A (SAA) have been used as early predictors of severity within the first 24 h. The last few years have witnessed a tremendous progress in understanding the pathogenesis and predicting the outcome of SAP. In this review we classified the prognostic markers into predictors of severity, pancreatic necrosis (PN), infected PN (IPN) and mortality. PMID:18205255

  4. Effect of acute hypoxia on the concentrations of potassium and phosphorus in the cardiomyocyte of a pregnant animal during early organogenesis.

    PubMed

    Pogorelov, A G

    2008-05-01

    The concentrations of potassium and phosphorus in the cardiomyocyte cytoplasm of the Wistar rat were measured by means of electron probe microanalysis. Pregnancy was accompanied by a decrease in cytoplasmic phosphorus concentration and an increase in cytoplasmic potassium concentration. Acute hypoxia modified the concentrations of these elements in the cytoplasm. PMID:19145292

  5. MANAGEMENT OF ACUTE SEVERE ULCERATIVE COLITIS: A CLINICAL UPDATE

    PubMed Central

    SOBRADO, Carlos Walter; SOBRADO, Lucas Faraco

    2016-01-01

    ABSTRACT Introduction: Acute severe colitis is a potentially lethal medical emergency and, even today, its treatment remains a challenge for clinicians and surgeons. Intravenous corticoid therapy, which was introduced into the therapeutic arsenal in the 1950s, continues to be the first-line treatment and, for patients who are refractory to this, the rescue therapy may consist of clinical measures or emergency colectomy. Objective: To evaluate the indications for and results from drug rescue therapy (cyclosporine, infliximab and tacrolimus), and to suggest a practical guide for clinical approaches. Methods: The literature was reviewed using the Medline/PubMed, Cochrane library and SciELO databases, and additional information from institutional websites of interest, by cross-correlating the following keywords: acute severe colitis, fulminating colitis and treatment. Results: Treatments for acute severe colitis have avoided colectomy in 60-70% of the cases, provided that they have been started early on, with multidisciplinary follow-up. Despite the adverse effects of intravenous cyclosporine, this drug has been indicated in cases of greater severity with an imminent risk of colectomy, because of its fast action, short half-life and absence of increased risk of surgical complications. Therapy using infliximab has been reserved for less severe cases and those in which immunosuppressants are being or have been used (AZA/6-MP). Indication of biological agents has recently been favored because of their ease of therapeutic use, their good short and medium-term results, the possibility of maintenance therapy and also their action as a "bridge" for immunosuppressant action (AZA/6-MP). Colectomy has been reserved for cases in which there is still no response five to seven days after rescue therapy and in cases of complications (toxic megacolon, profuse hemorrhage and perforation). Conclusion: Patients with a good response to rescue therapy who do not undergo emergency

  6. Acute, Severe Cryptosporidiosis in an Immunocompetent Pediatric Patient

    PubMed Central

    Tallant, Caitlin; Huddleston, Patrick; Alshanberi, Asim

    2016-01-01

    Severe diarrheal illness in children can be attributed to a number of different microbiological agents. Without appropriate microbiological testing of stool samples, patients who present with multiple days of severe diarrhea might have a delay in proper diagnosis and treatment. Here, we report a case of an immunocompetent pediatric patient presenting with acute cryptosporidiosis. Humans and bovine species are known hosts of cryptosporidium and several studies have evaluated the zoonotic transmission of cryptosporidium from cattle to humans. Adding diagnostic tests for cryptosporidium like Ziehl-Neelsen staining of stool or fecal rapid antigen detection techniques should be considered in the workup of patients presenting with undifferentiated, severe diarrheal illness, especially in those who have close contact with livestock. PMID:27478580

  7. Severe hypophosphataemia during recovery from acute respiratory acidosis.

    PubMed

    Storm, T L

    1984-08-25

    Three elderly patients with established chronic obstructive airways disease were admitted with a short history of increasing dyspnoea and tiredness and (in two cases) a deterioration in mental state. Acute respiratory acidosis was diagnosed and mechanical ventilation instituted. Two hours after beginning mechanical ventilation the mean arterial pH had risen to 7.40, but all patients showed a dramatic fall in the serum phosphate concentration (lowest value 0.3 mmol/l (0.9 mg/100 ml] accompanied by a low urinary excretion of phosphate. No patient could tolerate withdrawal of mechanical ventilation until the serum and urinary concentrations of phosphate had returned to normal. Recovery from acute respiratory acidosis should be added to the list of conditions associated with severe hypophosphataemia.

  8. Acute fatty liver of pregnancy associated with severe acute pancreatitis: A case report

    PubMed Central

    de Oliveira, Cássio Vieira; Moreira, Alecsandro; Baima, Julio P; Franzoni, Leticia de C; Lima, Talles B; Yamashiro, Fabio da S; Coelho, Kunie Yabuki Rabelo; Sassaki, Ligia Y; Caramori, Carlos Antonio; Romeiro, Fernando G; Silva, Giovanni F

    2014-01-01

    Acute fatty liver of pregnancy is a rare disease that affects women in the third trimester of pregnancy. Although infrequent, the disease can cause maternal mortality. The diagnosis is not always clear until the pregnancy is terminated, and significant complications, such as acute pancreatitis, can occur. Pancreatic involvement typically only occurs in severe cases after the development of hepatic and renal impairment. To date, little knowledge is available regarding how the disease causes pancreatitis. Treatment involves supportive measures and pregnancy interruption. In this report, we describe a case of a previously healthy 26-year-old woman at a gestational age of 27 wk and 6 d who was admitted with severe abdominal pain and vomiting. This case illustrates the clinical and laboratory overlap between acute fatty liver of pregnancy and pancreatitis, highlighting the difficulties in differentiating each disease. Furthermore, the hypothesis for this overlapping is presented, and the therapeutic options are discussed. PMID:25068005

  9. Acute fatty liver of pregnancy associated with severe acute pancreatitis: A case report.

    PubMed

    de Oliveira, Cássio Vieira; Moreira, Alecsandro; Baima, Julio P; Franzoni, Leticia de C; Lima, Talles B; Yamashiro, Fabio da S; Coelho, Kunie Yabuki Rabelo; Sassaki, Ligia Y; Caramori, Carlos Antonio; Romeiro, Fernando G; Silva, Giovanni F

    2014-07-27

    Acute fatty liver of pregnancy is a rare disease that affects women in the third trimester of pregnancy. Although infrequent, the disease can cause maternal mortality. The diagnosis is not always clear until the pregnancy is terminated, and significant complications, such as acute pancreatitis, can occur. Pancreatic involvement typically only occurs in severe cases after the development of hepatic and renal impairment. To date, little knowledge is available regarding how the disease causes pancreatitis. Treatment involves supportive measures and pregnancy interruption. In this report, we describe a case of a previously healthy 26-year-old woman at a gestational age of 27 wk and 6 d who was admitted with severe abdominal pain and vomiting. This case illustrates the clinical and laboratory overlap between acute fatty liver of pregnancy and pancreatitis, highlighting the difficulties in differentiating each disease. Furthermore, the hypothesis for this overlapping is presented, and the therapeutic options are discussed. PMID:25068005

  10. Temporal dynamics of lactate concentration in the human brain during acute inspiratory hypoxia

    PubMed Central

    Harris, Ashley D; Roberton, Victoria H; Huckle, Danielle L; Saxena, Neeraj; Evans, C John; Murphy, Kevin; Hall, Judith E; Bailey, Damian M; Mitsis, Georgios; Edden, Richard A E; Wise, Richard G

    2012-01-01

    Purpose To demonstrate the feasibility of measuring the temporal dynamics of cerebral lactate concentration and examine these dynamics in human subjects using MRS during hypoxia. Methods A respiratory protocol consisting of 10 min baseline normoxia, 20 min inspiratory hypoxia and ending with 10 min normoxic recovery was used, throughout which lactate-edited MRS was performed. This was repeated four times in three subjects. A separate session was performed to measure blood lactate. Impulse response functions using end-tidal oxygen and blood lactate as system inputs and cerebral lactate as the system output were examined to describe the dynamics of the cerebral lactate response to a hypoxic challenge. Results The average lactate increase was 20%±15% during the last half of the hypoxic challenge. Significant changes in cerebral lactate concentration were observed after 400s. The average relative increase in blood lactate was 188%±95%. The temporal dynamics of cerebral lactate concentration was reproducibly demonstrated with 200s time bins of MRS data (coefficient of variation 0.063±0.035 between time bins in normoxia). The across subject coefficient of variation was 0.333. Conclusions The methods for measuring the dynamics of the cerebral lactate response developed here would be useful to further investigate the brain’s response to hypoxia. PMID:23197421

  11. [Protocol for the treatment of severe acute pancreatitis with necrosis].

    PubMed

    Barreda, Luis; Targarona, Javier; Rodriguez, César

    2005-01-01

    The Severe Acute Pancreatic Unit of Edgardo Rebagliati Martins National Hospital was officially created in the year 2000. Up to date, we have cared for more than 195 patients with Pancreatic Necrosis. All of them have been treated under a management protocol presented by us. This has helped us to standardize treatment and also to compare results with work groups around the world. This Protocol comes from our own experience and that of our colleagues abroad with a wide knowledge in this kind of pathology abroad, with whom we maintain close ties.

  12. Cerebral Hypoxia

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Cerebral Hypoxia Information Page Synonym(s): Hypoxia, Anoxia Table of Contents ( ... Trials Organizations Publicaciones en Español What is Cerebral Hypoxia? Cerebral hypoxia refers to a condition in which ...

  13. NIV-Helmet in Severe Hypoxemic Acute Respiratory Failure

    PubMed Central

    Martins, Joana; Nunes, P.; Silvestre, C.; Abadesso, C.; Loureiro, H.; Almeida, H.

    2015-01-01

    Noninvasive ventilation (NIV) is a method to be applied in acute respiratory failure, given the possibility of avoiding tracheal intubation and conventional ventilation. A previous healthy 5-month-old boy developed low-grade intermittent fever, flu-like symptoms, and dry cough for 3 days. On admission, he showed severe respiratory distress with SpO2/FiO2 ratio of 94. Subsequent evaluation identified an RSV infection complicated with an increase of inflammatory parameters (reactive C protein 15 mg/dL). Within the first hour after NIV-helmet CPAP SpO2/FiO2 ratio increased to 157. This sustained improvement allowed the continuing of this strategy. After 102 h, he was disconnected from the helmet CPAP device. The NIV use in severe hypoxemic acute respiratory failure should be carefully monitored as the absence of clinical improvement has a predictive value in the need to resume to intubation and mechanical ventilation. We emphasize that SpO2/FiO2 ratio is a valuable monitoring instrument. Helmet interface use represents a more comfortable alternative for providing ventilatory support, particularly to small infants, which constitute a sensitive group within pediatric patients. PMID:26000189

  14. Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury

    PubMed Central

    Gralinski, Lisa E.; Bankhead, Armand; Jeng, Sophia; Menachery, Vineet D.; Proll, Sean; Belisle, Sarah E.; Matzke, Melissa; Webb-Robertson, Bobbie-Jo M.; Luna, Maria L.; Shukla, Anil K.; Ferris, Martin T.; Bolles, Meagan; Chang, Jean; Aicher, Lauri; Waters, Katrina M.; Smith, Richard D.; Metz, Thomas O.; Law, G. Lynn; Katze, Michael G.; McWeeney, Shannon; Baric, Ralph S.

    2013-01-01

    ABSTRACT Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV. PMID:23919993

  15. The Role of Peritoneal Lavage in Severe Acute Pancreatitis

    PubMed Central

    Ranson, John H. C.; Spencer, Frank C.

    1978-01-01

    Encouraged by reports of the therapeutic efficacy of peritoneal lavage in small series of five or six patients with acute pancreatitis, we have evaluated this treatment in 24 patients with “severe” pancreatitis. One hundred and three patients with “severe” pancreatitis (28% mortality) were separated from 347 with “mild” pancreatitis (0.9% mortality) by previously described early objective signs. Early treatment (Day 0-7) of “severe” pancreatitis included peritoneal lavage through catheters placed nonoperatively in 18 (Group A) and by catheters placed at laparotomy in six (Group C). Early treatment of nonlavaged patients with “severe” pancreatitis was by standard nonoperative measures in 61 (Group B) and included early operation in 18 (Group D). Lavage was continued for 48-96 hours, usually using 36-48 L/24 hours of balanced isotonic dialysate fluid, and was uncomplicated. Lavage led to striking immediate clinical improvement and no lavaged patient (Groups A and C) died during the first 10 days of treatment of pancreatitis. By contrast, 45% of deaths in nonlavaged patients (Group B and D) occurred during this early period, usually from cardiovascular or respiratory failure. Although lavage reduced mortality in subgroups of patients, ultimate overall survival was no affected (Group A, 83%; B, 84%; C, 33%; D,33%). Late peripancreatic abscesses caused most deaths in lavaged patients. These data show that peritoneal complications of severe acute pancreatitis and dramatically reduces early mortality. Lavage does not prevent the late local sequelae of peripancreatic necrosis. PMID:646497

  16. An indolent case of severe acute respiratory syndrome.

    PubMed

    Lam, Man-Fai; Ooi, Gaik C; Lam, Bing; Ho, James C; Seto, Wing H; Ho, Pak L; Wong, Poon C; Liang, Raymond; Lam, Wah K; Tsang, Kenneth W

    2004-01-01

    Severe acute respiratory syndrome (SARS) is a highly contagious and typically rapidly progressive form of atypical pneumonia, which spread from Asia to many parts of the world in early 2003. Clinical diagnosis of SARS requires the presence of unremitting fever and progressive pneumonia despite antibiotic therapy, particularly in the presence of lymphopenia and raised transaminase levels. We report the case of a woman who had undergone a successful allogeneic bone marrow transplant for acute myeloid leukemia. She presented initially with fever and a normal chest radiograph. Her indolent clinical course of SARS was punctuated by resolution of fever, but there was progressive radiologic deterioration and increasing serum antibody titer against SARS coronavirus. Treatment with oral prednisolone and ribavirin normalized her lymphopenia, altered transaminases, chest radiograph and high-resolution computed tomography appearances rapidly. Our experience should alert other clinicians in recognizing this atypical indolent presentation of SARS, to protect health care workers and the community at large and to ensure that these patients are properly treated.

  17. Supra- and Sub-Baseline Phosphocreatine Recovery in Developing Brain after Transient Hypoxia-Ischaemia: Relation to Baseline Energetics, Insult Severity and Outcome

    ERIC Educational Resources Information Center

    Iwata, Osuke; Iwata, Sachiko; Bainbridge, Alan; De Vita, Enrico; Matsuishi, Toyojiro; Cady, Ernest B.; Robertson, Nicola J.

    2008-01-01

    Following hypoxia-ischaemia (HI), an early biomarker of insult severity is desirable to target neuroprotective therapies to patients most likely to benefit; currently there are no biomarkers within the "latent phase" period before the establishment of secondary energy failure. Brief transient phosphocreatine (PCr) recovery overshoot (measured…

  18. Severe acute respiratory syndrome (SARS): epidemiology and clinical features

    PubMed Central

    Hui, D; Chan, M; Wu, A; Ng, P

    2004-01-01

    Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease with a significant morbidity and mortality. The major clinical features include persistent fever, chills/rigor, myalgia, malaise, dry cough, headache, and dyspnoea. Older subjects may present without the typical febrile response. Common laboratory features include lymphopenia, thrombocytopenia, raised alanine transaminases, lactate dehydrogenase, and creatine kinase. The constellation of compatible clinical and laboratory findings, together with certain characteristic radiological features and lack of clinical response to broad spectrum antibiotics, should arouse suspicion of SARS. Measurement of serum RNA by real time reverse transcriptase-polymerase chain reaction technique has a detection rate of 75%–80% in the first week of the illness. PMID:15254300

  19. Severe acute respiratory syndrome diagnostics using a coronavirus protein microarray.

    PubMed

    Zhu, Heng; Hu, Shaohui; Jona, Ghil; Zhu, Xiaowei; Kreiswirth, Nate; Willey, Barbara M; Mazzulli, Tony; Liu, Guozhen; Song, Qifeng; Chen, Peng; Cameron, Mark; Tyler, Andrea; Wang, Jian; Wen, Jie; Chen, Weijun; Compton, Susan; Snyder, Michael

    2006-03-14

    To monitor severe acute respiratory syndrome (SARS) infection, a coronavirus protein microarray that harbors proteins from SARS coronavirus (SARS-CoV) and five additional coronaviruses was constructed. These microarrays were used to screen approximately 400 Canadian sera from the SARS outbreak, including samples from confirmed SARS-CoV cases, respiratory illness patients, and healthcare professionals. A computer algorithm that uses multiple classifiers to predict samples from SARS patients was developed and used to predict 206 sera from Chinese fever patients. The test assigned patients into two distinct groups: those with antibodies to SARS-CoV and those without. The microarray also identified patients with sera reactive against other coronavirus proteins. Our results correlated well with an indirect immunofluorescence test and demonstrated that viral infection can be monitored for many months after infection. We show that protein microarrays can serve as a rapid, sensitive, and simple tool for large-scale identification of viral-specific antibodies in sera.

  20. Infants born to mothers with severe acute respiratory syndrome.

    PubMed

    Shek, Chi C; Ng, Pak C; Fung, Genevieve P G; Cheng, Frankie W T; Chan, Paul K S; Peiris, Malik J S; Lee, Kim H; Wong, Shell F; Cheung, Hon M; Li, Albert M; Hon, Ellis K L; Yeung, Chung K; Chow, Chun B; Tam, John S; Chiu, Man C; Fok, Tai F

    2003-10-01

    Severe acute respiratory syndrome (SARS) is a newly discovered infectious disease caused by a novel coronavirus. During the community outbreak in Hong Kong, 5 liveborn infants were born to pregnant women with SARS. A systematic search for perinatal transmission of the SARS-associated coronavirus, including serial reverse transcriptase-polymerase chain reaction assays, viral cultures, and paired serologic titers, failed to detect the virus in any of the infants. In addition, none of the infants developed clinical, radiologic, hematologic, or biochemical evidence suggestive of SARS. One preterm infant developed jejunal perforation and another developed necrotizing enterocolitis with ileal perforation shortly after birth. This case series is the first report to describe the clinical course of the first cohort of liveborn infants born to pregnant women with SARS. PMID:14523207

  1. Severe acute kidney injury as presentation of Burkitt's lymphoma.

    PubMed

    ter Haar, Eva; Labarque, Veerle; Tousseyn, Thomas; Mekahli, Djalila

    2016-01-01

    We discuss a case of acute kidney injury (AKI) at a very young age caused by primary lymphomatous renal infiltration due to Burkitt's lymphoma and analyse the literature on this rare condition. At presentation, clinical examination showed impressive bilateral nephromegaly and hypertension. Blood analysis indicated severe AKI, mild anaemia and normal serum electrolytes. There were no signs of tumour lysis syndrome. Urine sediment was normal, with neither haematuria nor proteinuria. Abdominal ultrasound demonstrated bilateral renal enlargement (+12 SD), with increased corticomedullar differentiation. MRI demonstrated the presence of a homogenous renal enlargement with features of an infiltrative lesion. Ultimately, microscopic and immunohistochemical analysis of the renal biopsy confirmed the diagnosis of Burkitt's lymphoma. Early and aggressive therapy is the key to ensure a good outcome. PMID:27118748

  2. ‘Cross-adaptation’: habituation to short repeated cold-water immersions affects the response to acute hypoxia in humans

    PubMed Central

    Lunt, Heather C; Barwood, Martin J; Corbett, Jo; Tipton, Michael J

    2010-01-01

    Adaptation to an environmental stressor is usually studied in isolation, yet these stressors are often encountered in combination in the field, an example being cold and hypoxia at altitude. There has been a paucity of research in this area, although work with rodents indicates that habituation to repeated short cold exposures has a cross-adaptive effect during hypoxia. The present study tested the hypothesis that cross-adaptation is also possible with humans. Thirty-two male volunteers were exposed to 10 min bouts of normoxic and hypoxic ( 0.12) rest and exercise (100 W on a recumbent cycle ergometer). These were repeated after a 96 h interval, during which participants completed six, 5 min immersions in either cold (12°C, CW) or thermoneutral water (35°C, TW). Venous blood samples were taken immediately after each bout, for determination of catecholamine concentrations. A three-lead ECG was recorded throughout and the final 5 min of each bout was analysed for heart rate variability using fast fourier transformations (and displayed as log transformed data (ln)). In comparison with the first hypoxic exercise exposure, the second exposure of the CW group resulted in an increased ln high frequency (ln HF) power (P < 0.001) and reduced adrenaline (P < 0.001) and noradrenaline concentrations (P < 0.001). Adrenaline and noradrenaline concentrations were lower in the CW group during the second hypoxic exercise compared to the TW group (P = 0.042 and P = 0.003), but ln HF was not. When separated into hypoxic sensitive and hypoxic insensitive subgroups, ln HF was higher in the hypoxic sensitive CW group during the second hypoxic exercise than in any of the other subgroups. Cold habituation reduced the sympathetic response (indicated by the reduced catecholamine concentrations) and elevated the parasympathetic activity (increased ln HF power) to hypoxic exercise. These data suggest a generic autonomic cross-adaptive effect between cold habituation and exposure to acute

  3. Effects of acute hypoxia on cardiopulmonary responses to head-down tilt

    NASA Technical Reports Server (NTRS)

    Loeppky, J. A.; Luft, U. C.; Scotto, P.; Chick, T. W.

    1990-01-01

    Six male subjects were exposed on two separate occasions to simulated microgravity with 28 deg head-down tilt (HD) for 1 h with baseline followed by recovery at + 17 deg head-up. Pulmonary ventilation, gas exchange, spirometry, and central and cerebral blood flow characteristics were compared while breathing ambient air and reduced F(I)O2 equivalent to 14,828 ft. With hypoxia (HY), the increased tidal volume served to attenuate the drop in arterial saturation by reducing deadspace ventilation. Arterial and mixed venous PO2, values, estimated from peripheral venous samples and cardiac output (CO), were both maintained during HD in HY. Mixed venous PO2 was elevated by an increase in CO associated with a reduction in systemic resistance. Changes in spirometric indices during HD were not accentuated by HY, making the presence of interstitial edema unlikely. Cerebral flow and resistance showed minor reductions with HD. Tissue oxygenation and cardiopulmonary function were not notably effected by HD during HY, but a combination of these two stressors may predispose subjects to subsequent orthostatic intolerance during initial recovery.

  4. Severe Acute Axonal Neuropathy following Treatment with Arsenic Trioxide for Acute Promyelocytic Leukemia: a Case Report

    PubMed Central

    Kühn, Marcus; Sammartin, Kety; Nabergoj, Mitja; Vianello, Fabrizio

    2016-01-01

    Peripheral neuropathy is a common complication of arsenic toxicity. Symptoms are usually mild and reversible following discontinuation of treatment. A more severe chronic sensorimotor polyneuropathy characterized by distal axonal-loss neuropathy can be seen in chronic arsenic exposure. The clinical course of arsenic neurotoxicity in patients with coexistence of thiamine deficiency is only anecdotally known but this association may potentially lead to severe consequences. We describe a case of acute irreversible axonal neuropathy in a patient with hidden thiamine deficiency who was treated with a short course of arsenic trioxide for acute promyelocytic leukemia. Thiamine replacement therapy and arsenic trioxide discontinuation were not followed by neurological recovery and severe polyneuropathy persisted at 12-month follow-up. Thiamine plasma levels should be measured in patients who are candidate to arsenic trioxide therapy. Prophylactic administration of vitamin B1 may be advisable. The appearance of polyneuropathy signs early during the administration of arsenic trioxide should prompt electrodiagnostic testing to rule out a pattern of axonal neuropathy which would need immediate discontinuation of arsenic trioxide. PMID:27158436

  5. Growth hormone transgenesis and polyploidy increase metabolic rate, alter the cardiorespiratory response and influence HSP expression in response to acute hypoxia in Atlantic salmon (Salmo salar) yolk-sac alevins.

    PubMed

    Polymeropoulos, Elias T; Plouffe, Debbie; LeBlanc, Sacha; Elliott, Nick G; Currie, Suzie; Frappell, Peter B

    2014-07-01

    Growth hormone (GH)-transgenic Atlantic salmon display accelerated growth rates compared with non-transgenics. GH-transgenic fish also display cardiorespiratory and metabolic modifications that accompany the increased growth rate. An elevated routine metabolic rate has been described for pre- and post-smolt GH-transgenic salmon that also display improvements in oxygen delivery to support the increased aerobic demand. The early ontogenic effects of GH transgenesis on the respiratory and cellular physiology of fish, especially during adverse environmental conditions, and the effect of polyploidy are unclear. Here, we investigated the effects of GH transgenesis and polyploidy on metabolic, heart and ventilation rates and heat shock protein (HSP) levels after exposure to acute hypoxia in post-hatch Atlantic salmon yolk-sac alevins. Metabolic rate decreased with decreasing partial pressures of oxygen in all genotypes. In normoxia, triploid transgenics displayed the highest mass-specific metabolic rates in comparison to diploid transgenics and non-transgenic triploids, which, in contrast, had higher rates than diploid non-transgenics. In hypoxia, we observed a lower mass-specific metabolic rate in diploid non-transgenics compared with all other genotypes. However, no evidence for improved O2 uptake through heart or ventilation rate was found. Heart rate decreased in diploid non-transgenics while ventilation rate decreased in both diploid non-transgenics and triploid transgenics in severe hypoxia. Regardless of genotype or treatment, inducible HSP70 was not expressed in alevins. Following hypoxia, the constitutive isoform of HSP70, HSC70, decreased in transgenics and HSP90 expression decreased in all genotypes. These data suggest that physiological changes through GH transgenesis and polyploidy are manifested during early ontogeny in Atlantic salmon.

  6. [Lactic acidosis in a child with acute severe asthma].

    PubMed

    Perrin, C; Savy, N; Lang, M; Caron, N; Labbé, A

    2014-10-01

    Lactic acidosis is a recognized event in adult patients with acute severe asthma (ASA). Only a few cases have been reported in children. Hereinafter is reported the case of a 2-year-old girl hospitalized in the pediatric intensive care unit for ASA, which was treated with high-flow oxygen therapy and intravenous methylprednisolone and salbutamol. During hospitalization, she had metabolic acidosis with a 7.29 pH, a 26mmHg hypocapnia, and a decrease in bicarbonates to 12 mmol/L. The anion gap was increased to 20 mmol/L and lactates to 8 mmol/L. The work-up for a congenital metabolic disease was normal. Progression was propitious with spontaneous improvement of lactic acidosis, and the child was discharged from the intensive care unit after 72 h. The origin of lactic acidosis during ASA seems to be multifactorial. Although its recovery can be spontaneous, it is important to know how to identify it because it can worsen respiratory symptoms and can lead to incongruous therapeutic escalation.

  7. Severe acute respiratory syndrome (SARS): a year in review.

    PubMed

    Skowronski, Danuta M; Astell, Caroline; Brunham, Robert C; Low, Donald E; Petric, Martin; Roper, Rachel L; Talbot, Pierre J; Tam, Theresa; Babiuk, Lorne

    2005-01-01

    Severe acute respiratory syndrome (SARS) emerged from China as an untreatable and rapidly spreading respiratory illness of unknown etiology. Following point source exposure in February 2003, more than a dozen guests infected at a Hong Kong hotel seeded multi-country outbreaks that persisted through the spring of 2003. The World Health Organization responded by invoking traditional public health measures and advanced technologies to control the illness and contain the cause. A novel coronavirus was implicated and its entire genome was sequenced by mid-April 2003. The urgency of responding to this threat focused scientific endeavor and stimulated global collaboration. Through real-time application of accumulating knowledge, the world proved capable of arresting the first pandemic threat of the twenty-first century, despite early respiratory-borne spread and global susceptibility. This review synthesizes lessons learned from this remarkable achievement. These lessons can be applied to re-emergence of SARS or to the next pandemic threat to arise. PMID:15660517

  8. Epidemiology of severe acute respiratory syndrome (SARS): adults and children.

    PubMed

    Zhong, Nan-Shan; Wong, Gary W K

    2004-12-01

    Severe acute respiratory syndrome (SARS) is a newly described respiratory infection with pandemic potential. The causative agent is a new strain of coronavirus most likely originating from wild animals. This disease first emerged in November 2002 in Guangdong Province, China. Early in the outbreak the infection had been transmitted primarily via household contacts and healthcare settings. In late February 2003 the infection was transmitted to Hong Kong when an infected doctor from the mainland visited there. During his stay in Hong Kong at least 17 guests and visitors were infected at the hotel at which he stayed. By modern day air travel, the infection was rapidly spread to other countries including Vietnam, Singapore and Canada by these infected guests. With the implementation of effective control strategies including early isolation of suspected cases, strict infection control measures in the hospital setting, meticulous contact tracing and quarantine, the outbreak was finally brought under control by July 2003. In addition, there were another two events of SARS in China between the end of December 2003 and January 2004 and from March to May 2004; both were readily controlled without significant patient spread. PMID:15531250

  9. The severe acute respiratory syndrome epidemic in mainland China dissected

    PubMed Central

    Cao, Wu-Chun; de Vlas, Sake J.; Richardus, Jan Hendrik

    2011-01-01

    This paper provides a review of a recently published series of studies that give a detailed and comprehensive documentation of the severe acute respiratory syndrome (SARS) epidemic in mainland China, which severely struck the country in the spring of 2003. The epidemic spanned a large geographical extent but clustered in two areas: first in Guangdong Province, and about 3 months later in Beijing with its surrounding areas. Reanalysis of all available epidemiological data resulted in a total of 5327 probable cases of SARS, of whom 343 died. The resulting case fatality ratio (CFR) of 6.4% was less than half of that in other SARS-affected countries or areas, and this difference could only partly be explained by younger age of patients and higher number of community acquired infections. Analysis of the impact of interventions demonstrated that strong political commitment and a centrally coordinated response was the most important factor to control SARS in mainland China, whereas the most stringent control measures were all initiated when the epidemic was already dying down. The long-term economic consequence of the epidemic was limited, much consumption was merely postponed, but for Beijing irrecoverable losses to the tourist sector were considerable. An important finding from a cohort study was that many former SARS patients currently suffer from avascular osteonecrosis, as a consequence of the treatment with corticosteroids during their infection. The SARS epidemic provided valuable information and lessons relevant in controlling outbreaks of newly emerging infectious diseases, and has led to fundamental reforms of the Chinese health system. In particular, a comprehensive nationwide internet-based disease reporting system was established. PMID:24470901

  10. Physiological noise in murine solid tumours using T2*-weighted gradient-echo imaging: a marker of tumour acute hypoxia?

    NASA Astrophysics Data System (ADS)

    Baudelet, Christine; Ansiaux, Réginald; Jordan, Bénédicte F.; Havaux, Xavier; Macq, Benoit; Gallez, Bernard

    2004-08-01

    with no contrast enhancement as the result of vessel functional impairment. Furthermore, transient fluctuations appeared to occur preferentially in neoangiogenic hyperpermeable vessels. The present study suggests that spontaneous T2*-weighted GRE fluctuations are very likely to be related to the spontaneous fluctuations in blood flow and oxygenation associated with the pathophysiology of acute hypoxia in tumours. The disadvantage of the T2*-weighted GRE MRI technique is the complexity of signal interpretation with regard to pO2 changes. Compared to established techniques such as intravital microscopy or histological assessments, the major advantage of the MRI technique lies in its capacity to provide simultaneously both temporal and detailed spatial information on spontaneous fluctuations throughout the tumour.

  11. Respiratory autoresuscitation following severe acute hypoxemia in anesthetized adult rats.

    PubMed

    Krause, A; Nowak, Z; Srbu, R; Bell, H J

    2016-10-01

    In the present study we investigated the pattern and efficacy of respiratory autoresuscitation in spontaneously breathing adult male rats across three separate anesthetic backgrounds. Each animal was administered one of three injectable anesthetics to achieve a surgical plane of anesthesia: ketamine-xylazine (KET, n=10), pentobarbital (PEN, n=10), or urethane (URE, n=10). Animals were tracheostomized and equipped with a femoral artery catheter to record airflow and arterial pressures. In response to a bout of breathing anoxic air, none of the 10 URE animals were able to mount a successful autoresuscitation response. In contrast, all KET and PEN animals survived all four consecutive anoxic exposures, restoring eupneic breathing in all cases. Moreover, only 4/10 URE animals expressed gasping breaths following the onset of respiratory arrest, and these were temporally delayed (p<0.001) and much smaller in volume (P≤0.012) compared to KET and PEN animals. URE animals showed no clear aberrations in their cardiovascular responses to anoxia, with the exception of lower arterial pulse pressures compared to either KET or PEN animals at specific points following RA. Ketamine-xylazine and pentobarbital anesthesia can be reliably and effectively used to create models for the study of autoresuscitation in adult rats. In contrast, urethane causes catastrophic failure of respiratory autoresuscitation, by delaying or outright preventing the elaboration of gasping breaths following anoxia-induced respiratory arrest. The neuronal and synaptic alterations accompanying urethane anesthesia may therefore provide a means of understanding potential pathological alterations in rhythm generation that can predispose the respiratory control system to failed autoresuscitation following an episode of acute severe hypoxemia. PMID:27378495

  12. [Severe acute respiratory syndrome: a global overview of the epidemic].

    PubMed

    Franco-Paredes, Carlos; Kuri-Morales, Pablo; Alvarez-Lucas, Carlos; Palacios-Zavala, Ethel; Nava-Frías, Margarita; Betancourt-Cravioto, Miguel; Santos-Preciado, José Ignacio; Tapia-Conyer, Roberto

    2003-01-01

    In early February 2003, the World Health Organization (WHO) began receiving reports of patients with a syndrome characterized by an atypical pneumonia with rapid progression to respiratory failure without an identified cause despite extensive diagnostic workups. Most of these reports pointed out that the outbreak started in Southern China, specifically in the Guandong Province. The initial outbreak in South East Asia has already spread to other Regions in Asia, Europe, North and South America, and South Africa. Many of these cases can be linked through chains of transmission to an index case from the Guandong Province who visited Hong Kong. Although the exact mode of transmission has not been clearly established, the etiology of this syndrome has already been identified. A novel Coronavirus has been identified by electron microscopy and molecular assays in multiple laboratories from respiratory specimens throughout the world. The syndrome has been defined as SARS (Severe Acute Respiratory Syndrome) by WHO, and is characterized by an incubation period between 1 and 10 days (average 5 days) and by a febrile phase that usually lasts approximately 3 days. During the respiratory phase that begins around day 3, patients start developing a dry cough, shortness of breath and hypoxemia. Mechanical ventilatory support is required in about 10 to 40% of cases and the case-fatality rate ranges between 3 and 16%. The laboratory findings in SARS cases include leukopenia, thrombocytopenia, and a rise in transaminases and lactic dehydrogenase levels. Treatment of SARS includes supportive measures and the empiric use of ribavirin. Respiratory isolation, use of respiratory masks, and compulsory hand hygiene constitute the principal preventive measures. The confirmation of a case can be performed at reference laboratories by serologic and molecular assays. From the onset of this epidemic Mexico established a surveillance system as well as clinical guidelines and recommendations for

  13. Studies on the roles of ATP, adenosine and nitric oxide in mediating muscle vasodilatation induced in the rat by acute systemic hypoxia.

    PubMed

    Skinner, M R; Marshall, J M

    1996-09-01

    1. In Saffan-anaesthetized rats, we have further investigated the mechanisms underlying the vasodilatation induced by adenosine in skeletal muscle by acute systemic hypoxia (breathing 8% O2 for 5 min). 2. In eleven rats the nitric oxide (NO) synthesis inhibitor nitro-L-arginine methyl ester (L-NAME, 10 mg kg-1, i.v.) reduced the increase in femoral vascular conductance (FVC) induced by hypoxia by approximately 50%. L-NAME had similar effects on the increase in FVC induced by intra-arterial (I.A.) infusion of adenosine (at 1.2 mg kg-1 min-1 for 5 min via the tail artery) and by ATP (I.A., 1 mg kg-1 min-1 for 5 min). Subsequent administration of the adenosine receptor antagonist 8-sulphophenyl theophylline (8-SPT, 20 mg kg-1, i.v.) virtually abolished the adenosine- and ATP-induced increase in FVC. 3. In a further nine rats, 8-SPT reduced the increase in FVC induced by hypoxia by approximately 50%. This remaining increase in FVC was substantially reduced by L-NAME. 4. In an additional nine rats, alpha,beta-methyleneADP (160 micrograms kg-1, i.v.) which inhibits the 5'-ectonucleotidase that degrades AMP to adenosine, reduced the peripheral vasodilatation (fall in arterial blood pressure, ABP) induced by ATP infusion, but had no effect on the increase in FVC or decrease in ABP evoked by systemic hypoxia. 5. These results provide the first evidence that the muscle vasodilatation induced by adenosine during systemic hypoxia is mainly dependent on NO synthesis. They also suggest that adenosine is released as such rather than being formed extracellularly from AMP. Given evidence that extraluminal adenosine acts in an NO-independent fashion we propose that hypoxia releases adenosine from the endothelium. Our results also indicate that hypoxia induces muscle vasodilatation that is adenosine independent but NO dependent: they allow the possibility that this is partly mediated by ATP released from the endothelium. PMID:8887765

  14. Severe acute respiratory syndrome: clinical and laboratory manifestations.

    PubMed

    Lam, Christopher W K; Chan, Michael H M; Wong, Chun K

    2004-05-01

    Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease with significant morbidity and mortality. An epidemic in 2003 affected 8,098 patients in 29 countries with 774 deaths. The aetiological agent is a new coronavirus spread by droplet transmission. Clinical and general laboratory manifestations included fever, chills, rigor, myalgia, malaise, diarrhoea, cough, dyspnoea, pneumonia, lymphopenia, neutrophilia, thrombocytopenia, and elevated serum lactate dehydrogenase (LD), alanine aminotransferase (ALT) and creatine kinase (CK) activities. Treatment has been empirical; initial potent antibiotic cover, followed by simultaneous ribavirin and corticosteroids, with or without pulse high-dose methylprednisolone, have been used. The postulated disease progression comprises (1) active viral infection, (2) hyperactive immune response, and (3) recovery or pulmonary destruction and death. We investigated serum LD isoenzymes and blood lymphocyte subsets of SARS patients, and found LD1 activity as the best biochemical prognostic indicator for death, while CD3+, CD4+, CD8+ and natural killer cell counts were promising predictors for intensive care unit (ICU) admission. Plasma cytokine and chemokine profiles showed markedly elevated Th1 cytokine interferon (IFN)-gamma, inflammatory cytokines interleukin (IL)-1beta, IL-6 and IL-12, neutrophil chemokine IL-8, monocyte chemoattractant protein-1 (MCP-1), and Th1 chemokine IFN-gamma-inducible protein-10 (IP-10) for at least two weeks after disease onset, but there was no significant elevation of inflammatory cytokine tumor necrosis factor (TNF)-alpha and anti-inflammatory cytokine IL-10. Corticosteroid reduced IL-8, MCP-1 and IP-10 concentrations from 5-8 days after treatment. Measurement of biochemical markers of bone metabolism demonstrated significant but transient increase in bone resorption from Day 28-44 after onset of fever, when pulse steroid was most frequently given. With tapering down of steroid

  15. Impaired Bile Acid Homeostasis in Children with Severe Acute Malnutrition

    PubMed Central

    Zhang, Ling; Voskuijl, Wieger; Mouzaki, Marialena; Groen, Albert K.; Alexander, Jennifer; Bourdon, Celine; Wang, Alice; Versloot, Christian J.; Di Giovanni, Valeria; Wanders, Ronald J. A.; Bandsma, Robert

    2016-01-01

    Objective Severe acute malnutrition (SAM) is a major cause of mortality in children under 5 years and is associated with hepatic steatosis. Bile acids are synthesized in the liver and participate in dietary fat digestion, regulation of energy expenditure, and immune responses. The aim of this work was to investigate whether SAM is associated with clinically relevant changes in bile acid homeostasis. Design An initial discovery cohort with 5 healthy controls and 22 SAM-patients was used to identify altered bile acid homeostasis. A follow up cohort of 40 SAM-patients were then studied on admission and 3 days after clinical stabilization to assess recovery in bile acid metabolism. Recruited children were 6–60 months old and admitted for SAM in Malawi. Clinical characteristics, feces and blood were collected on admission and prior to discharge. Bile acids, 7α-hydroxy-4-cholesten-3-one (C4) and FGF-19 were quantified. Results On admission, total serum bile acids were higher in children with SAM than in healthy controls and glycine-conjugates accounted for most of this accumulation with median and interquartile range (IQR) of 24.6 μmol/L [8.6–47.7] compared to 1.9 μmol/L [1.7–3.3] (p = 0.01) in controls. Total serum bile acid concentrations did not decrease prior to discharge. On admission, fecal conjugated bile acids were lower and secondary bile acids higher at admission compared to pre- discharge, suggesting increased bacterial conversion. FGF19 (Fibroblast growth factor 19), a marker of intestinal bile acid signaling, was higher on admission and was associated with decreased C4 concentrations as a marker of bile acid synthesis. Upon recovery, fecal calprotectin, a marker of intestinal inflammation, was lower. Conclusion SAM is associated with increased serum bile acid levels despite reduced synthesis rates. In SAM, there tends to be increased deconjugation of bile acids and conversion from primary to secondary bile acids, which may contribute to the

  16. Management of acute moderate and severe childhood malnutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acute childhood malnutrition affects about a tenth of the world's children under 5 years of age, particularly those living in circumstances of extreme poverty in the developing world. Malnutrition is typically the result of an inadequate diet and is one of the most common diagnoses in children in he...

  17. The effect of 10 days of heat acclimation on exercise performance in acute hypobaric hypoxia (4350 m)

    PubMed Central

    White, Ailish C.; Salgado, Roy M.; Astorino, Todd A.; Loeppky, Jack A.; Schneider, Suzanne M.; McCormick, James J.; McLain, Trisha A.; Kravitz, Len; Mermier, Christine M.

    2016-01-01

    ABSTRACT To examine the effect (“cross-tolerance”) of heat acclimation (HA) on exercise performance upon exposure to acute hypobaric hypoxia (4350 m). Eight male cyclists residing at 1600 m performed tests of maximal aerobic capacity (VO2max) at 1600 m and 4350 m, a 16 km time-trial at 4350 m, and a heat tolerance test at 1600 m before and after 10 d HA at 40°C, 20% RH. Resting blood samples were obtained pre-and post- HA to estimate changes in plasma volume (ΔPV). Successful HA was indicated by significantly lower exercise heart rate and rectal temperature on day 10 vs. day 1 of HA and during the heat tolerance tests. Heat acclimation caused a 1.9% ΔPV, however VO2max was not significantly different at 1600 m or 4350 m. Time-trial cycling performance improved 28 sec after HA (p = 0.07), suggesting a possible benefit for exercise performance at acute altitude and that cross-tolerance between these variables may exist in humans. These findings do not clearly support the use of HA to improve exercise capacity and performance upon acute hypobaric hypoxia, however they do indicate that HA is not detrimental to either exercise capacity or performance. PMID:27227084

  18. Preclinical evidence of mitochondrial nicotinamide adenine dinucleotide as an effective alarm parameter under hypoxia

    NASA Astrophysics Data System (ADS)

    Shi, Hua; Sun, Nannan; Mayevsky, Avraham; Zhang, Zhihong; Luo, Qingming

    2014-01-01

    Early detection of tissue hypoxia in the intensive care unit is essential for effective treatment. Reduced nicotinamide adenine dinucleotide (NADH) has been suggested to be the most sensitive indicator of tissue oxygenation at the mitochondrial level. However, no experimental evidence comparing the kinetics of changes in NADH and other physiological parameters has been provided. The aim of this study is to obtain the missing data in a systematic and reliable manner. We constructed four acute hypoxia models, including hypoxic hypoxia, hypemic hypoxia, circulatory hypoxia, and histogenous hypoxia, and measured NADH fluorescence, tissue reflectance, cerebral blood flow, respiration, and electrocardiography simultaneously from the induction of hypoxia until death. We found that NADH was not always the first onset parameter responding to hypoxia. The order of responses was mainly affected by the cause of hypoxia. However, NADH reached its alarm level earlier than the other monitored parameters, ranging from several seconds to >10 min. As such, we suggest that the NADH can be used as a hypoxia indicator, although the exact level that should be used must be further investigated. When the NADH alarm is detected, the body still has a chance to recover if appropriate and timely treatment is provided.

  19. Caspase-1 inhibition alleviates acute renal injury in rats with severe acute pancreatitis

    PubMed Central

    Zhang, Xiao-Hua; Li, Min-Li; Wang, Bin; Guo, Mei-Xia; Zhu, Ren-Min

    2014-01-01

    AIM: To assess the effect of inhibition of caspase-1 on acute renal injury in rats with severe acute pancreatitis (SAP). METHODS: Forty-two Sprague-Dawley rats were randomly divided into three groups: healthy controls (HC, n = 6), SAP rats treated with saline (SAP-S, n = 18), or SAP rats treated with a caspase-1/interleukin (IL)-1β-converting-enzyme (ICE) inhibitor (SAP-I-ICE, n = 18). SAP was induced by retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct. HC rats were subjected to identical treatment and surgical procedures without sodium taurocholate. Rats received an intraperitoneal injection of isotonic saline (SAP-S) or the inhibitor (SAP-ICE-I) at 2 and 12 h after induction of acute pancreatitis. Surviving rats were sacrificed at different time points after SAP induction; all samples were obtained and stored for subsequent analyses. The levels of blood urea nitrogen (BUN) and creatinine (Cr) were measured using automatic methods, and serum IL-1β concentrations were measured by an enzyme-linked immunosorbent assay. Intrarenal expression of IL-1β, IL-18 and caspase-1 mRNAs was detected by RT-PCR. IL-1β protein expression and the pathologic changes in kidney tissues were observed by microscopy after immunohistochemical or hematoxylin and eosin staining, respectively. RESULTS: The serum levels of BUN and Cr in the SAP-S group were 12.48 ± 2.30 mmol/L and 82.83 ± 13.89 μmol/L at 6 h, 23.53 ± 2.58 mmol/L and 123.67 ± 17.67 μmol/L at 12 h, and 23.60 ± 3.33 mmol/L and 125.33 ± 21.09 μmol/L at 18 h, respectively. All were significantly increased compared to HC rats (P < 0.01 for all). Levels in SAP-ICE-I rats were significantly decreased compared to SAP-S rats both at 12 and 18 h (P < 0.01 for all). Serum IL-1β levels in the SAP-S group were 276.77 ± 44.92 pg/mL at 6 h, 308.99 ± 34.95 pg/mL at 12 h, and 311.60 ± 46.51 pg/mL at 18 h; all significantly higher than those in the HC and SAP-ICE-I groups (P < 0.01 for all

  20. The oxidative stress response in freshwater-acclimated killifish (Fundulus heteroclitus) to acute copper and hypoxia exposure.

    PubMed

    Ransberry, Victoria E; Blewett, Tamzin A; McClelland, Grant B

    2016-01-01

    Aquatic organisms face multiple stressors in natural ecosystems. Here we examine the effects of moderate hypoxia and low-level copper (Cu) on freshwater (FW)-acclimated killifish. Both Cu and hypoxia can affect oxidative stress in fish, but it is unclear if in combination these two stressors would act synergistically. We exposed killifish for 96h to Cu in normoxia (total 23.4±0.9μg CuL(-1)), or either no Cu (2.33±0.01mg O2 L(-1)) or with Cu in hypoxia (23.6±0.8μg Cu L(-1); 2.51±0.04mg O2 L(-1)), and compared them to normoxic controls with no added Cu (0.7±0.1μg Cu L(-1); 9.10±0.00mg O2 L(-1)) at a hardness of 140mgL(-1) as CaCO3 equivalents. Gills showed significant Cu accumulation with both excess waterborne Cu in normoxia and in hypoxia. This was accompanied by increases in gill catalase (CAT) activity but with no significant changes in either protein carbonyls or lipid peroxidation (TBARS). Hypoxia alone decreased gill protein carbonyls. Liver showed no change in Cu load, but a significant decline in CAT activity occurred with Cu in normoxia. Liver showed an increase in TBARS with Cu in normoxia. Cu when combined with hypoxia caused a significant decline in cytochrome c oxidase (COX) and citrate synthase (CS) activity in gill and liver. Thus, low waterborne levels of Cu and moderate hypoxia both affected gill and liver phenotypes. However, killifish are tolerant of Cu and hypoxia, and there was no evidence of a synergistic response to exposure to the two stressors combined compared to each stressor alone. PMID:26297808

  1. [Electron probe microanalysis of the potassium and phosphorus content in cytoplasm of cardiomyocytes of pregnant rats after an acute hypoxia incident].

    PubMed

    Pogorelov, A G

    2008-01-01

    The concentration of the elements (K, P) in the cytoplasm of rat (Wistar) cardiomyocytes has been determined by the electron probe analysis. The intracellular content of potassium and phosphorus was determined in early organogenesis and in unfertilized animals. In pregnant animals, a decrease in the cytoplasmic concentration of phosphorus and an increase in the concentration of potassium were registered. It was shown that the acute hypobaric hypoxia changes the content of both elements in the cytoplasm. The data obtained are discussed in terms of the activation of the ion transport system, which is aimed at compensating the cellular acidosis and lactosis induced by the development of hypoxic deenergization in pregnant animals. PMID:19137687

  2. Severe Acute Asthma Exacerbation in Children: A Stepwise Approach for Escalating Therapy in a Pediatric Intensive Care Unit

    PubMed Central

    Nievas, I. Federico Fernandez; Anand, Kanwaljeet J. S.

    2013-01-01

    OBJECTIVES An increasing prevalence of pediatric asthma has led to increasing burdens of critical illness in children with severe acute asthma exacerbations, often leading to respiratory distress, progressive hypoxia, and respiratory failure. We review the definitions, epidemiology, pathophysiology, and clinical manifestations of severe acute asthma, with a view to developing an evidence-based, stepwise approach for escalating therapy in these patients. METHODS Subject headings related to asthma, status asthmaticus, critical asthma, and drug therapy were used in a MEDLINE search (1980–2012), supplemented by a manual search of personal files, references cited in the reviewed articles, and treatment algorithms developed within Le Bonheur Children's Hospital. RESULTS Patients with asthma require continuous monitoring of their cardiorespiratory status via noninvasive or invasive devices, with serial clinical examinations, objective scoring of asthma severity (using an objective pediatric asthma score), and appropriate diagnostic tests. All patients are treated with β-agonists, ipratropium, and steroids (intravenous preferable over oral preparations). Patients with worsening clinical status should be progressively treated with continuous β-agonists, intravenous magnesium, helium-oxygen mixtures, intravenous terbutaline and/or aminophylline, coupled with high-flow oxygen and non-invasive ventilation to limit the work of breathing, hypoxemia, and possibly hypercarbia. Sedation with low-dose ketamine (with or without benzodiazepines) infusions may allow better toleration of non-invasive ventilation and may also prepare the patient for tracheal intubation and mechanical ventilation, if indicated by a worsening clinical status. CONCLUSIONS Severe asthma can be a devastating illness in children, but most patients can be managed by using serial objective assessments and the stepwise clinical approach outlined herein. Following multidisciplinary education and training, this

  3. Soluble CD163 is increased in patients with acute pancreatitis independent of disease severity.

    PubMed

    Karrasch, Thomas; Brünnler, Tanja; Hamer, Okka W; Schmid, Karin; Voelk, Markus; Herfarth, Hans; Buechler, Christa

    2015-10-01

    Macrophages are crucially involved in the pathophysiology of acute pancreatitis. Soluble CD163 (sCD163) is specifically released from macrophages and systemic levels are increased in inflammatory diseases. Here, sCD163 was measured in serum of 50 patients with acute pancreatitis to find out possible associations with disease activity. Admission levels of systemic sCD163 were nearly three-fold higher in patients with acute pancreatitis compared to controls. In patients sCD163 did not correlate with C-reactive protein and leukocyte count as established markers of inflammation. Levels were not associated with disease severity assessed by the Schroeder score, Balthazar score, Acute Physiology, Age, and Chronic Health Evaluation (Apache) II score and peripancreatic necrosis score. Soluble CD163 was not related to complications of acute pancreatitis. These data show that serum sCD163 is increased in acute pancreatitis indicating activation of macrophages but is not associated with disease severity and outcome.

  4. Cerebral hypoxia

    MedlinePlus

    ... death. Treatment depends on the cause of the hypoxia. Basic life support is most important. Treatment involves: Breathing ... Complications of cerebral hypoxia include a prolonged vegetative ... sleep-wake cycle, and eye opening, but the person is not alert ...

  5. Acute Otitis Media Severity: Association with Cytokine Gene polymorphisms and other Risk Factors

    PubMed Central

    McCormick, David P.; Grady, James J.; Diego, Alejandro; Matalon, Reuben; Revai, Krystal; Patel, Janak A.; Han, Yimei; Chonmaitree, Tasnee

    2011-01-01

    Background We have previously shown an association between polymorphisms of proinflammatory cytokine genes and susceptibility to upper respiratory tract infection and acute otitis media. It has not been known whether polymorphisms or risk factors are associated with the severity of acute otitis media. Objective To evaluate the influences of proinflammatory cytokine gene polymorphisms and other risk factors on severity of acute otitis media following upper respiratory infection. Methods In a prospective, longitudinal study, children aged 6-35 months were followed for one year for occurrences of upper respiratory tract infection and acute otitis media. Children were studied for TNFα-308, interleukin (IL)- 6-174 and IL-1 ß+3953 polymorphisms, taking into account age, gender, race, family history of otitis, tobacco smoke exposure, breast feeding, day of upper respiratory tract infection at the time of diagnosis and pneumococcal vaccine status. Symptoms and signs of acute otitis media were graded according to a validated scale. The association between acute otitis media clinical severity, polymorphic genotypes, and risk factors was analyzed using statistical models that account for multiple episodes of acute otitis media per child. Results A total of 295 episodes of acute otitis media in 128 subjects were included. More severe acute otitis media symptoms were associated with young age (P=0.01), family history of acute otitis media (P=0.002), tobacco smoke exposure (P=0.008), and early diagnosis of otitis after onset of upper respiratory tract infection (P=0.02). Among children with a bulging or perforated tympanic membrane (206 episodes, 104 subjects), those who had the IL- 1 ß+3953 polymorphism, experienced higher symptom scores (P<0.02). Conclusion This is the first report of the association between risk factors and acute otitis media severity. Risk factors such as tobacco smoke exposure and a positive family history appear to be more significantly associated with

  6. Severe acute hepatitis in the DRESS syndrome: Report of two cases.

    PubMed

    Lens, Sabela; Crespo, Gonzalo; Carrión, Jose A; Miquel, Rosa; Navasa, Miquel

    2010-01-01

    The DRESS (drug rash, eosinophilia and systemic symptoms) syndrome, also known as DIHS (drug-induced hypersensitivity syndrome), is a severe idiosyncratic reaction to several drugs, mainly antiepileptics and antibiotics, which can occasionally produce acute liver failure. In this article we present two cases of the DRESS syndrome presenting with severe acute hepatitis, including the first case of DRESS associated with levetiracetam. Although both cases finally resolved with good outcomes, DRESS can lead to acute liver failure and has a bad prognosis when liver damage is present. Rapid diagnosis is crucial since withdrawal of the offending drug is the key of treatment, while the potential role of corticosteroids is discussed. PMID:20526017

  7. Home-based therapy for severe acute malnutrition with ready-to-use food

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Severe acute malnutrition is a devastating condition afflicting children under 5 years in many developing countries, but concentrated in sub-Saharan Africa. This paper examines the development of home-based lipid-nutrient therapeutic foods for the treatment of acute malnutrition in sub-Saharan Afric...

  8. Hypoxia in paradise: widespread hypoxia tolerance in coral reef fishes.

    PubMed Central

    Nilsson, Göran E; Ostlund-Nilsson, Sara

    2004-01-01

    Using respirometry, we examined the hypoxia tolerance of 31 teleost fish species (seven families) inhabiting coral reefs at a 2-5 m depth in the lagoon at Lizard Island (Great Barrier Reef, Australia). All fishes studied maintained their rate of oxygen consumption down to relatively severe hypoxia (20-30% air saturation). Indeed, most fishes appeared unaffected by hypoxia until the oxygen level fell below 10% of air saturation. This, hitherto unrecognized, hypoxia tolerance among coral reef fishes could reflect adaptations to nocturnal hypoxia in tide pools. It may also be needed to enable fishes to reside deep within branching coral at night to avoid predation. Widespread hypoxia tolerance in a habitat with such an extreme biodiversity as coral reefs indicate that there is a wealth of hypoxia related adaptations to be discovered in reef fishes. PMID:15101411

  9. Predictors of severity and necrosis in acute pancreatitis.

    PubMed

    Papachristou, Georgios I; Whitcomb, David C

    2004-12-01

    C-reactive protein remains the single standard biochemical marker for predicting the severity of AP. Because the combination of clinical-physiological scores and CRP provide good information at 48 hours, research has focused on the predictive ability of various markers when applied in the initial 24 hours after admission to the hospital. After detailed review of the literature, the authors conclude that there is no single tool that serves as the optimal predictor of severity. There are, however, data that support the use of certain tests to improve upon the clinician's early predictive ability on the subsequent course of AP. These include an APACHE II score greater than 7 and IL-6 at the time of admission, and urine TAP, urine trypsinogen-2, and serum PMN elastase at 24 hours (Table 4). These markers only will be able to help the clinician's predictive ability if they can be performed locally and if the results can be available ina timely manner. Future research should focus on promising markers such as procalcitonin, IL-8, IL-I ra, sTNFR, CAPAP, PLA-2, novel markers, and the combined use of more than one marker. The conventional research approach in predicting severity used in the last 15 years has limitations and appears to have reached its maximal potential. Novel conceptions and approaches, such as identification of genetic polymorphisms that predispose to severe course and complications of AP or other approaches are needed for a quantum step forward.

  10. Inflammatory markers of disease severity in acute pancreatitis.

    PubMed

    Papachristou, Georgios I; Whitcomb, David C

    2005-03-01

    To date, CRP remains the single standard biochemical marker for predicting the severity of AP. Because the combination of clinico-physiological scores and CRP provides good information at 48 hours, research has focused on the predictive ability of various markers when applied in the initial 24 hours after admission to the hospital. After detailed review of the literature, the authors conclude that there is no single tool that serves as the optimal predictor of severity. There are, however, data supporting the use of certain tests to improve upon the clinician's early predictive ability on the subsequent course of AP. These include an APACHE II score greater than seven, IL-6 at the time of admission, and urine TAP, urine trypsinogen-2,and serum PMN-elastase at 24 hours (Box 1). These markers will only be able to help the clinician's predictive ability if they can be performed locally and if the results can be available in a timely manner. Future research should focus on markers such as procalcitonin, IL-8, IL-I ra, sTNFR,CAPAP, PLA-2, novel markers, and the combined use of more than one marker. The conventional research approach in predicting severity used in the last15 years has limitations and appears to have reached its maximal potential. Novel conceptions and approaches, such as identification of genetic polymorphisms that predispose to severe course and complications of AP, are needed for a quantum step forward.

  11. Relationship of the serum procalcitonin level with the severity of acute pancreatitis.

    PubMed

    Sato, Nobuhiro; Endo, Shigeatsu; Kasai, Takeshi; Inoue, Yoshihiro; Fujino, Yasuhisa; Onodera, Makoto; Imai, Satoko; Takahashi, Gaku; Miyata, Michiko; Kitamura, Michihiko; Wakabayashi, Go

    2004-01-01

    The procalcitonin (PCT) level in the blood was determined in cases of acute pancreatitis. The PCT level was found to show a significant correlation with the severity of acute pancreatitis. Furthermore, the PCT level was significantly higher in the cases which developed MODS than in those which did not. The PCT level was significantly higher in the patients who eventually died than in those who survived. A significant correlation was observed between the serum PCT level and the serum tumor necrosis factor alpha level. Thus, PCT level was found to be a reliable indicator of the severity of acute pancreatitis.

  12. [Effect of acute hypoxia on the intensity of free radical processes in the basal nuclei of the brain, and the rat behaviour in the open field test under conditions of altered photoperiod].

    PubMed

    Sopova, I Iu; Zamorskiĭ, I I

    2011-03-01

    The effect of acute hypoxia on the intensity of free radical processes in the basal nuclei (the nucleus caudatus, globus pallidus. nucleus accumbens. amygdaloid complex) of the brain, and the rat behaviour in the open field test has been studied under conditions of altered photoperiod. It has been shown that constant darkness levels the effect of acute hypoxia on the intensity of lipid peroxidation, preserves the activity of superoxide dismutase and catalase at a higher level, lowers the activity of glutathione peroxidase. Under light, the sensitivity of basal nuclei neurons to acute hypoxia is enhanced, the latter being reflected in intensification of lipid peroxidation at the expense of increased formation of dien conjugates. The activity of catalase at that considerably exceeds the level of even intact rats in all the structures. It has been established that an altered photoperiod modulates the effect of acute hypoxia on the parameters of rat's activity in the open field, the character of their change depending on the nature of a photophase change.

  13. Celiac disease unmasked by acute severe iron deficiency anemia.

    PubMed

    Meseeha, Marcelle G; Attia, Maximos N; Kolade, Victor O

    2016-01-01

    The prevalence of celiac disease (CD) appears to be increasing in the United States. However, the proportion of new CD cases with atypical presentations is also rising. We present the case of a 49-year-old woman who was diagnosed with CD in the setting of new, severe iron-deficiency anemia, 13 years into treatment of diarrhea-predominant irritable bowel syndrome associated with chronic mildly elevated liver function tests. While CD and iron deficiency anemia are common, this is a rare presentation of CD. PMID:27406450

  14. Celiac disease unmasked by acute severe iron deficiency anemia

    PubMed Central

    Meseeha, Marcelle G.; Attia, Maximos N.; Kolade, Victor O.

    2016-01-01

    The prevalence of celiac disease (CD) appears to be increasing in the United States. However, the proportion of new CD cases with atypical presentations is also rising. We present the case of a 49-year-old woman who was diagnosed with CD in the setting of new, severe iron-deficiency anemia, 13 years into treatment of diarrhea-predominant irritable bowel syndrome associated with chronic mildly elevated liver function tests. While CD and iron deficiency anemia are common, this is a rare presentation of CD. PMID:27406450

  15. Phase I dynamics of cardiac output, systemic O2 delivery, and lung O2 uptake at exercise onset in men in acute normobaric hypoxia.

    PubMed

    Lador, Frédéric; Tam, Enrico; Azabji Kenfack, Marcel; Cautero, Michela; Moia, Christian; Morel, Denis R; Capelli, Carlo; Ferretti, Guido

    2008-08-01

    We tested the hypothesis that vagal withdrawal plays a role in the rapid (phase I) cardiopulmonary response to exercise. To this aim, in five men (24.6+/-3.4 yr, 82.1+/-13.7 kg, maximal aerobic power 330+/-67 W), we determined beat-by-beat cardiac output (Q), oxygen delivery (QaO2), and breath-by-breath lung oxygen uptake (VO2) at light exercise (50 and 100 W) in normoxia and acute hypoxia (fraction of inspired O2=0.11), because the latter reduces resting vagal activity. We computed Q from stroke volume (Qst, by model flow) and heart rate (fH, electrocardiography), and QaO2 from Q and arterial O2 concentration. Double exponentials were fitted to the data. In hypoxia compared with normoxia, steady-state fH and Q were higher, and Qst and VO2 were unchanged. QaO2 was unchanged at rest and lower at exercise. During transients, amplitude of phase I (A1) for VO2 was unchanged. For fH, Q and QaO2, A1 was lower. Phase I time constant (tau1) for QaO2 and VO2 was unchanged. The same was the case for Q at 100 W and for fH at 50 W. Qst kinetics were unaffected. In conclusion, the results do not fully support the hypothesis that vagal withdrawal determines phase I, because it was not completely suppressed. Although we can attribute the decrease in A1 of fH to a diminished degree of vagal withdrawal in hypoxia, this is not so for Qst. Thus the dual origin of the phase I of Q and QaO2, neural (vagal) and mechanical (venous return increase by muscle pump action), would rather be confirmed.

  16. Hearts of Hypoxia-inducible Factor Prolyl 4-Hydroxylase-2 Hypomorphic Mice Show Protection against Acute Ischemia-Reperfusion Injury*

    PubMed Central

    Hyvärinen, Jaana; Hassinen, Ilmo E.; Sormunen, Raija; Mäki, Joni M.; Kivirikko, Kari I.; Koivunen, Peppi; Myllyharju, Johanna

    2010-01-01

    Hypoxia-inducible factor (HIF) has a pivotal role in oxygen homeostasis and cardioprotection mediated by ischemic preconditioning. Its stability is regulated by HIF prolyl 4-hydroxylases (HIF-P4Hs), the inhibition of which is regarded as a promising strategy for treating diseases such as anemia and ischemia. We generated a viable Hif-p4h-2 hypomorph mouse line (Hif-p4h-2gt/gt) that expresses decreased amounts of wild-type Hif-p4h-2 mRNA: 8% in the heart; 15% in the skeletal muscle; 34–47% in the kidney, spleen, lung, and bladder; 60% in the brain; and 85% in the liver. These mice have no polycythemia and show no signs of the dilated cardiomyopathy or hyperactive angiogenesis observed in mice with broad spectrum conditional Hif-p4h-2 inactivation. We focused here on the effects of chronic Hif-p4h-2 deficiency in the heart. Hif-1 and Hif-2 were stabilized, and the mRNA levels of glucose transporter-1, several enzymes of glycolysis, pyruvate dehydrogenase kinase 1, angiopoietin-2, and adrenomedullin were increased in the Hif-p4h-2gt/gt hearts. When isolated Hif-p4h-2gt/gt hearts were subjected to ischemia-reperfusion, the recovery of mechanical function and coronary flow rate was significantly better than in wild type, while cumulative release of lactate dehydrogenase reflecting the infarct size was reduced. The preischemic amount of lactate was increased, and the ischemic versus preischemic [CrP]/[Cr] and [ATP] remained at higher levels in Hif-p4h-2gt/gt hearts, indicating enhanced glycolysis and an improved cellular energy state. Our data suggest that chronic stabilization of Hif-1α and Hif-2α by genetic knockdown of Hif-p4h-2 promotes cardioprotection by induction of many genes involved in glucose metabolism, cardiac function, and blood pressure. PMID:20185832

  17. The Glomerulus and Serum Sickness in Experimental Hypoxia

    PubMed Central

    Spear, G. S.; Kihara, I.

    1972-01-01

    The effect of prolonged continuous hypoxia with polycythaemia on the rabbit glomerulus was studied by light microscopy and their effect on experimental serum sickness in rabbits was studied by light and immunofluorescent microscopy. Engorgement and enlargement were the principal effects on the glomerulus of hypoxia and polycythaemia, but prominence of the mesangium and focal segmental sclerosis and hypercellularity sometimes occurred. The results of the studies on serum sickness suggested that prolonged hypoxia with polycythaemia did not diminish antibody formation, reactivity of antibody with antigen, or rapid antigen clearance; in fact antigen was cleared more rapidly in hypoxic animals. Chronic hypoxia and polycythaemia did not prevent acute serum sickness including acute glomerulonephritis. The incidence and severity of acute glomerulonephritis, however, may have been diminished whereas the incidence and severity of other visceral involvement by acute serum sickness was not. Although the experimental groups were not large, the possible implications of the data are important. Focal segmental glomerular sclerosis and hypercellularity, and mesangial prominence, to our knowledge have not previously been reported in association with chronic experimental hypoxia and polycythaemia. These lesions resembled some glomerular lesions of cyanotic congenital heart disease. Decrease in glomerulonephritis under conditions in which hydrostatic pressure in the glomerulus is presumably elevated and the glomerulus is subject to injury in some respects would be contrary to expectation. Finally, selective decrease in the glomerulonephritic but not the other lesions of acute serum sickness by altering non-immunological general experimental conditions would be highly unusual. More extensive studies are indicated. ImagesFigs. 1-5Figs. 6-12 PMID:5055712

  18. Differential and irreversible CNS ontogenic reduction in maximal MK-801 binding site number in the NMDA receptor after acute hypoxic hypoxia.

    PubMed

    Vacotto, M; Rodríguez Gil, D J; Mitridate de Novara, A; Fiszer de Plazas, S

    2003-06-27

    CNS exposure to hypoxia impairs excitatory and inhibitory neurotransmission. Our aim was to determine variations induced by normobaric acute hypoxic hypoxia (8% O(2) for 60 min) on the NMDA receptor complex, as well as their potential reversibility after normoxic recovery. To this end, [3H]MK-801 binding assays to a synaptic membrane fraction isolated from chick optic lobes were performed. Previous studies throughout development had disclosed a characteristic age-dependent pattern. Results at embryonic day (ED) 12 and 18 indicated two distinct MK-801 binding sites. Hypoxic treatment failed to alter either the high affinity site dissociation constant (K(d)) or its maximal binding capacity (B(max)), whereas the low affinity site B(max) was significantly decreased (50% and 30% at ED12 and 18, respectively), without alteration in its K(d) values. Hypoxic embryos restored for 48 h at ED12 to normoxic conditions displayed unchanged MK-801 binding reduction, unlike those treated likewise at ED18 whose values fully recovered control levels. To conclude, hypoxic treatment reduces low affinity MK-801 B(max) in the NMDA receptor which proves irreversible up to ED12. Such early neuronal vulnerability may be due to post-transcriptional changes, to endocytosis followed by receptor degradation, or alternatively to cell death.

  19. Early and Late Acute Kidney Injury in Severely Burned Patients

    PubMed Central

    Witkowski, Wojciech; Kawecki, Marek; Surowiecka-Pastewka, Agnieszka; Klimm, Wojciech; Szamotulska, Katarzyna; Niemczyk, Stanisław

    2016-01-01

    Background This study evaluated factors influencing early and late occurrence of AKI in severely burned patients and assessed the relationship between time of occurrence of AKI and mortality of AKI patients. Material/Methods Renal function was evaluated at 3 time points: at admission, at the critical point or middle point of hospitalization, and at the endpoint for which death or a discharge from the center was considered. AKI criteria were: decrease in GFR of less than 60 ml/min at admission, decrease in GFR of more than 75% compared to baseline, and decrease in the daily diuresis of less than 500 ml/24 h. Results At admission, 15.1% of the patients had eGFR <60 ml/min. AKI occurred in 38.5% of cases. The occurrence of AKI was associated with: elderly age (p<0.001), female sex (p=0.017), overweight and obesity (p=0.055); extent and depth of burns, respiratory failure, low protein concentration (for all p<0.001), low blood pressure (p=0.014), and high WBC (p=0.010). Early AKI was detected in 28% of patients. Mortality was 100% with the initial GFR ≥60, 100% with the initial GFR <60 and early deterioration of renal function, 80% with the initial GFR <60 and late worsening, and 60% with the initial GFR <60 and no worsening. Late AKI was observed in 10% of patients and mortality in this group was 79.2%. Mortality in the entire group with AKI was 88.0% versus 24.5%. Conclusions The frequent occurrence of AKI, especially early, worsens the prognosis for survival. Assessment of renal function should be included in the prognostic scales for burned patients. PMID:27746455

  20. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease

    PubMed Central

    Soler-Cataluna, J; Martinez-Garcia, M; Roman, S; Salcedo, E; Navarro, M; Ochando, R

    2005-01-01

    Background: Patients with chronic obstructive pulmonary disease (COPD) often present with severe acute exacerbations requiring hospital treatment. However, little is known about the prognostic consequences of these exacerbations. A study was undertaken to investigate whether severe acute exacerbations of COPD exert a direct effect on mortality. Methods: Multivariate techniques were used to analyse the prognostic influence of acute exacerbations of COPD treated in hospital (visits to the emergency service and admissions), patient age, smoking, body mass index, co-morbidity, long term oxygen therapy, forced spirometric parameters, and arterial blood gas tensions in a prospective cohort of 304 men with COPD followed up for 5 years. The mean (SD) age of the patients was 71 (9) years and forced expiratory volume in 1 second was 46 (17)%. Results: Only older age (hazard ratio (HR) 5.28, 95% CI 1.75 to 15.93), arterial carbon dioxide tension (HR 1.07, 95% CI 1.02 to 1.12), and acute exacerbations of COPD were found to be independent indicators of a poor prognosis. The patients with the greatest mortality risk were those with three or more acute COPD exacerbations (HR 4.13, 95% CI 1.80 to 9.41). Conclusions: This study shows for the first time that severe acute exacerbations of COPD have an independent negative impact on patient prognosis. Mortality increases with the frequency of severe exacerbations, particularly if these require admission to hospital. PMID:16055622

  1. Severe acute respiratory syndrome (SARS): lessons learnt in Hong Kong

    PubMed Central

    2013-01-01

    Many healthcare workers were infected while looking after the SARS patients on the medical wards in 2003. The high infectivity of the SARS coronavirus with peak viral load on day 10 of illness when patients were ill, overcrowding of the old medical wards with low air changes/hr (ACH), and aerosol-generating procedures while resuscitating the patients were the major factors. Procedures reported to present an increased risk of SARS transmission include tracheal intubation, non-invasive ventilation, tracheotomy and manual ventilation before intubation whereas oxygen therapy and bed distance <1 m were also implicated. Studies based on laser visualization technique with smoke particles as smokers in the human patient simulator has shown that oxygen therapy via Hudson mask and nasal cannula could disperse exhaled air of patients to 0.4 and 1 m respectively whereas jet nebulizer could disperse exhaled air >0.8 m from the patient. Bigger isolation rooms with 16 ACH are more effective than smaller isolation rooms with 12 ACH in removing exhaled air and preventing room contamination but at the expense of more noise and electricity consumption. Non-invasive ventilation via face masks and single circuit can disperse exhaled air from 0.4 to 1 m. Both higher inspiratory pressures and use of whisper swivel device (to facilitate carbon dioxide removal) could increase the exhaled air leakage and isolation room contamination during on-invasive ventilation. Addition of a viral-bacterial filter during manual ventilation by bagging may reduce the exhaled air leakage forward and yet increase the sideway leakage. N95 mask was more effective than surgical mask in preventing expelled air leakage during patient’s coughing but there was still significant sideway leakage to 15 cm. Clinicians should be aware of air leakage from the various face masks and adopt strict infection control measures during resuscitation of patients with severe respiratory infections. Carefully designed clinical

  2. Comparison of two simplified severity scores (SAPS and APACHE II) for patients with acute myocardial infarction.

    PubMed

    Moreau, R; Soupison, T; Vauquelin, P; Derrida, S; Beaucour, H; Sicot, C

    1989-05-01

    The Simplified Acute Physiology Score (SAPS), the Acute Physiology and Chronic Health Evaluation II (APACHE II), the Acute Physiology Score (APS), and the Coronary Prognostic Index (CPI), calculated within the first 24 h of ICU admission, were compared in 76 patients with acute myocardial infarction (AMI). Sixteen (21%) patients subsequently died in the ICU. The nonsurvivors had significantly higher SAPS, APACHE II, and CPI scores than the survivors. ROC curves drawn for each severity index were in a discriminating position. There were no significant differences either between the areas under the ROC curves drawn for SAPS, APACHE II, and CPI, or between the overall accuracies of these indices. APS provided less homogeneous information. We conclude that SAPS and APACHE II, two severity indices which are easy to use, assess accurately the short-term prognosis, i.e., the ICU outcome, of patients with AMI. PMID:2707010

  3. Two cases of acute atraumatic compartment syndrome complicated with severe heat stroke.

    PubMed

    Ikegami, Yukihiro; Hasegawa, Arifumi; Tsukada, Yasuhiko; Abe, Yoshinobu; Shimada, Jiro; Tase, Choichiro

    2010-12-01

    Acute compartment syndrome is a life-threatening complication in trauma patients. Not only regional neuromuscular disability, but also systemic organ disorders can result from prolonged tissue ischemia. In this report, we describe 2 cases of acute atraumatic compartment syndrome complicated with severe heat stroke. In both cases, emergency fasciotomy was rapidly performed after recognition of the syndrome, but serious regional neuromuscular disabilities remained. Microvascular endothelial injury is an important mechanism of acute atraumatic compartment syndrome. Thrombi diffusely formed in the compartmental space hinder establishment of reperfusion even after fasciotomy. Furthermore, disruption of fibrinolysis due to heat stroke could enhance this damage.

  4. Recurrent Acute Decompensated Heart Failure Owing to Severe Iron Deficiency Anemia Caused by Inappropriate Habitual Bloodletting

    PubMed Central

    Lim, Woo-Hyun; Kim, Hack-Lyoung; Kim, Ki-Hwan; Na, Sang Hoon; Lee, Hyun-Jung; Kang, Eun Gyu; Seo, Jae-Bin; Chung, Woo-Young; Zo, Joo-Hee; Hong, Jung Ae; Kim, Kwangyoun; Kim, Myung-A

    2015-01-01

    A 68-year-old woman visited the emergency department twice with symptoms of acute heart failure including shortness of breath, general weakness, and abdominal distension. Laboratory findings showed extremely low level of serum hemoglobin at 1.4 g/dL. Echocardiographic examination demonstrated dilated left ventricular cavity with systolic dysfunction and moderate amount of pericardial effusion. In this patient, acute heart failure due to severe iron deficiency anemia was caused by inappropriate habitual bloodletting. PMID:26755934

  5. Severe Acute Respiratory Syndrome and the Delivery of Continuing Medical Education: Case Study from Toronto

    ERIC Educational Resources Information Center

    Davis, Dave; Ryan, David; Sibbald, Gary; Rachlis, Anita; Davies, Sharon; Manchul, Lee; Parikh, Sagar

    2004-01-01

    Introduction: Severe acute respiratory syndrome (SARS) struck Toronto in the spring of 2003, causing many deaths, serious morbidity, forced quarantine of thousands of individuals, and the closure of all provincial hospitals for several weeks. Given the direction by public health authorities to cancel or postpone all continuing medical education…

  6. Severe pancytopenia due to acute folate deficiency despite normal folate erythrocyte level.

    PubMed

    Huguenin, Antoine; Barraud, Sara; Daliphard, Sylvie; Marot, Didier; Garnotel, Roselyne; Bani-Sadr, Firouzé

    2016-06-01

    We report the case of an alcoholic patient with severe pancytopenia with low plasma folate level but normal erythrocyte folates and cobalamin levels. The bone marrow smear concluded to a pancytopenia due to folates and/or cobalamin deficiency. Severe pancytopenia due to acute plasma folate deficiency can be observed despite normal erythrocyte folates level which reflects the organism's folates store. PMID:27108778

  7. Effects of acute alcohol withdrawal on nest building in mice selectively bred for alcohol withdrawal severity.

    PubMed

    Greenberg, Gian D; Phillips, Tamara J; Crabbe, John C

    2016-10-15

    Nest building has been used to assess thermoregulatory behavior and positive motivational states in mice. There are known genetic influences on ethanol withdrawal severity as well as individual/thermoregulatory nest building. Withdrawal Seizure-Prone (WSP-1, WSP-2) and Withdrawal Seizure-Resistant (WSR-1, WSR-2) mice were selectively bred for high vs low handling-induced convulsion (HIC) severity, respectively, during withdrawal from chronic ethanol vapor inhalation. They also differ in HIC severity during withdrawal from an acute, 4g/kg ethanol injection. In our initial study, withdrawal from an acute dose of ethanol dose-dependently impaired nest building over the initial 24h of withdrawal in genetically segregating Withdrawal Seizure Control (WSC) mice. In two further studies, acute ethanol withdrawal suppressed nest building for up to two days in WSP-1 females. Deficits in nest building from ethanol were limited to the initial 10h of withdrawal in WSR-1 females and to the initial 24h of withdrawal in WSP-1 and WSR-1 males. Effects of ethanol on nest building for up to two days were found in WSP-2 and WSR-2 mice of both sexes. Nest building deficits in female mice from the first replicate could not be explained by a general decrease in locomotor behavior. These results suggest that nest building is a novel behavioral phenotype for indexing the severity of acute ethanol withdrawal, and that genes contributing to this trait differ from those affecting acute withdrawal HIC severity. PMID:27503811

  8. Measurement of the acute metabolic response to hypoxia in rat tumours in vivo using magnetic resonance spectroscopy and hyperpolarised pyruvate

    PubMed Central

    Bluff, Joanne E.; Reynolds, Steven; Metcalf, Stephen; Alizadeh, Tooba; Kazan, Samira M.; Bucur, Adriana; Wholey, Emily G.; Bibby, Becky A.S.; Williams, Leigh; Paley, Martyn N.; Tozer, Gillian M.

    2015-01-01

    Purpose To estimate the rate constant for pyruvate to lactate conversion in tumours in response to a hypoxic challenge, using hyperpolarised 13C1-pyruvate and magnetic resonance spectroscopy. Methods and materials Hypoxic inspired gas was used to manipulate rat P22 fibrosarcoma oxygen tension (pO2), confirmed by luminescence decay of oxygen-sensitive probes. Hyperpolarised 13C1-pyruvate was injected into the femoral vein of anaesthetised rats and slice-localised 13C magnetic resonance (MR) spectra acquired. Spectral integral versus time curves for pyruvate and lactate were fitted to a precursor-product model to estimate the rate constant for tumour conversion of pyruvate to lactate (kpl). Mean arterial blood pressure (MABP) and oxygen tension (ArtpO2) were monitored. Pyruvate and lactate concentrations were measured in freeze-clamped tumours. Results MABP, ArtpO2 and tumour pO2 decreased significantly during hypoxia. kpl increased significantly (p < 0.01) from 0.029 ± 0.002 s−1 to 0.049 ± 0.006 s−1 (mean ± SEM) when animals breathing air were switched to hypoxic conditions, whereas pyruvate and lactate concentrations were minimally affected by hypoxia. Both ArtpO2 and MABP influenced the estimate of kpl, with a strong negative correlation between kpl and the product of ArtpO2 and MABP under hypoxia. Conclusion The rate constant for pyruvate to lactate conversion, kpl, responds significantly to a rapid reduction in tumour oxygenation. PMID:25824978

  9. In Vivo Imaging of Retinal Hypoxia in a Model of Oxygen-Induced Retinopathy

    PubMed Central

    Uddin, Md. Imam; Evans, Stephanie M.; Craft, Jason R.; Capozzi, Megan E.; McCollum, Gary W.; Yang, Rong; Marnett, Lawrence J.; Uddin, Md. Jashim; Jayagopal, Ashwath; Penn, John S.

    2016-01-01

    Ischemia-induced hypoxia elicits retinal neovascularization and is a major component of several blinding retinopathies such as retinopathy of prematurity (ROP), diabetic retinopathy (DR) and retinal vein occlusion (RVO). Currently, noninvasive imaging techniques capable of detecting and monitoring retinal hypoxia in living systems do not exist. Such techniques would greatly clarify the role of hypoxia in experimental and human retinal neovascular pathogenesis. In this study, we developed and characterized HYPOX-4, a fluorescence-imaging probe capable of detecting retinal-hypoxia in living animals. HYPOX-4 dependent in vivo and ex vivo imaging of hypoxia was tested in a mouse model of oxygen-induced retinopathy (OIR). Predicted patterns of retinal hypoxia were imaged by HYPOX-4 dependent fluorescence activity in this animal model. In retinal cells and mouse retinal tissue, pimonidazole-adduct immunostaining confirmed the hypoxia selectivity of HYPOX-4. HYPOX-4 had no effect on retinal cell proliferation as indicated by BrdU assay and exhibited no acute toxicity in retinal tissue as indicated by TUNEL assay and electroretinography (ERG) analysis. Therefore, HYPOX-4 could potentially serve as the basis for in vivo fluorescence-based hypoxia-imaging techniques, providing a tool for investigators to understand the pathogenesis of ischemic retinopathies and for physicians to address unmet clinical needs. PMID:27491345

  10. A study of the clinical profile of acute pancreatitis and its correlation with severity indices

    PubMed Central

    Vengadakrishnan, K.; Koushik, A. K.

    2015-01-01

    Background Acute pancreatitis is a common disease with wide clinical variation and its incidence is increasing. Acute pancreatitis may vary in severity, from mild self-limiting pancreatic inflammation to pancreatic necrosis with life-threatening sequelae. Severity of acute pancreatitis is linked to the presence of systemic organ dysfunctions and/or necrotizing pancreatitis. Aim and objectives The present study was aimed to assess the clinical profile of acute pancreatitis and to assess the efficacy of various severity indices in predicting the outcome of patients. Methodology This was a prospective study done in Sri Ramachandra Medical College and Hospital from April 2012–September 2014. All patients with a diagnosis of acute pancreatitis were included in this study. Along with routine lab parameters, serum amylase, lipase, lipid profile, calcium, CRP, LDH, CT abdomen, CXR and 2D Echo was done for all patients. Results A total of 110 patients were analysed. 50 patients required Intensive care, among them 9 patients (18%) died. 20 patients (18.2%) had MODS, 15 patients (13.6%) had pleural effusion, 9 patients (8.2%) had pseudocyst, 2 patients(1.8%) had hypotension, 2 patients(1.8%) had ARDS and 2 patients(1.8%) had DKA. In relation to various severity indices, high score of CRP, LDH and CT severity index was associated with increased morbidity and mortality. 15 patients (13.6%) underwent open necrosectomy surgery, 3 patients (2.7%) underwent laparoscopic necrosectomy and 7 patients (6.4%) were tried step up approach but could not avoid surgery. Step up approach and surgery did not have a significant reduction in the mortality. Conclusion Initial assessment of severity by CRP, LDH and lipase could be reliable indicators of outcome in acute pancreatitis PMID:26715920

  11. Percutaneous mechanical assist for severe cardiogenic shock due to acute right ventricular failure.

    PubMed

    Kipp, Ryan; Raval, Amish N

    2015-05-01

    Acute right ventricular failure can lead to severe cardiogenic shock and death. Recovery may be achieved with early supportive measures. In many patients, intravenous fluid and inotropic resuscitation is inadequate to improve cardiac output. In these cases, percutaneous mechanical assist may provide a non-surgical bridge to recovery. Herein, we describe a case series of patients with severe, refractory cardiogenic shock due to acute right ventricular failure who received a continuous flow percutaneous ventricular device primarily utilizing the right internal jugular vein for out flow cannula placement.

  12. Hypoxia-inducible factor 2α regulates macrophage function in mouse models of acute and tumor inflammation

    PubMed Central

    Imtiyaz, Hongxia Z.; Williams, Emily P.; Hickey, Michele M.; Patel, Shetal A.; Durham, Amy C.; Yuan, Li-Jun; Hammond, Rachel; Gimotty, Phyllis A.; Keith, Brian; Simon, M. Celeste

    2010-01-01

    Hypoxia-inducible factor 1α (HIF-1α) and HIF-2α display unique and sometimes opposing activities in regulating cellular energy homeostasis, cell fate decisions, and oncogenesis. Macrophages exposed to hypoxia accumulate both HIF-1α and HIF-2α, and overexpression of HIF-2α in tumor-associated macrophages (TAMs) is specifically correlated with high-grade human tumors and poor prognosis. However, the precise role of HIF-2α during macrophage-mediated inflammatory responses remains unclear. To fully characterize cellular hypoxic adaptations, distinct functions of HIF-1α versus HIF-2α must be elucidated. We demonstrate here that mice lacking HIF-2α in myeloid cells (Hif2aΔ/Δ mice) are resistant to lipopolysaccharide-induced endotoxemia and display a marked inability to mount inflammatory responses to cutaneous and peritoneal irritants. Furthermore, HIF-2α directly regulated proinflammatory cytokine/chemokine expression in macrophages activated in vitro. Hif2aΔ/Δ mice displayed reduced TAM infiltration in independent murine hepatocellular and colitis-associated colon carcinoma models, and this was associated with reduced tumor cell proliferation and progression. Notably, HIF-2α modulated macrophage migration by regulating the expression of the cytokine receptor M-CSFR and the chemokine receptor CXCR4, without altering intracellular ATP levels. Collectively, our data identify HIF-2α as an important regulator of innate immunity, suggesting it may be a useful therapeutic target for treating inflammatory disorders and cancer. PMID:20644254

  13. Progressive multicystic encephalopathy: is there more than hypoxia-ischemia?

    PubMed

    Garten, Lars; Hueseman, Dieter; Stoltenburg-Didinger, Gisela; Felderhoff-Mueser, Ursula; Weizsaecker, Katharina; Scheer, Ianina; Boltshauser, Eugen; Obladen, Michael

    2007-05-01

    Progressive multicystic encephalopathy following prenatal or perinatal hypoxia-ischemia is a well-described phenomenon in the literature. The authors report on a term infant with a devastating encephalopathy and severe neuronal dysfunction immediately after delivery without a known antecedent of prenatal or perinatal hypoxia or distress. Clinical and paraclinical findings in the patient are compared with those described in the literature. The authors focus on the specific results guiding to the final diagnosis of progressive multicystic encephalopathy and the timing of morphologic changes. As in this case, if the criteria of an acute hypoxic event sufficient to cause neonatal encephalopathy are not met, then factors other than hypoxia-ischemia may be leading to progressive multicystic encephalopathy.

  14. Valproic Acid-Induced Severe Acute Pancreatitis with Pseudocyst Formation: Report of a Case

    PubMed Central

    Khamrui, Sujan; Kataria, Mohnish; Biswas, Jayanta; Saha, Suman

    2015-01-01

    Valproic acid is the most widely used anti-epilep­tic drug in children, and it is probably the most frequent cause of drug-induced acute pancreatitis. Outcomes for patients with valproic acid-associated pancreatitis vary from full recovery after discontinuation of the drug to severe acute pancreatitis and death. Here, we present a case of valproic acid-induced severe acute pancreatitis with pseudocyst formation in a 10-year-old girl with cerebral palsy and generalized tonic-clonic seizure. There was no resolution of the pseudocyst after discontinuation of valproic acid. The patient became symptomatic with a progressive increase in the size of the pseudocyst. She was successfully treated with cystogastrostomy and was well at 12-month follow-up. PMID:26366333

  15. Abdominal compartment syndrome in severe acute pancreatitis treated with percutaneous catheter drainage.

    PubMed

    Park, Soonyoung; Lee, Seungho; Lee, Hyo Deok; Kim, Min; Kim, Kyeongmin; Jeong, Yusook; Park, Seon Mee

    2014-09-01

    Acute pancreatitis is one of the main causes of intra-abdominal hypertension (IAH). IAH contributes to multiple physiologic alterations and leads to the development of abdominal compartment syndrome (ACS) that induces multiorgan failure. We report a case of ACS in a patient with severe acute pancreatitis. A 44-year-old man who was admitted in a drunk state was found to have severe acute pancreatitis. During management with fluid resuscitation in an intensive care unit, drowsy mentality, respiratory acidosis, shock requiring inotropes, and oliguria developed in the patient, with his abdomen tensely distended. With a presumptive diagnosis of ACS, abdominal decompression through percutaneous catheter drainage was performed immediately. The intraperitoneal pressure measured with a drainage catheter was 31 mm Hg. After abdominal decompression, the multiorgan failure was reversed. We present a case of ACS managed with percutaneous catheter decompression. PMID:25325011

  16. The volatile anesthetic isoflurane differentially suppresses the induction of erythropoietin synthesis elicited by acute anemia and systemic hypoxemia in mice in an hypoxia-inducible factor-2-dependent manner.

    PubMed

    Kai, Shinichi; Tanaka, Tomoharu; Matsuyama, Tomonori; Suzuki, Kengo; Hirota, Kiichi

    2014-06-01

    Erythropoietin (EPO) is a glycoprotein hormone essential for the regulation of erythroid homeostasis. Although EPO production is prominent in the kidney and liver, its production in the central nervous system has also been detected. Tissue hypoxia due to systemic or local hypoxemia and acute anemia due to blood loss occurs frequently during various clinical settings, leading to a high possibility of elevated plasma EPO levels. However, it is largely unknown whether volatile anesthetic agents affect EPO production elicited by acute hypoxia in vivo. Male C57BL/6N CrSlc mice were exposed to a hypoxic insult as a result of bleeding-related anemia or hypoxemia while they were under anesthetized using various concentrations of isoflurane. EPO protein concentrations were assessed by enzyme-linked immunosorbent assay and mRNA levels were measured by quantitative real-time reverse transcriptase-polymerase chain reaction. Plasma EPO concentration was induced as early as 3h following acute anemic and hypoxemic hypoxia and suppressed by clinically relevant doses of isoflurane in a dose-dependent manner. Anemic hypoxia induced EPO mRNA and protein synthesis in the kidney. In the kidney, isoflurane inhibited EPO induction caused by anemia but not that caused by hypoxemia. On the other hand, in the brain hypoxemia-induced EPO production was suppressed by isoflurane. Finally, qRT-PCR studies demonstrate that isoflurane differentially inhibit HIF-1α and HIF-2α mRNA expression in brain and kidney, indicating the involvement of HIF-2 in the hypoxia-induced EPO expression and inhibition of the induction by isoflurane. PMID:24680923

  17. Different effects of tianeptine pretreatment in rats exposed to acute stress and repeated severe stress.

    PubMed

    Kasar, M; Mengi, M; Yildirim, E A; Yurdakos, E

    2009-04-01

    In this study we aim to discuss the relationship between stress and learning and emotionality in an experimental model using two different stress conditions: acute stress (single restraint stress for 20 min) and repeated severe stress (6-h daily restraint for 21 days). We studied the effects of tianeptine, which has been suggested to have anxiolytic and cognition-enhancing effects under stressful conditions. After acute stress, the increase in the duration of immobility (F = 5.753 and 3.664) in the open field and holeboard tests and the decrease in rearing (F = 3.891) in the holeboard test were significant when compared to controls (P < 0.05). Results for repeated severe stress showed that in both the open field and holeboard tests the decrease in rearing (F = 4.494 and 4.530, respectively), increase in the duration of immobility (F = 6.069 and 4.742, respectively) and decrease in head dips (F = 4.938) in the holeboard test were statistically significant (P < 0.05). The group pretreated with tianeptine showed no significant difference from controls for either acute or repeated severe stress conditions. In the Morris water maze test, acute stress led to a prolongation of average escape latency, which indicated a spatial learning deficit. Treatment with tianeptine prior to acute stress prevented this spatial deficit. Repeated severe stress also led to spatial learning deficits in rats, but this deficit was not prevented by treatment with tianeptine. Our study demonstrates that pretreatment with tianeptine had different effects on stress-induced spatial learning deficits under acute and repeated stress conditions, while the effects on emotionality and anxiety-like behavior were similar. The mechanisms implicated in stress-induced emotional and memory deficits will be discussed.

  18. A randomised, double blind, multicentre trial of octreotide in moderate to severe acute pancreatitis

    PubMed Central

    Uhl, W; Buchler, M; Malfertheiner, P; Beger, H; Adler, G; Gaus, W; the, G

    1999-01-01

    BACKGROUND—The pharmacological inhibition of exocrine pancreatic secretion with the somatostatin analogue octreotide has been advocated as a specific treatment of acute pancreatitis.
AIM—To investigate the efficacy of octreotide in acute pancreatitis in a randomised, placebo controlled trial.
METHODS—302 patients from 32 hospitals, fulfilling the criteria for moderate to severe acute pancreatitis within 96 hours of the onset of symptoms, were randomly assigned to one of three treatment groups: group P (n=103) received placebo, while groups O1 (n=98) and O2 (n=101) received 100 and 200 µg of octreotide, respectively, by subcutaneous injection three times daily for seven days. The primary outcome variable was a score composed of mortality and 15 typical complications of acute pancreatitis.
RESULTS—The three groups were well matched with respect to pretreatment characteristics. An intent to treat analysis of all 302 patients revealed no significant differences among treatment groups with respect to mortality (P: 16%; O1: 15%; O2: 12%), the rate of newly developed complications, the duration of pain, surgical interventions, or the length of the hospital stay. A valid for efficacy analysis (251 patients) also revealed no significant differences.
CONCLUSIONS—This trial shows no benefit of octreotide in the treatment of acute pancreatitis.


Keywords: acute pancreatitis; somatostatin; octreotide; randomised controlled multicentre trial PMID:10369711

  19. Social support and response to AIDS and severe acute respiratory syndrome.

    PubMed

    Nandi, Arijit; Tracy, Melissa; Aiello, Allison; Des Jarlais, Don C; Galea, Sandro

    2008-05-01

    Negative public reactions to emerging infectious diseases can adversely affect population health. We assessed whether social support was associated with knowledge of, worry about, and attitudes towards AIDS and severe acute respiratory syndrome. Our findings suggest that social support may be central to our understanding of public responses to emerging infectious diseases.

  20. Exploring the Roles and Nature of Science: A Case Study of Severe Acute Respiratory Syndrome

    ERIC Educational Resources Information Center

    Lee, Yeung Chung

    2008-01-01

    The roles of science in society and the nature of science are the focus of many science curricula. Current views about these two aspects of science have largely been informed by the history of scientific development. This article uses the outbreak of severe acute respiratory syndrome--a recent health scare--as a case study to explore the roles of…

  1. Fear of Severe Acute Respiratory Syndrome (SARS) among Health Care Workers

    ERIC Educational Resources Information Center

    Ho, Samuel M. Y.; Kwong-Lo, Rosalie S. Y.; Mak, Christine W. Y.; Wong, Joe S.

    2005-01-01

    In this study, the authors examined fear related to severe acute respiratory syndrome (SARS) among 2 samples of hospital staff in Hong Kong. Sample 1 included health care workers (n = 82) and was assessed during the peak of the SARS epidemic. Sample 2 included hospital staff who recovered from SARS (n = 97). The results show that participants in…

  2. Management of severe acute malnutrition in low-income and middle-income countries

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Kwashiorkor and marasmus, collectively termed severe acute malnutrition (SAM), account for at least 10% of all deaths among children under 5 years of age worldwide, virtually all of them in low-income and middle-income countries. A number of risk factors, including seasonal food insecurity, environm...

  3. Gut DNA viromes of Malawian twins discordant for severe acute malnutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The bacterial component of the human gut microbiota undergoes a definable program of postnatal development. Evidence is accumulating that this program is disrupted in children with severe acute malnutrition (SAM) and that their persistent gut microbiota immaturity, which is not durably repaired with...

  4. Severe Acute Respiratory Syndrome Epidemic and Change of People's Health Behavior in China

    ERIC Educational Resources Information Center

    Tan, Xiaodong; Li, Shiyue; Wang, Chunhong; Chen, Xiaoqing; Wu, Xiaomin

    2004-01-01

    Severe Acute Respiratory Syndrome (SARS) has become a new worldwide epidemic whose origin was until recently unknown. It is the unpredictable nature of this epidemic that makes people want answers to some important questions about what they can do to protect themselves. This study presents an inquiry into peoples knowledge and self-reported…

  5. Toward an Improved Scale for Assessing Symptom Severity in Children With Acute Otitis Media.

    PubMed

    Shaikh, Nader; Hoberman, Alejandro; Rockette, Howard E; Kurs-Lasky, Marcia; Paradise, Jack L

    2015-12-01

    The objective of the present study was to determine whether changes in the previously developed 7-item Acute Otitis Media Severity of Symptoms scale could improve its responsiveness and its longitudinal construct validity. The items "diminished activity" and "diminished appetite" had low or borderline levels of responsiveness and longitudinal construct validity. Dropping these items seems to be potentially advantageous.

  6. Colonic fistula associated with severe acute pancreatitis: report of two cases.

    PubMed

    Suzuki, Atsushi; Suzuki, Shohachi; Sakaguchi, Takanori; Oishi, Kosuke; Fukumoto, Kazuhiko; Ota, Shigeyasu; Inaba, Keisuke; Takehara, Yasuo; Sugimura, Haruhiko; Uchiyama, Takashi; Konno, Hiroyuki

    2008-01-01

    Colonic fistula is a rare and potentially critical sequela of severe acute pancreatitis, which requires surgical treatment. We report two cases that were successfully treated by a colectomy for colonic fistula associated with severe acute pancreatitis. Case 1 is a 71-year-old man infected with pseudocysts owing to severe acute pancreatitis that developed into a colonic fistula as an early complication with a resulting pancreatic abscess. This patient underwent a left hemicolectomy, a transverse colostomy, and drainage of the pancreatic abscess. He has done well without recurrent disease for 35 months following surgery. Case 2 is a 58-year-old woman who had a past history of drainage during a laparotomy for a pancreatic abscess induced by endoscopic retrograde cholangiopancreatography 10 years earlier. She was admitted to our hospital with left lateral abdominal pain and low-grade fever. Abdominal magnetic resonance imaging showed a retroperitoneal abscess and fistula to the descending colon. She underwent a left hemicolectomy and drainage of the retroperitoneal abscess. She has remained symptom-free for 20 months following surgery. The colonic fistula should therefore be recognized as a late complication during long-term follow-up as well as an early sequela associated with severe acute pancreatitis.

  7. Acute severe asthma. A prospective study of the precipitating factors in 40 children.

    PubMed

    Potter, P C; Weinberg, E; Shore, S C

    1984-09-15

    A prospective study was undertaken to determine the factors precipitating acute severe asthma in children attending the Red Cross War Memorial Children's Hospital, Cape Town. A comparison in terms of recent exposure to possible precipitating factors was made between 40 known asthmatics presenting with acute severe asthma and 40 known asthmatics who were clinically well. Exposure to known allergens had occurred in 7 cases. The time of onset of symptoms bore no relationship to meteorological changes in temperature, humidity or average pressure. Drug compliance in both groups was of the order of 50%. The majority of severe asthma attacks were associated with infection of the respiratory tract. The importance of infection as a precipitating factor in a severe asthma attack is discussed with reference to the cholinergic, adrenergic and immunological mechanisms.

  8. High-mobility group box 1 protein and its role in severe acute pancreatitis.

    PubMed

    Shen, Xiao; Li, Wei-Qin

    2015-02-01

    The high mobility group box 1 (HMGB1), which belongs to the subfamily of HMG-1/-2, is a highly conserved single peptide chain consisting of 215 amino acid residues with a molecular weight of approximately 24894 Da. HMGB1 is a ubiquitous nuclear protein in mammals and plays a vital role in inflammatory diseases. Acute pancreatitis is one of the most common causes of acute abdominal pain with a poor prognosis. Acute pancreatitis is an acute inflammatory process of the pancreas (duration of less than six months), for which the severe form is called severe acute pancreatitis (SAP). More and more studies have shown that HMGB1 has a bidirectional effect in the pathogenesis of SAP. Extracellular HMGB1 can aggravate the pancreatic inflammatory process, whereas intracellular HMGB1 has a protective effect against pancreatitis. The mechanism of HMGB1 is multiple, mainly through the nuclear factor-κB pathway. Receptors for advanced glycation end-products and toll-like receptors (TLR), especially TLR-2 and TLR-4, are two major types of receptors mediating the inflammatory process triggered by HMGB1 and may be also the main mediators in the pathogenesis of SAP. HMGB1 inhibitors, such as ethyl pyruvate, pyrrolidine dithiocarbamate and Scolopendra subspinipes mutilans, can decrease the level of extracellular HMGB1 and are the promising targets in the treatment of SAP.

  9. Correlation between single nucleotide polymorphisms in hypoxia-related genes and susceptibility to acute high-altitude pulmonary edema.

    PubMed

    Wu, A L; Xiong, Y S; Li, Z Q; Liu, Y G; Quan, Q; Wu, L J

    2015-01-01

    This study aimed to explore the relationship between genetic changes and high-altitude pulmonary edema (HAPE) susceptibility, and to screen for the key single nucleotide polymorphism (SNP) loci in the HAPE-susceptibility gene, by investigating the SNPs occurring in hypoxia-related genes in HAPE-susceptible and control (non-susceptible) populations. This research was conducted on Han recruits, who travelled to the Lhasa plateau (altitude, 3658 m). Ten loci located on ten genes extracted from the HAPE and healthy populations were amplified by polymerase chain reaction, and subsequently sequenced. The investigated genes included those coding for aldosterone synthase 2 (CYP11B2), angiotensin-converting enzyme (ACE), heat-shock protein 70 (HSP70), nuclear factor kappa B (NF-κB), surfactant protein A2 (SP-A2), plasminogen activator inhibitor-1 (PAI-1), nitric oxide synthetase (NOS), vascular endothelial growth factor (VEGF), prolyl hydroxylase (EGLN1), and zinc finger protein A20. The gene distribution of each SNP loci and its correlation with HAPE was analyzed. Statistical analyses of the genotype frequencies of the SNPs revealed significant differences in the ACE (rs4309), EGLN1 (rs480902), SP-A2 (rs1965708), HSP70 (rs1008438), PAI-1 (rs1799889), and NOS (rs199983) expressions between the HAPE and healthy control groups (P < 0.05); therefore, these SNP loci were believed to indicate HAPE susceptibility. HAPE is correlated with multiple- SNP loci. A correlation analysis between genetic polymorphism and HAPE susceptibility revealed that 6 hypoxia-related genes were key sites accounting for HAPE. These findings could help assess the risk of HAPE in populations expressing different genotypes, in order to reduce the occurrence of HAPE. PMID:26436397

  10. Influence of sildenafil on lung diffusion during exposure to acute hypoxia at rest and during exercise in healthy humans

    PubMed Central

    Olson, Thomas P.; Johnson, Bruce D.; Frantz, Robert P.

    2009-01-01

    We sought to determine the influence of sildenafil on the diffusing capacity of the lungs for carbon monoxide (DLCO) and the components of DLCO (pulmonary capillary blood volume Vc, and alveolar–capillary membrane conductance DM) at rest and following exercise with normoxia and hypoxia. This double-blind placebo-controlled, cross-over study included 14 healthy subjects (age = 33 ± 11 years, ht = 181 ± 8 cm, weight = 85 ± 14 kg, BMI = 26 ± 3 kg/m2, peak normoxic VO2 = 36 ± 6 ml/kg, mean ± SD). Subjects were randomized to placebo or 100 mg sildenafil 1 h prior to entering a hypoxic tent with an FiO2 of 12.5% for 90 min. DLCO, Vc, and DM were assessed at rest, every 3 min during exercise, at peak exercise, and 10 and 30 min post exercise. Sildenafil attenuated the elevation in PAP at rest and during recovery with exposure to hypoxia, but pulmonary arterial pressure immediately post exercise was not different between sildenafil and placebo. Systemic O2 saturation and VO2peak did not differ between the two conditions. DLCO was not different between groups at any time point. VC was higher with exercise in the placebo group, and the difference in DM between sildenafil and placebo was significant only when corrected for changes in Vc (DM/Vc = 0.57 ± 0.29 vs. 0.41 ± 0.16, P = 0.04). These results suggest no effect of sildenafil on DLCO, but an improvement in DM when corrected for changes in Vc during short-term hypoxic exposure with exercise. PMID:18369657

  11. The economic impact of the insured patients with severe chronic and acute illnesses: a qualitative approach

    PubMed Central

    Aji, Budi; Yamamoto, Shelby Suzanne; Sauerborn, Rainer

    2014-01-01

    Background Little research has focused on the economic hardship among the insured with severe illnesses and high treatment costs, in particular, the consequence of poorer insurance coverage for high-cost illnesses. Therefore, we presented the case for identifying the experiences of insured patients with severe chronic and acute illnesses. This study identified a qualitative understanding of the economic impact of severe chronic and acute illnesses and household strategies to deal with high treatment costs. Design Interviews were conducted with 19 insured households of three different health insurance programs with a family member that had been hospitalized for severe chronic or acute illnesses in either Banyumas or Margono Sukarjo hospitals in Banyumas, Central Java, Indonesia. A thematic analysis was applied to guide the interpretation of the data. Results Insured households with a family member that had been hospitalized for severe chronic and acute illnesses were greatly affected by the high treatment costs. Four major issues emerged from this qualitative study: insured patients are still burdened with high out-of-pocket payments, households adopt various strategies to cope with the high cost of treatments, households experience financial hardships, and positive and negative perceptions of the insured regarding their health insurance coverage for acute and chronic illnesses. Conclusions Askes and Jamsostek patients faced financial burdens from high cost sharing for hospital amenities, non-covered drugs, and treatments and other indirect costs. Meanwhile, Jamkesmas beneficiaries faced no financial burden for related medical services but were rather burdened with indirect costs for the carers. Households relied on internal resources to cover hospital bills as the first strategy, which included the mobilization of savings, sale of assets, and borrowing of money. External support was tapped secondarily and included financial support from extended family members

  12. Chronic hypoxia enhances adenosine release in rat PC12 cells by altering adenosine metabolism and membrane transport.

    PubMed

    Kobayashi, S; Zimmermann, H; Millhorn, D E

    2000-02-01

    Acute exposure to hypoxia causes a release of adenosine (ADO) that is inversely related to the O2 levels in oxygen-sensitive pheochromocytoma (PC12) cells. In the current study, chronic exposure (48 h) of PC12 cells to moderate hypoxia (5% O2) significantly enhanced the release of ADO during severe, acute hypoxia (1% O2). Investigation into the intra- and extracellular mechanisms underpinning the secretion of ADO in PC12 cells chronically exposed to hypoxia revealed changes in gene expression and activities of several key enzymes associated with ADO production and metabolism, as well as the down-regulation of a nucleoside transporter. Decreases in the enzymatic activities of ADO kinase and ADO deaminase accompanied by an increase in those of cytoplasmic and ecto-5'-nucleotidases bring about an increased capacity to produce intra- and extracellular ADO. This increased potential to generate ADO and decreased capacity to metabolize ADO indicate that PC12 cells shift toward an ADO producer phenotype during hypoxia. The reduced function of the rat equilibrative nucleoside transporter rENT1 also plays a role in controlling extracellular ADO levels. The hypoxia-induced alterations in the ADO metabolic enzymes and the rENT1 transporter seem to increase the extracellular concentration of ADO. The biological significance of this regulation is unclear but is likely to be associated with modulating cellular activity during hypoxia. PMID:10646513

  13. Acute pandysautonomia and severe sensory deficit with poor recovery. A clinical, neurophysiological and pathological case study.

    PubMed Central

    Fagius, J; Westerberg, C E; Olsson, Y

    1983-01-01

    A patient with acute loss of autonomic functions and virtually all afferent functions of peripheral nerves is described. The course was chronic and the outcome fatal. The clinical course was followed with measurements of sensory thresholds and conduction velocities, autonomic tests and microneurographic recordings. Neuropathological changes were severe and localised in the peripheral nervous system. Previously reported similar cases were reviewed. It was concluded that acute pandysautonomia is a disorder similar to the Guillain-Barré syndrome; the course is often protracted and residual neurological deficit common. Images PMID:6886716

  14. Oxidation-Reduction Potential as a Biomarker for Severity and Acute Outcome in Traumatic Brain Injury

    PubMed Central

    Levy, Stewart; Carrick, Matthew; Mains, Charles W.; Slone, Denetta S.

    2016-01-01

    There are few reliable markers for assessing traumatic brain injury (TBI). Elevated levels of oxidative stress have been observed in TBI patients. We hypothesized that oxidation-reduction potential (ORP) could be a potent biomarker in TBI. Two types of ORP were measured in patient plasma samples: the static state of oxidative stress (sORP) and capacity for induced oxidative stress (icORP). Differences in ORP values as a function of time after injury, severity, and hospital discharge were compared using ANOVAs with significance at p ≤ 0.05. Logit regression analyses were used to predict acute outcome comparing ORP, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS), and Glasgow Coma Scale (GCS). Antioxidant capacity (icORP) on day 4 was prognostic for acute outcomes (p < 0.05). An odds ratio of 4.08 was associated with poor acute outcome when icORP > 7.25 μC. IcORP was a better predictor than ISS, AIS, or GCS scores. sORP increased in those with the highest ISS values (p < 0.05). Based on these findings ORP is useful biomarker for severity and acute outcome in TBI patients. Changes in ORP values on day 4 after injury were the most prognostic, suggesting that patients' response to brain injury over time is a factor that determines outcome.

  15. Oxidation-Reduction Potential as a Biomarker for Severity and Acute Outcome in Traumatic Brain Injury.

    PubMed

    Bjugstad, Kimberly B; Rael, Leonard T; Levy, Stewart; Carrick, Matthew; Mains, Charles W; Slone, Denetta S; Bar-Or, David

    2016-01-01

    There are few reliable markers for assessing traumatic brain injury (TBI). Elevated levels of oxidative stress have been observed in TBI patients. We hypothesized that oxidation-reduction potential (ORP) could be a potent biomarker in TBI. Two types of ORP were measured in patient plasma samples: the static state of oxidative stress (sORP) and capacity for induced oxidative stress (icORP). Differences in ORP values as a function of time after injury, severity, and hospital discharge were compared using ANOVAs with significance at p ≤ 0.05. Logit regression analyses were used to predict acute outcome comparing ORP, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS), and Glasgow Coma Scale (GCS). Antioxidant capacity (icORP) on day 4 was prognostic for acute outcomes (p < 0.05). An odds ratio of 4.08 was associated with poor acute outcome when icORP > 7.25 μC. IcORP was a better predictor than ISS, AIS, or GCS scores. sORP increased in those with the highest ISS values (p < 0.05). Based on these findings ORP is useful biomarker for severity and acute outcome in TBI patients. Changes in ORP values on day 4 after injury were the most prognostic, suggesting that patients' response to brain injury over time is a factor that determines outcome. PMID:27642494

  16. Signal Intensity of Superb Microvascular Imaging Correlates with the Severity of Acute Cholecystitis

    PubMed Central

    Tomizawa, Minoru; Shinozaki, Fuminobu; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Ishige, Naoki

    2016-01-01

    Evaluation of the severity of acute cholecystitis is critical for the management of this condition. Superb microvascular imaging (SMI) enables the assessment of slow blood flow of small vessels without any contrast medium. An 84-year-old man visited our hospital with right upper abdominal pain. Computed tomography and abdominal ultrasonography showed a slight thickening of the gallbladder. White blood cell count and C-reactive protein levels were elevated. He was diagnosed with acute cholecystitis and treated conservatively with antibiotics. Two days later, his condition worsened and percutaneous transhepatic gallbladder drainage (PTGBD) was performed. The patient recovered and was discharged, and his drainage was withdrawn 7 days later. On admission, color-coded SMI (cSMI) showed pulsatory signals on the slightly thickened gallbladder wall. On the day of PTGBD, the intensity of the signal on cSMI had increased. Once the patient was cured, no further signal was observed on the gallbladder wall with either cSMI or mSMI. In conclusion, the strong pulsatory signal correlated with the severity of acute cholecystitis observed with cSMI and mSMI. Illustrating the signal intensity is useful for the evaluation of the severity of acute cholecystitis. PMID:27721732

  17. Oxidation-Reduction Potential as a Biomarker for Severity and Acute Outcome in Traumatic Brain Injury

    PubMed Central

    Levy, Stewart; Carrick, Matthew; Mains, Charles W.; Slone, Denetta S.

    2016-01-01

    There are few reliable markers for assessing traumatic brain injury (TBI). Elevated levels of oxidative stress have been observed in TBI patients. We hypothesized that oxidation-reduction potential (ORP) could be a potent biomarker in TBI. Two types of ORP were measured in patient plasma samples: the static state of oxidative stress (sORP) and capacity for induced oxidative stress (icORP). Differences in ORP values as a function of time after injury, severity, and hospital discharge were compared using ANOVAs with significance at p ≤ 0.05. Logit regression analyses were used to predict acute outcome comparing ORP, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS), and Glasgow Coma Scale (GCS). Antioxidant capacity (icORP) on day 4 was prognostic for acute outcomes (p < 0.05). An odds ratio of 4.08 was associated with poor acute outcome when icORP > 7.25 μC. IcORP was a better predictor than ISS, AIS, or GCS scores. sORP increased in those with the highest ISS values (p < 0.05). Based on these findings ORP is useful biomarker for severity and acute outcome in TBI patients. Changes in ORP values on day 4 after injury were the most prognostic, suggesting that patients' response to brain injury over time is a factor that determines outcome. PMID:27642494

  18. Oxidation-Reduction Potential as a Biomarker for Severity and Acute Outcome in Traumatic Brain Injury.

    PubMed

    Bjugstad, Kimberly B; Rael, Leonard T; Levy, Stewart; Carrick, Matthew; Mains, Charles W; Slone, Denetta S; Bar-Or, David

    2016-01-01

    There are few reliable markers for assessing traumatic brain injury (TBI). Elevated levels of oxidative stress have been observed in TBI patients. We hypothesized that oxidation-reduction potential (ORP) could be a potent biomarker in TBI. Two types of ORP were measured in patient plasma samples: the static state of oxidative stress (sORP) and capacity for induced oxidative stress (icORP). Differences in ORP values as a function of time after injury, severity, and hospital discharge were compared using ANOVAs with significance at p ≤ 0.05. Logit regression analyses were used to predict acute outcome comparing ORP, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS), and Glasgow Coma Scale (GCS). Antioxidant capacity (icORP) on day 4 was prognostic for acute outcomes (p < 0.05). An odds ratio of 4.08 was associated with poor acute outcome when icORP > 7.25 μC. IcORP was a better predictor than ISS, AIS, or GCS scores. sORP increased in those with the highest ISS values (p < 0.05). Based on these findings ORP is useful biomarker for severity and acute outcome in TBI patients. Changes in ORP values on day 4 after injury were the most prognostic, suggesting that patients' response to brain injury over time is a factor that determines outcome.

  19. Acute encephalomyelitis complicated with severe neurological sequelae after intrathecal administration of methotrexate in a patient with acute lymphoblastic leukemia.

    PubMed

    Nishikawa, Takuro; Okamoto, Yasuhiro; Maruyama, Shinsuke; Tanabe, Takayuki; Kurauchi, Koichiro; Kodama, Yuichi; Nakagawa, Shunsuke; Shinkoda, Yuichi; Kawano, Yoshifumi

    2014-11-01

    A four-year-old girl on maintenance therapy for acute lymphoblastic leukemia (ALL) complained of a headache and low back pain on the day she received her 21st intrathecal methotrexate (it-MTX) administration, and the next day experienced numbness and pain in her foot. This numbness gradually spread to her hand. She thereafter developed a fever and was hospitalized on day 8. After antibiotic therapy, the fever disappeared. However, her lower limbs became paralyzed, and she also developed urinary retention. On day 12, her paralysis progressed upwards, and she also developed paralysis of the upper limbs. Finally, she experienced convulsions with an impairment of consciousness. A magnetic resonance imaging study of the brain and spinal cord showed abnormal signals in the brain cortex and anterior horn. Accordingly, we diagnosed acute encephalomyelitis associated with it-MTX. High-dose intravenous immunoglobulin, steroid pulse therapy, plasma exchange, and dextromethorphan administration were initiated, while she received mechanical ventilation. Despite this intensive treatment, she suffered severe neurological damage and had to be maintained on mechanical ventilation due to persistent flaccid quadriplegia one year after the onset. When patients have symptoms of ascending paralysis during it-MTX treatment, clinicians should carefully consider the possibility of acute encephalomyelitis due to it-MTX. PMID:25501412

  20. Heat acclimation attenuates physiological strain and the HSP72, but not HSP90α, mRNA response to acute normobaric hypoxia.

    PubMed

    Gibson, Oliver R; Turner, Gareth; Tuttle, James A; Taylor, Lee; Watt, Peter W; Maxwell, Neil S

    2015-10-15

    Heat acclimation (HA) attenuates physiological strain in hot conditions via phenotypic and cellular adaptation. The aim of this study was to determine whether HA reduced physiological strain, and heat shock protein (HSP) 72 and HSP90α mRNA responses in acute normobaric hypoxia. Sixteen male participants completed ten 90-min sessions of isothermic HA (40°C/40% relative humidity) or exercise training [control (CON); 20°C/40% relative humidity]. HA or CON were preceded (HYP1) and proceeded (HYP2) by a 30-min normobaric hypoxic exposure [inspired O2 fraction = 0.12; 10-min rest, 10-min cycling at 40% peak O2 uptake (V̇O2 peak), 10-min cycling at 65% V̇O2 peak]. HA induced greater rectal temperatures, sweat rate, and heart rates (HR) than CON during the training sessions. HA, but not CON, reduced resting rectal temperatures and resting HR and increased sweat rate and plasma volume. Hemoglobin mass did not change following HA nor CON. HSP72 and HSP90α mRNA increased in response to each HA session, but did not change with CON. HR during HYP2 was lower and O2 saturation higher at 65% V̇O2 peak following HA, but not CON. O2 uptake/HR was greater at rest and 65% V̇O2 peak in HYP2 following HA, but was unchanged after CON. At rest, the respiratory exchange ratio was reduced during HYP2 following HA, but not CON. The increase in HSP72 mRNA during HYP1 did not occur in HYP2 following HA. In CON, HSP72 mRNA expression was unchanged during HYP1 and HYP2. In HA and CON, increases in HSP90α mRNA during HYP1 were maintained in HYP2. HA reduces physiological strain, and the transcription of HSP72, but not HSP90α mRNA in acute normobaric hypoxia.

  1. Heat acclimation attenuates physiological strain and the HSP72, but not HSP90α, mRNA response to acute normobaric hypoxia.

    PubMed

    Gibson, Oliver R; Turner, Gareth; Tuttle, James A; Taylor, Lee; Watt, Peter W; Maxwell, Neil S

    2015-10-15

    Heat acclimation (HA) attenuates physiological strain in hot conditions via phenotypic and cellular adaptation. The aim of this study was to determine whether HA reduced physiological strain, and heat shock protein (HSP) 72 and HSP90α mRNA responses in acute normobaric hypoxia. Sixteen male participants completed ten 90-min sessions of isothermic HA (40°C/40% relative humidity) or exercise training [control (CON); 20°C/40% relative humidity]. HA or CON were preceded (HYP1) and proceeded (HYP2) by a 30-min normobaric hypoxic exposure [inspired O2 fraction = 0.12; 10-min rest, 10-min cycling at 40% peak O2 uptake (V̇O2 peak), 10-min cycling at 65% V̇O2 peak]. HA induced greater rectal temperatures, sweat rate, and heart rates (HR) than CON during the training sessions. HA, but not CON, reduced resting rectal temperatures and resting HR and increased sweat rate and plasma volume. Hemoglobin mass did not change following HA nor CON. HSP72 and HSP90α mRNA increased in response to each HA session, but did not change with CON. HR during HYP2 was lower and O2 saturation higher at 65% V̇O2 peak following HA, but not CON. O2 uptake/HR was greater at rest and 65% V̇O2 peak in HYP2 following HA, but was unchanged after CON. At rest, the respiratory exchange ratio was reduced during HYP2 following HA, but not CON. The increase in HSP72 mRNA during HYP1 did not occur in HYP2 following HA. In CON, HSP72 mRNA expression was unchanged during HYP1 and HYP2. In HA and CON, increases in HSP90α mRNA during HYP1 were maintained in HYP2. HA reduces physiological strain, and the transcription of HSP72, but not HSP90α mRNA in acute normobaric hypoxia. PMID:26205540

  2. [Severe hypertriglyceridemia induced acute pancreatitis: a case report and review of the literature].

    PubMed

    Herrera Del Águila, Dwight Denis; Garavito Rentería, Jorge; Linarez Medina, Karen; Lizarzaburu Rodríguez, Víctor

    2015-01-01

    Hypertriglyceridemia-induced acute pancreatitis occurs in about 1-4% of the cases. It is the third leading cause of pancreatitis after biliary and alcoholic etiology. Hypertriglyceridemia can be caused by primary causes, lipid metabolism disorders and secondary causes. A 32 year old man, born in Huancayo, with a history of diabetes mellitus type 2, severe mixed dyslipidemia with primary hypertriglyceridemia, was admitted to emergency with 10 days of abdominal pain with moderate intensity in epigastrium and left hypochondrium spreading to dorsal region after intake of high-fat meal. 24 hours before admission, pain exacerbates increasing intensity and causing nausea and bilious vomits. Therefore, all laboratory examinations are carried out resulting in hypertriglyceridemia-induced acute pancreatitis. For that reason, an adequate clinical history physical examination associated with laboratory and image examinations are important to consider hypertriglyceridemia as part of the etiology of acute pancreatitis.

  3. A new pathological scoring method for adrenal injury in rats with severe acute pancreatitis.

    PubMed

    Deng, Wenhong; Hui, Yuanjian; Yu, Jia; Wang, Weixing; Xu, Sheng; Chen, Chen; Xiong, Xincheng

    2014-12-01

    These studies investigated the appearance and function of adrenal glands in rats with severe acute pancreatitis (SAP) and established a new histopathological score to evaluate adrenal histopathological changes. Severe acute pancreatitis relied on retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct. The damage of SAP was estimated by serum amylase, secretory phospholipase A2 and pancreatic histopathology. Light and electron microscopy of adrenal gland, and the levels of serum corticosterone were investigated. These results showed that the generally ascending trend of adrenal pathological score was inversely proportional to the generally descending trend of serum corticosterone levels, but parallel with the changes of pancreatic histopathology. Herein, the new adrenal histopathological score was effective in the evaluation of adrenal injury following SAP. It may indirectly reflect the variation of serum cortisol levels and the severity of pancreatitis to a certain extent.

  4. [Biochemical markers in assessment of severity and prognosis of acute pancreatitis].

    PubMed

    Petricusić, Lidija; Banić, Marko; Cabrijan, Zeljko; Urek-Crncević, Marija; Hulak-Karlak, Vanja; Grgurević, Ivica

    2009-01-01

    The authors reveal and discuss the role of novel biochemical parameters in early diagnosis of acute pancreatitis and assessment of the severity of the disease. These biochemical parameters, beside routinely used amilase and lipase, might enable us to early identify those patients who are at risk of developing severe form of pancreatitis or complications. These parameters include trypsinogen activation peptide (TAP), C-reactive protein (CRP, tripsinogen-2, procalcitonin, phospholipase-A2 (PLA2), carboxypeptidase activation peptide (CAPAP) and interleukin-6 and 8 (IL-6, IL-8). Although these markers are still not incorporated in routine clinical practice, IL-6, IL-10, procalcitonin and trypsinogen activation peptide seem to have a good chance to be used as a new biochemical markers in assessment of severity and prognosis of acute pancreatitis.

  5. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus.

    PubMed

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit; Escherich, Gabriele; Frandsen, Thomas Leth; Halsey, Christina; Hough, Rachael; Jeha, Sima; Kato, Motohiro; Liang, Der-Cherng; Mikkelsen, Torben Stamm; Möricke, Anja; Niinimäki, Riitta; Piette, Caroline; Putti, Maria Caterina; Raetz, Elizabeth; Silverman, Lewis B; Skinner, Roderick; Tuckuviene, Ruta; van der Sluis, Inge; Zapotocka, Ester

    2016-06-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment. PMID:27299279

  6. Alterations of acute phase reaction and cytokine production in patients following severe burn injury.

    PubMed

    Dehne, Marius G; Sablotzki, Armin; Hoffmann, Andreas; Mühling, Jörg; Dietrich, Friedrich E; Hempelmann, Gunter

    2002-09-01

    To determine the acute immunologic reaction, mediated by cytokines, interleukines (ILs) and growth factors and the susceptibility to infections and sepsis after severe burn injury a prospective, single unit, longitudinal study of acute phase reactants and mediators who performed. After approval by the ethics committee of our hospital, we investigated the plasma concentrations of IL-2, -6, -8, -10, and -13, the soluble IL-2 receptor (sIL-2R), and the acute phase proteins procalcitonin (PCT) and C-reactive protein (CRP) at admission and every 3 days in 24 patients over a time course of 28 days after thermal injury and categorized by percent burn: < or =30% (group 1; n=12) and >30% (group 2; n=12). Shortly after burn injury we found higher concentrations of IL-2, -6, -10 and PCT in those patients >30% TBSA. During the study period, we found significant higher levels of acute phase proteins, IL-6 and -8 in patients >30% TBSA. The incidence of SIRS and MODS was three times increased in patients >30% TBSA. Our results show different patterns of cytokines and acute phase proteins in patients with different burned surface areas over a long time and continuous monitoring of a more distinct inflammatory response in these patients.

  7. Geographic Access to High Capability Severe Acute Respiratory Failure Centers in the United States

    PubMed Central

    Wallace, David J.; Angus, Derek C.; Seymour, Christopher W.; Yealy, Donald M.; Carr, Brendan G.; Kurland, Kristen; Boujoukos, Arthur; Kahn, Jeremy M.

    2014-01-01

    Objective Optimal care of adults with severe acute respiratory failure requires specific resources and expertise. We sought to measure geographic access to these centers in the United States. Design Cross-sectional analysis of geographic access to high capability severe acute respiratory failure centers in the United States. We defined high capability centers using two criteria: (1) provision of adult extracorporeal membrane oxygenation (ECMO), based on either 2008–2013 Extracorporeal Life Support Organization reporting or provision of ECMO to 2010 Medicare beneficiaries; or (2) high annual hospital mechanical ventilation volume, based 2010 Medicare claims. Setting Nonfederal acute care hospitals in the United States. Measurements and Main Results We defined geographic access as the percentage of the state, region and national population with either direct or hospital-transferred access within one or two hours by air or ground transport. Of 4,822 acute care hospitals, 148 hospitals met our ECMO criteria and 447 hospitals met our mechanical ventilation criteria. Geographic access varied substantially across states and regions in the United States, depending on center criteria. Without interhospital transfer, an estimated 58.5% of the national adult population had geographic access to hospitals performing ECMO and 79.0% had geographic access to hospitals performing a high annual volume of mechanical ventilation. With interhospital transfer and under ideal circumstances, an estimated 96.4% of the national adult population had geographic access to hospitals performing ECMO and 98.6% had geographic access to hospitals performing a high annual volume of mechanical ventilation. However, this degree of geographic access required substantial interhospital transfer of patients, including up to two hours by air. Conclusions Geographic access to high capability severe acute respiratory failure centers varies widely across states and regions in the United States. Adequate

  8. Update on medical and surgical options for patients with acute severe ulcerative colitis: What is new?

    PubMed Central

    Andrew, Rachel E; Messaris, Evangelos

    2016-01-01

    Acute severe ulcerative colitis (UC) is a highly morbid condition that requires both medical and surgical management through the collaboration of gastroenterologists and colorectal surgeons. First line treatment for patients presenting with acute severe UC consists of intravenous steroids, but those who do not respond require escalation of therapy or emergent colectomy. The mortality of emergent colectomy has declined significantly in recent decades, but due to the morbidity of this procedure, second line agents such as cyclosporine and infliximab have been used as salvage therapy in an attempt to avoid emergent surgery. Unfortunately, protracted medical therapy has led to patients presenting for surgery in a poorer state of health leading to poorer post-operative outcomes. In this era of multiple medical modalities available in the treatment of acute severe UC, physicians must consider the advantages and disadvantages of prolonged medical therapy in an attempt to avoid surgery. Colectomy remains a mainstay in the treatment of severe ulcerative colitis not responsive to corticosteroids and rescue therapy, and timely referral for surgery allows for improved post-operative outcomes with lower risk of sepsis and improved patient survival. Options for reconstructive surgery include three-stage ileal pouch-anal anastomosis or a modified two-stage procedure that can be performed either open or laparoscopically. The numerous avenues of medical and surgical therapy have allowed for great advances in the treatment of patients with UC. In this era of options, it is important to maintain a global view, utilize biologic therapy when indicated, and then maintain an appropriate threshold for surgery. The purpose of this review is to summarize the growing number of medical and surgical options available in the treatment of acute, severe UC. PMID:27721922

  9. Imaging hypoxia in gliomas

    PubMed Central

    Mendichovszky, I; Jackson, A

    2011-01-01

    Hypoxia plays a central role in tumour development, angiogenesis, growth and resistance to treatment. Owing to constant developments in medical imaging technology, significant advances have been made towards in vitro and in vivo imaging of hypoxia in a variety of tumours, including gliomas of the central nervous system. The aim of this article is to review the literature on imaging approaches currently available for measuring hypoxia in human gliomas and provide an insight into recent advances and future directions in this field. After a brief overview of hypoxia and its importance in gliomas, several methods of measuring hypoxia will be presented. These range from invasive monitoring by Eppendorf polarographic O2 microelectrodes, positron electron tomography (PET) tracers based on 2-nitroimidazole compounds [18F-labelled fluoro-misonidazole (18F-MISO) or 1-(2-[(18)F]fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole (FRP-170)], 64Cu-ATSM Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) or 99mTc- and 68Ga-labelled metronidazole (MN) agents to advanced MRI methods, such as blood oxygenation level dependent (BOLD) MRI, oxygen-enhanced MRI, diffusion-weighted MRI (DWI-MRI), dynamic contrast-enhanced MRI (DCE-MRI) and 1H-magnetic resonance spectroscopy. PMID:22433825

  10. Progressive hypoxia decouples activity and aerobic performance of skate embryos

    PubMed Central

    Di Santo, Valentina; Tran, Anna H.; Svendsen, Jon C.

    2016-01-01

    Although fish population size is strongly affected by survival during embryonic stages, our understanding of physiological responses to environmental stressors is based primarily on studies of post-hatch fishes. Embryonic responses to acute exposure to changes in abiotic conditions, including increase in hypoxia, could be particularly important in species exhibiting long developmental time, as embryos are unable to select a different environment behaviourally. Given that oxygen is key to metabolic processes in fishes and aquatic hypoxia is becoming more severe and frequent worldwide, organisms are expected to reduce their aerobic performance. Here, we examined the metabolic and behavioural responses of embryos of a benthic elasmobranch fish, the little skate (Leucoraja erinacea), to acute progressive hypoxia, by measuring oxygen consumption and movement (tail-beat) rates inside the egg case. Oxygen consumption rates were not significantly affected by ambient oxygen levels until reaching 45% air saturation (critical oxygen saturation, Scrit). Below Scrit, oxygen consumption rates declined rapidly, revealing an oxygen conformity response. Surprisingly, we observed a decoupling of aerobic performance and activity, as tail-beat rates increased, rather than matching the declining metabolic rates, at air saturation levels of 55% and below. These results suggest a significantly divergent response at the physiological and behavioural levels. While skate embryos depressed their metabolic rates in response to progressive hypoxia, they increased water circulation inside the egg case, presumably to restore normoxic conditions, until activity ceased abruptly around 9.8% air saturation. PMID:27293746

  11. Acute inhibition of glial cells in the NTS does not affect respiratory and sympathetic activities in rats exposed to chronic intermittent hypoxia.

    PubMed

    Costa, Kauê M; Moraes, Davi J A; Machado, Benedito H

    2013-02-16

    Recent studies suggest that neuron-glia interactions are involved in multiple aspects of neuronal activity regulation. In the nucleus tractus solitarius (NTS) neuron-glia interactions are thought to participate in the integration of autonomic responses to physiological challenges. However, it remains to be shown whether NTS glial cells might influence breathing and cardiovascular control, and also if they could be integral to the autonomic and respiratory responses to hypoxic challenges. Here, we investigated whether NTS glia play a tonic role in the modulation of central respiratory and sympathetic activities as well as in the changes in respiratory-sympathetic coupling induced by exposure to chronic intermittent hypoxia (CIH), a model of central autonomic and respiratory plasticity. We show that bilateral microinjections of fluorocitrate (FCt), a glial cell inhibitor, into the caudal and intermediate subnuclei of the NTS did not alter baseline respiratory and sympathetic parameters in in situ preparations of juvenile rats. Similar results were observed in rats previously exposed to CIH. Likewise, CIH-induced changes in respiratory-sympathetic coupling were unaffected by FCt-mediated inhibition. However, microinjection of FCt into the ventral medulla produced changes in respiratory frequency. Our results show that acute glial inhibition in the NTS does not affect baseline respiratory and sympathetic control. Additionally, we conclude that NTS glial cells may not be necessary for the continuous manifestation of sympathetic and respiratory adaptations to CIH. Our work provides evidence that neuron-glia interactions in the NTS do not participate in baseline respiratory and sympathetic control.

  12. Influence of age, previous health status, and severity of acute illness on outcome from intensive care.

    PubMed

    Le Gall, J R; Brun-Buisson, C; Trunet, P; Latournerie, J; Chantereau, S; Rapin, M

    1982-09-01

    Age, previous health status (HS), and severity of acute illness were assessed prospectively on 228 unselected patients admitted over 1 yr to the multidisciplinary ICU, to determine their influence on outcome. One hundred and fifty patients (66%) were discharged from the ICU, but the survival rate fell to 50% at 6 months, and was similar after 1 yr (49%). Over a 6-month period, there was improved HS in survivors which gradually leveled off. Compared to prior HS, the final HS was worsened in 37% of survivors. Three factors were important predictors of late survival: age under 50, good previous HS, and less than two visceral failures. We conclude that evaluation of ICU outcome should provide information on 6-month survival and HS and include important variables as age, previous HS, and severity of acute illness. PMID:7105766

  13. Rat reaction to hypokinesia after prior adaptation to hypoxia

    NASA Technical Reports Server (NTRS)

    Barashova, Z. I.; Tarakanova, O. I.

    1980-01-01

    The effect of prior hypoxia adaptation on body tolerance to hypokinesia was investigated. Rats trained to a 50 day period of hypokinesia and hypoxia with a preliminary month of adaptation to hypoxia showed less weight loss, higher indices for red blood content, heightened reactivity of the overall organism and the central nervous system to acute hypoxia, and decreased modification of the skeletal muscles compared to rats subjected to hypokinesia alone.

  14. Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model.

    PubMed

    Ossetrova, Natalia I; Ney, Patrick H; Condliffe, Donald P; Krasnopolsky, Katya; Hieber, Kevin P

    2016-08-01

    Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome. PMID:27356057

  15. [Comments on treatment of severe acute respiratory syndrome by integrated traditional Chinese and western medicine].

    PubMed

    Wang, Xin-Lu; Zhou, Yong-Hong

    2003-07-01

    There are obvious advantages of the integrated traditional Chinese and western medicine on the treatment of severe acute respiratory syndrome (SARS). Combining the ancient and present literature with the special epidemic patterns, pathological changes and clinical symptoms of SARS, the paper discussed the methods of application of the integrated traditional Chinese and western medicine on the treatment of SARS, and some matters needing attention in clinic.

  16. Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model.

    PubMed

    Ossetrova, Natalia I; Ney, Patrick H; Condliffe, Donald P; Krasnopolsky, Katya; Hieber, Kevin P

    2016-08-01

    Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome.

  17. Platelet-rich plasma (PRP) treatment of sports-related severe acute hamstring injuries

    PubMed Central

    Guillodo, Yannick; Madouas, Gwénaelle; Simon, Thomas; Le Dauphin, Hermine; Saraux, Alain

    2015-01-01

    Summary Purpose hamstring injury is the most common musculoskeletal disorder and one of the main causes of missed sporting events. Shortening the time to return to play (TTRTP) is a priority for athletes and sports medicine practitioners. Hypothesis platelet-rich plasma (PRP) injection at the site of severe acute hamstring injury increases the healing rate and shortens the TTRTP. Study design Cohort study. Methods all patients with ultrasonography and MRI evidence of severe acute hamstring injury between January 2012 and March 2014 were offered PRP treatment. Those who accepted received a single intramuscular PRP injection within 8 days post-injury; the other patients served as controls. The same standardized rehabilitation program was used in both groups. A physical examination and ultrasonography were performed 10 and 30 days post-injury, then a phone interview 120 days post-injury, to determine the TTRTP at the pre-injury level. Results of 34 patients, 15 received PRP and 19 did not. Mean TTRTP at the pre-injury level was 50.9±10.7 days in the PRP group and 52.8±15.7 days in the control group. The difference was not statistically significant. Conclusion a single intramuscular PRP injection did not shorten the TTRTP in sports people with severe acute hamstring injuries. PMID:26958537

  18. [Severe acute asthma in the emergency room: amelioration of decreased peak flow rate is interpreted with difficulty].

    PubMed

    Bouvard, E; Bellocq, A; Bernier, C; Meyniel, D

    1999-09-01

    We report a severe acute asthma case whose course was marked by persistent hypoxemia whereas proximal flows were normalized. This discordance reveals a ventilation/perfusion mismatch. This data suggests that care must be taken in interpreting the peak flow improvement during acute severe asthma management.

  19. The role of hypoxia and HIF1α in the regulation of STAR-mediated steroidogenesis in granulosa cells.

    PubMed

    Kowalewski, Mariusz Pawel; Gram, Aykut; Boos, Alois

    2015-02-01

    The adaptive responses to hypoxia are mediated by hypoxia-inducible factor 1 alpha (HIF1α). Its role, however, in regulating steroidogenesis remains poorly understood. We examined the role of hypoxia and HIF1α in regulating steroid acute regulatory protein (STAR) expression and steroidogenesis in immortalized (KK1) mouse granulosa cells under progressively lowering O2 concentrations (20%, 15%, 10%, 5%, 1%). Basal and dbcAMP-stimulated progesterone synthesis was decreased under severe hypoxia (1% and 5% O2). The partial hypoxia revealed opposing effects, with a significant increase in steroidogenic response at 10% O2 in dbcAMP-treated cells: Star-promoter activity, mRNA and protein expression were increased. The hypoxia-stimulated STAR expression was PKA-dependent. Binding of HIF1α to the Star-promoter was potentiated under partial hypoxia. Inhibition of the transcriptional activity or expression of HIF1α suppressed STAR-expression. HIF1α appears to be a positive regulator of basal and stimulated STAR-expression, which under partial hypoxia is capable of increasing the steroidogenic capacity of granulosa cells.

  20. Upregulation of PIAS1 protects against sodium taurocholate-induced severe acute pancreatitis associated with acute lung injury.

    PubMed

    Chen, Ping; Huang, Liya; Sun, Yunwei; Yuan, Yaozong

    2011-06-01

    The regulator of cytokine signaling known as protein inhibitor of activated STAT-1 (PIAS1) is increasingly understood to have diverse regulatory functions for inflammation, but its effect in inflammatory conditions such as severe acute pancreatitis (SAP) has not previously been reported. The aim of this study was to investigate the effect of upregulation of PIAS1 on SAP associated with acute lung injury (ALI), and its subsequent effect on disease severity. Sprague-Dawley rats were given an IV injection of adenovirus serotype 5 (Ad5)/F35-PIAS1, Ad5/F35-vector or saline before induction of SAP. The control group received only a sham operation. Lung and pancreas samples were harvested 16h after induction. The protein levels of PIAS1 in tissue were investigated. The severity of pancreatic injury was determined by a histological score of pancreatic injury, serum amylase, and pancreatic water content. The lung injury was evaluated by measurement of pulmonary microvascular permeability, lung myeloperoxidase activity and malondialdehyde levels. The survival rates of rats were also analyzed. The results found that in Ad5/F35-PIAS1 treated rats, serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 levels were decreased but showed no influence on the levels of IL-10, and the severity of pancreatic tissue injury was less compared with either untreated SAP or Ad5/F35-vector treated rats (P<0.01). The administration of Ad5/F35-PIAS1 in SAP-induced rats downregulated the activity of the signal transducer and activator of transcription-1 (STAT1) pathway and the expressions of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule (ICAM)-1 protein in lung. Thus, compared with the untreated SAP rats, the inflammatory response and the severity of ALI decreased, and the survival rates increased (P<0.01). These findings suggest that PIAS1 could augment anti-inflammatory activity by inhibiting STAT1, thus attenuating the severity of SAP associated with ALI.

  1. FDG uptake, a surrogate of tumour hypoxia?

    PubMed Central

    Van de Wiele, Christophe

    2008-01-01

    Introduction Tumour hyperglycolysis is driven by activation of hypoxia-inducible factor-1 (HIF-1) through tumour hypoxia. Accordingly, the degree of 2-fluro-2-deoxy-d-glucose (FDG) uptake by tumours might indirectly reflect the level of hypoxia, obviating the need for more specific radiopharmaceuticals for hypoxia imaging. Discussion In this paper, available data on the relationship between hypoxia and FDG uptake by tumour tissue in vitro and in vivo are reviewed. In pre-clinical in vitro studies, acute hypoxia was consistently shown to increase FDG uptake by normal and tumour cells within a couple of hours after onset with mobilisation or modification of glucose transporters optimising glucose uptake, followed by a delayed response with increased rates of transcription of GLUT mRNA. In pre-clinical imaging studies on chronic hypoxia that compared FDG uptake by tumours grown in rat or mice to uptake by FMISO, the pattern of normoxic and hypoxic regions within the human tumour xenografts, as imaged by FMISO, largely correlated with glucose metabolism although minor locoregional differences could not be excluded. In the clinical setting, data are limited and discordant. Conclusion Further evaluation of FDG uptake by various tumour types in relation to intrinsic and bioreductive markers of hypoxia and response to radiotherapy or hypoxia-dependent drugs is needed to fully assess its application as a marker of hypoxia in the clinical setting. PMID:18509637

  2. Melatonin prevents acute kidney injury in severely burned rats via the activation of SIRT1

    PubMed Central

    Bai, Xiao-Zhi; He, Ting; Gao, Jian-Xin; Liu, Yang; Liu, Jia-Qi; Han, Shi-Chao; Li, Yan; Shi, Ji-Hong; Han, Jun-Tao; Tao, Ke; Xie, Song-Tao; Wang, Hong-Tao; Hu, Da-Hai

    2016-01-01

    Acute kidney injury (AKI) is a common complication after severe burns. Melatonin has been reported to protect against multiple organ injuries by increasing the expression of SIRT1, a silent information regulator that regulates stress responses, inflammation, cellular senescence and apoptosis. This study aimed to investigate the protective effects of melatonin on renal tissues of burned rats and the role of SIRT1 involving the effects. Rat severely burned model was established, with or without the administration of melatonin and SIRT1 inhibitor. The renal function and histological manifestations were determined to evaluate the severity of kidney injury. The levels of acetylated-p53 (Ac-p53), acetylated-p65 (Ac-p65), NF-κB, acetylated-forkhead box O1 (Ac-FoxO1), Bcl-2 and Bax were analyzed to study the underlying mechanisms. Our results suggested that severe burns could induce acute kidney injury, which could be partially reversed by melatonin. Melatonin attenuated oxidative stress, inflammation and apoptosis accompanied by the increased expression of SIRT1. The protective effects of melatonin were abrogated by the inhibition of SIRT1. In conclusion, we demonstrate that melatonin improves severe burn-induced AKI via the activation of SIRT1 signaling. PMID:27599451

  3. Melatonin prevents acute kidney injury in severely burned rats via the activation of SIRT1.

    PubMed

    Bai, Xiao-Zhi; He, Ting; Gao, Jian-Xin; Liu, Yang; Liu, Jia-Qi; Han, Shi-Chao; Li, Yan; Shi, Ji-Hong; Han, Jun-Tao; Tao, Ke; Xie, Song-Tao; Wang, Hong-Tao; Hu, Da-Hai

    2016-01-01

    Acute kidney injury (AKI) is a common complication after severe burns. Melatonin has been reported to protect against multiple organ injuries by increasing the expression of SIRT1, a silent information regulator that regulates stress responses, inflammation, cellular senescence and apoptosis. This study aimed to investigate the protective effects of melatonin on renal tissues of burned rats and the role of SIRT1 involving the effects. Rat severely burned model was established, with or without the administration of melatonin and SIRT1 inhibitor. The renal function and histological manifestations were determined to evaluate the severity of kidney injury. The levels of acetylated-p53 (Ac-p53), acetylated-p65 (Ac-p65), NF-κB, acetylated-forkhead box O1 (Ac-FoxO1), Bcl-2 and Bax were analyzed to study the underlying mechanisms. Our results suggested that severe burns could induce acute kidney injury, which could be partially reversed by melatonin. Melatonin attenuated oxidative stress, inflammation and apoptosis accompanied by the increased expression of SIRT1. The protective effects of melatonin were abrogated by the inhibition of SIRT1. In conclusion, we demonstrate that melatonin improves severe burn-induced AKI via the activation of SIRT1 signaling. PMID:27599451

  4. Methylprednisolone pulse therapy in acute severe asthma. A randomized, double-blind study.

    PubMed

    Engel, T; Dirksen, A; Frølund, L; Heinig, J H; Svendsen, U G; Pedersen, B K; Weeke, B

    1990-04-01

    Methylprednisolone pulse therapy (MPPT) has been shown to possess a long-lasting effect in other immune-inflammatory diseases without the well-known side effects caused by long-term treatment with glucocorticosteroids. In an attempt to reduce the long-term use of oral steroids in asthmatics, we conducted this double-blind, double-dummy study to compare the use of MPPT (1 g of methylprednisolone intravenously) (8 patients) with a short course of oral prednisolone (10 patients) in asthmatics presenting with acute severe asthma. Both treatments were effective in relieving the acute attack of asthma. The MPPT-treated patients did not show a faster resolution than did the orally treated group. No patients needed assisted ventilation, and no deaths occurred. One week after the treatment FEV1 tended to decrease in the methylprednisolone group compared with the oral prednisolone group (P = 0.06). The patients initially receiving MPPT needed supplementary prednisolone earlier and in higher doses than did the patients receiving oral prednisolone as initial treatment. At the end of the 12 weeks' study period, the groups reached identical FEV1. In conclusion, we did not find intravenous methylprednisolone superior to oral prednisolone in the treatment of acute attacks of severe asthma, but methylprednisolone pulse therapy had a shorter duration as regards protection against future asthma attacks. PMID:2183645

  5. Does virus-bacteria coinfection increase the clinical severity of acute respiratory infection?

    PubMed

    Damasio, Guilherme A C; Pereira, Luciane A; Moreira, Suzana D R; Duarte dos Santos, Claudia N; Dalla-Costa, Libera M; Raboni, Sonia M

    2015-09-01

    This retrospective cohort study investigated the presence of bacteria in respiratory secretions of patients hospitalized with acute respiratory infections and analyzed the impact of viral and bacterial coinfection on severity and the mortality rate. A total of 169 patients with acute respiratory infections were included, viruses and bacteria in respiratory samples were detected using molecular methods. Among all samples, 73.3% and 59.7% were positive for viruses and bacteria, respectively; 45% contained both virus and bacteria. Bacterial coinfection was more frequent in patients infected by community respiratory viruses than influenza A H1N1pdm (83.3% vs. 40.6%). The most frequently bacteria detected were Streptococcus pneumoniae and Haemophilus influenzae. Both species were co-detected in 54 patients and identified alone in 22 and 21 patients, respectively. Overall, there were no significant differences in the period of hospitalization, severity, or mortality rate between patients infected with respiratory viruses alone and those coinfected by viruses and bacteria. The detection of mixed respiratory pathogens is frequent in hospitalized patients with acute respiratory infections, but its impact on the clinical outcome does not appear substantial. However, it should be noted that most of the patients received broad-spectrum antibiotic therapy, which may have contributed to this favorable outcome.

  6. Baroreflex control of heart rate during sleep in severe obstructive sleep apnoea: effects of acute CPAP.

    PubMed

    Bonsignore, M R; Parati, G; Insalaco, G; Castiglioni, P; Marrone, O; Romano, S; Salvaggio, A; Mancia, G; Bonsignore, G; Di Rienzo, M

    2006-01-01

    Baroreflex control of heart rate during sleep (baroreflex sensitivity; BRS) has been shown to be depressed in obstructive sleep apnoea (OSA), and improved after treatment with continuous positive airway pressure (CPAP). Whether CPAP also acutely affects BRS during sleep in uncomplicated severe OSA is still debatable. Blood pressure was monitored during nocturnal polysomnography in 18 patients at baseline and during first-time CPAP application. Spontaneous BRS was analysed by the sequence method, and estimated as the mean sequence slope. CPAP did not acutely affect mean blood pressure or heart rate but decreased cardiovascular variability during sleep. Mean BRS increased slightly during CPAP application (from 6.5+/-2.4 to 7.5+/-2.9 ms x mmHg(-1)), mostly in response to decreasing blood pressure. The change in BRS did not correlate with changes in arterial oxygen saturation or apnoea/hypopnoea index. The small change in baroreflex control of heart rate during sleep at first application of continuous positive airway pressure in severe obstructive sleep apnoea was unrelated to the acute resolution of nocturnal hypoxaemia, and might reflect autonomic adjustments to positive intrathoracic pressure, and/or improved sleep architecture. The small increase in baroreflex control of heart rate during sleep may be of clinical relevance as it was accompanied by reduced cardiovascular variability, which is acknowledged as an independent cardiovascular risk factor.

  7. Effects of angiotensin II on leptin and downstream leptin signaling in the carotid body during acute intermittent hypoxia.

    PubMed

    Moreau, J M; Messenger, S A; Ciriello, J

    2015-12-01

    Angiotensin II (ANG II) is known to promote leptin production and secretion. Although ANG II type 1 receptors (AT1Rs) and leptin are expressed within the carotid body, it is not known whether AT1R and leptin are co-expressed in the same glomus cells nor if these peptides are affected within the carotid body by intermittent hypoxia (IH). This study was done to investigate whether ANG II modulated leptin signaling in the carotid body during IH. Rats were treated with captopril (Capt) or the AT1R blocker losartan (Los) in the drinking water for 3days prior to being exposed to IH (8h) or normoxia (8h). IH induced increases in plasma ANG II and leptin compared to normoxic controls. Capt treatment abolished the plasma leptin changes to IH, whereas Los treatment had no effect on the IH induced increase in plasma leptin. Additionally, carotid body glomus cells containing both leptin and the long form of the leptin receptor (OB-Rb) were found to co-express AT1R protein, and IH increased the expression of only AT1R protein within the carotid body in both Capt- and non-Capt-treated animals. On the other hand, Los treatment did not modify AT1R protein expression to IH. Additionally, Capt and Los treatment eliminated the elevated carotid body leptin protein expression, and the changes in phosphorylated signal transducer and activator of transcription three protein, the short form of the leptin receptor (OB-R100), suppressor of cytokine signaling 3, and phosphorylated extracellular-signal-regulated kinase 1/2 protein expression induced by IH. However, Capt elevated the expression of OB-Rb protein, whereas Los abolished the changes in OB-Rb protein to IH. These findings, taken together with the previous observation that ANG II modifies carotid body chemosensitivity, suggest that the increased circulating levels of ANG II and leptin induced by IH act at the carotid body to alter leptin signaling within the carotid body which in turn may influence chemoreceptor function.

  8. Severity of Spatial Neglect During Acute Inpatient Rehabilitation Predicts Community Mobility After Stroke

    PubMed Central

    Oh-Park, Mooyeon; Hung, Cynthia; Chen, Peii; Barrett, A.M.

    2014-01-01

    Objective To examine whether stroke survivors with more severe spatial neglect during their acute inpatient rehabilitation had poorer mobility after returning to their communities. Design A prospective observational study. Setting Acute inpatient rehabilitation and follow-up in the community. Participants Thirty-one consecutive stroke survivors with right-brain damage (women, n = 15 [48.4%]), with the mean (standard deviation) age of 60 ± 11.5 years, were included in the study if they demonstrated spatial neglect within 2 months after stroke. Methods Spatial neglect was assessed with the Behavioral Inattention Test (BIT) (range, 0-146 [a lower score indicates more severity]) and the Catherine Bergego Scale (range, 0-30 [a higher score indicates more severity]). A score of the Behavioral Inattention Test <129 or of the Catherine Bergego Scale >0 defined the presence of spatial neglect. Main Outcome Measurements The outcome measure is community mobility, defined by the extent and frequency of traveling within the home and in the community, and is assessed with the University of Alabama at Birmingham Study of Aging Life-Space Assessment (range, 0-120 [a lower score indicates less mobile]). This measure was assessed after participants returned home ≥6 months after stroke. The covariates were age, gender, functional independence at baseline; follow-up interval; and depressed mood, which may affect the relationship between spatial neglect and community mobility. Results A lower Behavioral Inattention Test score was a significant predictor of a lower Life-Space Assessment score after controlling for all the covariates (β = 0.009 [95% confidence interval, 0.008-0.017]); P = .020). The proportion of participants unable to travel independently beyond their homes was 0%, 27.3%, and 72.7% for those with mild, moderate, and severe acute neglect, respectively (Catherine Bergego Scale range, 1-10, 11-20, and 21-30, respectively). Conclusions Our result indicates that acute

  9. Successful use of extracorporeal life support after double traumatic tracheobronchial injury in a patient with severe acute asthma.

    PubMed

    Valette, Xavier; Desjouis, Aurélie; Massetti, Massimo; Hanouz, Jean-Luc; Icard, Philippe

    2011-01-01

    We report the case of an asthmatic patient with blunt trachea and left main bronchus injuries who developed acute severe asthma after surgical repair. Despite medical treatment and ventilatory support, asthma persisted with high airway pressures and severe respiratory acidosis. We proposed venovenous extracorporeal life support for CO(2) removal which allowed arterial blood gas normalization and airway pressures decrease. Extracorporeal life support was removed on day five after medical treatment of acute severe asthma. So we report the successful use of extracorporeal life support for operated double blunt tracheobronchial injury with acute severe asthma. PMID:22135742

  10. Nicardipine-induced acute pulmonary edema: a rare but severe complication of tocolysis.

    PubMed

    Serena, Claire; Begot, Emmanuelle; Cros, Jérôme; Hodler, Charles; Fedou, Anne Laure; Nathan-Denizot, Nathalie; Clavel, Marc

    2014-01-01

    We report four cases of acute pulmonary edema that occurred during treatment by intravenous tocolysis using nicardipine in pregnancy patients with no previous heart problems. Clinical severity justified hospitalization in intensive care unit (ICU) each time. Acute dyspnea has begun at an average of 63 hours after initiation of treatment. For all patients, the first diagnosis suspected was pulmonary embolism. The patients' condition improved rapidly with appropriate diuretic treatment and by modifying the tocolysis. The use of intravenous nicardipine is widely used for tocolysis in France even if its prescription does not have a marketing authorization. The pathophysiological mechanisms of this complication remain unclear. The main reported risk factors are spontaneous preterm labor, multiple pregnancy, concomitant obstetrical disease, association with beta-agonists, and fetal lung maturation corticotherapy. A better knowledge of this rare but serious adverse event should improve the management of patients. Nifedipine or atosiban, the efficiency of which tocolysis was also studied, could be an alternative. PMID:25215245

  11. Ethical and legal challenges posed by severe acute respiratory syndrome: implications for the control of severe infectious disease threats.

    PubMed

    Gostin, Lawrence O; Bayer, Ronald; Fairchild, Amy L

    2003-12-24

    The appearance and spread of severe acute respiratory syndrome (SARS) on a global level raised vital legal and ethical issues. National and international responses to SARS have profound implications for 3 important ethical values: privacy, liberty, and the duty to protect the public's health. This article examines, through legal and ethical lenses, various methods that countries used in reaction to the SARS outbreak: surveillance and contact tracing, isolation and quarantine, and travel restrictions. These responses, at least in some combination, succeeded in bringing the outbreak to an end. The article articulates a set of legal and ethical recommendations for responding to infectious disease threats, seeking to reconcile the tension between the public's health and individual rights to privacy, liberty, and freedom of movement. The ethical values that inform the recommendations include the precautionary principle, the least restrictive/intrusive alternative, justice, and transparency. Development of a set of legal and ethical recommendations becomes even more essential when, as was true with SARS and will undoubtedly be the case with future epidemics, scientific uncertainty is pervasive and urgent public health action is required.

  12. 17β-Estradiol mediates superior adaptation of right ventricular function to acute strenuous exercise in female rats with severe pulmonary hypertension.

    PubMed

    Lahm, Tim; Frump, Andrea L; Albrecht, Marjorie E; Fisher, Amanda J; Cook, Todd G; Jones, Thomas J; Yakubov, Bakhtiyor; Whitson, Jordan; Fuchs, Robyn K; Liu, Aiping; Chesler, Naomi C; Brown, M Beth

    2016-08-01

    17β-Estradiol (E2) exerts protective effects on right ventricular (RV) function in pulmonary arterial hypertension (PAH). Since acute exercise-induced increases in afterload may lead to RV dysfunction in PAH, we sought to determine whether E2 allows for superior RV adaptation after an acute exercise challenge. We studied echocardiographic, hemodynamic, structural, and biochemical markers of RV function in male and female rats with sugen/hypoxia (SuHx)-induced pulmonary hypertension, as well as in ovariectomized (OVX) SuHx females, with or without concomitant E2 repletion (75 μg·kg(-1)·day(-1)) immediately after 45 min of treadmill running at 75% of individually determined maximal aerobic capacity (75% aerobic capacity reserve). Compared with males, intact female rats exhibited higher stroke volume and cardiac indexes, a strong trend for better RV compliance, and less pronounced increases in indexed total pulmonary resistance. OVX abrogated favorable RV adaptations, whereas E2 repletion after OVX markedly improved RV function. E2's effects on pulmonary vascular remodeling were complex and less robust than its RV effects. Postexercise hemodynamics in females with endogenous or exogenous E2 were similar to hemodynamics in nonexercised controls, whereas OVX rats exhibited more severely altered postexercise hemodynamics. E2 mediated inhibitory effects on RV fibrosis and attenuated increases in RV collagen I/III ratio. Proapoptotic signaling, endothelial nitric oxide synthase phosphorylation, and autophagic flux markers were affected by E2 depletion and/or repletion. Markers of impaired autophagic flux correlated with endpoints of RV structure and function. Endogenous and exogenous E2 exerts protective effects on RV function measured immediately after an acute exercise challenge. Harnessing E2's mechanisms may lead to novel RV-directed therapies. PMID:27288487

  13. [Hot issues on the treatment of severe acute pancreatitis by Integrated Traditional Chinese and Western Medicine].

    PubMed

    Xia, Qing; Deng, Li-Hui

    2013-11-01

    Severe acute pancreatitis (SAP) is recognized as critical refractory disease. The case fatality rate of SAP is as high as 36%-50%. Although significant progress has been achieved on the treatment of severe acute pancreatitis (SAP) by Integrated Traditional Chinese Medicine (TCM) and Western Medicine (WM), there still exist some difficulties hindering the further improvement of therapeutic efficacy. The hot issues includes: unconfirmative curative effects and diverse treatment principles, complicated predictive scoring systems and inaccurate markers for the severity stratification, unproved new therapeutic tools and controversial methods waiting more high qualified evidence, unclarified mechanism of Integrated TCM and WM. In order to overcome the difficulties, we aim to launch the clinical pathway of Integrated TCM and WM, to strengthen the unity of multidisciplinary cooperation. We also need to keep the efforts on screening the markers for early evaluation and prediction of disease severity, improving the diagnosis and treatment, exploring the mechanism of Traditional Chinese Medicine in treating SAP with more high quality basic and clinical research. Based on these efforts, we could provide better treatments and prognosis for SAP patients.

  14. Acute Serum Hormone Levels: Characterization and Prognosis after Severe Traumatic Brain Injury

    PubMed Central

    McCullough, Emily H.; Niyonkuru, Christian; Ozawa, Haishin; Loucks, Tammy L.; Dobos, Julie A.; Brett, Christopher A.; Santarsieri, Martina; Dixon, C. Edward; Berga, Sarah L.; Fabio, Anthony

    2011-01-01

    Abstract Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples (n=536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls (n=14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global

  15. Inpatient management of children with severe acute malnutrition: a review of WHO guidelines

    PubMed Central

    Tickell, Kirkby D

    2016-01-01

    Abstract Objective To understand how the World Health Organization’s (WHO’s) guidelines on the inpatient care of children with complicated severe acute malnutrition may be strengthened to improve outcomes. Methods In December 2015, we searched Google scholar and WHO’s website for WHO recommendations on severe acute malnutrition management and evaluated the history and cited evidence behind these recommendations. We systematically searched WHO International Clinical Trials Registry Platform, clinicaltrials.gov and the Controlled Trials metaRegister until 10 August 2015 for recently completed, ongoing, or pending trials. Findings WHO’s guidelines provide 33 recommendations on the topic. However, 16 (48.5%) of these recommendations were based solely on expert opinion – unsupported by published evidence. Another 11 (33.3%) of the recommendations were supported by the results of directly relevant research – i.e. either randomized trials (8) or observational studies (3). The other six recommendations (18.2%) were based on studies that were not conducted among children with complicated severe malnutrition or studies of treatment that were not identical to the recommended intervention. Trials registries included 20 studies related to the topic, including nine trials of alternative feeding regimens. Acute medical management and follow-up care studies were minimally represented. Conclusion WHO’s guidelines on the topic have a weak evidence base and have undergone limited substantive adjustments over the past decades. More trials are needed to make that evidence base more robust. If the mortality associated with severe malnutrition is to be reduced, inpatient and post-discharge management trials, supported by studies on the causes of mortality, are needed. PMID:27708469

  16. Hypoxia response in asthma: differential modulation on inflammation and epithelial injury.

    PubMed

    Ahmad, Tanveer; Kumar, Manish; Mabalirajan, Ulaganathan; Pattnaik, Bijay; Aggarwal, Shilpi; Singh, Ranjana; Singh, Suchita; Mukerji, Mitali; Ghosh, Balaram; Agrawal, Anurag

    2012-07-01

    Oxygen-sensing prolyl-hydroxylase (PHD)-2 negatively regulates hypoxia-inducible factor (HIF)1-α and suppresses the hypoxic response. Hypoxia signaling is thought to be proinflammatory but also attenuates cellular injury and apoptosis. Although increased hypoxic response has been noted in asthma, its functional relevance is unknown. The objectives of this study were to dissect the mechanisms and role of the hypoxic response in asthma pathophysiology. Experimental studies were conducted in mice using acute and chronic allergic models of asthma. The hypoxic response in allergically inflamed lungs was modulated by using pharmacologic PHD inhibitors (ethyl-3-4-dihydroxybenzoic acid [DHB], 1-10 mg/kg) or siRNA-mediated genetic knockdowns. Increased hypoxia response led to exacerbation of the asthma phenotype, with HIF-1α knockdown being beneficial. Chronically inflamed lungs from mice treated with 10 mg/kg DHB showed diffuse up-regulation of the hypoxia response, severe airway remodeling, and inflammation. Fatal asphyxiation during methacholine challenge was noted. However, bronchial epithelium restricted up-regulation of the hypoxia response seen with low-dose DHB (1 mg/kg) reduced epithelial injury and attenuated the asthmatic phenotype. Up-regulation of the hypoxia response was associated with increased expression of CX3CR1, a lymphocyte survival factor, and increased inflammatory cell infiltrate. This study shows that an exaggerated hypoxia response may contribute to airway inflammation, remodeling, and the development of asthma. However, the hypoxia response may also be protective of epithelial apoptosis at lower levels, and the net effects of modulating the hypoxia response may vary based on the context.

  17. [CLINICAL AND LABORATORY FEATURES OF ACUTE PANCREATITIS BILIARY ETIOLOGY COURSE IN PATIENTS WITH DIABETES MELLITUS].

    PubMed

    Godlevskiy, A I; Savolyuk, S I; Tomashevskiy, Ya V

    2015-07-01

    The dynamics of cytopathic hypoxia markers in patients with acute pancreatitis (AP) biliary etiology (BE), depending on the presence of concomitant diabetes mellitus (DM), which is an independent factor of premorbid severity increase and increase in the degree of operational and anesthetic risk. Markers of cytopathic hypoxia use as methods for early diagnosis of acute liver failure (ALF) and monitoring the effectiveness of its correction promising. In terms of cytopathic hypoxia may be at the stage of laboratory diagnostics to distinguish between destructive and non-destructive forms APBE, and for markers of endothelial dysfunction--destructive forms on the area and depth of destruction of the pancreas.

  18. [CLINICAL AND LABORATORY FEATURES OF ACUTE PANCREATITIS BILIARY ETIOLOGY COURSE IN PATIENTS WITH DIABETES MELLITUS].

    PubMed

    Godlevskiy, A I; Savolyuk, S I; Tomashevskiy, Ya V

    2015-07-01

    The dynamics of cytopathic hypoxia markers in patients with acute pancreatitis (AP) biliary etiology (BE), depending on the presence of concomitant diabetes mellitus (DM), which is an independent factor of premorbid severity increase and increase in the degree of operational and anesthetic risk. Markers of cytopathic hypoxia use as methods for early diagnosis of acute liver failure (ALF) and monitoring the effectiveness of its correction promising. In terms of cytopathic hypoxia may be at the stage of laboratory diagnostics to distinguish between destructive and non-destructive forms APBE, and for markers of endothelial dysfunction--destructive forms on the area and depth of destruction of the pancreas. PMID:26591209

  19. Vaccines to prevent severe acute respiratory syndrome coronavirus-induced disease

    PubMed Central

    Enjuanes, Luis; DeDiego, Marta L.; Álvarez, Enrique; Deming, Damon; Sheahan, Tim; Baric, Ralph

    2009-01-01

    An important effort has been performed after the emergence of severe acute respiratory syndrome (SARS) epidemic in 2003 to diagnose and prevent virus spreading. Several types of vaccines have been developed including inactivated viruses, subunit vaccines, virus-like particles (VLPs), DNA vaccines, heterologous expression systems, and vaccines derived from SARS-CoV genome by reverse genetics. This review describes several aspects essential to develop SARS-CoV vaccines, such as the correlates of protection, virus serotypes, vaccination side effects, and bio-safeguards that can be engineered into recombinant vaccine approaches based on the SARS-CoV genome. The production of effective and safe vaccines to prevent SARS has led to the development of promising vaccine candidates, in contrast to the design of vaccines for other coronaviruses, that in general has been less successful. After preclinical trials in animal models, efficacy and safety evaluation of the most promising vaccine candidates described has to be performed in humans. PMID:17416434

  20. Adenosine receptors mediate the hypoxic ventilatory response but not the hypoxic metabolic response in the naked mole rat during acute hypoxia.

    PubMed

    Pamenter, Matthew E; Dzal, Yvonne A; Milsom, William K

    2015-02-01

    Naked mole rats are the most hypoxia-tolerant mammals identified; however, the mechanisms underlying this tolerance are poorly understood. Using whole-animal plethysmography and open-flow respirometry, we examined the hypoxic metabolic response (HMR), hypoxic ventilatory response (HVR) and hypoxic thermal response in awake, freely behaving naked mole rats exposed to 7% O₂ for 1 h. Metabolic rate and ventilation each reversibly decreased 70% in hypoxia (from 39.6 ± 2.9 to 12.1 ± 0.3 ml O₂ min(-1) kg(-1), and 1412 ± 244 to 417 ± 62 ml min(-1) kg(-1), respectively; p < 0.05), whereas body temperature was unchanged and animals remained awake and active. Subcutaneous injection of the general adenosine receptor antagonist aminophylline (AMP; 100 mg kg(-1), in saline), but not control saline injections, prevented the HVR but had no effect on the HMR. As a result, AMP-treated naked mole rats exhibited extreme hyperventilation in hypoxia. These animals were also less tolerant to hypoxia, and in some cases hypoxia was lethal following AMP injection. We conclude that in naked mole rats (i) hypoxia tolerance is partially dependent on profound hypoxic metabolic and ventilatory responses, which are equal in magnitude but occur independently of thermal changes in hypoxia, and (ii) adenosine receptors mediate the HVR but not the HMR.

  1. Adenosine receptors mediate the hypoxic ventilatory response but not the hypoxic metabolic response in the naked mole rat during acute hypoxia

    PubMed Central

    Pamenter, Matthew E.; Dzal, Yvonne A.; Milsom, William K.

    2015-01-01

    Naked mole rats are the most hypoxia-tolerant mammals identified; however, the mechanisms underlying this tolerance are poorly understood. Using whole-animal plethysmography and open-flow respirometry, we examined the hypoxic metabolic response (HMR), hypoxic ventilatory response (HVR) and hypoxic thermal response in awake, freely behaving naked mole rats exposed to 7% O2 for 1 h. Metabolic rate and ventilation each reversibly decreased 70% in hypoxia (from 39.6 ± 2.9 to 12.1 ± 0.3 ml O2 min−1 kg−1, and 1412 ± 244 to 417 ± 62 ml min−1 kg−1, respectively; p < 0.05), whereas body temperature was unchanged and animals remained awake and active. Subcutaneous injection of the general adenosine receptor antagonist aminophylline (AMP; 100 mg kg−1, in saline), but not control saline injections, prevented the HVR but had no effect on the HMR. As a result, AMP-treated naked mole rats exhibited extreme hyperventilation in hypoxia. These animals were also less tolerant to hypoxia, and in some cases hypoxia was lethal following AMP injection. We conclude that in naked mole rats (i) hypoxia tolerance is partially dependent on profound hypoxic metabolic and ventilatory responses, which are equal in magnitude but occur independently of thermal changes in hypoxia, and (ii) adenosine receptors mediate the HVR but not the HMR. PMID:25520355

  2. Intrahepatic microcirculatory disorder, parenchymal hypoxia and NOX4 upregulation result in zonal differences in hepatocyte apoptosis following lipopolysaccharide- and D-galactosamine-induced acute liver failure in rats

    PubMed Central

    TANAKA, MASATAKE; TANAKA, KOSUKE; MASAKI, YUKO; MIYAZAKI, MASAYUKI; KATO, MASAKI; KOTOH, KAZUHIRO; ENJOJI, MUNECHIKA; NAKAMUTA, MAKOTO; TAKAYANAGI, RYOICHI

    2014-01-01

    Although the mechanisms responsible for acute liver failure (ALF) have not yet been fully elucidated, studies have indicated that intrahepatic macrophage activation plays an important role in the pathogenesis of ALF through intrahepatic microcirculatory disorder and consequent parenchymal cell death. Intrahepatic microcirculatory disorder has been demonstrated in animal models using intravital microscopy; however, the limitations of this method include simultaneously evaluating blood flow and the surrounding pathological changes. Therefore, in this study, we devised a novel method involving tetramethylrhodamine isothiocyanate (TRITC)-dextran administration for the pathological assessment of hepatic microcirculation. In addition, we aimed to elucidate the mechanisms through which intrahepatic microcirculatory disorder progresses with relation to activated macrophages. ALF was induced in Wistar rats by exposure to lipopolysaccharide and D-galactosamine. Intrahepatic microcirculation and microcirculatory disorder in zone 3 (pericentral zone) of the livers of rats with ALF was observed. Immunohistochemical examinations in conjunction with TRITC-dextran images revealed that the macrophages were mainly distributed in zone 2 (intermediate zone), while cleaved caspase-3-positive hepatocytes, pimonidazole and hypoxia-inducible factor 1-α were abundant in zone 3. We also found that 4-hydroxy-2-nonenal and nicotinamide adenine dinucleotide phosphate oxidase (NOX)4-positive cells were predominantly located in the zone 3 parenchyma. The majority of apoptotic hepatocytes in zone 3 were co-localized with NOX4. Our results revealed that the apoptotic cells in zone 3 were a result of hypoxic conditions induced by intrahepatic microcirculatory disorder, and were not induced by activated macrophages. The increased levels of oxidative stress in zone 3 may contribute to the progression of hepatocyte apoptosis. PMID:24317376

  3. Applying Pharmacokinetics to Optimize Dosing of Anti-TNF Biologics in Acute Severe Ulcerative Colitis

    PubMed Central

    Rosen, Michael J.; Minar, Philip; Vinks, Alexander A.

    2015-01-01

    Background Acute severe ulcerative colitis (ASUC), the most aggressive presentation ulcerative colitis (UC), occurs in 15 percent of adults and children with UC. First line therapy with intravenous corticosteroids is ineffective in half of adults and one third of children. Therapeutic monoclonal antibodies against TNF (anti-TNF therapy) are emerging as a common treatment for ASUC due to their similar efficacy to calcineurin inhibitors and more favorable adverse effect profile. Aim To comprehensively review the evidence for anti-TNF therapy for ASUC in children and adults with regard to outcomes and pharmacokinetics. Methods PubMed and recent conference proceedings were searched using the terms “ulcerative colitis”, “acute severe ulcerative colitis”, “anti-TNF”, “pharmacokinetics”, and the generic names of specific anti-TNF agents. Results Outcomes after anti-TNF therapy for ASUC remain suboptimal with aboutone half of children and adults undergoing colectomy. While several randomized controlled trials have demonstrated the efficacy of anti-TNF therapy for ambulatory patients with moderate to severely active UC, patients in these studies were less ill than those with ASUC. Patients with ASUC may exhibit more rapid clearance of anti-TNF biologics due pharmacokinetic mechanisms influenced by disease severity. Conclusions Conventional weight-based dosing effective in patients with moderately to severely active UC, may not be equally effective in those with ASUC. Personalized anti-TNF dosing strategies that integratepatient factors and early measures of pharmacokinetics and response hold promise for ensuring sustained drug exposure and maximizing early mucosal healing in patients with ASUC. PMID:25809869

  4. From Moderately Severe to Severe Hypertriglyceridemia Induced Acute Pancreatitis: Circulating MiRNAs Play Role as Potential Biomarkers

    PubMed Central

    Xia, Min; Jiang, Lisha; Lu, Guoming; Huang, Mindan; Guo, Jizhong; Liu, Side

    2014-01-01

    The incidence of hypertriglyceridemia induced acute pancreatitis (HTAP) continues to rise in China. It has systemic complications and high mortality, making the early assessment of the severity of this disease even more important. Circulating microRNAs (miRNAs) could be novel, non-invasive biomarkers for disease progression judgment. This study aimed to identify the potential role of serum miRNAs as novel biomarkers of HTAP progression. HTAP patients were divided into two groups: moderately severe (HTMSAP) and severe (HTSAP), healthy people were used as control group. The serum miRNA expression profiles of these three groups were determined by microarray and verified by qRT-PCR. The functions and pathways of the targeted genes of deregulated miRNAs were predicted, using bioinformatics analysis; miRNA-mRNA network was generated. Moreover, the correlation between miR-181a-5p and pancreatitis metabolism related substances were studied and the serum concentration of inflammatory cytokines and miRNAs at different time points during the MSAP and SAP were investigated, respectively. Finally, the receiver operating characteristic (ROC) curve of miRNAs was studied. Significant changes in the serum concentration of the following miRNAs of HTAP patients (P<0.05) were discovered: miR24-3p, 361-5p, 1246, and 222-3p (constantly upregulated), and 181a-5p (constantly downregulated) (P<0.05). Bioinformatics analysis predicted that 13 GOs and 36 pathways regulated by overlap miRNAs were involved in glucose, fat, calcium (Ca++), and insulin metabolism (P<0.001). miRNA-mRNA network revealed that the overlap miRNAs targeted genes participating in pancreas metabolism and miR-181a-5p, the only downregulated miRNA, had good negative correlation with triglyceride (TG), total cholesterol (TC), and fast blood glucose (FBG), but a positive correlation with Ca++. When compared with inflammatory cytokines, the changes of all five overlap miRNAs were more stable. It was found that when used for

  5. Induction of alternatively activated macrophages enhances pathogenesis during severe acute respiratory syndrome coronavirus infection.

    PubMed

    Page, Carly; Goicochea, Lindsay; Matthews, Krystal; Zhang, Yong; Klover, Peter; Holtzman, Michael J; Hennighausen, Lothar; Frieman, Matthew

    2012-12-01

    Infection with severe acute respiratory syndrome coronavirus (SARS-CoV) causes acute lung injury (ALI) that often leads to severe lung disease. A mouse model of acute SARS-CoV infection has been helpful in understanding the host response to infection; however, there are still unanswered questions concerning SARS-CoV pathogenesis. We have shown that STAT1 plays an important role in the severity of SARS-CoV pathogenesis and that it is independent of the role of STAT1 in interferon signaling. Mice lacking STAT1 have greater weight loss, severe lung pathology with pre-pulmonary-fibrosis-like lesions, and an altered immune response following infection with SARS-CoV. We hypothesized that STAT1 plays a role in the polarization of the immune response, specifically in macrophages, resulting in a worsened outcome. To test this, we created bone marrow chimeras and cell-type-specific knockouts of STAT1 to identify which cell type(s) is critical to protection from severe lung disease after SARS-CoV infection. Bone marrow chimera experiments demonstrated that hematopoietic cells are responsible for the pathogenesis in STAT1(-/-) mice, and because of an induction of alternatively activated (AA) macrophages after infection, we hypothesized that the AA macrophages were critical for disease severity. Mice with STAT1 in either monocytes and macrophages (LysM/STAT1) or ciliated lung epithelial cells (FoxJ1/STAT1) deleted were created. Following infection, LysM/STAT1 mice display severe lung pathology, while FoxJ1/STAT1 mice display normal lung pathology. We hypothesized that AA macrophages were responsible for this STAT1-dependent pathology and therefore created STAT1/STAT6(-/-) double-knockout mice. STAT6 is essential for the development of AA macrophages. Infection of the double-knockout mice displayed a lack of lung disease and prefibrotic lesions, suggesting that AA macrophage production may be the cause of STAT1-dependent lung disease. We propose that the control of AA

  6. Resolution of primary severe acute respiratory syndrome-associated coronavirus infection requires Stat1.

    PubMed

    Hogan, Robert J; Gao, Guangping; Rowe, Thomas; Bell, Peter; Flieder, Douglas; Paragas, Jason; Kobinger, Gary P; Wivel, Nelson A; Crystal, Ronald G; Boyer, Julie; Feldmann, Heinz; Voss, Thomas G; Wilson, James M

    2004-10-01

    Intranasal inhalation of the severe acute respiratory syndrome coronavirus (SARS CoV) in the immunocompetent mouse strain 129SvEv resulted in infection of conducting airway epithelial cells followed by rapid clearance of virus from the lungs and the development of self-limited bronchiolitis. Animals resistant to the effects of interferons by virtue of a deficiency in Stat1 demonstrated a markedly different course following intranasal inhalation of SARS CoV, one characterized by replication of virus in lungs and progressively worsening pulmonary disease with inflammation of small airways and alveoli and systemic spread of the virus to livers and spleens.

  7. Managing severe acute respiratory syndrome (SARS) intellectual property rights: the possible role of patent pooling.

    PubMed Central

    Simon, James H. M.; Claassen, Eric; Correa, Carmen E.; Osterhaus, Albert D. M. E.

    2005-01-01

    Patent applications that incorporate the genomic sequence of the severe acute respiratory syndrome (SARS) coronavirus, have been filed by a number of organizations. This is likely to result in a fragmentation of intellectual property (IP) rights which in turn may adversely affect the development of products, such as vaccines, to combat SARS. Placing these patent rights into a patent pool to be licensed on a non-exclusive basis may circumvent these difficulties and set a key precedent for the use of this form of mechanism in other areas of health care, leading to benefits to public health. PMID:16211163

  8. Preparing to prevent severe acute respiratory syndrome and other respiratory infections.

    PubMed

    Ho, Mei-Shang; Su, Ih-Jen

    2004-11-01

    Globalisation and its effect on human development has rendered an environment that is conducive for the rapid international spread of severe acute respiratory syndrome (SARS), and other new infectious diseases yet to emerge. After the unprecedented multi-country outbreak of avian influenza with human cases in the winter of 2003-2004, an influenza pandemic is a current threat. A critical review of problems and solutions encountered during the 2003-2004 SARS epidemics will serve as the basis for considering national preparedness steps that can be taken to facilitate the early detection of avian influenza, and a rapid response to an influenza pandemic should it occur.

  9. Post-Traumatic Hypoxia Is Associated with Prolonged Cerebral Cytokine Production, Higher Serum Biomarker Levels, and Poor Outcome in Patients with Severe Traumatic Brain Injury

    PubMed Central

    Yan, Edwin B.; Satgunaseelan, Laveniya; Paul, Eldho; Bye, Nicole; Nguyen, Phuong; Agyapomaa, Doreen; Kossmann, Thomas; Rosenfeld, Jeffrey V.

    2014-01-01

    Abstract Secondary hypoxia is a known contributor to adverse outcomes in patients with traumatic brain injury (TBI). Based on the evidence that hypoxia and TBI in isolation induce neuroinflammation, we investigated whether TBI combined with hypoxia enhances cerebral cytokine production. We also explored whether increased concentrations of injury biomarkers discriminate between hypoxic (Hx) and normoxic (Nx) patients, correlate to worse outcome, and depend on blood–brain barrier (BBB) dysfunction. Forty-two TBI patients with Glasgow Coma Scale ≤8 were recruited. Cerebrospinal fluid (CSF) and serum were collected over 6 days. Patients were divided into Hx (n=22) and Nx (n=20) groups. Eight cytokines were measured in the CSF; albumin, S100, myelin basic protein (MBP) and neuronal specific enolase (NSE) were quantified in serum. CSF/serum albumin quotient was calculated for BBB function. Glasgow Outcome Scale Extended (GOSE) was assessed at 6 months post-TBI. Production of granulocye macrophage-colony stimulating factor (GM-CSF) was higher, and profiles of GM-CSF, interferon (IFN)-γ and, to a lesser extent, tumor necrosis factor (TNF), were prolonged in the CSF of Hx but not Nx patients at 4–5 days post-TBI. Interleukin (IL)-2, IL-4, IL-6, and IL-10 increased similarly in both Hx and Nx groups. S100, MBP, and NSE were significantly higher in Hx patients with unfavorable outcome. Among these three biomarkers, S100 showed the strongest correlations to GOSE after TBI-Hx. Elevated CSF/serum albumin quotients lasted for 5 days post-TBI and displayed similar profiles in Hx and Nx patients. We demonstrate for the first time that post-TBI hypoxia is associated with prolonged neuroinflammation, amplified extravasation of biomarkers, and poor outcome. S100 and MBP could be implemented to track the occurrence of post-TBI hypoxia, and prompt adequate treatment. PMID:24279428

  10. Aging, Tolerance to High Altitude, and Cardiorespiratory Response to Hypoxia.

    PubMed

    Richalet, Jean-Paul; Lhuissier, François J

    2015-06-01

    Richalet, Jean-Paul, and François J. Lhuissier. Aging, tolerance to high altitude, and cardiorespiratory response to hypoxia. High Alt Med Biol. 16:117-124, 2015.--It is generally accepted that aging is rather protective, at least at moderate altitude. Some anecdotal reports even mention successful ascent of peaks over 8000 m and even Everest by elderly people. However, very few studies have explored the influence of aging on tolerance to high altitude and prevalence of acute high altitude related diseases, taking into account all confounding factors such as speed of ascent, altitude reached, sex, training status, and chemo-responsiveness. Changes in physiological responses to hypoxia with aging were assessed through a cross-sectional 20-year study including 4675 subjects (2789 men, 1886 women; 14-85 yrs old) and a longitudinal study including 30 subjects explored at a mean 10.4-year interval. In men, ventilatory response to hypoxia increased, while desaturation was less pronounced with aging. Cardiac response to hypoxia was blunted with aging in both genders. Similar results were found in the longitudinal study, with a decrease in cardiac and an increase in ventilatory response to hypoxia with aging. These adaptive responses were less pronounced or absent in post-menopausal untrained women. In conclusion, in normal healthy and active subjects, aging has no deleterious effect on cardiac and ventilatory responses to hypoxia, at least up to the eighth decade. Aging is not a contraindication for high altitude, as far as no pathological condition interferes and physical fitness is compatible with the intensity of the expected physical demand of one's individual. Physiological evaluation through hypoxic exercise testing before going to high altitude is helpful to detect risk factors of severe high altitude-related diseases.

  11. Intermittent hypoxia and neurorehabilitation.

    PubMed

    Gonzalez-Rothi, Elisa J; Lee, Kun-Ze; Dale, Erica A; Reier, Paul J; Mitchell, Gordon S; Fuller, David D

    2015-12-15

    In recent years, it has become clear that brief, repeated presentations of hypoxia [i.e., acute intermittent hypoxia (AIH)] can boost the efficacy of more traditional therapeutic strategies in certain cases of neurologic dysfunction. This hypothesis derives from a series of studies in animal models and human subjects performed over the past 35 yr. In 1980, Millhorn et al. (Millhorn DE, Eldridge FL, Waldrop TG. Respir Physiol 41: 87-103, 1980) showed that electrical stimulation of carotid chemoafferent neurons produced a persistent, serotonin-dependent increase in phrenic motor output that outlasts the stimulus for more than 90 min (i.e., a "respiratory memory"). AIH elicits similar phrenic "long-term facilitation" (LTF) by a mechanism that requires cervical spinal serotonin receptor activation and de novo protein synthesis. From 2003 to present, a series of studies demonstrated that AIH can induce neuroplasticity in the injured spinal cord, causing functional recovery of breathing capacity after cervical spinal injury. Subsequently, it was demonstrated that repeated AIH (rAIH) can induce recovery of limb function, and the functional benefits of rAIH are greatest when paired with task-specific training. Since uncontrolled and/or prolonged intermittent hypoxia can elicit pathophysiology, a challenge of intermittent hypoxia research is to ensure that therapeutic protocols are well below the threshold for pathogenesis. This is possible since many low dose rAIH protocols have induced functional benefits without evidence of pathology. We propose that carefully controlled rAIH is a safe and noninvasive modality that can be paired with other neurorehabilitative strategies including traditional activity-based physical therapy or cell-based therapies such as intraspinal transplantation of neural progenitors. PMID:25997947

  12. Applying a low-flow CO2 removal device in severe acute hypercapnic respiratory failure.

    PubMed

    Sharma, Ajay S; Weerwind, Patrick W; Strauch, Uli; van Belle, Arne; Maessen, Jos G; Wouters, Emiel F M

    2016-03-01

    A novel and portable extracorporeal CO2-removal device was evaluated to provide additional gas transfer, auxiliary to standard therapy in severe acute hypercapnic respiratory failure. A dual-lumen catheter was inserted percutaneously in five subjects (mean age 55 ± 0.4 years) and, subsequently, connected to the CO2-removal device. The median duration on support was 45 hours (interquartile range 26-156), with a blood flow rate of approximately 500 mL/min. The mean PaCO2 decreased from 95.8 ± 21.9 mmHg to 63.9 ± 19.6 mmHg with the pH improving from 7.11 ± 0.1 to 7.26 ± 0.1 in the initial 4 hours of support. Three subjects were directly weaned from the CO2-removal device and mechanical ventilation, one subject was converted to ECMO and one subject died following withdrawal of support. No systemic bleeding or device complications were observed. Low-flow CO2 removal adjuvant to standard therapy was effective in steadily removing CO2, limiting the progression of acidosis in subjects with severe acute hypercapnic respiratory failure.

  13. Interventional Treatment of Abdominal Compartment Syndrome during Severe Acute Pancreatitis: Current Status and Historical Perspective

    PubMed Central

    Radenkovic, Dejan V.; Johnson, Colin D.; Milic, Natasa; Gregoric, Pavle; Ivancevic, Nenad; Bezmarevic, Mihailo; Bilanovic, Dragoljub; Cijan, Vladimir; Antic, Andrija; Bajec, Djordje

    2016-01-01

    Abdominal compartment syndrome (ACS) in patients with severe acute pancreatitis (SAP) is a marker of severe disease. It occurs as combination of inflammation of retroperitoneum, visceral edema, ascites, acute peripancreatic fluid collections, paralytic ileus, and aggressive fluid resuscitation. The frequency of ACS in SAP may be rising due to more aggressive fluid resuscitation, a trend towards conservative treatment, and attempts to use a minimally invasive approach. There remains uncertainty about the most appropriate surgical technique for the treatment of ACS in SAP. Some unresolved questions remain including medical treatment, indications, timing, and interventional techniques. This review will focus on interventional treatment of this serious condition. First line therapy is conservative treatment aiming to decrease IAP and to restore organ dysfunction. If nonoperative measures are not effective, early abdominal decompression is mandatory. Midline laparostomy seems to be method of choice. Since it carries significant morbidity we need randomized studies to establish firm advantages over other described techniques. After ACS resolves efforts should be made to achieve early primary fascia closure. Additional data are necessary to resolve uncertainties regarding ideal timing and indication for operative treatment. PMID:26839539

  14. Viruses as Sole Causative Agents of Severe Acute Respiratory Tract Infections in Children

    PubMed Central

    Moesker, Fleur M.; van Kampen, Jeroen J. A.; van Rossum, Annemarie M. C.; de Hoog, Matthijs; Koopmans, Marion P. G.; Osterhaus, Albert D. M. E.; Fraaij, Pieter L. A.

    2016-01-01

    Background Respiratory syncytial virus (RSV) and influenza A viruses are known to cause severe acute respiratory tract infections (SARIs) in children. For other viruses like human rhinoviruses (HRVs) this is less well established. Viral or bacterial co-infections are often considered essential for severe manifestations of these virus infections. Objective The study aims at identifying viruses that may cause SARI in children in the absence of viral and bacterial co-infections, at identifying disease characteristics associated with these single virus infections, and at identifying a possible correlation between viral loads and disease severities. Study Design Between April 2007 and March 2012, we identified children (<18 year) with or without a medical history, admitted to our paediatric intensive care unit (PICU) with SARI or to the medium care (MC) with an acute respiratory tract infection (ARTI) (controls). Data were extracted from the clinical and laboratory databases of our tertiary care paediatric hospital. Patient specimens were tested for fifteen respiratory viruses with real-time reverse transcriptase PCR assays and we selected patients with a single virus infection only. Typical bacterial co-infections were considered unlikely to have contributed to the PICU or MC admission based on C-reactive protein-levels or bacteriological test results if performed. Results We identified 44 patients admitted to PICU with SARI and 40 patients admitted to MC with ARTI. Twelve viruses were associated with SARI, ten of which were also associated with ARTI in the absence of typical bacterial and viral co-infections, with RSV and HRV being the most frequent causes. Viral loads were not different between PICU-SARI patients and MC-ARTI patients. Conclusion Both SARI and ARTI may be caused by single viral pathogens in previously healthy children as well as in children with a medical history. No relationship between viral load and disease severity was identified. PMID:26964038

  15. Imaging hypoxia in tumors.

    PubMed

    Ballinger, J R

    2001-10-01

    For many years, it has been known that hypoxia affects the response to radiotherapy in human cancers. Hypoxic regions can develop as a tumor grows beyond the ability of its blood supply to deliver oxygen to the full extent of the tumor, exacerbated by vascular spasm or compression caused by increased interstitial fluid pressure. However, hypoxia is heterogeneous, and tumors that appear identical by clinical and radiographic criteria can vary greatly in their extent of hypoxia. Several invasive procedures to measure hypoxia in tumors have been developed and are predictive of response to therapy, but none of these is in routine clinical use because of technical complexity, inconvenience, and inability to obtain repeated measures. Noninvasive imaging with a hypoxia-directed radiopharmaceutical could be of great clinical utility. Most such radiopharmaceuticals under development use 2-nitroimidazole as the targeting moiety. 2-Nitroimidazole, which is selectively reduced and bound in hypoxic tissues, has been labeled with F-18, Cu-64/67, I-123, and Tc-99m. Of these, F-18-fluoromisonidazole and I-123-iodoazomycin arabinoside (IAZA) have been most widely studied clinically. Non-nitro-containing bioreductive complexes, such as the Cu-60/62/64 thiosemicarbazone ATSM and Tc-99m butylene amineoxime (BnAO or HL91), have also been evaluated. In particular, 1-123-IAZA and Cu-60-ATSM have shown correlation with response to radiotherapy in preliminary clinical studies. However, more preclinical studies comparing imaging with validated invasive methods and clinical studies with outcome measures are required. Nuclear medicine is poised to play an important role in optimizing the therapy of patients with hypoxic tumors.

  16. Oxygen sensing by the carotid body: mechanisms and role in adaptation to hypoxia.

    PubMed

    López-Barneo, José; González-Rodríguez, Patricia; Gao, Lin; Fernández-Agüera, M Carmen; Pardal, Ricardo; Ortega-Sáenz, Patricia

    2016-04-15

    Oxygen (O2) is fundamental for cell and whole-body homeostasis. Our understanding of the adaptive processes that take place in response to a lack of O2(hypoxia) has progressed significantly in recent years. The carotid body (CB) is the main arterial chemoreceptor that mediates the acute cardiorespiratory reflexes (hyperventilation and sympathetic activation) triggered by hypoxia. The CB is composed of clusters of cells (glomeruli) in close contact with blood vessels and nerve fibers. Glomus cells, the O2-sensitive elements in the CB, are neuron-like cells that contain O2-sensitive K(+)channels, which are inhibited by hypoxia. This leads to cell depolarization, Ca(2+)entry, and the release of transmitters to activate sensory fibers terminating at the respiratory center. The mechanism whereby O2modulates K(+)channels has remained elusive, although several appealing hypotheses have been postulated. Recent data suggest that mitochondria complex I signaling to membrane K(+)channels plays a fundamental role in acute O2sensing. CB activation during exposure to low Po2is also necessary for acclimatization to chronic hypoxia. CB growth during sustained hypoxia depends on the activation of a resident population of stem cells, which are also activated by transmitters released from the O2-sensitive glomus cells. These advances should foster further studies on the role of CB dysfunction in the pathogenesis of highly prevalent human diseases.

  17. Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia.

    PubMed

    Lumbroso, Delphine; Joseph, Vincent

    2009-08-01

    We tested the hypothesis that neonatal exposure to hypoxia alters acclimatization to chronic hypoxia later in life. Rat pups were exposed to normobaric hypoxia (12% O(2); nHx group) in a sealed chamber, or to normoxia (21% O(2); nNx group) from the day before birth to postnatal day 10. The animals were then raised in normal conditions until reaching 12 wk of age. At this age, we assessed ventilatory and hematological acclimatization to chronic hypoxia by exposing male and female nHx and nNx rats for 2 wk to 10% O(2). Minute ventilation, metabolic rate, hypoxic ventilatory response, hematocrit, and hemoglobin levels were measured both before and after acclimatization. We also quantified right ventricular hypertrophy as an index of pulmonary hypertension both before and after acclimatization. There was a significant effect of neonatal hypoxia that decreases ventilatory response (relative to metabolic rate, VE/VCO(2)) to acute hypoxia before acclimatization in males but not in females. nHx rats had an impaired acclimatization to chronic hypoxia characterized by altered respiratory pattern and elevated hematocrit and hemoglobin levels after acclimatization, in both males and females. Right ventricular hypertrophy was present before and after acclimatization in nHx rats, indicating that neonatal hypoxia results in pulmonary hypertension in adults. We conclude that neonatal hypoxia impairs acclimatization to chronic hypoxia in adults and may be a factor contributing to the establishment of chronic mountain sickness in humans living at high altitude.

  18. Endotoxin adsorption therapy using polymyxin B-immobilized fiber as a treatment for septic shock-associated severe acute cholangitis.

    PubMed

    Inoue, Yoshihiro; Fujino, Yasuhisa; Onodera, Makoto; Kikuchi, Satoshi; Takahashi, Gaku; Kojika, Masahiro; Endo, Shigeatsu

    2013-10-01

    The application of endotoxin adsorption therapy for severe acute cholangitis is controversial. We present a survival case of septic shock and multiple organ failure due to severe acute cholangitis. The patient was treated by endotoxin adsorption therapy using polymyxin B-immobilized fiber because he continued to remain in shock even after successful endoscopic nasobiliary drainage. The patient was an 84-year-old male diagnosed with acute cholangitis and acute pancreatitis who was transferred to our department because of shock and severe dyspnea. The patient had already developed acute respiratory failure, acute renal failure, and disseminated intravascular coagulation. We performed endoscopic nasobiliary drainage immediately, but the patient continued to remain in shock and plasma endotoxin level was markedly elevated at 133.6 pg/mL. Therefore, we performed direct hemoperfusion with polymyxin B-immobilized fiber. On starting the hemoperfusion, blood pressure and urine volume increased, and the plasma endotoxin level reduced considerably. On the basis of our experience in this case, we think that direct hemoperfusion with polymyxin B-immobilized fiber may be a useful modality in the management of severe acute cholangitis.

  19. The significance of tubular and glomerular proteinuria in critically ill patients with severe acute kidney injury

    PubMed Central

    Lim, Christopher Thiam Seong; Tan, Han Khim; Lau, Yeow Kok

    2014-01-01

    Objective: Critically ill patients with acute kidney injury (AKI) frequently need acute renal replacement therapy (aRRT). We evaluated an inexpensive, rapid quantitative and qualitative analysis of proteinuria on the course of AKI patients requiring aRRT in intensive care. Method: This was a prospective, observational study of critically ill patients with severe established AKI or Acute on Chronic Kidney Injury (AoCKI) requiring aRRT. Urine samples were analyzed using Sodium-Dodecyl-Sulphate-Polyacryamide Gel Electrophoresis (SDS-PAGE). Results: A total of 30 critically ill patients were studied. Those who died have higher APACHE II (29 ± 6 vs. 20 ± 5, p<0.001), multi-organ failure (0.7 ± 0.5 vs. 0.2 ± 0.4, p < 0.02) and Tubular/Glomerular ratio (114 ± 60 vs. 75± 37, p < 0.05).The renal non-recoverers have higher baseline creatinine (415 ± 328 vs. 125± 19 umol/l, p < 0.01), urinary Dipstick value (1.8±0.8 vs. 0.5±0, p <0.05) and Glomerular score (3.0 ± 1.8 vs. 0.6 ± 0.2, p < 0.02).Heavy tubular proteinuria also predicts a longer duration of interim dialysis support and mortality whereas glomerular proteinuria correlates with development of chronicity and End Stage Renal Disease (ESRD). Conclusions: The dominant presence of tubular proteinuria is associated with poor survival in patients who have high APACHE II score and multi-organ failure. It also correlates with a longer duration of dialysis support in survivals. Renal Non-recoverers had heavy dominant presence of glomerular proteinuria. SDS-PAGE proteinuria analysis offers a reliable and inexpensive method to prognosticate proteinuria in this group of critically ill patients. PMID:25674105

  20. Hypoxia and the antipredator behaviours of fishes.

    PubMed

    Domenici, P; Lefrançois, C; Shingles, A

    2007-11-29

    Hypoxia is a phenomenon occurring in marine coastal areas with increasing frequency. While hypoxia has been documented to affect fish activity and metabolism, recent evidence shows that hypoxia can also have a detrimental effect on various antipredator behaviours. Here, we review such evidence with a focus on the effect of hypoxia on fish escape responses, its modulation by aquatic surface respiration (ASR) and schooling behaviour. The main effect of hypoxia on escape behaviour was found in responsiveness and directionality. Locomotor performance in escapes was expected to be relatively independent of hypoxia, since escape responses are fuelled anaerobically. However, hypoxia decreased locomotor performance in some species (Mugilidae) although only in the absence of ASR in severe hypoxia. ASR allows fish to show higher escape performance than fish staying in the water column where hypoxia occurs. This situation provides a trade-off whereby fish may perform ASR in order to avoid the detrimental effects of hypoxia, although they would be subjected to higher exposure to aerial predation. As a result of this trade-off, fishes appear to minimize surfacing behaviour in the presence of aerial predators and to surface near shelters, where possible. For many fish species, schooling can be an effective antipredator behaviour. Severe hypoxia may lead to the disruption of the school unit. At moderate levels, hypoxia can increase school volume and can change the shuffling behaviour of individuals. By altering school structure and dynamics, hypoxia may affect the well functioning of schooling in terms of synchronization and execution of antipredator manoeuvres. School structure and volume appear to be the results of numerous trade-offs, where school shape may be dictated by the presence of predators, the need for energy saving via hydrodynamic advantages and oxygen level. The effects of hypoxia on aquatic organisms can be taxon specific. While hypoxia may not necessarily

  1. The Acute Asthma Severity Assessment Protocol (AASAP) study: objectives and methods of a study to develop an acute asthma clinical prediction rule.

    PubMed

    Arnold, Donald H; Gebretsadik, Tebeb; Abramo, Thomas J; Sheller, James R; Resha, Donald J; Hartert, Tina V

    2012-06-01

    Acute asthma exacerbations are one of the most common reasons for paediatric emergency department visits and hospitalisations, and a relapse frequently necessitates repeat urgent care. While care plans exist, there are no acute asthma prediction rules (APRs) to assess severity and predict outcome. The primary objective of the Acute Asthma Severity Assessment Protocol study is to develop a multivariable APR for acute asthma exacerbations in paediatric patients. A prospective, convenience sample of paediatric patients aged 5-17 years with acute asthma exacerbations who present to an urban, academic, tertiary paediatric emergency department was enrolled. The study protocol and data analysis plan conform to accepted biostatistical and clinical standards for clinical prediction rule development. Modelling of the APR will be performed once the entire sample size of 1500 has accrued. It is anticipated that the APR will improve resource utilisation in the emergency department, aid in standardisation of disease assessment and allow physician and non-physician providers to participate in earlier objective decision making. The objective of this report is to describe the study objectives and detailed methodology of the Acute Asthma Severity Assessment Protocol study.

  2. Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis

    PubMed Central

    Skouras, Christos; Zheng, Xiaozhong; Binnie, Margaret; Homer, Natalie Z. M.; Murray, Toby B. J.; Robertson, Darren; Briody, Lesley; Paterson, Finny; Spence, Heather; Derr, Lisa; Hayes, Alastair J.; Tsoumanis, Andreas; Lyster, Dawn; Parks, Rowan W.; Garden, O. James; Iredale, John P.; Uings, Iain J.; Liddle, John; Wright, Wayne L.; Dukes, George; Webster, Scott P.; Mole, Damian J.

    2016-01-01

    Inhibition of kynurenine 3-monooxygenase (KMO) protects against multiple organ dysfunction (MODS) in experimental acute pancreatitis (AP). We aimed to precisely define the kynurenine pathway activation in relation to AP and AP-MODS in humans, by carrying out a prospective observational study of all persons presenting with a potential diagnosis of AP for 90 days. We sampled peripheral venous blood at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. We measured tryptophan metabolite concentrations and analysed these in the context of clinical data and disease severity indices, cytokine profiles and C-reactive protein (CRP) concentrations. 79 individuals were recruited (median age: 59.6 years; 47 males, 59.5%). 57 met the revised Atlanta definition of AP: 25 had mild, 23 moderate, and 9 severe AP. Plasma 3-hydroxykynurenine concentrations correlated with contemporaneous APACHE II scores (R2 = 0.273; Spearman rho = 0.581; P < 0.001) and CRP (R2 = 0.132; Spearman rho = 0.455, P < 0.001). Temporal profiling showed early tryptophan depletion and contemporaneous 3-hydroxykynurenine elevation. Furthermore, plasma concentrations of 3-hydroxykynurenine paralleled systemic inflammation and AP severity. These findings support the rationale for investigating early intervention with a KMO inhibitor, with the aim of reducing the incidence and severity of AP-associated organ dysfunction. PMID:27669975

  3. Modified Da Chengqi granules improvement in immune function in early severe acute pancreatitis patients.

    PubMed

    Jiang, D-L; Yang, J; Jiang, S-Y; Yuan, F-L; Gu, Y-L; Li, J-P; Pei, Z-J

    2016-01-01

    We investigated the role of modified Da Chengqi granules in improving immune function in early severe acute pancreatitis patients. Early severe acute pancreatitis patients who agreed to receive combined treatment of traditional Chinese and Western medicine were randomly assigned to the experimental or control group. All subjects received conventional therapy to support organ function. The experimental group also received modified Da Chengqi granules. Cytokine (interleukin-6, interleukin-10, and tumor necrosis factor-α) levels, immunological markers (HLA-DR, Treg, and Th1/Th2), urinary lactulose/mannitol ratio, and endotoxin levels were measured at 1, 3, 7, and 14 days after hospital admission. The total mortality rate was 11.69% (9/77), which was significantly lower in the experimental group [4.88% (2/41)] than in the control group [19.44% (7/36); χ(2) = 3.940, P < 0.05]. Serum interleukin-6, interleukin-10, tumor necrosis factor-α and endotoxin levels and the lactulose/mannitol ratio were significantly lower on day 7 and day 14 than on day 1 in experimental and control groups (P < 0.01). Immunological indices were significantly lower in the experimental group than in the control group on day 14 (all P < 0.01 or 0.05). HLA-DR-positive cell ratio gradually increased over 14 days in experimental and control groups (P < 0.01 vs day 1), but was higher in the experimental group than in the control group by day 14 (P < 0.05). Notably, Treg cell prevalence and Th1/Th2 cell ratio deteriorated within 7 days in both groups (P < 0.01 vs day 1), but then returned to day 1 levels (P < 0.01 or 0.05 vs day 1). Significant differences in Treg levels and Th1/Th2 cell ratio between experimental and control groups were observed on day 14 (P < 0.01). These results show that modified Da Chengqi granules can improve immune function in early severe acute pancreatitis patients.

  4. Physiological effects of intermittent hypoxia.

    PubMed

    Powell, F L; Garcia, N

    2000-01-01

    Intermittent hypoxia (IH), or periodic exposure to hypoxia interrupted by return to normoxia or less hypoxic conditions, occurs in many circumstances. In high altitude mountaineering, IH is used to optimize acclimatization although laboratory studies have not generally revealed physiologically significant benefits. IH enhances athletic performance at sea level if blood oxygen capacity increases and the usual level of training is not decreased significantly. IH for high altitude workers who commute from low altitude homes is of considerable practical interest and the ideal commuting schedule for physical and mental performance is being studied. The effect of oxygen enrichment at altitude (i.e., intermittent normoxia on a background of chronic hypoxia) on human performance is under study also. Physiological mechanisms of IH, and specifically the differences between effects of IH and acute or chronic continuous hypoxia remains to be determined. Biomedical researchers are defining the molecular and cellular mechanisms for effects of hypoxia on the body in health and disease. A comparative approach may provide additional insight about the biological significance of these effects.

  5. Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia

    PubMed Central

    Remolina, Yuly Andrea; Ulloa, María Mercedes; Vargas, Hernán; Díaz, Liliana; Gómez, Sandra Liliana; Saavedra, Alfredo; Sánchez, Edgar; Cortés, Jorge Alberto

    2015-01-01

    Objectives To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. Design A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. Setting Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia. Participants Ninety-one adult patients with acute respiratory infection (55% were female). Measurements Viral identification, intensive care unit admission, hospital stay, and mortality. Results Viral identification was achieved for 63 patients (69.2%). Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients. Conclusions The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality. PMID:26576054

  6. Severe envenomation by Cerastes cerastes viper: an unusual mechanism of acute ischemic stroke.

    PubMed

    Rebahi, Houssam; Nejmi, Hicham; Abouelhassan, Taoufik; Hasni, Khadija; Samkaoui, Mohamed-Abdenasser

    2014-01-01

    Cerebral complications after snake bites--particularly ischemic complications--are rare. Very few cases of cerebral infarction resulting from a viper bite have been reported, and we call attention to this uncommon etiology. We discuss 3 authenticated reports of acute ischemic cerebrovascular accidents after 3 typical severe envenomations by Cerastes cerastes vipers. The 3 patients developed extensive local swelling and life-threatening systemic envenomation characterized by disseminated intravascular coagulopathy, increased fibrinolysis, thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure. This clinical picture involved atypical neurologic manifestations. These patients had either low Glasgow Coma Scale (GCS) or hemiparesis within hours to 4 days after being bitten, and they were found to have computed tomographic evidence of single or multiple ischemic (nonhemorrhagic) strokes of small- to large-vessel territories of the brain. One patient had good clinical recovery without neurologic deficits. Thrombotic complications occurred an average of 36 hours after being bitten, and their importance depends on the degree of envenomation. The possible mechanisms for cerebral infarction in these cases include generalized prothrombotic action of the venom (consumptive coagulopathy), toxin-induced vasculitis, and endothelial damage.

  7. Differential acute effects of selenomethionine and sodium selenite on the severity of colitis.

    PubMed

    Hiller, Franziska; Oldorff, Lisa; Besselt, Karolin; Kipp, Anna Patricia

    2015-04-01

    The European population is only suboptimally supplied with the essential trace element selenium. Such a selenium status is supposed to worsen colitis while colitis-suppressive effects were observed with adequate or supplemented amounts of both organic selenomethionine (SeMet) and inorganic sodium selenite. In order to better understand the effect of these selenocompounds on colitis development we examined colonic phenotypes of mice fed supplemented diets before the onset of colitis or during the acute phase. Colitis was induced by treating mice with 1% dextran sulfate sodium (DSS) for seven days. The selenium-enriched diets were either provided directly after weaning (long-term) or were given to mice with a suboptimal selenium status after DSS withdrawal (short-term). While long-term selenium supplementation had no effect on colitis development, short-term selenite supplementation, however, resulted in a more severe colitis. Colonic selenoprotein expression was maximized in all selenium-supplemented groups independent of the selenocompound or intervention time. This indicates that the short-term selenite effect appears to be independent from colonic selenoprotein expression. In conclusion, a selenite supplementation during acute colitis has no health benefits but may even aggravate the course of disease. PMID:25867950

  8. Ghrelin, GLP-1, and leptin responses during exposure to moderate hypoxia.

    PubMed

    Morishima, Takuma; Goto, Kazushige

    2016-04-01

    Severe hypoxia has been indicated to cause acute changes in appetite-related hormones, which attenuate perceived appetite. However, the effects of moderate hypoxia on appetite-related hormonal regulation and perceived appetite have not been elucidated. Therefore, we examined the effects of moderate hypoxia on appetite-related hormonal regulation and perceived appetite. Eight healthy males (21.0 ± 0.6 years; 173 ± 2.3 cm; 70.6 ± 5.0 kg; 23.4 ± 1.1 kg/m(2)) completed two experimental trials on separate days: a rest trial in normoxia (FiO2 = 20.9%) and a rest trial in hypoxia (FiO2 = 15.0%). The experimental trials were performed over 7 h in an environmental chamber. Blood samples and scores of subjective appetite were collected over 7 h. Standard meals were provided 1 h (745 kcal) and 4 h (731 kcal) after initiating exposure to hypoxia or normoxia within the chamber. Although each meal significantly reduced plasma active ghrelin concentrations (P < 0.05), the response did not differ significantly between the trials over 7 h. No significant differences in the area under the curves for plasma active ghrelin concentrations over 7 h were observed between the two trials. No significant differences were observed in glucagon-like peptide 1 or leptin concentrations over 7 h between the trials. The subjective feeling of hunger and fullness acutely changed in response to meal ingestions. However, these responses were not affected by exposure to moderate hypoxia. In conclusion, 7 h of exposure to moderate hypoxia did not change appetite-related hormonal responses or perceived appetite in healthy males.

  9. Comorbidity as a contributor to frequent severe acute exacerbation in COPD patients

    PubMed Central

    Jeong, Suk Hyeon; Lee, Hyun; Carriere, KC; Shin, Sun Hye; Moon, Seong Mi; Jeong, Byeong-Ho; Koh, Won-Jung; Park, Hye Yun

    2016-01-01

    Background Comorbidities have a serious impact on the frequent severe acute exacerbations (AEs) in patients with COPD. Previous studies have used the Charlson comorbidity index to represent a conglomerate of comorbidities; however, the respective contribution of each coexisting disease to the frequent severe AEs remains unclear. Methods A retrospective, observational study was performed in 77 COPD patients who experienced severe AE between January 2012 and December 2014 and had at least 1-year follow-up period from the date of admission for severe AE. We explored the incidence of frequent severe AEs (≥2 severe AEs during 1-year period) in these patients and investigated COPD-related factors and comorbidities as potential risk factors of these exacerbations. Results Out of 77 patients, 61 patients (79.2%) had at least one comorbidity. During a 1-year follow-up period, 29 patients (37.7%) experienced frequent severe AEs, approximately two-thirds (n=19) of which occurred within the first 90 days after admission. Compared with patients not experiencing frequent severe AEs, these patients were more likely to have poor lung function and receive home oxygen therapy and long-term oral steroids. In multiple logistic regression analysis, coexisting asthma (adjusted odds ratio [OR] =4.02, 95% confidence interval [CI] =1.30–12.46, P=0.016), home oxygen therapy (adjusted OR =9.39, 95% CI =1.60–55.30, P=0.013), and C-reactive protein (adjusted OR =1.09, 95% CI =1.01–1.19, P=0.036) were associated with frequent severe AEs. In addition, poor lung function, as measured by forced expiratory volume in 1 second (adjusted OR =0.16, 95% CI =0.04–0.70, P=0.015), was inversely associated with early (ie, within 90 days of admission) frequent severe AEs. Conclusion Based on our study, among COPD-related comorbidities, coexisting asthma has a significant impact on the frequent severe AEs in COPD patients. PMID:27536097

  10. Severe acute respiratory failure secondary to acute fibrinous and organizing pneumonia requiring mechanical ventilation: a case report and literature review.

    PubMed

    López-Cuenca, Sonia; Morales-García, Silvia; Martín-Hita, Ana; Frutos-Vivar, Fernando; Fernández-Segoviano, Pilar; Esteban, Andrés

    2012-08-01

    A 27-year-old woman was admitted to our ICU with acute hypoxemic respiratory failure and criteria for ARDS. Despite an F(IO(2)) of 1.0 and a lung protective strategy, the patient died on day 15 without any improvement. The relatives gave consent for post-mortem analysis. The histopathologic study of the lung showed findings typical of an acute fibrinous and organizing pneumonia. Apropos of this case we performed a PubMed search. We found 13 articles, including a total of 29 patients. Acute fibrinous and organizing pneumonia is an unusual cause of acute lung injury. The diagnostic criterion is histopathologic. There is little information regarding the pathophysiology of this illness. Important questions remain regarding this disease, including predisposing factors and management. Patients who require mechanical ventilation have poor outcomes.

  11. Dopamine transporters are involved in the onset of hypoxia-induced dopamine efflux in striatum as revealed by in vivo microdialysis.

    PubMed

    Orset, Cyrille; Parrot, Sandrine; Sauvinet, Valérie; Cottet-Emard, Jean-Marie; Bérod, Anne; Pequignot, Jean-Marc; Denoroy, Luc

    2005-06-01

    Although many studies have revealed alterations in neurotransmission during ischaemia, few works have been devoted to the neurochemical effects of mild hypoxia, a situation encountered during life in altitude or in several pathologies. In that context, the present work was undertaken to determine the in vivo mechanisms underlying the striatal dopamine efflux induced by mild hypoxaemic hypoxia. For that purpose, the extracellular concentrations of dopamine and its metabolite 3,4-dihydroxyphenyl acetic acid were simultaneously measured using brain microdialysis during acute hypoxic exposure (10% O(2), 1h) in awake rats. Hypoxia induced a +80% increase in dopamine. Application of the dopamine transporters inhibitor, nomifensine (10 microM), just before the hypoxia prevented the rise in dopamine during the early part of hypoxia; in contrast the application of nomifensine after the beginning of hypoxia, failed to alter the increase in dopamine. Application of the voltage-dependent Na(+) channel blocker tetrodotoxin abolished the increase in dopamine, whether administered just before or after the beginning of hypoxia. These data show that the neurochemical mechanisms of the dopamine efflux may change over the course of the hypoxic exposure, dopamine transporters being involved only at the beginning of hypoxia.

  12. Severe acute interstitial nephritis after combination immune-checkpoint inhibitor therapy for metastatic melanoma

    PubMed Central

    Murakami, Naoka; Borges, Thiago J.; Yamashita, Michifumi; Riella, Leonardo V.

    2016-01-01

    Immune-checkpoint inhibitors are emerging as revolutionary drugs for certain malignancies. However, blocking the co-inhibitory signals may lead to immune-related adverse events, mainly in the spectrum of autoimmune diseases including colitis, endocrinopathies and nephritis. Here, we report a case of a 75-year-old man with metastatic malignant melanoma treated with a combination of nivolumab (anti-PD1-antibody) and ipilimumab (anti-CTLA-4 antibody) who developed systemic rash along with severe acute tubulointerstitial nephritis after two doses of combination therapy. Kidney biopsy and peripheral blood immune profile revealed highly proliferative and cytotoxic T cell features. Herein, we discuss the pathophysiology and management of immune checkpoint blockade-related adverse events. PMID:27274826

  13. Progress in Global Surveillance and Response Capacity 10 Years after Severe Acute Respiratory Syndrome

    PubMed Central

    Braden, Christopher R.; Dowell, Scott F.; Jernigan, Daniel B.

    2013-01-01

    Ten years have elapsed since the World Health Organization issued its first global alert for an unexplained illness named severe acute respiratory syndrome (SARS). The anniversary provides an opportunity to reflect on the international response to this new global microbial threat. While global surveillance and response capacity for public health threats have been strengthened, critical gaps remain. Of 194 World Health Organization member states that signed on to the International Health Regulations (2005), <20% had achieved compliance with the core capacities required by the deadline in June 2012. Lessons learned from the global SARS outbreak highlight the need to avoid complacency, strengthen efforts to improve global capacity to address the next pandemic using all available 21st century tools, and support research to develop new treatment options, countermeasures, and insights while striving to address the global inequities that are the root cause of many of these challenges. PMID:23731871

  14. Prospects for Emerging Infections in East and Southeast Asia 10 Years after Severe Acute Respiratory Syndrome

    PubMed Central

    Pfeiffer, Dirk; Oshitani, Hitoshi

    2013-01-01

    It is 10 years since severe acute respiratory syndrome (SARS) emerged, and East and Southeast Asia retain a reputation as a hot spot of emerging infectious diseases. The region is certainly a hot spot of socioeconomic and environmental change, and although some changes (e.g., urbanization and agricultural intensification) may reduce the probability of emerging infectious diseases, the effect of any individual emergence event may be increased by the greater concentration and connectivity of livestock, persons, and products. The region is now better able to detect and respond to emerging infectious diseases than it was a decade ago, but the tools and methods to produce sufficiently refined assessments of the risks of disease emergence are still lacking. Given the continued scale and pace of change in East and Southeast Asia, it is vital that capabilities for predicting, identifying, and controlling biologic threats do not stagnate as the memory of SARS fades. PMID:23738977

  15. Progress in global surveillance and response capacity 10 years after severe acute respiratory syndrome.

    PubMed

    Braden, Christopher R; Dowell, Scott F; Jernigan, Daniel B; Hughes, James M

    2013-06-01

    Ten years have elapsed since the World Health Organization issued its first global alert for an unexplained illness named severe acute respiratory syndrome (SARS). The anniversary provides an opportunity to reflect on the international response to this new global microbial threat. While global surveillance and response capacity for public health threats have been strengthened, critical gaps remain. Of 194 World Health Organization member states that signed on to the International Health Regulations (2005), <20% had achieved compliance with the core capacities required by the deadline in June 2012. Lessons learned from the global SARS outbreak highlight the need to avoid complacency, strengthen efforts to improve global capacity to address the next pandemic using all available 21st century tools, and support research to develop new treatment options, countermeasures, and insights while striving to address the global inequities that are the root cause of many of these challenges. PMID:23731871

  16. Prospects for emerging infections in East and southeast Asia 10 years after severe acute respiratory syndrome.

    PubMed

    Horby, Peter W; Pfeiffer, Dirk; Oshitani, Hitoshi

    2013-06-01

    It is 10 years since severe acute respiratory syndrome (SARS) emerged, and East and Southeast Asia retain a reputation as a hot spot of emerging infectious diseases. The region is certainly a hot spot of socioeconomic and environmental change, and although some changes (e.g., urbanization and agricultural intensification) may reduce the probability of emerging infectious diseases, the effect of any individual emergence event may be increased by the greater concentration and connectivity of livestock, persons, and products. The region is now better able to detect and respond to emerging infectious diseases than it was a decade ago, but the tools and methods to produce sufficiently refined assessments of the risks of disease emergence are still lacking. Given the continued scale and pace of change in East and Southeast Asia, it is vital that capabilities for predicting, identifying, and controlling biologic threats do not stagnate as the memory of SARS fades.

  17. Study progress on mechanism of severe acute pancreatitis complicated with hepatic injury.

    PubMed

    Zhang, Xi-ping; Wang, Lei; Zhang, Jie

    2007-04-01

    Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis (SAP) in multiple organ injury is a hotspot in the surgical field. In clinical practice, the main complicated organ dysfunctions are shock, respiratory failure, renal failure, encephalopathy, with the rate of hepatic diseases being closely next to them. The hepatic injury caused by SAP cannot only aggravate the state of pancreatitis, but also develop into hepatic failure and cause patient death. Its complicated pathogenic mechanism is an obstacle in clinical treatment. Among many pathogenic factors, the changes of vasoactive substances, participation of inflammatory mediators as well as OFR (oxygen free radical), endotoxin, etc. may play important roles in its progression.

  18. Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis

    PubMed Central

    Wu, Xian-lin; Li, Jie-xing; Li, Zhen-dong; Liu, Da-sheng; Lu, Su-hong; Liu, Kang-li; Duan, Hong-yan; Luo, Yu-hong

    2015-01-01

    Tet is a type of alkaloid extracted from Stephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP). The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance. PMID:26557854

  19. Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis.

    PubMed

    Wu, Xian-Lin; Li, Jie-Xing; Li, Zhen-Dong; Liu, Da-Sheng; Lu, Su-Hong; Liu, Kang-Li; Duan, Hong-Yan; Luo, Yu-Hong

    2015-01-01

    Tet is a type of alkaloid extracted from Stephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP). The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance. PMID:26557854

  20. Spatial dynamics of an epidemic of severe acute respiratory syndrome in an urban area.

    PubMed Central

    Wang, Jinfeng; McMichael, Anthony J.; Meng, Bin; Becker, Niels G.; Han, Weiguo; Glass, Kathryn; Wu, Jilei; Liu, Xuhua; Liu, Jiyuan; Li, Xiaowen; Zheng, Xiaoying

    2006-01-01

    OBJECTIVE: To map risk of exposure to severe acute respiratory syndrome (SARS) in an urban area and assess the ability of traditional interventions to control dispersion of the disease. METHODS: Data on the Beijing SARS epidemic were used to map spatial clusters of identified contacts and to estimate transmission of SARS using a model with a time-dependent transmission rate. RESULTS: The estimated transmission rate decreased dramatically from 20 to 30 April 2003. The total number of cases in the epidemic in Beijing was estimated to be 2521. Hierarchical clustering revealed that risk-exposures were widespread, but clustered in a pattern that is distinctly related to the Beijing urban ring roads. CONCLUSION: Traditional control measures can be very effective at reducing transmission of SARS. Spatial patterns of risk-exposures can inform disease surveillance, prediction and control by identifying spatial target areas on which interventions should be focused. PMID:17242832

  1. Acute Onset Peripartum Cardiomyopathy in a Woman with Severe Pre-eclamptia: A Diagnostic Dilemma

    PubMed Central

    Basak, Sonela; Rudra, Pallab

    2013-01-01

    Peripartum cardiomyopathy (PPCM) is a form of dilated cardiomyopathy that can present as acute life-threatening pulmonary oedema in late pregnancy or early puerperium, its diagnosis is mainly by exclusion of other causes. Morbidity is high due to the reduced physiological reserve in pregnancy. PPCM and severe pre-eclampsia can co-exist and their clinical presentation may overlap, making the diagnosis more difficult and often delayed, with potentially devastating consequences. Here, we would like to share our experience of such a case and present to the readers how we dealt with the challenge. As obstetricians we often do not resort to transthoracic echocardiography, which in our case prompted the diagnosis timely. Lateral thinking and a heightened suspicion does help. Proper diagnosis is extremely important not only for the immediate appropriate management but also for advising long-term lifestyle modifications to minimize risk and counselling for future pregnancy.

  2. Cardiac K(ATP) channel alterations associated with acclimation to hypoxia in goldfish (Carassius auratus L.).

    PubMed

    Cameron, John S; DeWitt, Judy Park; Ngo, Thanh Thu; Yajnik, Tanya; Chan, Stefanie; Chung, Emma; Kang, Esther

    2013-04-01

    Goldfish (Carassius auratus L.) are highly tolerant of environmental hypoxia, and with appropriate acclimation may survive and remain active for several days in the complete absence of oxygen. Previous work suggests that the hypoxia-induced activation of cardiac ATP-sensitive potassium (KATP) channels serves to increase tolerance of low oxygen in many species. For goldfish, we have previously characterized a nitric oxide (NO)- and cGMP-dependent pathway by which this channel activation occurs in acute hypoxia. The purpose of the present study was to resolve alterations in KATP channel activity and relevant gene expression in response to acclimation under moderately hypoxic conditions (2.6mg O2/L for seven days at 22°C). Intracellular action potential duration in excised ventricles from hypoxia-acclimated animals was significantly (p<0.05) reduced at both 50% and 90% of full repolarization relative to those from normoxia-acclimated fish. In cell-attached ventricular membrane patches from hypoxia-acclimated goldfish, sarcolemmal KATP channel open probability (NPo) was significantly enhanced vs. control. Of the two genes coding for the pore-forming subunits of cardiac KATP channels (Kir6.1 and Kir6.2), mRNA transcription of kcnj8 (revealed by quantitative real-time PCR) was unchanged while kcnj11 was downregulated in response to chronic low oxygen. The mRNA levels for hif1a (hypoxia inducible factor 1α) in the hearts of hypoxia-acclimated fish were significantly enhanced, as was nitric oxide synthase (nos2) and the sulfonylurea receptor regulatory subunit (sur2, abcc9). These data suggest that prior whole-animal acclimation to chronic hypoxia enhances cardioprotective sarcolemmal KATP currents by altering transcription of regulatory proteins.

  3. [Risk factors for severe acute lower respiratory tract infection in Bogota, 2001].

    PubMed

    Jaimes, María Belén; Cáceres, Diana C; de la Hoz, Fernando; Gutiérrez, Camilo; Herrera, Diana; Pinilla, Jairo; Porras, Alexandra; Rodríguez, Fabio; Velandia, Martha

    2003-09-01

    Severity of acute respiratory infection is higher in developing countries, especially among the socioeconomically underprivileged. Viral pneumonias are more common, especially among children. A prospective hospital-based case control study was undertaken in Bogota between November 2000 and August 2001, aimed to identify factors related to severe low acute respiratory infection (SLARI). Cases were limited to children aged between 2 months and 5 years who filled WHO criteria for SLARI. Controls were children at the same hospital with ARI in a similar age range, but without symptoms of chest drawing. A total of 638 children (277 cases and 361 controls) were included. The most important risk factors included the following: living in borrowed houses (odds ratio (OR) = 2.7; 95% Confidence Interval (CI): 1.06-7.07), sharing the bed (OR = 1.88, CI: 1.0-3.7), living with more than 9 people (OR = 1.82, CI: 1.0-3.51), and living with smokers (OR = 1.4, CI: 1.0-2.05). Of the 114 samples collected (from children at third day after beginning of symptoms), 98 had viruses, sincitial respiratory virus was the most frequently identified virus (41.8%), followed by influenza A virus (3.1%) and influenza B virus (1%). All positive isolates for influenza A and B were sent to the United States Center for Disease Control (CDC) in Atlanta, where they were classified as influenza A/PANAMA/2007/99-like and influenza B/SICHUAN/379/99-like, respectively. PMID:14582331

  4. [Risk factors for severe acute lower respiratory tract infection in Bogota, 2001].

    PubMed

    Jaimes, María Belén; Cáceres, Diana C; de la Hoz, Fernando; Gutiérrez, Camilo; Herrera, Diana; Pinilla, Jairo; Porras, Alexandra; Rodríguez, Fabio; Velandia, Martha

    2003-09-01

    Severity of acute respiratory infection is higher in developing countries, especially among the socioeconomically underprivileged. Viral pneumonias are more common, especially among children. A prospective hospital-based case control study was undertaken in Bogota between November 2000 and August 2001, aimed to identify factors related to severe low acute respiratory infection (SLARI). Cases were limited to children aged between 2 months and 5 years who filled WHO criteria for SLARI. Controls were children at the same hospital with ARI in a similar age range, but without symptoms of chest drawing. A total of 638 children (277 cases and 361 controls) were included. The most important risk factors included the following: living in borrowed houses (odds ratio (OR) = 2.7; 95% Confidence Interval (CI): 1.06-7.07), sharing the bed (OR = 1.88, CI: 1.0-3.7), living with more than 9 people (OR = 1.82, CI: 1.0-3.51), and living with smokers (OR = 1.4, CI: 1.0-2.05). Of the 114 samples collected (from children at third day after beginning of symptoms), 98 had viruses, sincitial respiratory virus was the most frequently identified virus (41.8%), followed by influenza A virus (3.1%) and influenza B virus (1%). All positive isolates for influenza A and B were sent to the United States Center for Disease Control (CDC) in Atlanta, where they were classified as influenza A/PANAMA/2007/99-like and influenza B/SICHUAN/379/99-like, respectively.

  5. Safety and Efficacy of Acute Clopidogrel Load in Patients with Moderate and Severe Ischemic Strokes

    PubMed Central

    Monlezun, Dominique J.; Rincon, Natalia; Tiu, Jonathan; Valmoria, Melisa

    2016-01-01

    Objective. To study the safety and efficacy of a clopidogrel loading dose in patients with moderate and severe acute ischemic strokes. Background. The safety of clopidogrel loading has been extensively investigated in patients with minor strokes and transient ischemic attacks. Methods. Acute ischemic stroke patients presenting consecutively to our center from 07/01/08 to 07/31/13 were screened. Clopidogrel loading was defined as at least 300 mg dose (with or without aspirin) given within 6 hours of admission. We compared outcomes in patients with baseline NIHSS > 3 with and without clopidogrel loading. Results. Inclusion criteria were met for 1011 patients (43.6% females, 69.1% black, median age 63). Patients with clopidogrel loading had lower baseline NIHSS than patients who were not loaded (8 versus 9, p = 0.005). The two groups had similar risk for hemorrhagic transformation (p = 0.918) and symptomatic hemorrhage (p = 0.599). Patients who were loaded had a lower rate of neurological worsening (38.9% versus 48.3%, p = 0.031) and less in-hospital mortality (4.3% versus 13.4%, p = 0.001) compared to those who were not loaded. The likelihood of having a poor functional outcome did not differ between the two groups after adjusting for NIHSS on admission (OR = 0.71, 95% CI 0.4633–1.0906, p = 0.118). Conclusion. Clopidogrel loading dose was not associated with increased risk for hemorrhagic transformation or symptomatic intracranial hemorrhage in our retrospective study and was associated with reduced rates of neuroworsening following moderate and severe stroke.

  6. Severe but reversible acute kidney injury resulting from Amanita punctata poisoning

    PubMed Central

    Kang, Eunjung; Cheong, Ka-Young; Lee, Min-Jeong; Kim, Seirhan; Shin, Gyu-Tae; Kim, Heungsoo; Park, In-Whee

    2015-01-01

    Mushroom-related poisoning can cause acute kidney injury. Here we report a case of acute kidney injury after ingestion of Amanita punctata, which is considered an edible mushroom. Gastrointestinal symptoms occurred within 24 hours from the mushroom intake and were followed by an asymptomatic period, acute kidney injury, and elevation of liver and pancreatic enzymes. Kidney function recovered with supportive care. Nephrotoxic mushroom poisoning should be considered as a cause of acute kidney injury. PMID:26779427

  7. Severe Acute Respiratory Illness (SARI) Surveillance in Louisiana, 2013-2014.

    PubMed

    Hand, Julie P; Serrano, Jose; Johnson, Jenna I; Jespersen, Megan; Ratard, Raoult C

    2015-01-01

    The objectives of this article are to describe the severe acute respiratory illness (SARI) surveillance implemented in Louisiana during the 2013-2014 influenza season, present the epidemiology of reported SARI cases, and identify ways to improve this system by incorporating formal SARI surveillance into the influenza surveillance program. Of the 212 SARI cases, 181 (85%) had at least one underlying medical condition, 54 (25.7%) had two conditions, 43 (20.3%) had three conditions, and 25 (11.8%) reported four or more. The most common four underlying conditions were: obesity (43.4%), chronic cardiac conditions (39.6%), diabetes (29.7%), and chronic pulmonary conditions (26.9%). While obesity was the most reported underlying condition, it was three times more likely to be reported in less than 65 years old rather than those >65. Continuation of SARI data collection in future seasons will allow comparisons regarding severity, populations affected, and identify risk factors most commonly associated with severe illness. Reporting of SARI cases also increased influenza-associated adult mortality reporting to the Office of Public Health's Office of Infectious Diseases Epidemiology (ID Epi). Though all influenza-associated mortality is reportable in Louisiana, adult mortality was reported rarely prior to the 2013-2014 season. PMID:27159455

  8. Cortisol levels and the severity and outcomes of acute stroke: a systematic review.

    PubMed

    Barugh, Amanda Jayne; Gray, Paul; Shenkin, Susan Deborah; MacLullich, Alasdair Maurice Joseph; Mead, Gillian Elizabeth

    2014-03-01

    Studies in non-stroke patients have shown an association between dysregulation of the hypothalamic-pituitary-adrenal axis and morbidity and mortality. We conducted a systematic review to evaluate cortisol levels in acute stroke and their associations with outcome. We searched MEDLINE and EMBASE for articles up to April 2013 and PsychINFO for articles up to July 2013, using the keywords "cortisol" and "stroke" and associated terms or synonyms. We included studies published in peer-reviewed journals that recruited 10 or more participants and measured cortisol at least once in the first year following stroke. Data were extracted regarding cortisol levels, including changes over time and their relationship to stroke severity, and outcome. Of 11,240 abstracts, 101 full texts were obtained and 48 fulfilled our inclusion criteria. Cortisol levels were high in the first week after stroke in the majority of studies (26 studies, n = 1,340). Higher cortisol was associated with dependency (8/11 studies, n = 822), delirium (5/6 studies, n = 269) depression (3/5 studies n = 117) and mortality (8/10 studies, n = 856). Five studies adjusted for stroke severity; one found an association between higher cortisol and dependency, and three found an association between higher cortisol and mortality. Cortisol levels are high for at least 7 days after stroke. Elevated cortisol after stroke is associated with dependency, morbidity, and mortality; however, there is insufficient evidence to conclude that these relationships are independent of stroke severity.

  9. Diagnosis of acute myeloid leukemia in a dental hospital; report of a case with severe gingival hypertrophy.

    PubMed

    Misirlioglu, M; Adisen, M Z; Yilmaz, S

    2015-01-01

    Acute myeloid leukemias (AMLs) are aggressive hematopoietic neoplasms that, if untreated, can lead to death within days. Owing to its high morbidity rate, early diagnosis and appropriate medical therapy is essential. Oral lesions may be the presenting feature of acute leukemias and are, therefore, important diagnostic indicators of the disease. Erythematous or cyanotic gingival hyperplasia with or without necrosis is reported to be the most consistent symptom leading to a diagnosis of acute leukemia that directs the patient to seek early dental consultation. This report refers to a patient with AML that was provisionally diagnosed in the dental hospital due to severe gingival enlargements.

  10. Soluble P-selectin promotes acute myocardial infarction onset but not severity.

    PubMed

    Guo, Ling; Sun, Guizhi; Wang, Guoyu; Ning, Wenhu; Zhao, Kan

    2015-03-01

    P‑selectin, an integral membrane glycoprotein of platelets and endothelial cells, and the soluble form of P‑selectin are hypothesized to play a role in the initiation of atherosclerosis and acute myocardial infarction (AMI). However, limited data are available with which to evaluate the main role of soluble P‑selectin (sP‑selectin) in the onset or the severity of AMI. In the present study, we investigated 15 patients who suffered from angina, 10 patients who underwent percutaneous coronary intervention (PCI) therapy and 10 patients who underwent thrombolysis therapy, compared with 15 volunteers with no cardiovascular disease. We confirmed that the plasma sP‑selectin levels were increased in patients with obesity (particularly pericardial obesity) and hyperlipidemia, positively correlated with plasma tumor necrosis factor (TNF)‑α and strongly negatively correlated with adiponectin in all patients regardless of AMI status. Furthermore, sP‑selectin levels were significantly higher in PCI and thrombolysis patients compared with angina patients and the control cohort. However, we observed that sP‑selectin levels did not change following PCI and thrombolysis therapy. In addition, there was no correlation between sP‑selectin levels and the severity of AMI in the cohort which received PCI or thrombolysis therapy. Therefore, we deduced that sP‑selectin only induced the onset of AMI but did not promote its severity. To confirm this hypothesis, a P‑selectin inhibitor was administered to an atherosclerosis formation model, plaque rapture model and neointimal hyperplasia model. We revealed that atherosclerotic plaque formation and rupture, neointimal formation and neointimal bleeding were suppressed by the sP‑selectin inhibitor. We concluded that sP‑selectin, induced by systemic inflammation in conditions including obesity and hyperlipidemia, promoted atherosclerotic plaque and neointimal formation, plaque rapture and neointimal bleeding, further

  11. Severity of Acute Respiratory Distress Syndrome in haematology patients: long-term impact and early predictive factors.

    PubMed

    Lagier, D; Platon, L; Chow-Chine, L; Sannini, A; Bisbal, M; Brun, J-P; Blache, J-L; Faucher, M; Mokart, D

    2016-09-01

    Severe forms of acute respiratory distress syndrome in patients with haematological diseases expose clinicians to specific medical and ethical considerations. We prospectively followed 143 patients with haematological malignancies, and whose lungs were mechanically ventilated for more than 24 h, over a 5-y period. We sought to identify prognostic factors of long-term outcome, and in particular to evaluate the impact of the severity of acute respiratory distress syndrome in these patients. A secondary objective was to identify the early (first 48 h from ICU admission) predictive factors for acute respiratory distress syndrome severity. An evolutive haematological disease (HR 1.71; 95% CI 1.13-2.58), moderate to severe acute respiratory distress syndrome (HR 1.81; 95% CI 1.13-2.69) and need for renal replacement therapy (HR 2.24; 95% CI 1.52-3.31) were associated with long-term mortality. Resolution of neutropaenia during ICU stay (HR 0.63; 95% CI 0.42-0.94) and early microbiological documentation (HR 0.62; 95% CI 0.42-0.91) were associated with survival. The extent of pulmonary infiltration observed on the first chest X-ray and the diagnosis of invasive fungal infection were the most relevant early predictive factors of the severity of acute respiratory distress syndrome.

  12. Severity of Acute Respiratory Distress Syndrome in haematology patients: long-term impact and early predictive factors.

    PubMed

    Lagier, D; Platon, L; Chow-Chine, L; Sannini, A; Bisbal, M; Brun, J-P; Blache, J-L; Faucher, M; Mokart, D

    2016-09-01

    Severe forms of acute respiratory distress syndrome in patients with haematological diseases expose clinicians to specific medical and ethical considerations. We prospectively followed 143 patients with haematological malignancies, and whose lungs were mechanically ventilated for more than 24 h, over a 5-y period. We sought to identify prognostic factors of long-term outcome, and in particular to evaluate the impact of the severity of acute respiratory distress syndrome in these patients. A secondary objective was to identify the early (first 48 h from ICU admission) predictive factors for acute respiratory distress syndrome severity. An evolutive haematological disease (HR 1.71; 95% CI 1.13-2.58), moderate to severe acute respiratory distress syndrome (HR 1.81; 95% CI 1.13-2.69) and need for renal replacement therapy (HR 2.24; 95% CI 1.52-3.31) were associated with long-term mortality. Resolution of neutropaenia during ICU stay (HR 0.63; 95% CI 0.42-0.94) and early microbiological documentation (HR 0.62; 95% CI 0.42-0.91) were associated with survival. The extent of pulmonary infiltration observed on the first chest X-ray and the diagnosis of invasive fungal infection were the most relevant early predictive factors of the severity of acute respiratory distress syndrome. PMID:27418297

  13. Spectrum, antibiotic susceptibility and virulence factors of bacterial infections complicating severe acute pancreatitis.

    PubMed

    Israil, A M; Palade, R; Chifiriuc, M C; Vasile, D; Grigoriu, M; Voiculescu, D; Popa, D

    2011-01-01

    Secondary infection of pancreatic necrotic tissue and peripancreatic fluid is a serious complication of acute pancreatitis resulting in significant morbidity and mortality. The aim of this study was to find out the spectrum of bacterial infections, their antibiotic susceptibility patterns and virulence features in patients with severe acute pancreatitis (SAP). A total of 19 patients with acute pancreatitis were consecutively selected from 153 clinical cases of septic abdominal surgical emergencies (age 29-80, 12 males, 7 females) admitted during 2009-2011, in the First Surgical Clinic of the University Emergency Hospital of Bucharest. All 19 SAP cases were submitted to pre-operatory antibiotic empiric treatment. Ten cases were culture negative, in spite of the positive microscopy registered in eight of them. The rest of nine cases were culture positive, 17 different bacterial strains being isolated and identified as belonging to eight aerobic and four anaerobic species. Polymicrobial infection was seen in six patients and the etiology was dominated by Gram-negative bacilli, followed by gut anaerobic bacteria, attesting their colonic origin. The susceptibility testing of the isolated strains confirmed in vitro in all cases the efficiency of the antibiotics that had been used in the empiric pre-operatory treatment. Out of 19 cases submitted to pre-operatory empiric treatment, 14 proved a favorable evolution and five a lethal outcome. The host depending factors (sepsis and other co-morbidities), as well as the aggressivity of the isolated microbial strains (mediated by the presence of different factors implicated in adherence, toxicity and invasion) were found to contribute to the unfavorable, even lethal clinical outcome of SAP cases. In spite of all theoretical controversies, the antibiotic therapy remains at present a very important therapeutic mean for the SAP treatment; although it cannot solve the septic necrotizing pancreatitis in 100% of cases, however

  14. Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis.

    PubMed

    Nieto-Torres, Jose L; DeDiego, Marta L; Verdiá-Báguena, Carmina; Jimenez-Guardeño, Jose M; Regla-Nava, Jose A; Fernandez-Delgado, Raul; Castaño-Rodriguez, Carlos; Alcaraz, Antonio; Torres, Jaume; Aguilella, Vicente M; Enjuanes, Luis

    2014-05-01

    Deletion of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) envelope (E) gene attenuates the virus. E gene encodes a small multifunctional protein that possesses ion channel (IC) activity, an important function in virus-host interaction. To test the contribution of E protein IC activity in virus pathogenesis, two recombinant mouse-adapted SARS-CoVs, each containing one single amino acid mutation that suppressed ion conductivity, were engineered. After serial infections, mutant viruses, in general, incorporated compensatory mutations within E gene that rendered active ion channels. Furthermore, IC activity conferred better fitness in competition assays, suggesting that ion conductivity represents an advantage for the virus. Interestingly, mice infected with viruses displaying E protein IC activity, either with the wild-type E protein sequence or with the revertants that restored ion transport, rapidly lost weight and died. In contrast, mice infected with mutants lacking IC activity, which did not incorporate mutations within E gene during the experiment, recovered from disease and most survived. Knocking down E protein IC activity did not significantly affect virus growth in infected mice but decreased edema accumulation, the major determinant of acute respiratory distress syndrome (ARDS) leading to death. Reduced edema correlated with lung epithelia integrity and proper localization of Na+/K+ ATPase, which participates in edema resolution. Levels of inflammasome-activated IL-1β were reduced in the lung airways of the animals infected with viruses lacking E protein IC activity, indicating that E protein IC function is required for inflammasome activation. Reduction of IL-1β was accompanied by diminished amounts of TNF and IL-6 in the absence of E protein ion conductivity. All these key cytokines promote the progression of lung damage and ARDS pathology. In conclusion, E protein IC activity represents a new determinant for SARS-CoV virulence. PMID:24788150

  15. Acute toxicity of zinc to several aquatic species native to the Rocky Mountains.

    PubMed

    Brinkman, Stephen F; Johnston, Walter D

    2012-02-01

    National water-quality criteria for the protection of aquatic life are based on toxicity tests, often using organisms that are easy to culture in the laboratory. Species native to the Rocky Mountains are poorly represented in data sets used to derive national water-quality criteria. To provide additional data on the toxicity of zinc, several laboratory acute-toxicity tests were conducted with a diverse assortment of fish, benthic invertebrates, and an amphibian native to the Rocky Mountains. Tests with fish were conducted using three subspecies of cutthroat trout (Colorado River cutthroat trout Oncorhynchus clarkii pleuriticus, greenback cutthroat trout O. clarkii stomias, and Rio Grande cutthroat trout O. clarkii virginalis), mountain whitefish (Prosopium williamsoni), mottled sculpin (Cottus bairdi), longnose dace (Rhinichthys cataractae), and flathead chub (Platygobio gracilis). Aquatic invertebrate tests were conducted with mayflies (Baetis tricaudatus, Drunella doddsi, Cinygmula sp. and Ephemerella sp.), a stonefly (Chloroperlidae), and a caddis fly (Lepidostoma sp.). The amphibian test was conducted with tadpoles of the boreal toad (Bufo boreas). Median lethal concentrations (LC(50)s) ranged more than three orders of magnitude from 166 μg/L for Rio Grande cutthroat trout to >67,000 μg/L for several benthic invertebrates. Of the organisms tested, vertebrates were the most sensitive, and benthic invertebrates were the most tolerant. PMID:21811884

  16. Serum Levels of Substance P and Mortality in Patients with a Severe Acute Ischemic Stroke.

    PubMed

    Lorente, Leonardo; Martín, María M; Almeida, Teresa; Pérez-Cejas, Antonia; Ramos, Luis; Argueso, Mónica; Riaño-Ruiz, Marta; Solé-Violán, Jordi; Hernández, Mariano

    2016-01-01

    Substance P (SP), a member of tachykinin family, is involved in the inflammation of the central nervous system and in the appearance of cerebral edema. Higher serum levels of SP have been found in 18 patients with cerebral ischemia compared with healthy controls. The aim of our multi-center study was to analyze the possible association between serum levels of SP and mortality in ischemic stroke patients. We included patients with malignant middle cerebral artery infarction (MMCAI) and a Glasgow Coma Scale (GCS) lower than 9. Non-surviving patients at 30 days (n = 31) had higher serum concentrations of SP levels at diagnosis of severe MMCAI than survivors (n = 30) (p < 0.001). We found in multiple regression an association between serum concentrations of SP higher than 362 pg/mL and mortality at 30 days (Odds Ratio = 5.33; 95% confidence interval = 1.541-18.470; p = 0.008) after controlling for age and GCS. Thus, the major novel finding of our study was the association between serum levels of SP and mortality in patients suffering from severe acute ischemic stroke. PMID:27338372

  17. A case of severe acute exacerbation of Yokkaichi asthma treated with a vibrating mesh nebulizer.

    PubMed

    Yano, Takeshi; Yonaha, Tetsu; Hidaka, Koutaro; Nagahama, Masumi; Koshida, Tomohiro; Matsuoka, Hiroshi; Taniguchi, Masahiko; Tsuneyoshi, Isao

    2016-01-01

    Yokkaichi asthma was one of the most common environmental pollution diseases in Japan in the 1960s and 1970s. The problem of air pollution in Yokkaichi was solved in the 1970s. However, mortality and life expectancy were still affected by the late effects of air pollution in patients with Yokkaichi asthma even in the 2000s. In this case report, we described the experience of successful treatment of a patient with severe asthmatic status due to Yokkaichi asthma. A 40s-year-old man, who was officially certified as a patient with Yokkaichi asthma from his infancy, was admitted to hospital due to acute exacerbation of asthma. Mechanical ventilation, intravenous administration of aminophylline and dexamethasone, enteral administration of montelukast, and a transdermal patch of tulobuterol were started. However, because of the lack of improvement in clinical status, inhalation of procaterol using vibrating mesh nebulizer systems was started. Inhalation of procaterol was used three times a day. After using the vibrating mesh nebulizer, respiratory system compliance and hypercapnia rapidly improved. Bilateral expiratory wheezing was diminished. Weaning from mechanical ventilation was initiated, and on the eighth day of mechanical ventilation, the patient was extubated. Although intractable respiratory failure with decreased respiratory system compliance resulting from the late effects of air pollution and a long-time asthmatic inflammatory condition was observed, the use of a vibrating mesh nebulizer for the inhaled administration of procaterol was useful to relieve severe bronchospasm due to Yokkaichi asthma. PMID:27547723

  18. Serum Levels of Substance P and Mortality in Patients with a Severe Acute Ischemic Stroke

    PubMed Central

    Lorente, Leonardo; Martín, María M.; Almeida, Teresa; Pérez-Cejas, Antonia; Ramos, Luis; Argueso, Mónica; Riaño-Ruiz, Marta; Solé-Violán, Jordi; Hernández, Mariano

    2016-01-01

    Substance P (SP), a member of tachykinin family, is involved in the inflammation of the central nervous system and in the appearance of cerebral edema. Higher serum levels of SP have been found in 18 patients with cerebral ischemia compared with healthy controls. The aim of our multi-center study was to analyze the possible association between serum levels of SP and mortality in ischemic stroke patients. We included patients with malignant middle cerebral artery infarction (MMCAI) and a Glasgow Coma Scale (GCS) lower than 9. Non-surviving patients at 30 days (n = 31) had higher serum concentrations of SP levels at diagnosis of severe MMCAI than survivors (n = 30) (p < 0.001). We found in multiple regression an association between serum concentrations of SP higher than 362 pg/mL and mortality at 30 days (Odds Ratio = 5.33; 95% confidence interval = 1.541–18.470; p = 0.008) after controlling for age and GCS. Thus, the major novel finding of our study was the association between serum levels of SP and mortality in patients suffering from severe acute ischemic stroke. PMID:27338372

  19. Increased Gut Redox and Depletion of Anaerobic and Methanogenic Prokaryotes in Severe Acute Malnutrition

    PubMed Central

    Million, Matthieu; Tidjani Alou, Maryam; Khelaifia, Saber; Bachar, Dipankar; Lagier, Jean-Christophe; Dione, Niokhor; Brah, Souleymane; Hugon, Perrine; Lombard, Vincent; Armougom, Fabrice; Fromonot, Julien; Robert, Catherine; Michelle, Caroline; Diallo, Aldiouma; Fabre, Alexandre; Guieu, Régis; Sokhna, Cheikh; Henrissat, Bernard; Parola, Philippe; Raoult, Didier

    2016-01-01

    Severe acute malnutrition (SAM) is associated with inadequate diet, low levels of plasma antioxidants and gut microbiota alterations. The link between gut redox and microbial alterations, however, remains unexplored. By sequencing the gut microbiomes of 79 children of varying nutritional status from three centers in Senegal and Niger, we found a dramatic depletion of obligate anaerobes in malnutrition. This was confirmed in an individual patient data meta-analysis including 107 cases and 77 controls from 5 different African and Asian countries. Specifically, several species of the Bacteroidaceae, Eubacteriaceae, Lachnospiraceae and Ruminococceae families were consistently depleted while Enterococcus faecalis, Escherichia coli and Staphylococcus aureus were consistently enriched. Further analyses on our samples revealed increased fecal redox potential, decreased total bacterial number and dramatic Methanobrevibacter smithii depletion. Indeed, M. smithii was detected in more than half of the controls but in none of the cases. No causality was demonstrated but, based on our results, we propose a unifying theory linking microbiota specificity, lacking anaerobes and archaea, to low antioxidant nutrients, and lower food conversion. PMID:27183876

  20. Upwelling-driven nearshore hypoxia signals ecosystem and oceanographic changes in the northeast Pacific.

    PubMed

    Grantham, Brian A; Chan, Francis; Nielsen, Karina J; Fox, David S; Barth, John A; Huyer, Adriana; Lubchenco, Jane; Menge, Bruce A

    2004-06-17

    Seasonal development of dissolved-oxygen deficits (hypoxia) represents an acute system-level perturbation to ecological dynamics and fishery sustainability in coastal ecosystems around the globe. Whereas anthropogenic nutrient loading has increased the frequency and severity of hypoxia in estuaries and semi-enclosed seas, the occurrence of hypoxia in open-coast upwelling systems reflects ocean conditions that control the delivery of oxygen-poor and nutrient-rich deep water onto continental shelves. Upwelling systems support a large proportion of the world's fisheries, therefore understanding the links between changes in ocean climate, upwelling-driven hypoxia and ecological perturbations is critical. Here we report on the unprecedented development of severe inner-shelf (<70 m) hypoxia and resultant mass die-offs of fish and invertebrates within the California Current System. In 2002, cross-shelf transects revealed the development of abnormally low dissolved-oxygen levels as a response to anomalously strong flow of subarctic water into the California Current System. Our findings highlight the sensitivity of inner-shelf ecosystems to variation in ocean conditions, and the potential impacts of climate change on marine communities.

  1. Hypoxia signaling--license to metastasize.

    PubMed

    Vanharanta, Sakari; Massagué, Joan

    2013-10-01

    Hypoxia-inducible factors (HIF) have long been linked to malignant tumor phenotypes in various cancer types, and several downstream mediators of HIF action are deregulated in metastatic carcinomas. A new study links hypoxia-induced collagen remodeling to sarcoma progression, providing evidence for unifying mechanisms of carcinoma and sarcoma metastasis. PMID:24124230

  2. Hypoxia and fatty liver.

    PubMed

    Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito

    2014-11-01

    The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty liver disease, a major cause of chronic liver diseases worldwide, ranging from simple steatosis, through steatohepatitis and hepatic fibrosis, to liver cirrhosis. Altered hepatic metabolism and tissue remodeling in fatty liver disease further disrupt hepatic oxygen homeostasis, resulting in severe liver hypoxia. As master regulators of adaptive responses to hypoxic stress, hypoxia-inducible factors (HIFs) modulate various cellular and organ functions, including erythropoiesis, angiogenesis, metabolic demand, and cell survival, by activating their target genes during fetal development and also in many disease conditions such as cancer, heart failure, and diabetes. In the past decade, it has become clear that HIFs serve as key factors in the regulation of lipid metabolism and fatty liver formation. This review discusses the molecular mechanisms by which hypoxia and HIFs regulate lipid metabolism in the development and progression of fatty liver disease. PMID:25386057

  3. Hydrogen-rich saline attenuates acute renal injury in sodium taurocholate-induced severe acute pancreatitis by inhibiting ROS and NF-κB pathway.

    PubMed

    Shi, Qiao; Liao, Kang-Shu; Zhao, Kai-Liang; Wang, Wei-Xing; Zuo, Teng; Deng, Wen-Hong; Chen, Chen; Yu, Jia; Guo, Wen-Yi; He, Xiao-Bo; Abliz, Ablikim; Wang, Peng; Zhao, Liang

    2015-01-01

    Hydrogen (H2), a new antioxidant, was reported to reduce (•)OH and ONOO(-) selectively and inhibit certain proinflammatory mediators to product, without disturbing metabolic redox reactions or ROS involved in cell signaling. We herein aim to explore its protective effects on acute renal injury in sodium taurocholate-induced acute pancreatitis and its possible mechanisms. Rats were injected with hydrogen-rich saline (HRS group) or normal saline (SO and SAP group) through tail intravenously (6 mL/kg) and compensated subcutaneously (20 mL/kg) after successful modeling. Results showed that hydrogen-rich saline attenuated the following: (1) serum Cr and BUN, (2) pancreatic and renal pathological injuries, (3) renal MDA, (4) renal MPO, (5) serum IL-1β, IL-6, and renal TNF-α, HMGB1, and (6) tyrosine nitration, IκB degradation, and NF-κB activation in renal tissues. In addition, it increased the level of IL-10 and SOD activity in renal tissues. These results proved that hydrogen-rich saline attenuates acute renal injury in sodium taurocholate-induced acute pancreatitis, presumably because of its detoxification activity against excessive ROS, and inhibits the activation of NF-κB by affecting IκB nitration and degradation. Our findings highlight the potential value of hydrogen-rich saline as a new therapeutic method on acute renal injury in severe acute pancreatitis clinically.

  4. Hydrogen-Rich Saline Attenuates Acute Renal Injury in Sodium Taurocholate-Induced Severe Acute Pancreatitis by Inhibiting ROS and NF-κB Pathway

    PubMed Central

    Shi, Qiao; Liao, Kang-Shu; Zhao, Kai-Liang; Zuo, Teng; Deng, Wen-Hong; Chen, Chen; Yu, Jia; Guo, Wen-Yi; He, Xiao-Bo; Abliz, Ablikim; Wang, Peng; Zhao, Liang

    2015-01-01

    Hydrogen (H2), a new antioxidant, was reported to reduce •OH and ONOO− selectively and inhibit certain proinflammatory mediators to product, without disturbing metabolic redox reactions or ROS involved in cell signaling. We herein aim to explore its protective effects on acute renal injury in sodium taurocholate-induced acute pancreatitis and its possible mechanisms. Rats were injected with hydrogen-rich saline (HRS group) or normal saline (SO and SAP group) through tail intravenously (6 mL/kg) and compensated subcutaneously (20 mL/kg) after successful modeling. Results showed that hydrogen-rich saline attenuated the following: (1) serum Cr and BUN, (2) pancreatic and renal pathological injuries, (3) renal MDA, (4) renal MPO, (5) serum IL-1β, IL-6, and renal TNF-α, HMGB1, and (6) tyrosine nitration, IκB degradation, and NF-κB activation in renal tissues. In addition, it increased the level of IL-10 and SOD activity in renal tissues. These results proved that hydrogen-rich saline attenuates acute renal injury in sodium taurocholate-induced acute pancreatitis, presumably because of its detoxification activity against excessive ROS, and inhibits the activation of NF-κB by affecting IκB nitration and degradation. Our findings highlight the potential value of hydrogen-rich saline as a new therapeutic method on acute renal injury in severe acute pancreatitis clinically. PMID:25878401

  5. Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

    PubMed Central

    Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Justicia, Antonio; Rivero-Calle, Irene; Sumner, Edward; Fink, Colin

    2016-01-01

    Background Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. Objectives To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). Methods We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. Results 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. Conclusion The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role. PMID:27096199

  6. Cynomolgus Macaque as an Animal Model for Severe Acute Respiratory Syndrome

    PubMed Central

    Lawler, James V; Endy, Timothy P; Hensley, Lisa E; Garrison, Aura; Fritz, Elizabeth A; Lesar, May; Baric, Ralph S; Kulesh, David A; Norwood, David A; Wasieloski, Leonard P; Ulrich, Melanie P; Slezak, Tom R; Vitalis, Elizabeth; Huggins, John W; Jahrling, Peter B; Paragas, Jason

    2006-01-01

    Background The emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV) infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs) infected with SARS-CoV. Methods and Findings In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain. Conclusions SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children. PMID:16605302

  7. Risk taking in hospitalized patients with acute and severe traumatic brain injury.

    PubMed

    Fecteau, Shirley; Levasseur-Moreau, Jean; García-Molina, Alberto; Kumru, Hatiche; Vergara, Raúl Pelayo; Bernabeu, Monste; Roig, Teresa; Pascual-Leone, Alvaro; Tormos, José Maria

    2013-01-01

    Rehabilitation can improve cognitive deficits observed in patients with traumatic brain injury (TBI). However, despite rehabilitation, the ability of making a choice often remains impaired. Risk taking is a daily activity involving numerous cognitive processes subserved by a complex neural network. In this work we investigated risk taking using the Balloon Analogue Risk Task (BART) in patients with acute TBI and healthy controls. We hypothesized that individuals with TBI will take less risk at the BART as compared to healthy individuals. We also predicted that within the TBI group factors such as the number of days since the injury, severity of the injury, and sites of the lesion will play a role in risk taking as assessed with the BART. Main findings revealed that participants with TBI displayed abnormally cautious risk taking at the BART as compared to healthy subjects. Moreover, healthy individuals showed increased risk taking throughout the task which is in line with previous work. However, individuals with TBI did not show this increased risk taking during the task. We also investigated the influence of three patients' characteristics on their performance at the BART: Number of days post injury, Severity of the head injury, and Status of the frontal lobe. Results indicate that performance at the BART was influenced by the number of days post injury and the status of the frontal lobe, but not by the severity of the head injury. Reported findings are encouraging for risk taking seems to naturally improve with time postinjury. They support the need of conducting longitudinal prospective studies to ultimately identify impaired and intact cognitive skills that should be trained postinjury. PMID:24386232

  8. Metabolite Modulation in Human Plasma in the Early Phase of Acclimatization to Hypobaric Hypoxia

    PubMed Central

    Liao, Wen-Ting; Liu, Bao; Chen, Jian; Cui, Jian-Hua; Gao, Yi-Xing; Liu, Fu-Yu; Xu, Gang; Sun, Bing-Da; Zhang, Er-Long; Yuan, Zhi-Bin; Zhang, Gang; Gao, Yu-Qi

    2016-01-01

    The exposure of healthy subjects to high altitude represents a model to explore the pathophysiology of diseases related to tissue hypoxia. We explored a plasma metabolomics approach to detect alterations induced by the exposure of subjects to high altitude. Plasma samples were collected from 60 subjects both on plain and at high altitude (5300 m). Metabolite profiling was performed by gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS) in conjunction with univariate and multivariate statistical analyses. ELISA assays were further employed to measure the levels of several relevant enzymes together with perturbed metabolic pathways. The results showed that hypobaric hypoxia caused significant and comprehensive metabolic changes, as represented by significant changes of 44 metabolites and 4 relevant enzymes. Using MetaboAnalyst 3.0, it was found that several key metabolic pathways were acutely perturbed. In addition, 5 differentially expressed metabolites in pre-exposure samples from the acute mountain sickness-susceptible (AMS-S) group compared with those from the AMS-resistant (AMS-R) group are identified, which warrant further validation as potential predictive biomarkers for AMS-S individuals. These results provide new insights for further understanding the pathophysiological mechanism of early acclimatization to hypobaric hypoxia and other diseases correlated to tissue hypoxia. PMID:26940428

  9. Tumor Hypoxia: Causative Mechanisms, Microregional Heterogeneities, and the Role of Tissue-Based Hypoxia Markers.

    PubMed

    Vaupel, Peter; Mayer, Arnulf

    2016-01-01

    Tumor hypoxia is a hallmark of solid malignant tumor growth, profoundly influences malignant progression and contributes to the development of therapeutic resistance. Pathogenesis of tumor hypoxia is multifactorial, with contributions from both acute and chronic factors. Spatial distribution of hypoxia within tumors is markedly heterogeneous and often changes over time, e.g., during a course of radiotherapy. Substantial changes in the oxygenation status can occur within the distance of a few cell layers, explaining the inability of currently used molecular imaging techniques to adequately assess this crucial trait. Due to the possible importance of tumor hypoxia for clinical decision-making, there is a great demand for molecular tools which may provide the necessary resolution down to the single cell level. Exogenous and endogenous markers of tumor hypoxia have been investigated for this purpose. Their potential use may be greatly enhanced by multiparametric in situ methods in experimental and human tumor tissue. PMID:27526128

  10. Acute compartment syndrome--presenting as severe pain in an extremity out of proportion with the injury.

    PubMed

    Khan, M; Hodkinson, S L

    1997-10-01

    A 24 year old combat medic was admitted to the field hospital at Tomislavgrad in Bosnia, with a suspected forearm, fracture. Radiographs did not show any bony injury. Clinical examination showed marked swelling and tenderness over the extensor compartment. The pain became more severe over the following 12 hours with the pain becoming most intensely felt in the extensors on passive extension. Fasciotomy for suspected acute compartment syndrome was carried out. Acute compartment syndrome is a common complication of extremity injury, and is a clinical diagnosis which should be suspected in all injuries with marked swelling and severe pain.

  11. Severe acute oxidant exposure: morphological damage and aerobic metabolism in the lung

    SciTech Connect

    Montgomery, M.R.; Teuscher, F.; LaSota, I.; Niewoehner, D.E.

    1986-09-01

    Groups of male rats were exposed to acute doses of oxygen, ozone, or paraquat which produced equivalent mortality (25-30%) over a 28 day post-exposure period. Quantitative evaluation of morphological changes indicated the primary response to be edema and inflammation with only slight fibrosis being apparent by the end of the observation period. Aerobic pulmonary metabolism was inhibited in lungs from animals exposed to oxygen and ozone as evidenced by decreased oxygen consumption; however, this was transient and O/sub 2/ consumption returned to normal within 24 hours after removal from the exposure chamber. Conversely, treatment with paraquat caused an immediate, transient stimulation of O/sub 2/ consumption. Glucose metabolism was unaltered by the gas exposures and, as previously reported, was initially stimulated by paraquat treatment. In vitro, only paraquat altered both O/sub 2/ consumption and glucose metabolism when added to lung slice preparations; ozone had no effect. Oxygen did not alter O/sub 2/ consumption but caused a slight biphasic response in glucose metabolism. Aerobic metabolism is relatively unchanged by these doses of oxygen and ozone which result in the death of 25-30% of all treated animals. Even though paraquat produces similar morphologic changes, it may represent a more severe metabolic insult than ''equivalent'' doses of oxygen or ozone. Also, if interstitial pulmonary fibrosis is a desired result of experimental exposure, rats may not be a suitable model for oxidant induced lung injury.

  12. Severe acute respiratory syndrome: a challenge for public health practice in Hong Kong

    PubMed Central

    Lee, A; Abdullah, A

    2003-01-01

    Severe acute respiratory syndrome (SARS) is now a global challenge affecting more than 8000 patients in different continents. The dictum of public health practice especially for infectious disease is "prevention better than cure". It is especially true for SARS as the treatment strategies remain diverse and experimental. Maintaining a healthy and hygienic environment can be one of the effective public health measures to combat infectious disease. The major challenge is that some of the most important public health measures are to be taken outside the health sector. The community also needs to be strengthened and equipped with the health skills to promote better health and hygiene. There is also the need to create a supportive environment conducive to health for long term sustainability. The WHO approach of promoting health through setting approach would be one possible solution to face the challenge. This paper will describe some of the public health initiatives in Hong Kong through "setting approach" and "community development model" in helping the society fight against SARS. With the emergence of SARS, this might be the time to globalise public health medicine as an important component of medical practice. PMID:12933766

  13. Ulinastatin promotes T lymphocyte apoptosis in rats with severe acute pancreatitis via mitochondrial pathways.

    PubMed

    Wang, C L; Li, N; Ma, T; Zhang, P; You, S Y

    2015-05-25

    We explored the influence of ulinastatin on apoptosis of T lymphocytes in rats with severe acute pancreatitis (SAP) and the effect of ulinastatin on mitochondrial apoptosis pathways in spleen lymphocytes. Thirty-six Wistar rats were randomly divided into three groups (N = 12): a sham operated group, a SAP group, and an ulinastatin-treated SAP group. The SAP model was established by injecting 5% sodium taurocholate into the intrapancreatobiliary duct. Study rats were sacrificed after 24 h, and splenic lymphocytes were then collected. CD4(+) and CD8(+) T lymphocytes were labeled by direct immune fluorescence assays; the percentage of apoptotic cells, mitochondrial membrane potential levels, and mitochondria permeability transition pore opening levels were measured by flow cytometry. In the ulinastatin-treated SAP group, the ratio of CD4(+)/CD8(+) T lymphocytes was significantly higher than that in the SAP group, and the apoptosis percentage of CD4(+) T lymphocytes was significantly decreased. The percentage of lymphocytes with an abnormal opening of the mitochondrial permeability transition pore and lymphocytes with decreased mitochondrial membrane potential in the ulinastatin-treated SAP group were significantly lower than that in the SAP group. Ulinastatin can directly enhance immunological function and attenuate immune suppression in SAP rats through inhibiting the apoptosis of CD4(+) T lymphocytes. These study findings demonstrate that therapeutic effects may occur through inhibiting the apoptosis induced by mitochondrial signaling pathways.

  14. Transmission of severe acute respiratory syndrome in dynamical small-world networks

    NASA Astrophysics Data System (ADS)

    Masuda, Naoki; Konno, Norio; Aihara, Kazuyuki

    2004-03-01

    The outbreak of severe acute respiratory syndrome (SARS) is still threatening the world because of a possible resurgence. In the current situation that effective medical treatments such as antiviral drugs are not discovered yet, dynamical features of the epidemics should be clarified for establishing strategies for tracing, quarantine, isolation, and regulating social behavior of the public at appropriate costs. Here we propose a network model for SARS epidemics and discuss why superspreaders emerged and why SARS spread especially in hospitals, which were key factors of the recent outbreak. We suggest that superspreaders are biologically contagious patients, and they may amplify the spreads by going to potentially contagious places such as hospitals. To avoid mass transmission in hospitals, it may be a good measure to treat suspected cases without hospitalizing them. Finally, we indicate that SARS probably propagates in small-world networks associated with human contacts and that the biological nature of individuals and social group properties are factors more important than the heterogeneous rates of social contacts among individuals. This is in marked contrast with epidemics of sexually transmitted diseases or computer viruses to which scale-free network models often apply.

  15. Coronavirus Pathogenesis and the Emerging Pathogen Severe Acute Respiratory Syndrome Coronavirus

    PubMed Central

    Weiss, Susan R.; Navas-Martin, Sonia

    2005-01-01

    Coronaviruses are a family of enveloped, single-stranded, positive-strand RNA viruses classified within the Nidovirales order. This coronavirus family consists of pathogens of many animal species and of humans, including the recently isolated severe acute respiratory syndrome coronavirus (SARS-CoV). This review is divided into two main parts; the first concerns the animal coronaviruses and their pathogenesis, with an emphasis on the functions of individual viral genes, and the second discusses the newly described human emerging pathogen, SARS-CoV. The coronavirus part covers (i) a description of a group of coronaviruses and the diseases they cause, including the prototype coronavirus, murine hepatitis virus, which is one of the recognized animal models for multiple sclerosis, as well as viruses of veterinary importance that infect the pig, chicken, and cat and a summary of the human viruses; (ii) a short summary of the replication cycle of coronaviruses in cell culture; (iii) the development and application of reverse genetics systems; and (iv) the roles of individual coronavirus proteins in replication and pathogenesis. The SARS-CoV part covers the pathogenesis of SARS, the developing animal models for infection, and the progress in vaccine development and antiviral therapies. The data gathered on the animal coronaviruses continue to be helpful in understanding SARS-CoV. PMID:16339739

  16. 4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis

    PubMed Central

    Guo, Wen-yi; Zhao, Liang; Xiang, Ming-wei; Mei, Fang-chao; Abliz, Ablikim; Hu, Peng; Deng, Wen-hong; Yu, Jia

    2016-01-01

    Endoplasmic reticulum (ER) stress is a particular process with an imbalance of homeostasis, which plays an important role in pancreatitis, but little is known about how ER stress is implicated in severe acute pancreatitis (SAP) induced pancreatic beta-cell injury. To investigate the effect of 4-phenylbutyric acid (4-PBA) on the beta-cell injury following SAP and the underlying mechanism, twenty-four Sprague-Dawley rats were randomly divided into sham-operation (SO) group, SAP model group, and 4-PBA treatment group. SAP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. 4-PBA or normal saline was injected intraperitoneally for 3 days in respective group before successful modeling. Results showed that 4-PBA attenuated the following: (1) pancreas and islet pathological injuries, (2) serum TNF-α and IL-1β, (3) serum insulin and glucose, (4) beta-cell ultrastructural changes, (5) ER stress markers (BiP, ORP150, and CHOP), Caspase-3, and insulin expression in islet. These results suggested that 4-PBA mitigates pancreatic beta-cell injury and endocrine disorder in SAP, presumably because of its role in inhibiting excessive endoplasmic reticulum stress. This may serve as a new therapeutic target for reducing pancreatic beta-cell injury and endocrine disorder in SAP upon 4-PBA treatment.

  17. Infusion of Bone Marrow Mesenchymal Stem Cells Attenuates Experimental Severe Acute Pancreatitis in Rats

    PubMed Central

    Huang, Dandan; Gao, Jun; Gong, Yanfang; Wu, Hongyu; Xu, Aifang

    2016-01-01

    Background & Aims. Severe acute pancreatitis (SAP) remains a high-mortality disease. Bone marrow (BM) mesenchymal stem cells (MSCs) have been demonstrated to have plasticity of transdifferentiation and to have immunomodulatory functions. In the present study, we assessed the roles of MSCs in SAP and the therapeutic effects of MSC on SAP after transplantation. Methods. A pancreatitis rat model was induced by the injection of taurocholic acid (TCA) into the pancreatic duct. After isolation and characterization of MSC from BM, MSC transplantation was conducted 24 hrs after SAP induction by tail vein injection. The survival rate was observed and MSCs were traced after transplantation. The expression of TNF-α and IL-1β mRNA in the transplantation group was also analyzed. Results. The survival rate of the transplantation group was significantly higher compared to the control group (p < 0.05). Infused MSCs were detected in the pancreas and BM 3 days after transplantation. The expression of TNF-α and IL-1β mRNA in the transplantation group was significantly lower than in the control group in both the pancreas and the lungs (p < 0.05). Conclusions. MSC transplantation could improve the prognosis of SAP rats. Engrafted MSCs have the capacity of homing, migration, and planting during the treatment of SAP. PMID:27721836

  18. Severe Acute Respiratory Syndrome Coronavirus as an Agent of Emerging and Reemerging Infection

    PubMed Central

    Cheng, Vincent C. C.; Lau, Susanna K. P.; Woo, Patrick C. Y.; Yuen, Kwok Yung

    2007-01-01

    Before the emergence of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) in 2003, only 12 other animal or human coronaviruses were known. The discovery of this virus was soon followed by the discovery of the civet and bat SARS-CoV and the human coronaviruses NL63 and HKU1. Surveillance of coronaviruses in many animal species has increased the number on the list of coronaviruses to at least 36. The explosive nature of the first SARS epidemic, the high mortality, its transient reemergence a year later, and economic disruptions led to a rush on research of the epidemiological, clinical, pathological, immunological, virological, and other basic scientific aspects of the virus and the disease. This research resulted in over 4,000 publications, only some of the most representative works of which could be reviewed in this article. The marked increase in the understanding of the virus and the disease within such a short time has allowed the development of diagnostic tests, animal models, antivirals, vaccines, and epidemiological and infection control measures, which could prove to be useful in randomized control trials if SARS should return. The findings that horseshoe bats are the natural reservoir for SARS-CoV-like virus and that civets are the amplification host highlight the importance of wildlife and biosecurity in farms and wet markets, which can serve as the source and amplification centers for emerging infections. PMID:17934078

  19. Severe acute respiratory syndrome coronavirus E protein transports calcium ions and activates the NLRP3 inflammasome.

    PubMed

    Nieto-Torres, Jose L; Verdiá-Báguena, Carmina; Jimenez-Guardeño, Jose M; Regla-Nava, Jose A; Castaño-Rodriguez, Carlos; Fernandez-Delgado, Raul; Torres, Jaume; Aguilella, Vicente M; Enjuanes, Luis

    2015-11-01

    Severe acute respiratory syndrome coronavirus (SARS-CoV) envelope (E) protein is a viroporin involved in virulence. E protein ion channel (IC) activity is specifically correlated with enhanced pulmonary damage, edema accumulation and death. IL-1β driven proinflammation is associated with those pathological signatures, however its link to IC activity remains unknown. In this report, we demonstrate that SARS-CoV E protein forms protein-lipid channels in ERGIC/Golgi membranes that are permeable to calcium ions, a highly relevant feature never reported before. Calcium ions together with pH modulated E protein pore charge and selectivity. Interestingly, E protein IC activity boosted the activation of the NLRP3 inflammasome, leading to IL-1β overproduction. Calcium transport through the E protein IC was the main trigger of this process. These findings strikingly link SARS-CoV E protein IC induced ionic disturbances at the cell level to immunopathological consequences and disease worsening in the infected organism.

  20. Severe acute respiratory syndrome coronavirus papain-like protease: Structure of a viral deubiquitinating enzyme

    PubMed Central

    Ratia, Kiira; Saikatendu, Kumar Singh; Santarsiero, Bernard D.; Barretto, Naina; Baker, Susan C.; Stevens, Raymond C.; Mesecar, Andrew D.

    2006-01-01

    Replication of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) requires proteolytic processing of the replicase polyprotein by two viral cysteine proteases, a chymotrypsin-like protease (3CLpro) and a papain-like protease (PLpro). These proteases are important targets for development of antiviral drugs that would inhibit viral replication and reduce mortality associated with outbreaks of SARS-CoV. In this work, we describe the 1.85-Å crystal structure of the catalytic core of SARS-CoV PLpro and show that the overall architecture adopts a fold closely resembling that of known deubiquitinating enzymes. Key features, however, distinguish PLpro from characterized deubiquitinating enzymes, including an intact zinc-binding motif, an unobstructed catalytically competent active site, and the presence of an intriguing, ubiquitin-like N-terminal domain. To gain insight into the active-site recognition of the C-terminal tail of ubiquitin and the related LXGG motif, we propose a model of PLpro in complex with ubiquitin–aldehyde that reveals well defined sites within the catalytic cleft that help to account for strict substrate-recognition motifs. PMID:16581910

  1. Acute kidney injury in a shepherd with severe malaria: a case report

    PubMed Central

    Boushab, Boushab Mohamed; Fall-Malick, Fatim-Zahra; Savadogo, Mamoudou; Basco, Leonardo Kishi

    2016-01-01

    Malaria is one of the main reasons for outpatient consultation and hospitalization in Mauritania. Although four Plasmodium species, ie, Plasmodium (P.) falciparum, P. vivax, P. malariae, and P. ovale, cause malaria in Mauritania, recent data on their frequency is lacking. Since infections with P. falciparum generally result in serious disease, their identification is important. We report a case of oliguric renal injury associated with malaria in a 65-year-old shepherd. Clinical manifestations included anemia, oliguria, and elevated creatinine and urea. The rapid diagnostic test for malaria and microscopic examination of blood smears were positive for P. falciparum. On the basis of this, the patient was diagnosed as having acute kidney injury as a complication of severe malaria. The patient was treated for malaria with intravenous quinine for 4 days, followed by 3 days of oral treatment. Volume expansion, antipyretic treatment, and diuretics were administered. He also had two rounds of dialysis after which he partially recovered renal function. This outcome is not always the rule. Prognosis depends much on early diagnosis and appropriate supportive treatment. PMID:27785088

  2. Protecting healthcare staff from severe acute respiratory syndrome: filtration capacity of multiple surgical masks.

    PubMed

    Derrick, J L; Gomersall, C D

    2005-04-01

    Guidelines issued by the Centers for Disease Control and Prevention and the World Health Organisation state that healthcare workers should wear N95 masks or higher-level protection during all contact with suspected severe acute respiratory syndrome (SARS). In areas where N95 masks are not available, multiple layers of surgical masks have been tried to prevent transmission of SARS. The in vivo filtration capacity of a single surgical mask is known to be poor. However, the filtration capacity of a combination of masks is unknown. This was a crossover trial of one, two, three and five surgical masks in six volunteers to determine the in vivo filtration efficiency of wearing more than one surgical mask. We used a Portacount to measure the difference in ambient particle counts inside and outside the masks. The best combination of five surgical masks scored a fit factor of 13.7, which is well below the minimum level of 100 required for a half face respirator. Multiple surgical masks filter ambient particles poorly. They should not be used as a substitute for N95 masks unless there is no alternative. PMID:15749326

  3. 4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis

    PubMed Central

    Guo, Wen-yi; Zhao, Liang; Xiang, Ming-wei; Mei, Fang-chao; Abliz, Ablikim; Hu, Peng; Deng, Wen-hong; Yu, Jia

    2016-01-01

    Endoplasmic reticulum (ER) stress is a particular process with an imbalance of homeostasis, which plays an important role in pancreatitis, but little is known about how ER stress is implicated in severe acute pancreatitis (SAP) induced pancreatic beta-cell injury. To investigate the effect of 4-phenylbutyric acid (4-PBA) on the beta-cell injury following SAP and the underlying mechanism, twenty-four Sprague-Dawley rats were randomly divided into sham-operation (SO) group, SAP model group, and 4-PBA treatment group. SAP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. 4-PBA or normal saline was injected intraperitoneally for 3 days in respective group before successful modeling. Results showed that 4-PBA attenuated the following: (1) pancreas and islet pathological injuries, (2) serum TNF-α and IL-1β, (3) serum insulin and glucose, (4) beta-cell ultrastructural changes, (5) ER stress markers (BiP, ORP150, and CHOP), Caspase-3, and insulin expression in islet. These results suggested that 4-PBA mitigates pancreatic beta-cell injury and endocrine disorder in SAP, presumably because of its role in inhibiting excessive endoplasmic reticulum stress. This may serve as a new therapeutic target for reducing pancreatic beta-cell injury and endocrine disorder in SAP upon 4-PBA treatment. PMID:27656209

  4. 4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis.

    PubMed

    Hong, Yu-Pu; Guo, Wen-Yi; Wang, Wei-Xing; Zhao, Liang; Xiang, Ming-Wei; Mei, Fang-Chao; Abliz, Ablikim; Hu, Peng; Deng, Wen-Hong; Yu, Jia

    2016-01-01

    Endoplasmic reticulum (ER) stress is a particular process with an imbalance of homeostasis, which plays an important role in pancreatitis, but little is known about how ER stress is implicated in severe acute pancreatitis (SAP) induced pancreatic beta-cell injury. To investigate the effect of 4-phenylbutyric acid (4-PBA) on the beta-cell injury following SAP and the underlying mechanism, twenty-four Sprague-Dawley rats were randomly divided into sham-operation (SO) group, SAP model group, and 4-PBA treatment group. SAP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. 4-PBA or normal saline was injected intraperitoneally for 3 days in respective group before successful modeling. Results showed that 4-PBA attenuated the following: (1) pancreas and islet pathological injuries, (2) serum TNF-α and IL-1β, (3) serum insulin and glucose, (4) beta-cell ultrastructural changes, (5) ER stress markers (BiP, ORP150, and CHOP), Caspase-3, and insulin expression in islet. These results suggested that 4-PBA mitigates pancreatic beta-cell injury and endocrine disorder in SAP, presumably because of its role in inhibiting excessive endoplasmic reticulum stress. This may serve as a new therapeutic target for reducing pancreatic beta-cell injury and endocrine disorder in SAP upon 4-PBA treatment. PMID:27656209

  5. The severity of acute kidney injury predicts progression to chronic kidney disease

    PubMed Central

    Chawla, Lakhmir S; Amdur, Richard L; Amodeo, Susan; Kimmel, Paul L; Palant, Carlos E

    2011-01-01

    Acute kidney injury (AKI) is associated with progression to advanced chronic kidney disease (CKD). We tested whether patients who survive AKI and are at higher risk for CKD progression can be identified during their hospital admission, thus providing opportunities to intervene. This was assessed in patients in the Department of Veterans Affairs Healthcare System hospitalized with a primary diagnosis indicating AKI (ICD9 codes 584.xx). In the exploratory phase, three multivariate prediction models for progression to stage 4 CKD were developed. In the confirmatory phase, the models were validated in 11,589 patients admitted for myocardial infarction or pneumonia during the same time frame that had RIFLE codes R, I, or F and complete data for all predictor variables. Of the 5351 patients in the AKI group, 728 entered stage 4 CKD after hospitalization. Models 1, 2, and 3 were all significant with ‘c' statistics of 0.82, 0.81, and 0.77, respectively. In model validation, all three were highly significant when tested in the confirmatory patients, with moderate to large effect sizes and good predictive accuracy (‘c' 0.81–0.82). Patients with AKI who required dialysis and then recovered were at especially high risk for progression to CKD. Hence, the severity of AKI is a robust predictor of progression to CKD. PMID:21430640

  6. Severe hypercalcemia as a form of acute lymphoblastic leukemia presentation in children

    PubMed Central

    Martins, Andreia Luís; Moniz, Marta; Nunes, Pedro Sampaio; Abadesso, Clara; Loureiro, Helena Cristina; Duarte, Ximo; Almeida, Helena Isabel

    2015-01-01

    Hypercalcemia is a rare metabolic disorder in children and is potentially fatal. It has a wide differential diagnosis, including cancer. Here, we report the case of a previously healthy 3-year-old who was admitted to the emergency room with fatigue, hyporeactivity, fever and limping gait that had evolved over 5 days and that was progressively worsening. On examination the patient was unconscious (Glasgow coma score: 8). Laboratory tests indicated severe hypercalcemia (total calcium 21.39mg/dL, ionized calcium 2.93mmol/L) and microcytic anemia. Hyperhydration was initiated, and the child was transferred to the pediatric intensive care unit. Continuous venovenous hemodiafiltration with calcium-free solution was instituted, which brought progressive normalization of serum calcium and an improved state of consciousness. Zoledronate was administered, and metabolic and infectious causes and poisoning were excluded. The bone marrow smear revealed a diagnosis of acute lymphoblastic leukemia. Hypercalcemia associated with malignancy in children is rare and occurs as a form of cancer presentation or recurrence. Continuous venovenous hemodiafiltration should be considered in situations where there is imminent risk to life. PMID:26761480

  7. [Scoring of severity of patients' condition with acute surgical diseases and injuries of the abdominal cavity].

    PubMed

    Efimenko, N A; Lesik, P S; Kharisov, A M; Pashaev, A A

    2015-07-01

    Ten of the most frequent symptoms that do not require special methods of their determination except general clinical examinations established by any health care professional on pre-hospital stage were determined on the basis of analysis of more than one thousand records of patients with acute surgical abdominal diseases and clinical symptom load. The authors performed an assessment of each symptom depending on severity of patient's condition ranging from 1 point (satisfactory condition) till 5 points (critical condition). Information has been obtained: in case of satisfactory condition--up to 10 points, moderate--up to 20 points, heavy--up to 30 points, extremely heavy condition--up to 45 points and terminal condition--more than 45 points. Thus, conditional descriptive method of assessment of patient's condition during the clinical examination is combined with objective-scoring. The given method combines numeric expression with methods accepted in literature--"MFS-CA", "APACHE II" and allows to perform an objective assessment of the treatment process at different stages, to practice health care standards, to perform an analysis of outcomes. The article provides tables, which substantiate proposed method.

  8. [Severe acute respiratory syndrome: the first transmissible disease of the 21st century].

    PubMed

    Nicastri, Emanuele; Petrosillo, Nicola; Macrì, Giulia; Ippolito, Giuseppe

    2003-01-01

    The Severe Acute Respiratory Syndrome (SARS) is the first severe and easily transmissible disease to emerge in the 21st century. It is caused by the infection with a coronavirus, a single strand RNA capsulated virus, recently found in a small mammalian, the masked palm civet. It is likely to represent the source of human infection. The first cases of SARS have been reported in the Chinese province of Guangdong and, since then, probable cases have been reported world wide. The clinical picture is characterized by nonspecific symptoms such as fever, cough or dyspnea in patients affected by air-space opacities (unifocal involvement in the 54.6% of cases) or distress respiratory syndrome and linked to a recent exposure to a SARS case or to a travel/residence in an affected area. The empirical therapy is based on broad-spectrum antibiotics, steroids and ribavirin, but susceptibility testing have failed to demonstrate direct anti-viral activity of ribavirin against SARS-related coronavirus in vitro. The exposure to respiratory droplets and the contact with biologic fluids (respiratory and gastrointestinal secretions) represent the most efficient transmission modality of the SARS-related coronavirus. Hand hygiene is the most simple and cost effective measure of infection control to prevent contagion, and the use of airborne, contact and droplet precaution is strictly recommended to all health care workers taking care of such patients. The spread of SARS, to less developed country with limited resource for public health programs, represent the emerging alarming threat in the new global scenario.

  9. Comparison of laparoscopy and open surgery in treating severe acute pancreatitis and its relative aftercare.

    PubMed

    Zhang, J; Jiang, M X; Zheng, Y; Shu, M; Sun, S B

    2016-01-01

    This study was designed to determine the effects and compare laparoscopic intervention and open surgery in treating severe acute pancreatitis (SAP) and its relative aftercare, to improve the overall treatment of SAP. Ninety patients with SAP were enrolled from the 2nd Affiliated Hospital of Harbin Medical University from 2008 to 2014 and divided into a laparoscopic intervention group (25 cases) and an open surgery group (65 cases). Patients were asked for clinical symptoms, general hospital information, laboratory inspection, imageological examination, local and systemic complications, treatment and outcome. SAP patients’ relevant clinical indicators were compared between the two groups before and after the operation. Results revealed that there was no statistical significance in lesion range and main scoring indexes for reflecting the severity of the disease. For both groups statistical significance was found in blood loss (285.3±79.8 mL vs 362±91.6 mL), intensive care unit (ICU) monitoring time (9.04±6.35 d vs 12.48±8.34 d) and service time of breathing machine (9.47±6.24 d vs 12.98±8.25 d), and the laparoscopic operation group was superior to the open surgery group (p < 0.05). Besides, the laparoscopic operation group was also superior to the open surgery group in demand for main analgesics one week after the operation, as well as for recovery rate and incidence of complications (p < 0.05). Thus, it can be concluded that patients undergoing laparoscopic intervention are less likely to develop pulmonary infection and more likely to be cured in comparison with patients who receive open surgery. In addition, laparoscopic intervention results in less damage, lighter pain and fewer complications compared with open surgery. PMID:27049091

  10. Hydrogen-rich saline ameliorates the severity of L-arginine-induced acute pancreatitis in rats

    SciTech Connect

    Chen, Han; Sun, Yan Ping; Li, Yang; Liu, Wen Wu; Xiang, Hong Gang; Fan, Lie Ying; Sun, Qiang; Xu, Xin Yun; Cai, Jian Mei; Ruan, Can Ping; Su, Ning; Yan, Rong Lin; Sun, Xue Jun; Wang, Qiang

    2010-03-05

    Molecular hydrogen, which reacts with the hydroxyl radical, has been considered as a novel antioxidant. Here, we evaluated the protective effects of hydrogen-rich saline on the L-arginine (L-Arg)-induced acute pancreatitis (AP). AP was induced in Sprague-Dawley rats by giving two intraperitoneal injections of L-Arg, each at concentrations of 250 mg/100 g body weight, with an interval of 1 h. Hydrogen-rich saline (>0.6 mM, 6 ml/kg) or saline (6 ml/kg) was administered, respectively, via tail vein 15 min after each L-Arg administration. Severity of AP was assessed by analysis of serum amylase activity, pancreatic water content and histology. Samples of pancreas were taken for measuring malondialdehyde and myeloperoxidase. Apoptosis in pancreatic acinar cell was determined with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL). Expression of proliferating cell nuclear antigen (PCNA) and nuclear factor kappa B (NF-{kappa}B) were detected with immunohistochemistry. Hydrogen-rich saline treatment significantly attenuated the severity of L-Arg-induced AP by ameliorating the increased serum amylase activity, inhibiting neutrophil infiltration, lipid oxidation and pancreatic tissue edema. Moreover, hydrogen-rich saline treatment could promote acinar cell proliferation, inhibit apoptosis and NF-{kappa}B activation. These results indicate that hydrogen treatment has a protective effect against AP, and the effect is possibly due to its ability to inhibit oxidative stress, apoptosis, NF-{kappa}B activation and to promote acinar cell proliferation.

  11. Emergency room assessment and adrenaline treatment of patients with acute asthma of different severity.

    PubMed

    Limthongkul, S

    1989-06-01

    The adequacy of emergency room assessment and treatment of patients with acute severe asthmatic attacks was evaluated by analyzing the course of 451 visits of 348 patients to Chulalongkorn hospital's Emergency Room. Eighty-five per cent of the patients had an initial index score of greater than or equal to 4 and an average peak expiratory flow rate of 92.16 +/- 46.3 L/min. The discharge index score was 85 per cent with a score of less than or equal to 3 and an average peak expiratory flow rate of 192 +/- 40.3 L/min. Our study indicated that the predictive index proposed by Fischl et al correlated with the severity of airway obstruction; however, the initial index did not help with emergency room decision-making in predicting which patients might be hospitalized, have a relapse or be discharged. In fact, in our emergency room department, the index score to determine airway obstruction and the pattern of response to treatment were better predictors of the outcome, which was classified into three categories: non-responsive or minimally responsive, responsive, and partially responsive. By using conventional clinical criteria (i.e. recumbent position with elimination of laboured breathing, disappearance of dyspnea and reduction of wheezing), there was a 93 per cent accurate determination in the episodes of patients who responded sufficiently to the emergency room treatment to allow their discharge. The remaining 7 per cent of those seeking emergency treatment were hospitalized, which is a lower incidence than that of others series.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Severe acute otitis media caused by mucoid Streptococcus pyogenes in a previously healthy adult.

    PubMed

    Kakuta, Risako; Yano, Hisakazu; Hidaka, Hiroshi; Miyazaki, Hiromitsu; Irimada, Mihoko; Oda, Kiyoshi; Arai, Kazuaki; Ozawa, Daiki; Takahashi, Takashi; Kaku, Mitsuo; Katori, Yukio

    2014-01-01

    Streptococcus (S.) pyogenes is well recognized as the most common pathogen causing pharyngotonsillitis in school-age children. In Japan, mucoid Streptococcus pneumoniae is well known as a causative agent of severe acute otitis media (AOM); however, mucoid S. pyogenes has rarely been reported. To the best of our knowledge, this is the first report of an AOM patient caused by mucoid S. pyogenes in Japan. A 36-year-old previously healthy female was referred to our hospital with suspicion of cerebrospinal otorrhea due to increasing otalgia accompanied by headache following myringotomy. Bacterial cultures of middle ear secretions were performed, and mucoid-form colonies surrounded by zones of complete β-hemolysis were produced on sheep's blood agar. Antigen-agglutination test results were positive for S. pyogenes, and thus the patient received treatment with panipenem-betamipron 2.0 g/day for 10 days, which resolved nearly all symptoms. The bacteriological features of this strain were then investigated. The M-protein genotype encoded by the emm gene, the major virulence factor of S. pyogenes, was determined to be emm75. Generally, S. pyogenes forms colonies having non-mucoid matt appearances based on β-hemolysis of sheep's blood agar. The mucoid phenotype results from abundant production of hyaluronic acid capsular polysaccharide, a key virulence determinant. emm75 is common in noninvasive, but less common in invasive disease. In conclusion, mucoid S. pyogenes can cause severe infection even in previously healthy persons. Emergence of mucoid S. pyogenes and drug resistance trends should be monitored in the future. PMID:24727832

  13. Over-the-scope clip placement is effective rescue therapy for severe acute upper gastrointestinal bleeding

    PubMed Central

    Skinner, Matthew; Gutierrez, Juan P.; Neumann, Helmut; Wilcox, C. Mel; Burski, Chad; Mönkemüller, Klaus

    2014-01-01

    Background and study aim: The novel over-the-scope clip (OTSC) allows for excellent apposition of tissue, potentially permitting hemostasis to be achieved in various types of gastrointestinal lesions. This study aimed to evaluate the usefulness and safety of OTSCs for endoscopic hemostasis in patients with upper gastrointestinal bleeding in whom traditional endoscopic methods had failed. Patients and methods: A retrospective case series of all patients who underwent placement of an OTSC for severe recurrent upper gastrointestinal bleeding over a 14-month period was studied. Outcome data for the procedure included achievement of primary hemostasis, episodes of recurrent bleeding, and complications. Results: Twelve consecutive patients (67 % men; mean age 59, range 29 – 86) with ongoing upper gastrointestinal bleeding despite previous endoscopic management were included. They had a mean ASA score of 3 (range 2 – 4), a mean hemoglobin of 7.2 g/dL (range 5.2 – 9.1), and shock was present in 75 % of patients. They had all received packed red blood cells (mean 5.1 units, range 2 – 12). The etiology of bleeding was: duodenal ulcer (n = 6), gastric ulcer (n = 2) Dieulafoy lesion (n = 2), anastomotic ulceration (n = 1), Mallory – Weiss tear (n = 1). Hemostasis was achieved in all patients. Rebleeding occurred in two patients 1 day and 7 days after OTSC placement. There were no complications associated with OTSC application. Conclusions: OTSC use represents an effective, easily performed, and safe endoscopic therapy for various causes of severe acute gastrointestinal bleeding when conventional endoscopic techniques have failed. This therapy should be added to the armamentarium of therapeutic endoscopists. PMID:26134611

  14. Phenotyping community-acquired pneumonia according to the presence of acute respiratory failure and severe sepsis

    PubMed Central

    2014-01-01

    Background Acute respiratory failure (ARF) and severe sepsis (SS) are possible complications in patients with community-acquired pneumonia (CAP). The aim of the study was to evaluate prevalence, characteristics, risk factors and impact on mortality of hospitalized patients with CAP according to the presence of ARF and SS on admission. Methods This was a multicenter, observational, prospective study of consecutive CAP patients admitted to three hospitals in Italy, Spain, and Scotland between 2008 and 2010. Three groups of patients were identified: those with neither ARF nor SS (Group A), those with only ARF (Group B) and those with both ARF and SS (Group C) on admission. Results Among the 2,145 patients enrolled, 45% belonged to Group A, 36% to Group B and 20% to Group C. Patients in Group C were more severe than patients in Group B. Isolated ARF was correlated with age (p < 0.001), COPD (p < 0.001) and multilobar infiltrates (p < 0.001). The contemporary occurrence of ARF and SS was associated with age (p = 0.002), residency in nursing home (p = 0.007), COPD (p < 0.001), multilobar involvement (p < 0.001) and renal disease (p < 0.001). 4.2% of patients in Group A died, 9.3% in Group B and 26% in Group C, p < 0.001. After adjustment, the presence of only ARF had an OR for in-hospital mortality of 1.85 (p = 0.011) and the presence of both ARF and SS had an OR of 6.32 (p < 0.001). Conclusions The identification of ARF and SS on hospital admission can help physicians in classifying CAP patients into three different clinical phenotypes. PMID:24593040

  15. Gut Microbiota in Children Hospitalized with Oedematous and Non-Oedematous Severe Acute Malnutrition in Uganda

    PubMed Central

    Kristensen, Kia Hee Schultz; Wiese, Maria; Rytter, Maren Johanne Heilskov; Özçam, Mustafa; Hansen, Lars Hestbjerg; Namusoke, Hanifa; Friis, Henrik; Nielsen, Dennis Sandris

    2016-01-01

    Background Severe acute malnutrition (SAM) among children remains a major health problem in many developing countries. SAM manifests in both an oedematous and a non-oedematous form, with oedematous malnutrition in its most severe form also known as kwashiorkor. The pathogenesis of both types of malnutrition in children remains largely unknown, but gut microbiota (GM) dysbiosis has recently been linked to oedematous malnutrition. In the present study we aimed to assess whether GM composition differed between Ugandan children suffering from either oedematous or non-oedematous malnutrition. Methodology/Principal Findings As part of an observational study among children hospitalized with SAM aged 6–24 months in Uganda, fecal samples were collected at admission. Total genomic DNA was extracted from fecal samples, and PCR amplification was performed followed by Denaturing Gradient Gel Electrophoresis (DGGE) and tag-encoded 16S rRNA gene-targeted high throughput amplicon sequencing. Alpha and beta diversity measures were determined along with ANOVA mean relative abundance and G-test of independence followed by comparisons between groups. Of the 87 SAM children included, 62% suffered from oedematous malnutrition, 66% were boys and the mean age was 16.1 months. GM composition was found to differ between the two groups of children as determined by DGGE (p = 0.0317) and by high-throughput sequencing, with non-oedematous children having lower GM alpha diversity (p = 0.036). However, beta diversity analysis did not reveal larger differences between the GM of children with oedematous and non-oedematous SAM (ANOSIM analysis, weighted UniFrac, R = -0.0085, p = 0.584; unweighted UniFrac, R = 0.0719, p = 0.011). Conclusions/Significance Our results indicate that non-oedematous SAM children have lower GM diversity compared to oedematous SAM children, however no clear compositional differences were identified. PMID:26771456

  16. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities.

    PubMed

    Subissi, Lorenzo; Posthuma, Clara C; Collet, Axelle; Zevenhoven-Dobbe, Jessika C; Gorbalenya, Alexander E; Decroly, Etienne; Snijder, Eric J; Canard, Bruno; Imbert, Isabelle

    2014-09-16

    In addition to members causing milder human infections, the Coronaviridae family includes potentially lethal zoonotic agents causing severe acute respiratory syndrome (SARS) and the recently emerged Middle East respiratory syndrome. The ∼30-kb positive-stranded RNA genome of coronaviruses encodes a replication/transcription machinery that is unusually complex and composed of 16 nonstructural proteins (nsps). SARS-CoV nsp12, the canonical RNA-dependent RNA polymerase (RdRp), exhibits poorly processive RNA synthesis in vitro, at odds with the efficient replication of a very large RNA genome in vivo. Here, we report that SARS-CoV nsp7 and nsp8 activate and confer processivity to the RNA-synthesizing activity of nsp12. Using biochemical assays and reverse genetics, the importance of conserved nsp7 and nsp8 residues was probed. Whereas several nsp7 mutations affected virus replication to a limited extent, the replacement of two nsp8 residues (P183 and R190) essential for interaction with nsp12 and a third (K58) critical for the interaction of the polymerase complex with RNA were all lethal to the virus. Without a loss of processivity, the nsp7/nsp8/nsp12 complex can associate with nsp14, a bifunctional enzyme bearing 3'-5' exoribonuclease and RNA cap N7-guanine methyltransferase activities involved in replication fidelity and 5'-RNA capping, respectively. The identification of this tripartite polymerase complex that in turn associates with the nsp14 proofreading enzyme sheds light on how coronaviruses assemble an RNA-synthesizing machinery to replicate the largest known RNA genomes. This protein complex is a fascinating example of the functional integration of RNA polymerase, capping, and proofreading activities. PMID:25197083

  17. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities

    PubMed Central

    Subissi, Lorenzo; Posthuma, Clara C.; Collet, Axelle; Zevenhoven-Dobbe, Jessika C.; Gorbalenya, Alexander E.; Decroly, Etienne; Snijder, Eric J.; Canard, Bruno; Imbert, Isabelle

    2014-01-01

    In addition to members causing milder human infections, the Coronaviridae family includes potentially lethal zoonotic agents causing severe acute respiratory syndrome (SARS) and the recently emerged Middle East respiratory syndrome. The ∼30-kb positive-stranded RNA genome of coronaviruses encodes a replication/transcription machinery that is unusually complex and composed of 16 nonstructural proteins (nsps). SARS-CoV nsp12, the canonical RNA-dependent RNA polymerase (RdRp), exhibits poorly processive RNA synthesis in vitro, at odds with the efficient replication of a very large RNA genome in vivo. Here, we report that SARS-CoV nsp7 and nsp8 activate and confer processivity to the RNA-synthesizing activity of nsp12. Using biochemical assays and reverse genetics, the importance of conserved nsp7 and nsp8 residues was probed. Whereas several nsp7 mutations affected virus replication to a limited extent, the replacement of two nsp8 residues (P183 and R190) essential for interaction with nsp12 and a third (K58) critical for the interaction of the polymerase complex with RNA were all lethal to the virus. Without a loss of processivity, the nsp7/nsp8/nsp12 complex can associate with nsp14, a bifunctional enzyme bearing 3′-5′ exoribonuclease and RNA cap N7-guanine methyltransferase activities involved in replication fidelity and 5′-RNA capping, respectively. The identification of this tripartite polymerase complex that in turn associates with the nsp14 proofreading enzyme sheds light on how coronaviruses assemble an RNA-synthesizing machinery to replicate the largest known RNA genomes. This protein complex is a fascinating example of the functional integration of RNA polymerase, capping, and proofreading activities. PMID:25197083

  18. Unilateral Partial Nephrectomy with Warm Ischemia Results in Acute Hypoxia Inducible Factor 1-Alpha (HIF-1α) and Toll-Like Receptor 4 (TLR4) Overexpression in a Porcine Model

    PubMed Central

    Zhang, Zhiyong; Haimovich, Beatrice; Kwon, Young Suk; Lu, Tyler; Fyfe-Kirschner, Billie; Olweny, Ephrem Odoy

    2016-01-01

    Purpose Ischemia/reperfusion (I/R) during partial nephrectomy (PN) contributes to acute kidney injury (AKI), which is inaccurately assessed using existent clinical markers of renal function. We evaluated I/R-related changes in expression in hypoxia inducible factor 1α (HIF-1α) and toll-like receptor 4 (TLR4), within kidney tissue and peripheral blood leukocytes (PBL) in a porcine model of PN. Materials and Methods Three adult pigs each underwent unilateral renal hilar cross clamping for 180 min followed by a 15 min reperfusion. The contralateral kidney served as control. Biopsies of clamped kidneys were obtained at baseline (time 0), every 60 min during the hypoxic phase, and post-reperfusion. Control kidneys were biopsied once at 180 min. Peripheral blood was sampled at time 0, every 30 min during the hypoxic phase, and post-reperfusion. HIF-1α and TLR4 expression in kidney tissue and PBL were analyzed by Western blotting. I/R-related histological changes were assessed. Results Expression of HIF-1α in clamped kidneys and PBL was below detection level at baseline, rising to detectable levels after 60 min of hypoxia, and continuing to rise throughout the hypoxic and reperfusion phases. Expression of TLR-4 in clamped kidneys followed a similar trend with initial detection after 30–60 min of hypoxia. Control kidneys exhibited no change in HIF-1α or TLR-4 expression. I/R-related histologic changes were minimal, primarily mild tubular dilatation. Conclusions In a porcine model of PN, HIF-1α and TLR4 exhibited robust, I/R-related increases in expression in kidney tissue and PBL. Further studies investigating these molecules as potential markers of AKI are warranted. PMID:27149666

  19. Effects of Gender on Severity, Management and Outcome in Acute Biliary Pancreatitis

    PubMed Central

    Lu, Chin-Li; Li, Chung-Yi

    2013-01-01

    Background We conducted a population-based cross-sectional study to examine gender differences in severity, management, and outcome among patients with acute biliary pancreatitis (ABP) because available data are insufficient and conflicting. Methods We analyzed 13,110 patients (50.6% male) with first-attack ABP from Taiwan’s National Health Insurance Research Database between 2000 and 2009. The primary outcome was hospital mortality. Secondary outcomes included the development of severe ABP and the provision of treatment measures. Gender difference was assessed using multivariable analyses with generalized estimating equations models. Results The odds of gastrointestinal bleeding (adjusted odds ratio [aOR] 1.44, 95% confidence interval [CI] 1.18–1.76) and local complication (aOR 1.38, 95% CI 1.05–1.82) were 44% and 38% higher in men than in women, respectively. Compared with women, men had 24% higher odds of receiving total parenteral nutrition (aOR 1.24, 95% CI 1.00–1.52), but had 18% and 41% lower odds of receiving cholecystectomy (aOR 0.82, 95% CI 0.72–0.93) and hemodialysis (aOR 0.59, 95% CI 0.42–0.83), respectively. Hospital mortality was higher in men than in women (1.8% vs. 1.1%, p = 0.001). After adjustment for potential confounders, men had 81% higher odds of in-hospital death than women (aOR 1.81, 95% CI 1.15–2.86). Among patients with severe ABP, hospital mortality was 11.0% and 7.5% in men and women (p<0.001), respectively. The adjusted odds of death remained higher in men than in women with severe ABP (aOR 1.72, 95% CI 1.10–2.68). Conclusions Gender is an important determinant of outcome in patients with ABP and may affect their treatment measures. PMID:23469006

  20. Influence of Pneumococcal Conjugate Vaccine on Acute Otitis Media with Severe Middle Ear Inflammation: A Retrospective Multicenter Study

    PubMed Central

    Sugino, Hirotoshi; Tsumura, Shigeru; Kunimoto, Masaru; Noda, Masuhiro; Chikuie, Daisuke; Noda, Chieko; Yamashita, Mariko; Watanabe, Hiroshi; Ishii, Hidemasa; Tashiro, Toru; Iwata, Kazuhiro; Kono, Takashi; Tsumura, Kaoru; Sumiya, Takahiro; Takeno, Sachio; Hirakawa, Katsuhiro

    2015-01-01

    The Japanese guidelines for acute otitis media in children recommend classifying acute otitis media by age, manifestations and local findings, and also recommend myringotomy for moderate-grade cases with severe local findings, severe-grade cases, and treatment-resistant cases. The heptavalent pneumococcal conjugate vaccine was released in Japan in February 2010. In Hiroshima City, public funding allowing free inoculation with this vaccine was initiated from January 2011, and the number of vaccinated individuals has since increased dramatically. This study investigated changes in the number of myringotomies performed to treat acute otitis media during the 5-year period from January 2008 to December 2012 at two hospitals and five clinics in the Asa Area of Hiroshima City, Japan. A total of 3,165 myringotomies for acute otitis media were performed. The rate of procedures per child-year performed in <5-year-old children decreased by 29.1% in 2011 and by 25.2% in 2012 compared to the mean rate performed in the 3 years prior to the introduction of public funding. A total of 895 myringotomies were performed for 1-year-old infants. The rate of myringotomies per child-year performed for acute otitis media in 1-year-old infants decreased significantly in the 2 years after the introduction of public funding for heptavalent pneumococcal conjugate vaccine compared to all years before introduction (p<0.000001). Our results suggest a benefit of heptavalent pneumococcal conjugate vaccine for acute otitis media in reducing the financial burden of myringotomy. In addition, this vaccine may help prevent acute otitis media with severe middle ear inflammation in 1-year-old infants. PMID:26348230

  1. Influence of Pneumococcal Conjugate Vaccine on Acute Otitis Media with Severe Middle Ear Inflammation: A Retrospective Multicenter Study.

    PubMed

    Sugino, Hirotoshi; Tsumura, Shigeru; Kunimoto, Masaru; Noda, Masuhiro; Chikuie, Daisuke; Noda, Chieko; Yamashita, Mariko; Watanabe, Hiroshi; Ishii, Hidemasa; Tashiro, Toru; Iwata, Kazuhiro; Kono, Takashi; Tsumura, Kaoru; Sumiya, Takahiro; Takeno, Sachio; Hirakawa, Katsuhiro

    2015-01-01

    The Japanese guidelines for acute otitis media in children recommend classifying acute otitis media by age, manifestations and local findings, and also recommend myringotomy for moderate-grade cases with severe local findings, severe-grade cases, and treatment-resistant cases. The heptavalent pneumococcal conjugate vaccine was released in Japan in February 2010. In Hiroshima City, public funding allowing free inoculation with this vaccine was initiated from January 2011, and the number of vaccinated individuals has since increased dramatically. This study investigated changes in the number of myringotomies performed to treat acute otitis media during the 5-year period from January 2008 to December 2012 at two hospitals and five clinics in the Asa Area of Hiroshima City, Japan. A total of 3,165 myringotomies for acute otitis media were performed. The rate of procedures per child-year performed in <5-year-old children decreased by 29.1% in 2011 and by 25.2% in 2012 compared to the mean rate performed in the 3 years prior to the introduction of public funding. A total of 895 myringotomies were performed for 1-year-old infants. The rate of myringotomies per child-year performed for acute otitis media in 1-year-old infants decreased significantly in the 2 years after the introduction of public funding for heptavalent pneumococcal conjugate vaccine compared to all years before introduction (p<0.000001). Our results suggest a benefit of heptavalent pneumococcal conjugate vaccine for acute otitis media in reducing the financial burden of myringotomy. In addition, this vaccine may help prevent acute otitis media with severe middle ear inflammation in 1-year-old infants.

  2. Role of Inhaled Nitric Oxide in the Management of Severe Acute Respiratory Distress Syndrome

    PubMed Central

    Hunt, Juliette Lucinda; Bronicki, Ronald A.; Anas, Nick

    2016-01-01

    To date, there have been several systematic reviews with meta-analysis that have shown no reduction in mortality with the use of inhaled nitric oxide (iNO) in patients with acute respiratory distress syndrome (ARDS). Importantly, these reports fail to make a distinction between the pediatric and adult patient. The number of adult patients in these reviews are far greater than the number of pediatric patients, which makes it difficult to interpret the data regarding the role of iNO on the pediatric population. Extrapolating data from the adult population to the pediatric population is complicated as we know that physiology and the body’s response to disease can be different between adult and pediatric patients. iNO has been demonstrated to improve outcomes in term and near-term infants with hypoxic respiratory failure associated with pulmonary hypertension. Recently, Bronicki et al. published a prospective randomized control trial investigating the impact of iNO on the pediatric patient population with acute respiratory failure. In this study, a benefit of decreased duration of mechanical ventilation and an increased rate of ECMO-free survival was demonstrated in patients who were randomized to receiving iNO, suggesting that there may be benefit to the use of iNO in pediatric ARDS (PARDS) that has not been demonstrated in adults. iNO has repeatedly been shown to transiently improve oxygenation in all age groups, and yet neonates and pediatric patients have shown improvement in other outcomes that have not been seen in adults. The mechanism that explains improvement with the use of iNO in these patient populations are not well understood but does not appear to be solely a result of sustained improvement in oxygenation. There are physiologic studies that suggest alternative mechanisms for explaining the positive effects of iNO, such as platelet aggregation inhibition and reduction in systemic inflammation. Hence, the role of iNO by various mechanisms and in various

  3. Resistin is not an appropriate biochemical marker to predict severity of acute pancreatitis: A case-controlled study

    PubMed Central

    Al-Maramhy, Hamdi; Abdelrahman, Abdelrahman I; Sawalhi, Samer

    2014-01-01

    AIM: To assess levels of serum resistin upon hospital admission as a predictor of acute pancreatitis (AP) severity. METHODS: AP is both a common and serious disease, with severe cases resulting in a high mortality rate. Several predictive inflammatory markers have been used clinically to assess severity. This prospective study collected data from 102 patients who were diagnosed with an initial acute biliary pancreatitis between March 2010 and February 2013. Measurements of body mass index (BMI) and waist circumference (WC) were obtained and serum resistin levels were analyzed at the time of hospital admission using enzyme-linked immunosorbent assay. Additionally, resistin levels were measured from a control group after matching gender, BMI and age. RESULTS: A total of 102 patients (60 females and 42 males) were diagnosed with acute gallstone-induced pancreatitis. The mean age was 45 years, and mean BMI value was 30.5 kg/m2 (Obese, class I). Twenty-two patients (21.6%) had severe AP, while eighty-eight patients had mild pancreatitis (78.4%). Our results showed that BMI significantly correlated with pancreatitis severity (P = 0.007). Serum resistin did not correlate with BMI, weight or WC. Furthermore, serum resistin was significantly higher in patients with AP compared to control subjects (P < 0.0001). The mean resistin values upon admission were 17.5 ng/mL in the severe acute biliary pancreatitis group and 16.82 ng/mL in the mild AP group (P = 0.188), indicating that resistin is not an appropriate predictive marker of clinical severity. CONCLUSION: We demonstrate that obesity is a risk factor for developing severe AP. Further, although there is a correlation between serum resistin levels and AP at the time of hospital admission, resistin does not adequately serve as a predictive marker of clinical severity. PMID:25386084

  4. Hypoxia-targeted siRNA delivery.

    PubMed

    Perche, F; Biswas, S; Wang, T; Zhu, L; Torchilin, V P

    2014-03-24

    Altered vasculature and the resultant chaotic tumor blood flow lead to the appearance in fast-growing tumors of regions with gradients of oxygen tension and acute hypoxia (less than 1.4% oxygen). Due to its roles in tumorigenesis and resistance to therapy, hypoxia represents a problem in cancer therapy. Insufficient delivery of therapeutic agents to the hypoxic regions in solid tumors is recognized as one of the causes of resistance to therapy. This led to the development of hypoxia imaging agents, and the use of hypoxia-activated anticancer prodrugs. Here we show the first example of the hypoxia-induced siRNA uptake and silencing using a nanocarrier consisting of polyethyleneglycol 2000, azobenzene, polyethyleneimine (PEI)(1.8 kDa), and 1,2-dioleyl-sn-glycero-3-phosphoethanolamine (DOPE) units (the nanocarrier is referred to as PAPD), where azobenzene imparts hypoxia sensitivity and specificity. We report hypoxia-activated green fluorescent protein (GFP) silencing in vitro and its downregulation in GFP-expressing tumors after intravenous administration. The proposed nanoformulation represents a novel tumor-environment-responsive modality for cancer targeting and siRNA delivery. PMID:24554550

  5. Molecular Imaging of Tumor Hypoxia: Existing Problems and Their Potential Model-Based Solutions.

    PubMed

    Shi, Kuangyu; Ziegler, Sibylle I; Vaupel, Peter

    2016-01-01

    Molecular imaging of tissue hypoxia generates contrast in hypoxic areas by applying hypoxia-specific tracers in organisms. In cancer tissue, the injected tracer needs to be transported over relatively long distances and accumulates slowly in hypoxic regions. Thus, the signal-to-background ratio of hypoxia imaging is very small and a non-specific accumulation may suppress the real hypoxia-specific signals. In addition, the heterogeneous tumor microenvironment makes the assessment of the tissue oxygenation status more challenging. In this study, the diffusion potential of oxygen and of a hypoxia tracer for 4 different hypoxia subtypes: ischemic acute hypoxia, hypoxemic acute hypoxia, diffusion-limited chronic hypoxia and anemic chronic hypoxia are theoretically assessed. In particular, a reaction-diffusion equation is introduced to quantitatively analyze the interstitial diffusion of the hypoxia tracer [(18)F]FMISO. Imaging analysis strategies are explored based on reaction-diffusion simulations. For hypoxia imaging of low signal-to-background ratio, pharmacokinetic modelling has advantages to extract underlying specific binding signals from non-specific background signals and to improve the assessment of tumor oxygenation. Different pharmacokinetic models are evaluated for the analysis of the hypoxia tracer [(18)F]FMISO and optimal analysis model were identified accordingly. The improvements by model-based methods for the estimation of tumor oxygenation are in agreement with experimental data. The computational modelling offers a tool to explore molecular imaging of hypoxia and pharmacokinetic modelling is encouraged to be employed in the corresponding data analysis. PMID:27526129

  6. Community-based management of severe acute malnutrition in India: new evidence from Bihar123

    PubMed Central

    Burza, Sakib; Mahajan, Raman; Marino, Elisa; Sunyoto, Temmy; Shandilya, Chandra; Tabrez, Mohammad; Kumari, Kabita; Mathew, Prince; Jha, Amar; Salse, Nuria; Mishra, Kripa Nath

    2015-01-01

    Background: An estimated one-third of the world’s children who are wasted live in India. In Bihar state, of children <5 y old, 27.1% are wasted and 8.3% have severe acute malnutrition (SAM). In 2009, Médecins Sans Frontières (MSF) initiated a community-based management of acute malnutrition (CMAM) program for children aged 6–59 mo with SAM. Objective: In this report, we describe the characteristics and outcomes of 8274 children treated between February 2009 and September 2011. Design: Between February 2009 and June 2010, the program admitted children with a weight-for-height z score (WHZ) <−3 SD and/or midupper arm circumference (MUAC) <110 mm and discharged those who reached a WHZ >−2 SDs and MUAC >110 mm. These variables changed in July 2010 to admission on the basis of an MUAC <115 mm and discharge at an MUAC ≥120 mm. Uncomplicated SAM cases were treated as outpatients in the community by using a WHO-standard, ready-to-use, therapeutic lipid-based paste produced in India; complicated cases were treated as inpatients by using F75/F100 WHO-standard milk until they could complete treatment in the community. Results: A total of 8274 children were admitted including 5149 girls (62.2%), 6613 children aged 6–23 mo (79.9%), and 87.3% children who belonged to Scheduled Caste, Scheduled Tribe, or Other Backward Caste families or households. Of 3873 children admitted under the old criteria, 41 children (1.1%) died, 2069 children (53.4%) were discharged as cured, and 1485 children (38.3%) defaulted. Of 4401 children admitted under the new criteria, 36 children (0.8%) died, 2526 children (57.4%) were discharged as cured, and 1591 children (36.2%) defaulted. For children discharged as cured, the mean (±SD) weight gain and length of stay were 4.7 ± 3.1 and 5.1 ± 3.7 g · kg−1 · d−1 and 8.7 ± 6.1 and 7.3 ± 5.6 wk under the old and new criteria, respectively (P < 0.01). After adjustment, significant risk factors for default were as follows: no community

  7. Hypoxia and Hypoxia Inducible Factors: Diverse Roles in Liver Diseases

    PubMed Central

    Nath, Bharath; Szabo, Gyongyi

    2011-01-01

    Hypoxia has been shown to have a role in the pathogenesis of several forms of liver disease. The Hypoxia Inducible Factors (HIFs) are a family of evolutionarily conserved transcriptional regulators that affect a homeostatic response to low oxygen tension and have been identified as key mediators of angiogenesis, inflammation, and metabolism. In this review, we summarize the evidence for a role of HIFs across a range of hepatic pathophysiology. We describe regulation of the hypoxia inducible factors and review investigations that demonstrate a role for HIFs in the development of liver fibrosis, activation of innate immune pathways, hepatocellular carcinoma, as well as other liver diseases in both human disease as well as murine models. PMID:22120903

  8. Poisoning severity score, APACHE II and GCS: effective clinical indices for estimating severity and predicting outcome of acute organophosphorus and carbamate poisoning.

    PubMed

    Sam, Kishore Gnana; Kondabolu, Krishnakanth; Pati, Dipanwita; Kamath, Asha; Pradeep Kumar, G; Rao, Padma G M

    2009-07-01

    Self-poisoning with organophosphorus (OP) compounds is a major cause of morbidity and mortality across South Asian countries. To develop uniform and effective management guidelines, the severity of acute OP poisoning should be assessed through scientific methods and a clinical database should be maintained. A prospective descriptive survey was carried out to assess the utility of severity scales in predicting the outcome of 71 organophosphate (OP) and carbamate poisoning patients admitted during a one year period at the Kasturba Hospital, Manipal, India. The Glasgow coma scale (GCS) scores, acute physiology and chronic health evaluation II (APACHE II) scores, predicted mortality rate (PMR) and Poisoning severity score (PSS) were estimated within 24h of admission. Significant correlation (P<0.05) between PSS and GCS and APACHE II and PMR scores were observed with the PSS scores predicting mortality significantly (P< or =0.001). A total of 84.5% patients improved after treatment while 8.5% of the patients were discharged with severe morbidity. The mortality rate was 7.0%. Suicidal poisoning was observed to be the major cause (80.2%), while other reasons attributed were occupational (9.1%), accidental (6.6%), homicidal (1.6%) and unknown (2.5%) reasons. This study highlights the application of clinical indices like GCS, APACHE, PMR and severity scores in predicting mortality and may be considered for planning standard treatment guidelines.

  9. Unexpectedly Severe Acute Radiotherapy Side Effects Are Associated With Single Nucleotide Polymorphisms of the Melanocortin-1 Receptor

    SciTech Connect

    Fogarty, Gerald B.; Muddle, Rory; Sprung, Carl N.

    2010-08-01

    Purpose: The melanocortin-1 receptor (MC1R) regulates melanin biogenesis. Deoxyribonucleic acid sequence variants in the form of single nucleotide polymorphisms (SNPs) of MC1R affect melanin expression and are linked to skin phenotype. We aimed to determine whether SNPs of MC1R were associated with unexpectedly severe ionizing radiation reactions. Methods and Materials: The MC1R genotype of a cohort of Australians with unexpectedly severe acute and/or late reactions (Common Terminology Criteria Version 3 (CTCv3) Grade 3 or 4) to radiotherapy (RT) for cancer (n = 30) was analyzed. The findings were compared with control data from our previous study of MC1R representative of the general Australian population (n = 1,787). Results: The difference in frequency of alleles encoding a 'red hair color' phenotype in the cohort of patients with unexpectedly severe acute radiation reactions (n = 12) was significantly increased compared with the control population (p = 0.003). Acute radiosensitivity was especially associated with the R160W variant allele (odds ratio, 3.64 [95% confidence interval, 1.3-10.27]). The corresponding comparison of MC1R controls with unexpectedly severe late radiation reactions (n = 18) was not significant. It was also found that R160W as a part of the genotype in the patients with unexpectedly severe acute RT side effects as compared with the control group was also significant (p = 0.043). Conclusions: In this small cohort of cancer patients, deoxyribonucleic acid sequence variants of the MC1R gene, especially the R160W variant, have been associated with unexpectedly severe acute reactions to RT. This result needs to be verified in a larger cohort of patients.

  10. Distinct physiological strategies are used to cope with constant hypoxia and intermittent hypoxia in killifish (Fundulus heteroclitus).

    PubMed

    Borowiec, Brittney G; Darcy, Kimberly L; Gillette, Danielle M; Scott, Graham R

    2015-04-15

    Many fish encounter hypoxia on a daily cycle, but the physiological effects of intermittent hypoxia are poorly understood. We investigated whether acclimation to constant (sustained) hypoxia or to intermittent diel cycles of nocturnal hypoxia (12 h normoxia:12 h hypoxia) had distinct effects on hypoxia tolerance or on several determinants of O2 transport and O2 utilization in estuarine killifish. Adult killifish were acclimated to normoxia, constant hypoxia, or intermittent hypoxia for 7 or 28 days in brackish water (4 ppt). Acclimation to both hypoxia patterns led to comparable reductions in critical O2 tension and resting O2 consumption rate, but only constant hypoxia reduced the O2 tension at loss of equilibrium. Constant (but not intermittent) hypoxia decreased filament length and the proportion of seawater-type mitochondrion-rich cells in the gills (which may reduce ion loss and the associated costs of active ion uptake), increased blood haemoglobin content, and reduced the abundance of oxidative fibres in the swimming muscle. In contrast, only intermittent hypoxia augmented the oxidative and gluconeogenic enzyme activities in the liver and increased the capillarity of glycolytic muscle, each of which should facilitate recovery between hypoxia bouts. Neither exposure pattern affected muscle myoglobin content or the activities of metabolic enzymes in the brain or heart, but intermittent hypoxia increased brain mass. We conclude that the pattern of hypoxia exposure has an important influence on the mechanisms of acclimation, and that the optimal strategies used to cope with intermittent hypoxia may be distinct from those for coping with constant hypoxia.

  11. Dietary cysteine is used more efficiently by children with severe acute malnutrition with edema compared with those without edema

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Children with edematous severe acute malnutrition (SAM) produce less cysteine than do their nonedematous counterparts. They also have marked glutathione (GSH) depletion, hair loss, skin erosion, gut mucosal atrophy, and depletion of mucins. Because GSH, skin, hair, mucosal, and mucin proteins are ri...

  12. Dietary supplementation with aromatic amino acids increases protein synthesis in children wHh severe acute malnutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although 2 earlier studies reported that aromatic amino acid (AAA) supplementation of children with severe acute malnutrition (SAM) improved whole-body protein anabolism during the early postadmission (maintenance) phase of rehabilitation, it is not known whether this positive effect was maintained ...

  13. DO ACUTE PHASE PROTEINS REFLECT SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?

    EPA Science Inventory

    Title: DO ACUTE PHASE PROTEINS REFLECT THE SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?

    M. C. Schladweiler, BS 1, P. S. Gilmour, PhD 2, D. L. Andrews, BS 1, D. L. Costa, ScD 1, A. D. Ledbetter, BS 1, K. E. Pinkerton, PhD 3 and U. P. Kodavanti, ...

  14. Randomised, double blind, placebo controlled trial of intravenous antioxidant (n‐acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis

    PubMed Central

    Siriwardena, Ajith K; Mason, James M; Balachandra, Srinivasan; Bagul, Anil; Galloway, Simon; Formela, Laura; Hardman, Jonathan G; Jamdar, Saurabh

    2007-01-01

    Background Based on equivocal clinical data, intravenous antioxidant therapy has been used for the treatment of severe acute pancreatitis. To date there is no randomised comparison of this therapy in severe acute pancreatitis. Methods We conducted a randomised, double blind, placebo controlled trial of intravenous antioxidant (n‐acetylcysteine, selenium, vitamin C) therapy in patients with predicted severe acute pancreatitis. Forty‐three patients were enrolled from three hospitals in the Manchester (UK) area over the period June 2001 to November 2004. Randomisation stratified for APACHE‐II score and hospital site, and delivered groups that were similar at baseline. Results Relative serum levels of antioxidants rose while markers of oxidative stress fell in the active treatment group during the course of the trial. However, at 7 days, there was no statistically significant difference in the primary end point, organ dysfunction (antioxidant vs placebo: 32% vs 17%, p = 0.33) or any secondary end point of organ dysfunction or patient outcome. Conclusions This study provides no evidence to justify continued use of n‐acetylcysteine, selenium, vitamin C based antioxidant therapy in severe acute pancreatitis. In the context of any future trial design, careful consideration must be given to the risks raised by the greater trend towards adverse outcome in patients in the treatment arm of this study. PMID:17356040

  15. Evaluation of the routine use of amoxicillin as part of the home-based treatment of severe acute malnutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine whether the inclusion of amoxicillin correlates with better recovery rates in the home-based treatment of severe acute malnutrition with ready-to-use therapeutic food. This retrospective cohort study compared data from the treatment of two groups of children in Malawi aged 6-59 months w...

  16. Hypothyroidism Stimulates D2 Receptor-mediated Breathing in Response to Acute Hypoxia and alters D2 Receptors Levels in Carotid Bodies & Brain

    PubMed Central

    Schlenker, Evelyn H.; Schultz, Harold D.

    2011-01-01

    Hypothyroidism can depress breathing and alter dopamine D2 receptor expression and function. We hypothesized that relative to euthyroid hamsters (EH), hypothyroid hamsters (HH) contain increased D2 receptors in brain regions associated with breathing and carotid bodies (CB), and that stimulation of D2 receptors would decease ventilation more in the HH compared to the EH. Hamsters were treated with vehicle, carmoxirile (peripherally acting D2 receptor agonist), or bromocriptine (central and peripherally acting D2 receptor agonist) and breathing was evaluated during exposure to air, hypoxia, and then air. HH exhibited increased D2 receptor protein levels in the striatum and CB’s, but decreased levels in the paraventricular hypothalamic nucleus. Relative to vehicle, carmoxirole and bromocriptine stimulated ventilation in the HH during and following exposure to hypoxia. Only bromocriptine depressed ventilation in the EH during and after exposure to hypoxia. Thus,, hypothyroidism impacts the expression of D2 receptors in the carotid body, PVN and striatum, and D2 stimulation affects ventilation remarkably differently than in EH. PMID:22051191

  17. The prognostic value of pulmonary embolism severity index in acute pulmonary embolism: a meta-analysis

    PubMed Central

    2012-01-01

    Background Prognostic assessment is important for the management of patients with acute pulmonary embolism (APE). Pulmonary Embolism Severity Index (PESI) and simple PESI (sPESI) are new emerged prognostic assessment tools for APE. The aim of this meta-analysis is to assess the accuracy of the PESI and the sPESI to predict prognostic outcomes (all-cause and PE-related mortality, serious adverse events) in APE patients, and compare between these two PESIs. Methods MEDLINE and EMBASE database were searched up to June 2012 using the terms “Pulmonary Embolism Severity Index” and “pulmonary embolism”. Summary odds ratio (OR) with 95% confidence intervals (CIs) for prognostic outcomes in low risk PESI versus high risk PESI were calculated. Summary receiver operating characteristic curve (SROC) used to estimate overall predicting accuracies of prognostic outcomes. Results Twenty-one studies were included in this meta-analysis. The results showed low-risk PESI was significantly associated with lower all-cause mortality (OR 0.13; 95% CI 0.12 to 0.15), PE-related mortality (OR 0.09; 95% CI 0.05 to 0.17) and serious adverse events (OR 0.34; 95% CI 0.29 to 0.41), with no homogeneity across studies. In sPESI subgroup, the OR of all-cause mortality, PE-related mortality, and serious adverse events was 0.10 (95% CI 0.08 to 0.14), 0.09 (95% CI 0.03 to 0.26) and 0.40 (95% CI 0.31 to 0.51), respectively; while in PESI subgroup, the OR was 0.14 (95% CI 0.13 to 0.16), 0.09 (95% CI 0.04 to 0.21), and 0.30 (95% CI 0.23 to 0.38), respectively. For accuracy analysis, the pooled sensitivity, the pooled specificity, and the overall weighted AUC for PESI predicting all-cause mortality was 0.909 (95% CI: 0.900 to 0.916), 0.411 (95% CI: 0.407 to 0.415), and 0.7853±0.0058, respectively; for PE-related mortality, it was 0.953 (95% CI: 0.913 to 0.978), 0.374 (95% CI: 0.360 to 0.388), and 0.8218±0.0349, respectively; for serious adverse events, it was 0.821 (95% CI: 0.795 to 0.845), 0

  18. Infections in Children Admitted with Complicated Severe Acute Malnutrition in Niger

    PubMed Central

    Page, Anne-Laure; de Rekeneire, Nathalie; Sayadi, Sani; Aberrane, Said; Janssens, Ann-Carole; Rieux, Claire; Djibo, Ali; Manuguerra, Jean-Claude; Ducou-le-Pointe, Hubert; Grais, Rebecca F.; Schaefer, Myrto; Guerin, Philippe J.; Baron, Emmanuel

    2013-01-01

    Background Although malnutrition affects thousands of children throughout the Sahel each year and predisposes them to infections, there is little data on the etiology of infections in these populations. We present a clinical and biological characterization of infections in hospitalized children with complicated severe acute malnutrition (SAM) in Maradi, Niger. Methods Children with complicated SAM hospitalized in the intensive care unit of a therapeutic feeding center, with no antibiotics in the previous 7 days, were included. A clinical examination, blood, urine and stool cultures, and chest radiography were performed systematically on admission. Results Among the 311 children included in the study, gastroenteritis was the most frequent clinical diagnosis on admission, followed by respiratory tract infections and malaria. Blood or urine culture was positive in 17% and 16% of cases, respectively, and 36% had abnormal chest radiography. Enterobacteria were sensitive to most antibiotics, except amoxicillin and cotrimoxazole. Twenty-nine (9%) children died, most frequently from sepsis. Clinical signs were poor indicators of infection and initial diagnoses correlated poorly with biologically or radiography-confirmed diagnoses. Conclusions These data confirm the high level of infections and poor correlation with clinical signs in children with complicated SAM, and provide antibiotic resistance profiles from an area with limited microbiological data. These results contribute unique data to the ongoing debate on the use and choice of broad-spectrum antibiotics as first-line treatment in children with complicated SAM and reinforce the call for an update of international guidelines on management of complicated SAM based on more recent data. PMID:23874731

  19. Mechanisms of Host Receptor Adaptation by Severe Acute Respiratory Syndrome Coronavirus

    SciTech Connect

    Wu, Kailang; Peng, Guiqing; Wilken, Matthew; Geraghty, Robert J.; Li, Fang

    2012-12-10

    The severe acute respiratory syndrome coronavirus (SARS-CoV) from palm civets has twice evolved the capacity to infect humans by gaining binding affinity for human receptor angiotensin-converting enzyme 2 (ACE2). Numerous mutations have been identified in the receptor-binding domain (RBD) of different SARS-CoV strains isolated from humans or civets. Why these mutations were naturally selected or how SARS-CoV evolved to adapt to different host receptors has been poorly understood, presenting evolutionary and epidemic conundrums. In this study, we investigated the impact of these mutations on receptor recognition, an important determinant of SARS-CoV infection and pathogenesis. Using a combination of biochemical, functional, and crystallographic approaches, we elucidated the molecular and structural mechanisms of each of these naturally selected RBD mutations. These mutations either strengthen favorable interactions or reduce unfavorable interactions with two virus-binding hot spots on ACE2, and by doing so, they enhance viral interactions with either human (hACE2) or civet (cACE2) ACE2. Therefore, these mutations were viral adaptations to either hACE2 or cACE2. To corroborate the above analysis, we designed and characterized two optimized RBDs. The human-optimized RBD contains all of the hACE2-adapted residues (Phe-442, Phe-472, Asn-479, Asp-480, and Thr-487) and possesses exceptionally high affinity for hACE2 but relative low affinity for cACE2. The civet-optimized RBD contains all of the cACE2-adapted residues (Tyr-442, Pro-472, Arg-479, Gly-480, and Thr-487) and possesses exceptionally high affinity for cACE2 and also substantial affinity for hACE2. These results not only illustrate the detailed mechanisms of host receptor adaptation by SARS-CoV but also provide a molecular and structural basis for tracking future SARS-CoV evolution in animals.

  20. Gut DNA viromes of Malawian twins discordant for severe acute malnutrition.

    PubMed

    Reyes, Alejandro; Blanton, Laura V; Cao, Song; Zhao, Guoyan; Manary, Mark; Trehan, Indi; Smith, Michelle I; Wang, David; Virgin, Herbert W; Rohwer, Forest; Gordon, Jeffrey I

    2015-09-22

    The bacterial component of the human gut microbiota undergoes a definable program of postnatal development. Evidence is accumulating that this program is disrupted in children with severe acute malnutrition (SAM) and that their persistent gut microbiota immaturity, which is not durably repaired with current ready-to-use therapeutic food (RUTF) interventions, is causally related to disease pathogenesis. To further characterize gut microbial community development in healthy versus malnourished infants/children, we performed a time-series metagenomic study of DNA isolated from virus-like particles (VLPs) recovered from fecal samples collected during the first 30 mo of postnatal life from eight pairs of mono- and dizygotic Malawian twins concordant for healthy growth and 12 twin pairs discordant for SAM. Both members of discordant pairs were sampled just before, during, and after treatment with a peanut-based RUTF. Using Random Forests and a dataset of 17,676 viral contigs assembled from shotgun sequencing reads of VLP DNAs, we identified viruses that distinguish different stages in the assembly of the gut microbiota in the concordant healthy twin pairs. This developmental program is impaired in both members of SAM discordant pairs and not repaired with RUTF. Phage plus members of the Anelloviridae and Circoviridae families of eukaryotic viruses discriminate discordant from concordant healthy pairs. These results disclose that apparently healthy cotwins in discordant pairs have viromes associated with, although not necessarily mediators, of SAM; as such, they provide a human model for delineating normal versus perturbed postnatal acquisition and retention of the gut microbiota's viral component in populations at risk for malnutrition.

  1. Dietary supplementation with aromatic amino acids increases protein synthesis in children with severe acute malnutrition.

    PubMed

    Hsu, Jean W; Badaloo, Asha; Wilson, Lorraine; Taylor-Bryan, Carolyn; Chambers, Bentley; Reid, Marvin; Forrester, Terrence; Jahoor, Farook

    2014-05-01

    Although 2 earlier studies reported that aromatic amino acid (AAA) supplementation of children with severe acute malnutrition (SAM) improved whole-body protein anabolism during the early postadmission (maintenance) phase of rehabilitation, it is not known whether this positive effect was maintained during the catch-up growth and recovery phases of treatment. This study aimed to determine whether supplementation with an AAA cocktail (330 mg · kg(-1) · d(-1)) vs. isonitrogenous Ala would improve measures of protein kinetics in 22 children, aged 4-31 mo, during the catch-up growth and recovery phases of treatment for SAM. Protein kinetics were assessed by measuring leucine, phenylalanine, and urea kinetics with the use of standard stable isotope tracer methods in the fed state. Supplementation started at the end of the maintenance period when the children were clinically/metabolically stable and continued up to full nutritional recovery. Three experiments were performed: at the end of maintenance (at ∼13 d postadmission), at mid-catch-up growth (at ∼23 d post- admission when the children had replenished 50% of their weight deficit), and at recovery (at ∼48 d postadmission when they had achieved at least 90% weight for length). Children in the AAA group had significantly faster protein synthesis compared with those in the Ala group at mid-catch-up growth (101 ± 10 vs. 72 ± 7 μmol phenylalanine · kg(-1) · h(-1); P < 0.05) and better protein balance at mid-catch-up growth (49 ± 5 vs. 30 ± 2 μmol phenylalanine · kg(-1) · h(-1); P < 0.05) and at recovery (37 ± 8 vs. 11 ± 3 μmol phenylalanine · kg(-1) · h(-1); P < 0.05). We conclude that dietary supplementation with AAA accelerates net protein synthesis in children during nutritional rehabilitation for SAM.

  2. Changes in whole-blood PUFA and their predictors during recovery from severe acute malnutrition.

    PubMed

    Babirekere-Iriso, Esther; Mortensen, Charlotte G; Mupere, Ezekiel; Rytter, Maren J H; Namusoke, Hanifa; Michaelsen, Kim F; Briend, André; Stark, Ken D; Friis, Henrik; Lauritzen, Lotte

    2016-05-28

    Children with severe acute malnutrition (SAM) with complications require in-patient management including therapeutic feeding. Little attention has been given to the effects of these feeds on the essential fatty acid status of children with SAM. The objective of this study was to describe changes in the PUFA composition in whole blood in children with SAM during treatment and to determine predictors of change. This prospective study took place in a paediatric nutrition rehabilitation unit in Kampala, Uganda, and assessed whole-blood fatty acid composition of children with SAM at admission, transition, discharge and follow-up (8 and 16 weeks). ANCOVA was used to identify predictors of change in whole-blood PUFA. The study included 120 children with SAM and twenty-nine healthy control children of similar age and sex. Among the SAM children, 38 % were female and 64 % had oedema. Whole-blood n-6 PUFA proportions increased from admission to follow-up, except for arachidonic acid, which decreased by 0·79 (95 % CI 0·46, 1·12) fatty acid percentage (FA%) from admission to transition and 0·10 (95 % CI 0·23, 0·44) FA% at discharge. n-3 Long-chain (LC) PUFA decreased by 0·21 (95 % CI 0·03, 0·40) FA% at discharge and 0·22 (95 % CI 0·01, 0·42) FA% at 8 weeks of follow-up. This decrease was greater in children from families with recent fish intake and those with nasogastric tube feeding. Current therapeutic feeds do not correct whole-blood levels of LCPUFA, particularly n-3 LCPUFA, in children with SAM. Increased attention is needed to the contents of n-3 LCPUFA in therapeutic feeds. PMID:26996197

  3. The effect of severe acute respiratory syndrome (SARS) on emergency airway management.

    PubMed

    Wong, Evelyn; Ho, Khoy Kheng

    2006-07-01

    From early March 2003 to late May 2003, severe acute respiratory syndrome (SARS) was detected in Singapore. The increase in workload and new infection control procedures were thought to affect resuscitation and airway management. Our aim was to study the effects of wearing of personal protective equipment (PPE) and powered air-purifying respirator (PAPR) and the restriction in the number of resuscitation personnel on airway management during the SARS crisis. Data was collected prospectively through an ongoing emergency airway registry. The data was divided into three periods: (1) before PPE was instituted from 1 November 2002 to 31 March 2003; (2) during SARS (when PPE use was mandatory) from 1 April to 31 July 2003; (3) post-SARs (when PPE use was non-mandatory but encouraged) from 1 August to 31 March 2004. There was no change in patient demographics during the three periods. There were significant increases in the proportion of resuscitation cases and airway interventions during the SARS period compared to the pre-SARS period. The resident medical officer intubation rate decreased from 45.1% pre-SARS to 35.2% during SARS and 17.7% post-SARS. The complication rates were 10.5%, 9.9% and 9.4% in periods 1-3, respectively. Restriction in the number of healthcare staff attending to each patient may have influenced the department's decision to allow only the most confident or experienced personnel to manage the airway. The exposure of junior medical officers in emergency airway management during SARS and the immediate post-SARS period was decreased. This trend should be monitored further and intervention may be necessary should it continue to decline. PMID:16762480

  4. Gut DNA viromes of Malawian twins discordant for severe acute malnutrition

    PubMed Central

    Reyes, Alejandro; Blanton, Laura V.; Cao, Song; Zhao, Guoyan; Manary, Mark; Trehan, Indi; Smith, Michelle I.; Wang, David; Virgin, Herbert W.; Rohwer, Forest; Gordon, Jeffrey I.

    2015-01-01

    The bacterial component of the human gut microbiota undergoes a definable program of postnatal development. Evidence is accumulating that this program is disrupted in children with severe acute malnutrition (SAM) and that their persistent gut microbiota immaturity, which is not durably repaired with current ready-to-use therapeutic food (RUTF) interventions, is causally related to disease pathogenesis. To further characterize gut microbial community development in healthy versus malnourished infants/children, we performed a time-series metagenomic study of DNA isolated from virus-like particles (VLPs) recovered from fecal samples collected during the first 30 mo of postnatal life from eight pairs of mono- and dizygotic Malawian twins concordant for healthy growth and 12 twin pairs discordant for SAM. Both members of discordant pairs were sampled just before, during, and after treatment with a peanut-based RUTF. Using Random Forests and a dataset of 17,676 viral contigs assembled from shotgun sequencing reads of VLP DNAs, we identified viruses that distinguish different stages in the assembly of the gut microbiota in the concordant healthy twin pairs. This developmental program is impaired in both members of SAM discordant pairs and not repaired with RUTF. Phage plus members of the Anelloviridae and Circoviridae families of eukaryotic viruses discriminate discordant from concordant healthy pairs. These results disclose that apparently healthy cotwins in discordant pairs have viromes associated with, although not necessarily mediators, of SAM; as such, they provide a human model for delineating normal versus perturbed postnatal acquisition and retention of the gut microbiota’s viral component in populations at risk for malnutrition. PMID:26351661

  5. The effect of severe acute respiratory syndrome (SARS) on emergency airway management.

    PubMed

    Wong, Evelyn; Ho, Khoy Kheng

    2006-07-01

    From early March 2003 to late May 2003, severe acute respiratory syndrome (SARS) was detected in Singapore. The increase in workload and new infection control procedures were thought to affect resuscitation and airway management. Our aim was to study the effects of wearing of personal protective equipment (PPE) and powered air-purifying respirator (PAPR) and the restriction in the number of resuscitation personnel on airway management during the SARS crisis. Data was collected prospectively through an ongoing emergency airway registry. The data was divided into three periods: (1) before PPE was instituted from 1 November 2002 to 31 March 2003; (2) during SARS (when PPE use was mandatory) from 1 April to 31 July 2003; (3) post-SARs (when PPE use was non-mandatory but encouraged) from 1 August to 31 March 2004. There was no change in patient demographics during the three periods. There were significant increases in the proportion of resuscitation cases and airway interventions during the SARS period compared to the pre-SARS period. The resident medical officer intubation rate decreased from 45.1% pre-SARS to 35.2% during SARS and 17.7% post-SARS. The complication rates were 10.5%, 9.9% and 9.4% in periods 1-3, respectively. Restriction in the number of healthcare staff attending to each patient may have influenced the department's decision to allow only the most confident or experienced personnel to manage the airway. The exposure of junior medical officers in emergency airway management during SARS and the immediate post-SARS period was decreased. This trend should be monitored further and intervention may be necessary should it continue to decline.

  6. Predicting Outcome in Acute Organophosphorus Poisoning with a Poison Severity Score or the Glasgow Coma Scale

    PubMed Central

    Davies, James O. J.; Eddleston, Michael; Buckley, Nick A.

    2008-01-01

    Background: Organophosphorus pesticide poisoning kills around 200,000 people each year, principally due to self poisoning in the Asia-Pacific region. Aim: We wished to assess whether patients at high risk of death could be identified accurately using clinical parameters soon after hospital admission. Design: We evaluated the usefulness of the International Program on Chemical Safety Poison Severity Score (IPCS PSS) and the Glasgow Coma Score (GCS) prospectively for predicting death in patients poisoned by organophosphorus pesticides. Methods: Data were collected as part of a multicentre cohort study in Sri Lanka. Study doctors saw all patients on admission, collecting data on pulse, blood pressure, pupil size, need for intubation, and GCS. Results: 1365 patients with a history of acute organophosphorus poisoning were included. Receiver operating characteristic (ROC) curves were calculated for the IPCS PSS and GCS on admission. The IPCS PSS and GCS had similar ROC area under the curves (AUC) and best cut points as determined by Youden's index (AUC/sensitivity/specificity 0.81/0.78/0.79 for IPCS PSS ≥ grade 2 and 0.84/0.79/0.79 for GCS ≤13). The predictive value varied with the pesticide ingested, being more accurate for dimethoate poisoning and less accurate for fenthion poisoning (GCS AUC 0.91 compared to 0.69). Conclusions: GCS and the IPCS PSS were similarly effective at predicting outcome. Patients presenting with a GCS ≤ 13 need intensive monitoring and treatment. However, the identity of the organophosphate must be taken into account since the half of all patients who died from fenthion poisoning only had mild symptoms at presentation. PMID:18319295

  7. The hydrocortisone protection of glycocalyx on the intestinal capillary endothelium during severe acute pancreatitis.

    PubMed

    Gao, Shun-Liang; Zhang, Yun; Zhang, Shao-Yang; Liang, Zhong-Yan; Yu, Wen-Qiao; Liang, Ting-Bo

    2015-05-01

    Malfunctioning of the intestinal microcirculation secondary to severe acute pancreatitis (SAP) can cause injuries to the intestinal mucosal barrier, translocation of gut flora, and sepsis. The glycocalyx on the vascular endothelium helps maintain its normal function through multiple mechanisms, including regulation of vascular permeability and inhibition of intercellular adhesion. It is unknown that whether pancreatitis inflicts injuries to the intestinal mucosal barrier through damaging glycocalyx or stabilizing glycocalyx can be a potential therapeutic target in maintaining the integrity of the intestinal mucosal barrier during SAP. Injecting sodium taurocholate into the pancreatic duct of Sprague-Dawley rats induced SAP. Intestinal perfusion, changes in endothelial glycocalyx, and the associated molecular mechanisms were assessed by laser Doppler velocimetry, electron microscopy, and the levels of heparan sulfate, syndacan-1, and tumor necrosis factor-α (TNF-α) in the superior mesenteric vein. Protective effects of hydrocortisone treatment in the intestinal microcirculation during SAP were evaluated. Degradation of the glycocalyx in intestinal vascular endothelium developed 3 h after the onset of SAP in rats. By 12 h, significant reduction of intestinal perfusion was observed. The concomitant elevated levels of TNF-α in the superior mesenteric vein suggest that TNF-α is involved in the degradation of the glycocalyx. With the use of hydrocortisone, intestinal perfusion was improved and the degradation of glycocalyx was reduced. The degradation of glycocalyx is involved in the malfunction of the intestinal microcirculation. The massive release of TNF-α participates in this process and leads to glycocalyx degradation. Hydrocortisone may be a good therapy to prevent this process.

  8. Challenges of Estimating the Annual Caseload of Severe Acute Malnutrition: The Case of Niger

    PubMed Central

    Hallarou, Mahaman; Gérard, Jean-Christophe; Donnen, Philippe; Macq, Jean

    2016-01-01

    Introduction Reliable prospective estimates of annual severe acute malnutrition (SAM) caseloads for treatment are needed for policy decisions and planning of quality services in the context of competing public health priorities and limited resources. This paper compares the reliability of SAM caseloads of children 6–59 months of age in Niger estimated from prevalence at the start of the year and counted from incidence at the end of the year. Methods Secondary data from two health districts for 2012 and the country overall for 2013 were used to calculate annual caseload of SAM. Prevalence and coverage were extracted from survey reports, and incidence from weekly surveillance systems. Results The prospective caseload estimate derived from prevalence and duration of illness underestimated the true burden. Similar incidence was derived from two weekly surveillance systems, but differed from that obtained from the monthly system. Incidence conversion factors were two to five times higher than recommended. Discussion Obtaining reliable prospective caseloads was challenging because prevalence is unsuitable for estimating incidence of SAM. Different SAM indicators identified different SAM populations, and duration of illness, expected contact coverage and population figures were inaccurate. The quality of primary data measurement, recording and reporting affected incidence numbers from surveillance. Coverage estimated in population surveys was rarely available, and coverage obtained by comparing admissions with prospective caseload estimates was unrealistic or impractical. Conclusions Caseload estimates derived from prevalence are unreliable and should be used with caution. Policy and service decisions that depend on these numbers may weaken performance of service delivery. Niger may improve SAM surveillance by simplifying and improving primary data collection and methods using innovative information technologies for single data entry at the first contact with the health

  9. Impaired cardiovascular structure and function in adult survivors of severe acute malnutrition.

    PubMed

    Tennant, Ingrid A; Barnett, Alan T; Thompson, Debbie S; Kips, Jan; Boyne, Michael S; Chung, Edward E; Chung, Andrene P; Osmond, Clive; Hanson, Mark A; Gluckman, Peter D; Segers, Patrick; Cruickshank, J Kennedy; Forrester, Terrence E

    2014-09-01

    Malnutrition below 5 years remains a global health issue. Severe acute malnutrition (SAM) presents in childhood as oedematous (kwashiorkor) or nonoedematous (marasmic) forms, with unknown long-term cardiovascular consequences. We hypothesized that cardiovascular structure and function would be poorer in SAM survivors than unexposed controls. We studied 116 adult SAM survivors, 54 after marasmus, 62 kwashiorkor, and 45 age/sex/body mass index-matched community controls who had standardized anthropometry, blood pressure, echocardiography, and arterial tonometry performed. Left ventricular indices and outflow tract diameter, carotid parameters, and pulse wave velocity were measured, with systemic vascular resistance calculated. All were expressed as SD scores. Mean (SD) age was 28.8±7.8 years (55% men). Adjusting for age, sex, height, and weight, SAM survivors had mean (SE) reductions for left ventricular outflow tract diameter of 0.67 (0.16; P<0.001), stroke volume 0.44 (0.17; P=0.009), cardiac output 0.5 (0.16; P=0.001), and pulse wave velocity 0.32 (0.15; P=0.03) compared with controls but higher diastolic blood pressures (by 4.3; 1.2-7.3 mm Hg; P=0.007). Systemic vascular resistance was higher in marasmus and kwashiorkor survivors (30.2 [1.2] and 30.8 [1.1], respectively) than controls 25.3 (0.8), overall difference 5.5 (95% confidence interval, 2.8-8.4 mm Hg min/L; P<0.0001). No evidence of large vessel or cardiac remodeling was found, except closer relationships between these indices in former marasmic survivors. Other parameters did not differ between SAM survivor groups. We conclude that adult SAM survivors had smaller outflow tracts and cardiac output when compared with controls, yet markedly elevated peripheral resistance. Malnutrition survivors are thus likely to develop excess hypertension in later life, especially when exposed to obesity.

  10. Changes in whole-blood PUFA and their predictors during recovery from severe acute malnutrition.

    PubMed

    Babirekere-Iriso, Esther; Mortensen, Charlotte G; Mupere, Ezekiel; Rytter, Maren J H; Namusoke, Hanifa; Michaelsen, Kim F; Briend, André; Stark, Ken D; Friis, Henrik; Lauritzen, Lotte

    2016-05-28

    Children with severe acute malnutrition (SAM) with complications require in-patient management including therapeutic feeding. Little attention has been given to the effects of these feeds on the essential fatty acid status of children with SAM. The objective of this study was to describe changes in the PUFA composition in whole blood in children with SAM during treatment and to determine predictors of change. This prospective study took place in a paediatric nutrition rehabilitation unit in Kampala, Uganda, and assessed whole-blood fatty acid composition of children with SAM at admission, transition, discharge and follow-up (8 and 16 weeks). ANCOVA was used to identify predictors of change in whole-blood PUFA. The study included 120 children with SAM and twenty-nine healthy control children of similar age and sex. Among the SAM children, 38 % were female and 64 % had oedema. Whole-blood n-6 PUFA proportions increased from admission to follow-up, except for arachidonic acid, which decreased by 0·79 (95 % CI 0·46, 1·12) fatty acid percentage (FA%) from admission to transition and 0·10 (95 % CI 0·23, 0·44) FA% at discharge. n-3 Long-chain (LC) PUFA decreased by 0·21 (95 % CI 0·03, 0·40) FA% at discharge and 0·22 (95 % CI 0·01, 0·42) FA% at 8 weeks of follow-up. This decrease was greater in children from families with recent fish intake and those with nasogastric tube feeding. Current therapeutic feeds do not correct whole-blood levels of LCPUFA, particularly n-3 LCPUFA, in children with SAM. Increased attention is needed to the contents of n-3 LCPUFA in therapeutic feeds.

  11. [Hepatotoxicity in the critically ill patient. The liver under an acute severe insult].

    PubMed

    García de Lorenzo y Mateos, A; Rodríguez Montes, J A

    2008-05-01

    The liver plays an essential role in the metabolism of most of the nutrients since it is a mainly metabolic organ carrying out a series of physiological and metabolic processes related with protein and energy metabolism. The intestinal tract is considered a key element in the development of Multiorgan Dysfunction (MOD) or failure by loosing its barrier function (impaired permeability) against toxins, bio-products and occasionally intraluminal bacteria secondary to hypoxia, one of the main pathophysiogenic mechanisms being the insufficient blood flow to splacnic organs. Liver dysfunction and/or impairment of liver function test are a common event in critically ill patients. They may be due to previous liver cirrhosis or to more immediate causes of liver failure such as sepsis, drugs, liver transplant or any of the multiple etiologies for hepatitis. PMID:18714407

  12. Accessing Inpatient Rehabilitation after Acute Severe Stroke: Age, Mobility, Prestroke Function and Hospital Unit Are Associated with Discharge to Inpatient Rehabilitation

    ERIC Educational Resources Information Center

    Hakkennes, Sharon; Hill, Keith D.; Brock, Kim; Bernhardt, Julie; Churilov, Leonid

    2012-01-01

    The objective of this study was to identify the variables associated with discharge to inpatient rehabilitation following acute severe stroke and to determine whether hospital unit contributed to access. Five acute hospitals in Victoria, Australia participated in this study. Patients were eligible for inclusion if they had suffered an acute severe…

  13. NO-dependent mechanisms of adaptation to hypoxia.

    PubMed

    Malyshev, I Y; Zenina, T A; Golubeva, L Y; Saltykova, V A; Manukhina, E B; Mikoyan, V D; Kubrina, L N; Vanin, A F

    1999-01-01

    In studying NO-dependent mechanisms of resistance to hypoxia, it was shown that (1) acute hypoxia induces NO overproduction in brain and leaves unaffected NO production in liver of rats; (2) adaptation to hypoxia decreases NO production in liver and brain; and (3) adaptation to hypoxia prevents NO overproduction in brain and potentiates NO synthesis in liver in acute hypoxia. Dinitrosyl iron complex (DNIC, 200 microg/kg, single dose, iv), a NO donor, decreases the resistance of animals to acute hypoxia by 30%. Nomega-nitro-L-arginine (L-NNA, 50 mg/kg, single dose, ip), a NO synthase inhibitor, and diethyl dithiocarbamate (DETC, 200 mg/kg, single dose, iv), a NO trap, increases this parameter 1.3 and 2 times, respectively. Adaptation to hypoxia developed against a background of accumulation of heat shock protein HSP70 in liver and brain. A course of DNIC reproduced the antihypoxic effect of adaptation. A course of L-NNA during adaptation hampered both accumulation of HSP70 and development of the antihypoxic effect. Therefore, NO and the NO-dependent activation of HSP70 synthesis play important roles in adaptation to hypoxia. PMID:10369180

  14. Serum amyloid A, procalcitonin, and C-reactive protein in early assessment of severity of acute pancreatitis.

    PubMed

    Pezzilli, R; Melzi d'Eril, G V; Morselli-Labate, A M; Merlini, G; Barakat, B; Bosoni, T

    2000-06-01

    Amyloid A (SAA) and procalcitonin (PCT) have been reported as useful indicators of inflammation. Our aim was to assess the utility of SAA and PCT in establishing the severity of acute pancreatitis in comparison to C-reactive protein (CRP): Thirty-one patients with acute pancreatitis enrolled within 24 hr from the onset of pain and 31 healthy subjects were studied. Nineteen patients had mild acute pancreatitis, and 12 had severe pancreatitis. Serum SAA, PCT, and CRP were measured in all subjects at admission and, in acute pancreatitis patients, during the following five days. Patients with acute pancreatitis had serum concentrations of SAA, PCT, and CRP significantly higher (P < 0.001) than those of healthy subjects during the entire study period. Using cutoff values ranging from 240 to 250 mg/liter for SAA, from 0.252 to 0.255 ng/ml for PCT, and from 12.8 to 12.9 mg/dl for CRP, the sensitivity (calculated on patients with severe pancreatitis), the specificity (calculated on patients with mild pancreatitis), and the efficiency (calculated as the percentage of correct classifications) were 76.8%, 69.3%, and 72.4% for SAA; 21.7%, 83.2%, and 58.2% for PCT; and 60.9%, 89.1%, and 77.6% for CRP. In conclusion, the sensitivity of SAA is significantly higher than that of PCT and CRP in assessing the severity of pancreatitis, whereas PCT and CRP had a specificity significantly higher than SAA. The accuracy and efficiency were similar for SAA and CRP, and both these markers had an accuracy and efficiency significantly higher than those of PCT.

  15. Predictors of Severe Acute and Late Toxicities in Patients With Localized Head-and-Neck Cancer Treated With Radiation Therapy

    SciTech Connect

    Meyer, Francois; Fortin, Andre; Wang, Chang Shu; Liu, Geoffrey

    2012-03-15

    Purpose: Radiation therapy (RT) causes acute and late toxicities that affect various organs and functions. In a large cohort of patients treated with RT for localized head and neck cancer (HNC), we prospectively assessed the occurrence of RT-induced acute and late toxicities and identified characteristics that predicted these toxicities. Methods and Materials: We conducted a randomized trial among 540 patients treated with RT for localized HNC to assess whether vitamin E supplementation could improve disease outcomes. Adverse effects of RT were assessed using the Radiation Therapy Oncology Group Acute Radiation Morbidity Criteria during RT and one month after RT, and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme at six and 12 months after RT. The most severe adverse effect among the organs/tissues was selected as an overall measure of either acute or late toxicity. Grade 3 and 4 toxicities were considered as severe. Stepwise multivariate logistic regression models were used to identify all independent predictors (p < 0.05) of acute or late toxicity and to estimate odds ratios (OR) for severe toxicity with their 95% confidence intervals (CI). Results: Grade 3 or 4 toxicity was observed in 23% and 4% of patients, respectively, for acute and late toxicity. Four independent predictors of severe acute toxicity were identified: sex (female vs. male: OR = 1.72, 95% confidence interval [CI]: 1.06-2.80), Karnofsky Performance Status (OR = 0.67 for a 10-point increment, 95% CI: 0.52-0.88), body mass index (above 25 vs. below: OR = 1.88, 95% CI: 1.22-2.90), TNM stage (Stage II vs. I: OR = 1.91, 95% CI: 1.25-2.92). Two independent predictors were found for severe late toxicity: female sex (OR = 3.96, 95% CI: 1.41-11.08) and weight loss during RT (OR = 1.26 for a 1 kg increment, 95% CI: 1.12-1.41). Conclusions: Knowledge of these predictors easily collected in a clinical setting could help

  16. The impact of physical therapy in patients with severe traumatic brain injury during acute and post-acute rehabilitation according to coma duration.

    PubMed

    Lendraitienė, Eglė; Petruševičienė, Daiva; Savickas, Raimondas; Žemaitienė, Ieva; Mingaila, Sigitas

    2016-07-01

    [Purpose] The aim of study was to evaluate the impact of physical therapy on the recovery of motor and mental status in patients who sustained a severe traumatic brain injury, according to coma duration in acute and post-acute rehabilitation. [Subjects and Methods] The study population comprised patients with levels of consciousness ranging from 3 to 8 according to Glasgow Coma Scale score. The patients were divided into 2 groups based on coma duration as follows: group 1, those who were in a coma up to 1 week, and group 2, those who were in a coma for more than 2 weeks. The recovery of the patients' motor function was evaluated according to the Motor Assessment Scale and the recovery of mental status according to the Mini-Mental State Examination. [Results] The evaluation of motor and mental status recovery revealed that the patients who were in a coma up to 1 week recovered significantly better after physical therapy during the acute rehabilitation than those who were in a coma for longer than 2 weeks. [Conclusion] The recovery of motor and mental status of the patients in acute rehabilitation was significantly better for those in a coma for a shorter period.

  17. The impact of physical therapy in patients with severe traumatic brain injury during acute and post-acute rehabilitation according to coma duration.

    PubMed

    Lendraitienė, Eglė; Petruševičienė, Daiva; Savickas, Raimondas; Žemaitienė, Ieva; Mingaila, Sigitas

    2016-07-01

    [Purpose] The aim of study was to evaluate the impact of physical therapy on the recovery of motor and mental status in patients who sustained a severe traumatic brain injury, according to coma duration in acute and post-acute rehabilitation. [Subjects and Methods] The study population comprised patients with levels of consciousness ranging from 3 to 8 according to Glasgow Coma Scale score. The patients were divided into 2 groups based on coma duration as follows: group 1, those who were in a coma up to 1 week, and group 2, those who were in a coma for more than 2 weeks. The recovery of the patients' motor function was evaluated according to the Motor Assessment Scale and the recovery of mental status according to the Mini-Mental State Examination. [Results] The evaluation of motor and mental status recovery revealed that the patients who were in a coma up to 1 week recovered significantly better after physical therapy during the acute rehabilitation than those who were in a coma for longer than 2 weeks. [Conclusion] The recovery of motor and mental status of the patients in acute rehabilitation was significantly better for those in a coma for a shorter period. PMID:27512262

  18. The impact of physical therapy in patients with severe traumatic brain injury during acute and post-acute rehabilitation according to coma duration

    PubMed Central

    Lendraitienė, Eglė; Petruševičienė, Daiva; Savickas, Raimondas; Žemaitienė, Ieva; Mingaila, Sigitas

    2016-01-01

    [Purpose] The aim of study was to evaluate the impact of physical therapy on the recovery of motor and mental status in patients who sustained a severe traumatic brain injury, according to coma duration in acute and post-acute rehabilitation. [Subjects and Methods] The study population comprised patients with levels of consciousness ranging from 3 to 8 according to Glasgow Coma Scale score. The patients were divided into 2 groups based on coma duration as follows: group 1, those who were in a coma up to 1 week, and group 2, those who were in a coma for more than 2 weeks. The recovery of the patients’ motor function was evaluated according to the Motor Assessment Scale and the recovery of mental status according to the Mini-Mental State Examination. [Results] The evaluation of motor and mental status recovery revealed that the patients who were in a coma up to 1 week recovered significantly better after physical therapy during the acute rehabilitation than those who were in a coma for longer than 2 weeks. [Conclusion] The recovery of motor and mental status of the patients in acute rehabilitation was significantly better for those in a coma for a shorter period. PMID:27512262

  19. Interleukin-22 ameliorates acute severe pancreatitis-associated lung injury in mice

    PubMed Central

    Qiao, Ying-Ying; Liu, Xiao-Qin; Xu, Chang-Qin; Zhang, Zheng; Xu, Hong-Wei

    2016-01-01

    AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22 (rIL-22) on L-arginine-induced acute severe pancreatitis (SAP)-associated lung injury and the possible signaling pathway involved. METHODS: Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase (MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin (HE) staining. Expression of B cell lymphoma/leukemia-2 (Bcl-2), Bcl-xL and IL-22RA1 mRNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot. RESULTS: Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group (P < 0.05). In addition, the animals in the SAP group showed significant pancreatic and lung injuries. The expression of Bcl-2 and Bcl-xL mRNAs in the SAP group was decreased markedly, while the IL-22RA1 mRNA expression was increased significantly relative to the normal control group (P < 0.05). Pretreatment with PBS did not significantly affect the serum amylase levels, MPO activity or expression of Bcl-2, Bcl-xL or IL-22RA1 mRNA (P > 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the rIL-22 group were significantly lower than those in the SAP group (P < 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, rIL-22 stimulated the expression of Bcl-2, Bcl-xL and IL-22RA1 mRNAs in the lung (P < 0.05). In addition, the ratio of p-STAT3 to STAT3 protein in the rIL-22 group was significantly higher than that in the PBS group (P < 0.05). CONCLUSION

  20. ThermoSpots to Detect Hypothermia in Children with Severe Acute Malnutrition

    PubMed Central

    Mole, Thomas B.; Kennedy, Neil; Ndoya, Noel; Emond, Alan

    2012-01-01

    Introduction Hypothermia is a risk factor for increased mortality in children with severe acute malnutrition (SAM). Yet frequent temperature measurement remains unfeasible in under-resourced units in developing countries. ThermoSpot is a continuous temperature monitoring sticker designed originally for neonates. When applied to skin, its liquid crystals are designed to turn black with hypothermia and remain green with normothermia. Aims To (i) estimate the diagnostic accuracy of ThermoSpots for detecting WHO-defined hypothermia (core temperature <35.5°C or peripheral temperature <35.0°C) in children with SAM and (ii) determine their acceptability amongst mothers. Methods Children with SAM in a malnutrition unit in Malawi were enrolled during March-July 2010. The sensitivity and specificity of ThermoSpots were calculated by comparing the device colour against ‘gold standard’ rectal temperatures taken on admission and follow up peripheral temperatures taken until discharge. Guardians completed a questionnaire to assess acceptability. Results Hypothermia was uncommon amongst the 162 children enrolled. ThermoSpot successfully detected the one rectal temperature and two peripheral temperatures recorded that met the WHO definition of hypothermia. Overall, 3/846 (0.35%) temperature measurements were in the WHO-defined hypothermia range. Interpreting the brown transition colour (between black and green) as hypothermia improved sensitivities. For milder hypothermia definitions, sensitivities declined (<35.4°C, 50.0%; <35.9°C, 39.2%). Specificity was consistently above 94%. From questionnaires, 40/43 (93%) mothers reported they were 90–100% happy with the device overall. Free-text answers revealed themes of “Skin Rashes”, “User-satisfaction” and “Empowerment". Conclusion Although hypothermia was uncommon in this study, ThermoSpots successfully detected these episodes in malnourished children and were acceptable to mothers. Research in settings where

  1. Do Children with Uncomplicated Severe Acute Malnutrition Need Antibiotics? A Systematic Review and Meta-Analysis

    PubMed Central

    Alcoba, Gabriel; Kerac, Marko; Breysse, Serge; Salpeteur, Cécile; Galetto-Lacour, Annick; Briend, André; Gervaix, Alain

    2013-01-01

    Background Current (1999) World Health Organization guidelines recommend giving routine antibiotics (AB) for all children with severe acute malnutrition (SAM), even if they have uncomplicated disease with no clinically obvious infections. We examined the evidence behind this recommendation. Methods and Findings OVID-MEDLINE, EMBASE, COCHRANE, GLOBAL-HEALTH, CINAHL, POPLINE, AFRICA-WIDE-NiPAD, and LILACS were searched for AB efficacy, bacterial resistance, and infection rates in SAM. Following PRISMA guidelines, a systematic review and meta-analysis were performed. Three randomised controlled trials (RCT), five Cochrane reviews, and 37 observational studies were identified. One cohort-study showed no increase in nutritional-cure and mortality in uncomplicated SAM where no AB were used. (p>0.05). However, an unpublished RCT in this setting did show mortality benefits. Another RCT did not show superiority of ceftriaxone over amoxicilllin for these same outcomes, but adressed SAM children with and without complications (p = 0.27). Another RCT showed no difference between amoxicillin and cotrimoxazole efficacies for pneumonia in underweight, but not SAM. Our meta-analysis of 12 pooled susceptibility-studies for all types of bacterial isolates, including 2767 stricly SAM children, favoured amoxicillin over cotrimoxazole for susceptibility medians: 42% (IQR 27–55%) vs 22% (IQR 17–23%) and population-weighted-means 52.9% (range 23–57%) vs 35.4% (range 6.7–42%). Susceptibilities to second-line AB were better, above 80%. Prevalence of serious infections in SAM, pooled from 24 studies, ranged from 17% to 35.2%. No study infered any association of infection prevalence with AB regimens in SAM. Conclusions The evidence underlying current antibiotic recommendations for uncomplicated SAM is weak. Susceptibility-studies favour amoxicillin over cotrimoxazole. However, given that these antibiotics have side-effects, costs, and risks as well as benefits, their routine use

  2. Complete renal recovery from severe acute renal failure after thrombolysis of bilateral renal vein thrombosis.

    PubMed

    Ramadoss, Suresh; Jones, Robert G; Foggensteiner, Lukas; Willis, Andrew P; Duddy, Martin J

    2012-10-01

    A previously healthy young man presented with acute renal failure due to extensive spontaneous deep vein thrombosis, including the inferior vena cava (IVC) and both renal veins. The patient was treated with selectively delivered thrombolytic therapy over a 7-day-period, which resulted in renal vein patency and complete recovery of renal function. A stent was placed over a segment stenosis of the IVC. No thrombophilic factors were identified. Bilateral renal vein thrombosis in young fit individuals is an unusual cause of acute renal failure. Thrombolytic therapy, even with delay, can completely restore renal function.

  3. A Case of Idiopathic Severe Acute Pancreatitis following Cesarean Section Delivery.

    PubMed

    Kim, Jung; Choi, Jin Ho; Shin, Bang Sup; Nam, Joon Yeul; Kang, Eun Ae; Kim, Joo Seong; Hwang, Jin Hyeok; Kim, Jaihwan

    2016-09-25

    Acute pancreatitis rarely occurs in the postpartum period. Furthermore, there are very few reports of it after cesarean section delivery. A 35-year-old woman presented with dyspnea and abdominal distension on the third day after cesarean section delivery. Under a suspicion of acute pancreatitis, she was initially managed with conservative treatment. However, she developed intra-abdominal fluid collections and gastric bleeding, which were managed with percutaneous drainage, endoscopic hemostasis, and angiographic embolization. She was discharged with good clinical recovery. Postpartum pancreatitis, especially after cesarean section, is rare; however, its management is not different from that for usual pancreatitis. PMID:27646587

  4. [Importance of the case of coronavirus-associated severe acute respiratory syndrome detected in Hungary in 2005].

    PubMed

    Rókusz, László; Jankovics, István; Jankovics, Máté; Sarkadi, Júlia; Visontai, Ildikó

    2013-11-24

    Ten years have elapsed since the severe acute respiratory syndrome outbreak, which resulted in more than 8000 cases worldwide with more than 700 deaths. Recently, a new coronavirus, the Middle East Respiratory Syndrome Coronavirus emerged, causing serious respiratory cases and death. By the end of August 2013, 108 cases including 50 deaths were reported. The authors discuss a coronavirus-associated severe acute respiratory syndrome, which was detected in Hungary in 2005 and highlight its significance in 2013. In 2005 the patient was hospitalized and all relevant clinical and microbiological tests were performed. Based on the IgG antibody positivity of the serum samples, the patient was diagnosed as having severe acute respiratory syndrome coronavirus infection in the past. The time and source of the infection remained unknown. The condition of the patient improved and he was discharged from the hospital. The case raises the possibility of infections in Hungary imported from remote areas of the world and the importance of thorough examination of patients with severe respiratory syndrome with unknown etiology.

  5. Intermittent hypoxia-induced glucose intolerance is abolished by α-adrenergic blockade or adrenal medullectomy

    PubMed Central

    Shin, Mi-Kyung; Devera, Ronald; Yao, Qiaoling; Mesarwi, Omar; Bevans-Fonti, Shannon; Polotsky, Vsevolod Y.

    2014-01-01

    Obstructive sleep apnea causes intermittent hypoxia (IH) during sleep and is associated with dysregulation of glucose metabolism. We developed a novel model of clinically realistic IH in mice to test the hypothesis that IH causes hyperglycemia, glucose intolerance, and insulin resistance via activation of the sympathetic nervous system. Mice were exposed to acute hypoxia of graded severity (21, 14, 10, and 7% O2) or to IH of graded frequency [oxygen desaturation index (ODI) of 0, 15, 30, or 60, SpO2 nadir 80%] for 30 min to measure levels of glucose fatty acids, glycerol, insulin, and lactate. Glucose tolerance tests and insulin tolerance tests were then performed under each hypoxia condition. Next, we examined these outcomes in mice that were administered phentolamine (α-adrenergic blockade) or propranolol (β-adrenergic blockade) or that underwent adrenal medullectomy before IH exposure. In all experiments, mice were maintained in a thermoneutral environment. Sustained and IH induced hyperglycemia, glucose intolerance, and insulin resistance in a dose-dependent fashion. Only severe hypoxia (7% O2) increased lactate, and only frequent IH (ODI 60) increased plasma fatty acids. Phentolamine or adrenal medullectomy both prevented IH-induced hyperglycemia and glucose intolerance. IH inhibited glucose-stimulated insulin secretion, and phentolamine prevented the inhibition. Propranolol had no effect on glucose metabolism but abolished IH-induced lipolysis. IH-induced insulin resistance was not affected by any intervention. Acutely hypoxia causes hyperglycemia, glucose intolerance, and insulin resistance in a dose-dependent manner. During IH, circulating catecholamines act upon α-adrenoreceptors to cause hyperglycemia and glucose intolerance. PMID:25315697

  6. Brief communication: Legionnaire's disease successfully treated in acute myelocytic leukemia during severe neutropenia.

    PubMed

    Guthrie, T H; Mahizhnan, P

    1983-01-01

    A patient with acute nonlymphocytic leukemia developed progressive lung infiltrates and unremitting fevers during a profound neutropenic state. Legionnaire's disease was diagnosed by simple immunologic studies and successfully treated with erythromycin. This index case alerts physicians toward a treatable infection which would not normally be susceptible to the empiric antibiotic regimens given neutropenic patients with fevers.

  7. Immunohistochemical Detection of Changes in Tumor Hypoxia

    SciTech Connect

    Russell, James Carlin, Sean; Burke, Sean A.; Wen Bixiu; Yang, Kwang Mo; Ling, C. Clifton

    2009-03-15

    Purpose: Although hypoxia is a known prognostic factor, its effect will be modified by the rate of reoxygenation and the extent to which the cells are acutely hypoxic. We tested the ability of exogenous and endogenous markers to detect reoxygenation in a xenograft model. Our technique might be applicable to stored patient samples. Methods and Materials: The human colorectal carcinoma line, HT29, was grown in nude mice. Changes in tumor hypoxia were examined by injection of pimonidazole, followed 24 hours later by EF5. Cryosections were stained for these markers and for carbonic anhydrase IX (CAIX) and hypoxia-inducible factor 1{alpha} (HIF1{alpha}). Tumor hypoxia was artificially manipulated by carbogen exposure. Results: In unstressed tumors, all four markers showed very similar spatial distributions. After carbogen treatment, pimonidazole and EF5 could detect decreased hypoxia. HIF1{alpha} staining was also decreased relative to CAIX, although the effect was less pronounced than for EF5. Control tumors displayed small regions that had undergone spontaneous changes in tumor hypoxia, as judged by pimonidazole relative to EF5; most of these changes were reflected by CAIX and HIF1{alpha}. Conclusion: HIF1{alpha} can be compared with either CAIX or a previously administered nitroimidazole to provide an estimate of reoxygenation.

  8. Neuroprotective effects of bloodletting at Jing points combined with mild induced hypothermia in acute severe traumatic brain injury

    PubMed Central

    Tu, Yue; Miao, Xiao-mei; Yi, Tai-long; Chen, Xu-yi; Sun, Hong-tao; Cheng, Shi-xiang; Zhang, Sai

    2016-01-01

    Bloodletting at Jing points has been used to treat coma in traditional Chinese medicine. Mild induced hypothermia has also been shown to have neuroprotective effects. However, the therapeutic effects of bloodletting at Jing points and mild induced hypothermia alone are limited. Therefore, we investigated whether combined treatment might have clinical effectiveness for the treatment of acute severe traumatic brain injury. Using a rat model of traumatic brain injury, combined treatment substantially alleviated cerebral edema and blood-brain barrier dysfunction. Furthermore, neurological function was ameliorated, and cellular necrosis and the inflammatory response were lessened. These findings suggest that the combined effects of bloodletting at Jing points (20 μL, twice a day, for 2 days) and mild induced hypothermia (6 hours) are better than their individual effects alone. Their combined application may have marked neuroprotective effects in the clinical treatment of acute severe traumatic brain injury. PMID:27482221

  9. Association of Matrix Metalloproteinases -7, -8 and -9 and TIMP -1 with Disease Severity in Acute Pancreatitis. A Cohort Study

    PubMed Central

    Nukarinen, Eija; Lindström, Outi; Kuuliala, Krista; Kylänpää, Leena; Pettilä, Ville; Puolakkainen, Pauli; Kuuliala, Antti; Hämäläinen, Mari; Moilanen, Eeva; Repo, Heikki; Hästbacka, Johanna

    2016-01-01

    Objectives Several biomarkers for early detection of severe acute pancreatitis (SAP) have been presented. Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) are released early in inflammation. We aimed to assess levels of MMP-7, -8, -9 and TIMP-1 in acute pancreatitis (AP) and explore their ability to detect disease severity. Our second aim was to find an association between MMPs, TIMP and creatinine. Methods We collected plasma samples for MMP-7, -8, -9 and TIMP-1 analyses from 176 patients presenting within 96 h from onset of acute pancreatitis (AP) symptoms. We used samples from 32 control subjects as comparison. The revised Atlanta Classification was utilised to assess severity of disease. Receiver operating characteristic curve analysis and Spearman´s Rho-test were utilised for statistical calculations. Results Compared with controls, patients showed higher levels of all studied markers. MMP-8 was higher in moderately severe AP than in mild AP (p = 0.005) and MMP-8, -9 and TIMP-1 were higher in severe than in mild AP (p<0.001, p = 0.005 and p = 0.019). MMP-8 detected SAP with an AUC of 0.939 [95% CI 0.894–0.984], LR+ 9.03 [5.30–15.39]. MMP-8, -9 and TIMP-1 failed to discern moderately severe AP from SAP. MMP-7 was not different between patient groups. MMP-7 and TIMP-1 correlated weakly with creatinine (Rho = 0.221 and 0.243). MMP-8 might be a useful biomarker in early detection of SAP. PMID:27561093

  10. Dose-dependent effects of levetiracetam after hypoxia and hypothermia in the neonatal mouse brain.

    PubMed

    Strasser, Katja; Lueckemann, Laura; Kluever, Verena; Thavaneetharajah, Sinthuya; Hoeber, Daniela; Bendix, Ivo; Fandrey, Joachim; Bertsche, Astrid; Felderhoff-Mueser, Ursula

    2016-09-01

    Perinatal asphyxia to the developing brain remains a major cause of morbidity. Hypothermia is currently the only established neuroprotective treatment available for term born infants with hypoxic-ischemic encephalopathy, saving one in seven to eight infants from developing severe neurological deficits. Therefore, additional treatments with clinically applicable drugs are indispensable. This study investigates a potential additive neuroprotective effect of levetiracetam combined with hypothermia after hypoxia-induced brain injury in neonatal mice. 9-day-old C57BL/6-mice (P9) were subjected either to acute hypoxia or room-air. After 90min of systemic hypoxia (6% O2), pups were randomized into six groups: 1) vehicle, 2) low-dose levetiracetam (LEV), 3) high-dose LEV, 4) hypothermia (HT), 5) HT combined with low-dose LEV and 6) HT combined with high-dose LEV. Pro-apoptotic factors, neuronal structures, and myelination were analysed by histology and on protein level at appropriate time points. On P28 to P37 long-term outcome was assessed by neurobehavioral testing. Hypothermia confers acute and long-term neuroprotection by reducing apoptosis and preservation of myelinating oligodendrocytes and neurons in a model of acute hypoxia in the neonatal mouse brain. Low-dose LEV caused no adverse effects after neonatal hypoxic brain damage treated with hypothermia whereas administration of high-dose LEV alone or in combination with hypothermia increased neuronal apoptosis after hypoxic brain injury. LEV in low- dosage had no additive neuroprotective effect following acute hypoxic brain injury. PMID:27216570

  11. Natural history of premacular hemorrhage due to severe acute anemia: clinical and anatomical features in two untreated patients.

    PubMed

    Turco, Claudia Del; La Spina, Carlo; Mantovani, Elena; Gagliardi, Marco; Lattanzio, Rosangela; Pierro, Luisa

    2014-01-01

    Premacular retrohyaloid hemorrhage is a rare complication of acute severe anemia. The authors report two cases of premacular hemorrhage in which no treatment other than clinical and spectral-domain optical coherence tomography observation was performed. The natural history of this condition reveals that complete clinical resolution is not accompanied by full anatomical restoration. [Ophthalmic Surg Lasers Imaging Retina. 2014;45:E5-E7.]. PMID:24496165

  12. How Healthcare Provider Talk with Parents of Children Following Severe Traumatic Brain Injury is Perceived in Early Acute Care

    PubMed Central

    Savage, Teresa A.; Grant, Gerald; Philipsen, Gerry

    2013-01-01

    Healthcare provider talk with parents in early acute care following children’s severe traumatic brain injury (TBI) affects parents’ orientations to these locales, but this connection has been minimally studied. This lack of attention to this topic in previous research may reflect providers’ and researchers’ views that these locales are generally neutral or supportive to parents’ subsequent needs. This secondary analysis used data from a larger descriptive phenomenological study (2005 – 2007) with parents of children following moderate to severe TBI recruited from across the United States. Parents of children with severe TBI consistently had strong negative responses to the early acute care talk processes they experienced with providers, while parents of children with moderate TBI did not. Transcript data were independently coded using discourse analysis in the framework of ethnography of speaking. The purpose was to understand the linguistic and paralinguistic talk factors parents used in their meta-communications that could give a preliminary understanding of their cultural expectations for early acute care talk in these settings. Final participants included 27 parents of children with severe TBI from 23 families. We found the human constructed talk factors that parents reacted to were: a) access to the child, which is where information was; b) regular discussions with key personnel; c) updated information that is explained; d) differing expectations for talk in this context; and, e) perceived parental involvement in decisions. We found that the organization and nature of providers’ talk with parents was perceived by parents to positively or negatively shape their early acute care identities in these locales, which influenced how they viewed these locales as places that either supported them and decreased their workload or discounted them and increased their workload for getting what they needed. PMID:23746606

  13. Inhibition of pulmonary nuclear factor kappa-B decreases the severity of acute Escherichia coli pneumonia but worsens prolonged pneumonia

    PubMed Central

    2013-01-01

    Introduction Nuclear factor (NF)-κB is central to the pathogenesis of inflammation in acute lung injury, but also to inflammation resolution and repair. We wished to determine whether overexpression of the NF-κB inhibitor IκBα could modulate the severity of acute and prolonged pneumonia-induced lung injury in a series of prospective randomized animal studies. Methods Adult male Sprague-Dawley rats were randomized to undergo intratracheal instillation of (a) 5 × 109 adenoassociated virus (AAV) vectors encoding the IκBα transgene (5 × 109 AAV-IκBα); (b) 1 × 1010 AAV-IκBα; (c) 5 × 1010 AAV-IκBα; or (d) vehicle alone. After intratracheal inoculation with Escherichia coli, the severity of the lung injury was measured in one series over a 4-hour period (acute pneumonia), and in a second series after 72 hours (prolonged pneumonia). Additional experiments examined the effects of IκBα and null-gene overexpression on E. coli-induced and sham pneumonia. Results In acute pneumonia, IκBα dose-dependently decreased lung injury, improving arterial oxygenation and lung static compliance, reducing alveolar protein leak and histologic injury, and decreasing alveolar IL-1β concentrations. Benefit was maximal at the intermediate (1 × 1010) IκBα vector dose; however, efficacy was diminished at the higher (5 × 1010) IκBα vector dose. In contrast, IκBα worsened prolonged pneumonia-induced lung injury, increased lung bacterial load, decreased lung compliance, and delayed resolution of the acute inflammatory response. Conclusions Inhibition of pulmonary NF-κB activity reduces early pneumonia-induced injury, but worsens injury and bacterial load during prolonged pneumonia. PMID:23622108

  14. Altered energy state reversibly controls smooth muscle contractile function in human saphenous vein during acute hypoxia-reoxygenation: Role of glycogen, AMP-activated protein kinase, and insulin-independent glucose uptake.

    PubMed

    Pyla, Rajkumar; Pichavaram, Prahalathan; Fairaq, Arwa; Park, Mary Anne; Kozak, Mark; Kamath, Vinayak; Patel, Vijay S; Segar, Lakshman

    2015-09-01

    Hypoxia is known to promote vasodilation of coronary vessels through several mediators including cardiac-derived adenosine and endothelium-derived prostanoids and nitric oxide. To date, the impact of endogenous glycogen depletion in vascular smooth muscle and the resultant alterations in cellular energy state (e.g., AMP-activated protein kinase, AMPK) on the contractile response to G protein-coupled receptor agonists (e.g., serotonin, 5-HT) has not yet been studied. In the present study, ex vivo exposure of endothelium-denuded human saphenous vein rings to hypoxic and glucose-deprived conditions during KCl-induced contractions for 30 min resulted in a marked depletion of endogenous glycogen by ∼80% (from ∼1.78 μmol/g under normoxia to ∼0.36 μmol/g under hypoxia). Importantly, glycogen-depleted HSV rings, which were maintained under hypoxia/reoxygenation and glucose-deprived conditions, exhibited significant increases in basal AMPK phosphorylation (∼6-fold ↑) and 5-HT-induced AMPK phosphorylation (∼19-fold ↑) with an accompanying suppression of 5-HT-induced maximal contractile response (∼68% ↓), compared with respective controls. Exposure of glycogen-depleted HSV rings to exogenous D-glucose, but not the inactive glucose analogs, prevented the exaggerated increase in 5-HT-induced AMPK phosphorylation and restored 5-HT-induced maximal contractile response. In addition, the ability of exogenous D-glucose to rescue cellular stress and impaired contractile function occurred through GLUT1-mediated but insulin/GLUT4-independent mechanisms. Together, the present findings from clinically-relevant human saphenous vein suggest that the loss of endogenous glycogen in vascular smooth muscle and the resultant accentuation of AMPK phosphorylation by GPCR agonists may constitute a yet another mechanism of metabolic vasodilation of coronary vessels in ischemic heart disease.

  15. Altered energy state reversibly controls smooth muscle contractile function in human saphenous vein during acute hypoxia-reoxygenation: Role of glycogen, AMP-activated protein kinase, and insulin-independent glucose uptake

    PubMed Central

    Pyla, Rajkumar; Pichavaram, Prahalathan; Fairaq, Arwa; Park, Mary Anne; Kozak, Mark; Kamath, Vinayak; Patel, Vijay S.; Segar, Lakshman

    2015-01-01

    Hypoxia is known to promote vasodilation of coronary vessels through several mediators including cardiac-derived adenosine and endothelium-derived prostanoids and nitric oxide. To date, the impact of endogenous glycogen depletion in vascular smooth muscle and the resultant alterations in cellular energy state (e.g., AMP-activated protein kinase, AMPK) on the contractile response to G protein-coupled receptor agonists (e.g., serotonin, 5-HT) has not yet been studied. In the present study, ex vivo exposure of endothelium-denuded human saphenous vein rings to hypoxic and glucose-deprived conditions during KCl-induced contractions for 30 min resulted in a marked depletion of endogenous glycogen by ~80% (from ~1.78 μmol/g under normoxia to ~0.36 μmol/g under hypoxia). Importantly, glycogen-depleted HSV rings, which were maintained under hypoxia/reoxygenation and glucose-deprived conditions, exhibited significant increases in basal AMPK phosphorylation (~6-fold ↑) and 5-HT-induced AMPK phosphorylation (~19-fold ↑) with an accompanying suppression of 5-HT-induced maximal contractile response (~68% ↓), compared with respective controls. Exposure of glycogen-depleted HSV rings to exogenous D-glucose, but not the inactive glucose analogs, prevented the exaggerated increase in 5-HT-induced AMPK phosphorylation and restored 5-HT-induced maximal contractile response. In addition, the ability of exogenous D-glucose to rescue cellular stress and impaired contractile function occurred through GLUT1-mediated but insulin/GLUT4-independent mechanisms. Together, the present findings from clinically-relevant human saphenous vein suggest that the loss of endogenous glycogen in vascular smooth muscle and the resultant accentuation of AMPK phosphorylation by GPCR agonists may constitute a yet another mechanism of metabolic vasodilation of coronary vessels in ischemic heart disease. PMID:26212549

  16. Human resistin promotes neutrophil proinflammatory activation and neutrophil extracellular trap formation and increases severity of acute lung injury.

    PubMed

    Jiang, Shaoning; Park, Dae Won; Tadie, Jean-Marc; Gregoire, Murielle; Deshane, Jessy; Pittet, Jean Francois; Abraham, Edward; Zmijewski, Jaroslaw W

    2014-05-15

    Although resistin was recently found to modulate insulin resistance in preclinical models of type II diabetes and obesity, recent studies also suggested that resistin has proinflammatory properties. We examined whether the human-specific variant of resistin affects neutrophil activation and the severity of LPS-induced acute lung injury. Because human and mouse resistin have distinct patterns of tissue distribution, experiments were performed using humanized resistin mice that exclusively express human resistin (hRTN(+/-)(/-)) but are deficient in mouse resistin. Enhanced production of TNF-α or MIP-2 was found in LPS-treated hRtn(+/-/-) neutrophils compared with control Rtn(-/-/-) neutrophils. Expression of human resistin inhibited the activation of AMP-activated protein kinase, a major sensor and regulator of cellular bioenergetics that also is implicated in inhibiting inflammatory activity of neutrophils and macrophages. In addition to the ability of resistin to sensitize neutrophils to LPS stimulation, human resistin enhanced neutrophil extracellular trap formation. In LPS-induced acute lung injury, humanized resistin mice demonstrated enhanced production of proinflammatory cytokines, more severe pulmonary edema, increased neutrophil extracellular trap formation, and elevated concentration of the alarmins HMGB1 and histone 3 in the lungs. Our results suggest that human resistin may play an important contributory role in enhancing TLR4-induced inflammatory responses, and it may be a target for future therapies aimed at reducing the severity of acute lung injury and other inflammatory situations in which neutrophils play a major role.

  17. Extended-release morphine sulfate in treatment of severe acute and chronic pain

    PubMed Central

    Balch, Robert J; Trescot, Andrea

    2010-01-01

    Morphine is the archetypal opioid analgesic. Because it is a short-acting opioid, its use has been limited to the management of acute pain. The development of extended-release formulations have resulted in the increased utilization of morphine in chronic pain conditions. This review documents the history of morphine use in pain treatment, and describes the metabolism, pharmacodynamics, formulations, and efficacy of the currently available extended-release morphine medications. PMID:21197323

  18. Adenovirus type 7 associated with severe and fatal acute lower respiratory infections in Argentine children

    PubMed Central

    Carballal, Guadalupe; Videla, Cristina; Misirlian, Alicia; Requeijo, Paula V; Aguilar, María del Carmen

    2002-01-01

    Background Adenoviruses are the second most prevalent cause of acute lower respiratory infection of viral origin in children under four years of age in Buenos Aires, Argentina. The purpose of this study was to analyze the clinical features and outcome of acute lower respiratory infection associated with different adenovirus genotypes in children. Methods Twenty-four cases of acute lower respiratory infection and adenovirus diagnosis reported in a pediatric unit during a two-year period were retrospectively reviewed. Adenovirus was detected by antigen detection and isolation in HEp-2 cells. Adenovirus DNA from 17 isolates was studied by restriction enzyme analysis with Bam HI and Sma I. Results Subgenus b was found in 82.3% of the cases, and subgenus c in 17.7%. Within subgenus b, only genotype 7 was detected, with genomic variant 7h in 85.7% (12/14) and genomic variant 7i in 14.3% (2/14). Mean age was 8.8 ±; 6 months, and male to female ratio was 3.8: 1. At admission, pneumonia was observed in 71% of the cases and bronchiolitis in 29%. Malnutrition occurred in 37% of the cases; tachypnea in 79%; chest indrawing in 66%; wheezing in 58%; apneas in 16%; and conjunctivitis in 29%. Blood cultures for bacteria and antigen detection of other respiratory viruses were negative. During hospitalization, fatality rate was 16.7% (4 /24). Of the patients who died, three had Ad 7h and one Ad 7i. Thus, fatality rate for adenovirus type 7 reached 28.6% (4/14). Conclusions These results show the predominance of adenovirus 7 and high lethality associated with the genomic variants 7h and 7i in children hospitalized with acute lower respiratory infection. PMID:12184818

  19. SWI/SNF regulates the cellular response to hypoxia.

    PubMed

    Kenneth, Niall S; Mudie, Sharon; van Uden, Patrick; Rocha, Sonia

    2009-02-13

    Hypoxia induces a variety of cellular responses such as cell cycle arrest, apoptosis, and autophagy. Most of these responses are mediated by the hypoxia-inducible factor-1alpha. To induce target genes, hypoxia-inducible factor-1alpha requires a chromatin environment conducive to allow binding to specific sequences. Here, we have studied the role of the chromatin-remodeling complex SWI/SNF in the cellular response to hypoxia. We find that SWI/SNF is required for several of the cellular responses induced by hypoxia. Surprisingly, hypoxia-inducible factor-1alpha is a direct target of the SWI/SNF chromatin-remodeling complex. SWI/SNF components are found associated with the hypoxia-inducible factor-1alpha promoter and modulation of SWI/SNF levels results in pronounced changes in hypoxia-inducible factor-1alpha expression and its ability to transactivate target genes. Furthermore, impairment of SWI/SNF function renders cells resistant to hypoxia-induced cell cycle arrest. These results reveal a previously uncharacterized dependence of hypoxia signaling on the SWI/SNF complex and demonstrate a new level of control over the hypoxia-inducible factor-1alpha system.

  20. Clinical effects of laparotomy with perioperative continuous peritoneal lavage and postoperative hemofiltration in patients with severe acute pancreatitis

    PubMed Central

    2009-01-01

    Background The elevated serum and peritoneal cytokine concentrations responsible for the systemic response syndrome (SIRS) and multiorgan failure in patients with severe acute pancreatitis lead to high morbidity and mortality rates. Prompted by reports underlining the importance of reducing circulating inflammatory mediators in severe acute pancreatitis, we designed this study to evaluate the efficiency of laparotomy followed by continuous perioperative peritoneal lavage combined with postoperative continuous venovenous diahemofiltration (CVVDH) in managing critically ill patients refractory to intensive care therapy. As the major clinical outcome variables we measured morbidity, mortality and changes in the Acute Physiology and Chronic Health Evaluation (APACHE II) score and cytokine concentrations in serum and peritoneal lavage fluid over time. Methods From a consecutive group of 23 patients hospitalized for acute pancreatitis, we studied 6 patients all with Apache II scores ≥19, who underwent emergency surgery for acute complications (5 for an abdominal compartment syndrome and 1 for septic shock) followed by continuous perioperative peritoneal lavage and postoperative CVVDH. CVVDH was started within 12 hours after surgery and maintained for at least 72 hours, until the multiorgan dysfunction syndrome improved. Samples were collected from serum, peritoneal lavage fluid and CVVDH dialysate for cytokine assay. Apache II scores were measured daily and their association with cytokine levels was assessed. Results All six patients tolerated CVVDH well, and the procedure lasted a mean 6 days (range, 3-12). Five patients survived and one died of Acinetobacter infection after surgery (mortality rate 16.6%). The mean APACHE II score was ≥ 19 (range 19-22) before laparotomy and decreased significantly during peritoneal lavage and postoperative CVVDH (P = 0.013 by matched-pairs Students t-test). The decrease in cytokine concentrations in serum and lavage fluid was

  1. Impact of Hypoxia on the Metastatic Potential of Human Prostate Cancer Cells

    SciTech Connect

    Dai Yao; Bae, Kyungmi; Siemann, Dietmar W.

    2011-10-01

    Purpose: Intratumoral hypoxia is known to be associated with radioresistance and metastasis. The present study examined the effect of acute and chronic hypoxia on the metastatic potential of prostate cancer PC-3, DU145, and LNCaP cells. Methods and Materials: Cell proliferation and clonogenicity were tested by MTT assay and colony formation assay, respectively. 'Wound-healing' and Matrigel-based chamber assays were used to monitor cell motility and invasion. Hypoxia-inducible factor 1 alpha (HIF-1{alpha}) expression was tested by Western blot, and HIF-1-target gene expression was detected by real-time polymerase chain reaction. Secretion of matrix metalloproteinases (MMPs) was determined by gelatin zymography. Results: When PC-3 cells were exposed to 1% oxygen (hypoxia) for various periods of time, chronic hypoxia ({>=}24 h) decreased cell proliferation and induced cell death. In contrast, prostate cancer cells exposed to acute hypoxia ({<=}6 h) displayed increased motility, clonogenic survival, and invasive capacity. At the molecular level, both hypoxia and anoxia transiently stabilized HIF-1{alpha}. Exposure to hypoxia also induced the early expression of MMP-2, an invasiveness-related gene. Treatment with the HIF-1 inhibitor YC-1 attenuated the acute hypoxia-induced migration, invasion, and MMP-2 activity. Conclusions: The length of oxygen deprivation strongly affected the functional behavior of all three prostate cancer cell lines. Acute hypoxia in particular was found to promote a more aggressive metastatic phenotype.

  2. Hypoxia and metabolic adaptation of cancer cells

    PubMed Central

    Eales, K L; Hollinshead, K E R; Tennant, D A

    2016-01-01

    Low oxygen tension (hypoxia) is a pervasive physiological and pathophysiological stimulus that metazoan organisms have contended with since they evolved from their single-celled ancestors. The effect of hypoxia on a tissue can be either positive or negative, depending on the severity, duration and context. Over the long-term, hypoxia is not usually consistent with normal function and so multicellular organisms have had to evolve both systemic and cellular responses to hypoxia. Our reliance on oxygen for efficient adenosine triphosphate (ATP) generation has meant that the cellular metabolic network is particularly sensitive to alterations in oxygen tension. Metabolic changes in response to hypoxia are elicited through both direct mechanisms, such as the reduction in ATP generation by oxidative phosphorylation or inhibition of fatty-acid desaturation, and indirect mechanisms including changes in isozyme expression through hypoxia-responsive transcription factor activity. Significant regions of cancers often grow in hypoxic conditions owing to the lack of a functional vasculature. As hypoxic tumour areas contain some of the most malignant cells, it is important that we understand the role metabolism has in keeping these cells alive. This review will outline our current understanding of many of the hypoxia-induced changes in cancer cell metabolism, how they are affected by other genetic defects often present in cancers, and how these metabolic alterations support the malignant hypoxic phenotype. PMID:26807645

  3. Applying a Hypoxia-Incorporating TCP Model to Experimental Data on Rat Sarcoma

    SciTech Connect

    Ruggieri, Ruggero; Stavreva, Nadejda; Naccarato, Stefania; Stavrev, Pavel

    2012-08-01

    Purpose: To verify whether a tumor control probability (TCP) model which mechanistically incorporates acute and chronic hypoxia is able to describe animal in vivo dose-response data, exhibiting tumor reoxygenation. Methods and Materials: The investigated TCP model accounts for tumor repopulation, reoxygenation of chronic hypoxia, and fluctuating oxygenation of acute hypoxia. Using the maximum likelihood method, the model is fitted to Fischer-Moulder data on Wag/Rij rats, inoculated with rat rhabdomyosarcoma BA1112, and irradiated in vivo using different fractionation schemes. This data set is chosen because two of the experimental dose-response curves exhibit an inverse dose behavior, which is interpreted as due to reoxygenation. The tested TCP model is complex, and therefore, in vivo cell survival data on the same BA1112 cell line from Reinhold were added to Fischer-Moulder data and fitted simul