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- Apparent Diffusion Coefficient Scalars Correlate with Near-Infrared Spectroscopy Markers of Cerebrovascular Autoregulation in Neonates Cooled for Perinatal Hypoxic-Ischemic Injury. [JOURNAL ARTICLE]
- AJNR Am J Neuroradiol 2014 Aug 28.
Neurologic morbidity remains high in neonates with perinatal hypoxic-ischemic injury despite therapeutic hypothermia. DTI provides qualitative and quantitative information about the microstructure of the brain, and a near-infrared spectroscopy index can assess cerebrovascular autoregulation. We hypothesized that lower ADC values would correlate with worse autoregulatory function.Thirty-one neonates with hypoxic-ischemic injury were enrolled. ADC scalars were measured in 27 neonates (age range, 4-15 days) in the anterior and posterior centrum semiovale, basal ganglia, thalamus, posterior limb of the internal capsule, pons, and middle cerebellar peduncle on MRI obtained after completion of therapeutic hypothermia. The blood pressure range of each neonate with the most robust autoregulation was identified by using a near-infrared spectroscopy index. Autoregulatory function was measured by blood pressure deviation below the range with optimal autoregulation.In neonates who had MRI on day of life ≥10, lower ADC scalars in the posterior centrum semiovale (r = -0.87, P = .003, n = 9) and the posterior limb of the internal capsule (r = -0.68, P = .04, n = 9) correlated with blood pressure deviation below the range with optimal autoregulation during hypothermia. Lower ADC scalars in the basal ganglia correlated with worse autoregulation during rewarming (r = -0.71, P = .05, n = 8).Blood pressure deviation from the optimal autoregulatory range may be an early biomarker of injury in the posterior centrum semiovale, posterior limb of the internal capsule, and basal ganglia. Optimizing blood pressure to support autoregulation may decrease the risk of brain injury in cooled neonates with hypoxic-ischemic injury.
- Frostbite of the Hand. [REVIEW]
- J Hand Surg Am 2014 Sep; 39(9):1863-1868.
Frostbite is damage caused by the freezing of tissue owing to exposure to extreme cold. Clinically, it is often difficult to identify the severity of frostbite injury. There may be a wide discrepancy between the extent of damage to the skin versus that to the deeper structures. The initial clinical impression is usually worse than actual tissue damage. In addition to physical examination, diagnostic imaging, especially triple-phase bone scan, has been proposed to help differentiate between superficial and deep damage. Principles of treatment involve rapid rewarming to thaw the tissues and halt direct cellular damage, methods to minimize progressive dermal ischemia, and active wound care to promote timely healing. Pharmacological adjuncts, such as fibrinolytics, have been proposed to minimize tissue damage. Surgical therapy is postponed until there is clear demarcation between healthy and necrotic tissue.
- Reversible deactivation of higher order posterior parietal areas I: Alterations of receptive field characteristics in early stages of neocortical processing. [JOURNAL ARTICLE]
- J Neurophysiol 2014 Aug 20.
Somatosensory processing in the anesthetized macaque monkey was examined by reversibly deactivating posterior parietal areas 5L, 7b and motor/premotor cortex (M1/PM) using microfluidic thermal regulators developed by our laboratories. We examined changes in receptive field size and configuration for neurons in areas 1 and 2 that occurred during and after cooling deactivation. Together the deactivated fields and areas 1 and 2 form part of a network for reaching and grasping in human and non-human primates. Cooling area 7b had a dramatic effect on receptive field size for neurons in areas 1 and 2, while cooling area 5 had moderate effects, and cooling M1/PM had little effect. Specifically, cooling discrete locations in 7b resulted in expansions of the receptive fields for neurons in areas 1 and 2 that were greater in magnitude and occurred in a higher proportion of sites than similar changes evoked by cooling the other fields. At some sites, the neural receptive field returned to the precooling configuration within 5-22 minutes of rewarming, but at other sites changes in receptive fields persisted. These results indicate that there are profound top-down influences on sensory processing of early cortical areas in the somatosensory cortex.
- Changes in cardiac thrombomodulin and heat shock transcription factor 1 expression and peripheral thrombomodulin and catecholamines during hypothermia in rats. [JOURNAL ARTICLE]
- Stress 2014 Aug 11.:1-27.
Abstract Effects of hypothermia and rewarming on thrombomodulin, catecholamines and heat shock transcription factor 1 (HSF1) were studied in rats. The aims of the study were to clarify whether cold stress, under anaesthesia, is sufficient to change levels of thrombomodulin in healthy endothelium and in the circulation, and whether adrenaline, noradrenaline and HSF1 could act as regulators in the process. Rats were divided into control, mild hypothermia (2 and 4.5 hours at +21(o)C; MH1, MH2), severe hypothermia (2 and 4.5 hours at +10(o)C; SH1, SH2) and two rewarming groups (2 hours at +10(o)C followed by 2 hours at +21(o)C or 3 hours at +28(o)C; SHW1, SHW2) (n=15/group, except n=6 in MH1). Fentanyl-fluanisone-midazolam was used as anesthetic. Low levels of thrombomodulin in plasma and myocardial arterioles/venules measured by ELISA and immunohistochemistry were associated with significant increase of thrombomodulin transcript level in SH1 rats analyzed by quantitative PCR. Plasma adrenaline correlated negatively with the relative amount of myocardial thrombomodulin transcripts and positively with plasma thrombomodulin in severe hypothermia. Transcript levels of thrombomodulin and HSF1 correlated strongly (r = 0.83; P <0.001) in severe hypothermia. Plasma/urine ratio of thrombomodulin and plasma adrenaline (r = 0.87; P = 0.005) or noradrenaline (r = 0.78; P = 0.023) were strongly correlated in SHW1 rats. Hence cellular and soluble levels of thrombomodulin are modified by cold stress in healthy rats, possibly via catecholamines and HSF1.
- Prolonged mild therapeutic hypothermia versus fever control with tight hemodynamic monitoring and slow rewarming in patients with severe traumatic brain injury: a randomized controlled trial. [JOURNAL ARTICLE]
- J Neurotrauma 2014 Aug 6.
Although mild therapeutic hypothermia is an effective neuroprotective strategy for cardiac arrest/resuscitated patients, and asphyxic new-borns, recent randomized controlled trials (RCTs) have equally shown good neurological outcome between targeted temperature management at 33°C versus 36°C and have not shown consistent benefits in patients with traumatic brain injury (TBI). We aimed to determine the effect of therapeutic hypothermia while avoiding some limitations of earlier studies, which include patient selection based on Glasgow coma scale (GCS), delayed initiation of cooling, short duration of cooling, inter-center variation in patient care, and relatively rapid rewarming. We conducted a multicenter RCT in patients with severe TBI (GCS 4-8). Patients were randomly assigned (2:1 allocation ratio) to either therapeutic hypothermia (32-34°C, n = 98) or fever control (35.5-37°C, n =50). Patients with therapeutic hypothermia were cooled as soon as possible for ≥ 72 h and rewarmed at a rate of < 1°C/day. All patients received tight hemodynamic monitoring under intensive neurological care. The Glasgow Outcome Scale was assessed at 6 months by physicians who were masked to the treatment allocation. The overall rates of poor neurological outcomes were 53% and 48 % in the therapeutic hypothermia and fever control groups, respectively. There were no significant differences in the likelihood of poor neurological outcome (relative risk [RR] 1.24, 95% confidence interval [CI] 0.62-2.48, p =0.597) or mortality (RR 1.82, 95% CI 0.82-4.03, p =0.180) between the two groups. We concluded that tight hemodynamic management and slow rewarming, together with prolonged therapeutic hypothermia (32-34°C) for severe TBI, did not improve the neurological outcomes or risk of mortality compared with strict temperature control (35.5-37°C).
- Pediatric submersion injuries: emergency care and resuscitation. [Journal Article]
- Pediatr Emerg Med Pract 2014 Jun; 11(6):1-21; quiz 21-2.
Drowning and submersion injuries are highly prevalent, yet preventable, causes of childhood mortality and morbidity. Although much of the resuscitation of the drowning pediatric victim is basic to all respiratory and cardiac arrest situations, there are some caveats for treatment of this type of injury. Risk factors for drowning victims include epilepsy, underlying cardiac dysrhythmias, hyperventilation, hypoglycemia, hypothermia, and alcohol and illicit drug use. Prehospital care should focus on restoring normal ventilation and circulation as quickly as possible to limit the extent of hypoxic insult. Diagnostic testing for symptomatic patients may include blood glucose level, arterial blood gas level, complete blood count, electrolytes levels, chest radiography, and cardiorespiratory monitoring with pulse oximetry and a rhythm strip. In this review, passive external, active external, and active internal rewarming techniques for treatment of hypothermic patients are discussed. A systematic approach to treatment and disposition or admission of pediatric drowning victims is also included, with extensive clinical pathways for quick reference.
- The use of amplitude-integrated electroencephalography combined with continuous conventional electroencephalography during therapeutic hypothermia for an infant with postnatal cardiac arrest. [Journal Article]
- Springerplus 2014.:373.
Amplitude-integrated electroencephalography (aEEG) has been employed in therapeutic hypothermia (TH) trials of neonates after perinatal hypoxic-ischemic encephalopathy (HIE). We present a case report involving the use of aEEG during TH with continuous conventional electroencephalography (cEEG) for an infant who experienced postnatal intraoperative cardiac arrest.A five-month-old infant developed cardiac arrest during operation. Return of spontaneous circulation was achieved after one hour of cardiopulmonary resuscitation. Therapeutic hypothermia was applied with neuromuscular blockades. During the TH, the brain function and seizures were monitored with aEEG, which can also display continuous cEEG. Intermittent and discrete seizures were detected on aEEG and confirmed with raw cEEG during the TH and rewarming periods. Several kinds of antiepileptic drugs (AEDs) were administered to manage seizures according to the findings of aEEG with cEEG. Seizures were controlled by the treatments, and she showed no clinical seizures after TH and AED discontinuation.This case indicated the possibility that the use of aEEG with continuous cEEG for a postnatal infant after cardiac arrest was feasible to detect and assess seizures and the effects of antiepileptic therapy while undergoing TH.
- The effects of conjugated linoleic acid isomers cis-9,trans-11 and trans-10,cis-12 on in vitro bovine embryo production and cryopreservation. [JOURNAL ARTICLE]
- J Dairy Sci 2014 Jul 30.
Conjugated linoleic acid (CLA) isomers can affect the lipid profile and signaling of cells and thereby alter their function. A total of 5,700 bovine oocytes were used in a structured series of experiments to test the effects of cis-9,trans-11 CLA and trans-10,cis-12 CLA in vitro. In experiment 1, high doses of each CLA isomer during in vitro maturation (IVM) were compared with high or low doses during the entire in vitro culture (IVC) of parthenogenetic embryos. High doses of the CLA isomers ranged from 50 to 200 μM and low doses were 15 and 25 μM. In experiment 2, the low doses of each CLA isomer were tested during IVM/IVC on embryos produced by in vitro fertilization (IVF). Experiment 3 compared the effects of 15 μM doses of each CLA isomer during IVM or IVC of IVF embryos. In experiment 4, post-rewarming survival rates and blastomere counts were assessed for embryos supplemented with each CLA isomer during IVM or for 36 h before vitrification. In experiment 1, when either CLA isomer was provided only during IVM, we observed no effects on overall rates of maturation, cleavage, or blastocysts (92.2 ± 1.6%, 78.3 ± 4.1%, and 28.9 ± 5.1%, respectively). However, high doses of each CLA isomer, but not low doses, during the entire embryo culture period decreased blastocyst rates (5-20%) in a dose-dependent manner. Cleavage rates improved with 15 or 50 μM CLA trans-10,cis-12. Progesterone concentrations in maturation media were significantly increased by high doses of each CLA isomer compared with control, but low doses of CLA isomers had no effect. In experiment 2 with IVF embryos, low doses of each CLA isomer did not alter cleavage rates (average 84.9 ± 1.9%) and only 25 μM CLA trans-10,cis-12 during IVC reduced blastocyst rates below those of controls (25.5 ± 2.1 vs. 38.2 ± 2.3%). The lipid content of embryos was increased and relative expression of the BIRC5 (baculoviral IAP repeat containing 5) gene was depressed by CLA trans-10,cis-12. In experiment 3, low doses (15 μM) of each CLA isomer during IVC significantly reduced blastocyst rates (20.6 ± 2.4% and 27.7 ± 1.2% vs. 34.18 ± 1.2% for CLA trans-10,cis-12 and CLA cis-9,trans-11 compared with control, respectively) with less effect of each CLA during IVM. In experiment 4, adding 100 μM CLA cis-9,trans-11 during the final 36 h of culture resulted in a high survival rate after rewarming and culture, and the higher embryo blastomere count was comparable to that of control embryos not undergoing vitrification. In conclusion, supplementation with either CLA isomer did not improve embryo production, but inclusion of CLA cis-9,trans-11 before vitrification improved the quality of bovine IVF embryos after rewarming and culture.
- The effect of ethnicity on the vascular responses to cold exposure of the extremities. [JOURNAL ARTICLE]
- Eur J Appl Physiol 2014 Aug 1.
Cold injuries are more prevalent in individuals of African descent (AFD). Therefore, we investigated the effect of extremity cooling on skin blood flow (SkBF) and temperature (T sk) between ethnic groups.Thirty males [10 Caucasian (CAU), 10 Asian (ASN), 10 AFD] undertook three tests in 30 °C air whilst digit T sk and SkBF were measured: (i) vasomotor threshold (VT) test-arm immersed in 35 °C water progressively cooled to 10 °C and rewarmed to 35 °C to identify vasoconstriction and vasodilatation; (ii) cold-induced vasodilatation (CIVD) test-hand immersed in 8 °C water for 30 min followed by spontaneous warming; (iii) cold sensitivity (CS) test-foot immersed in 15 °C water for 2 min followed by spontaneous warming. Cold sensory thresholds of the forearm and finger were also assessed.In the VT test, vasoconstriction and vasodilatation occurred at a warmer finger T sk in AFD during cooling [21.2 (4.4) vs. 17.0 (3.1) °C, P = 0.034] and warming [22.0 (7.9) vs. 12.1 (4.1) °C, P = 0.002] compared with CAU. In the CIVD test, average SkBF during immersion was greater in CAU [42 (24) %] than ASN [25 (8) %, P = 0.036] and AFD [24 (13) %, P = 0.023]. Following immersion, SkBF was higher and rewarming faster in CAU [3.2 (0.4) °C min(-1)] compared with AFD [2.5 (0.7) °C min(-1), P = 0.037], but neither group differed from ASN [3.0 (0.6) °C min(-1)]. Responses to the CS test and cold sensory thresholds were similar between groups.AFD experienced a more intense protracted finger vasoconstriction than CAU during hand immersion, whilst ASN experienced an intermediate response. This greater sensitivity to cold may explain why AFD are more susceptible to cold injuries.
- Cardiac arrest patients have an impaired immune response, which is not influenced by induced hypothermia. [JOURNAL ARTICLE]
- Crit Care 2014 Jul 30; 18(4):R162.
Induced hypothermia is increasingly applied as a therapeutic intervention in ICUs. One of the underlying mechanisms of the beneficial effects of hypothermia is proposed to be reduction of the inflammatory response. However, a fear of reducing the inflammatory response is an increased infection risk. Therefore, we studied the effect of induced hypothermia on immune response after cardiac arrest.Prospective observational cohort study in a mixed surgical-medical ICU. Patients admitted at the ICU after surviving cardiac arrest were included and during 24 hours body temperature was strictly regulated at 33°C or 36°C. Blood was drawn at 3 time points: after reaching target temperature, at the end of the target temperature protocol and after rewarming to 37°C. Plasma cytokine levels and response of blood leucocytes to stimulation with toll-like receptor (TLR) ligands lipopolysaccharide (LPS) from Gram-negative bacteria and lipoteicoic acid (LTA) from Gram-positive bacteria were measured. Also, monocyte HLA-DR expression was determined.In total 20 patients were enrolled in the study. Compared to healthy controls, cardiac arrest patients kept at 36°C (n = 9) had increased plasma cytokines levels, which was not apparent in patients kept at 33°C (n = 11). Immune response to TLR ligands in patients after cardiac arrest was generally reduced and associated with lower HLA-DR expression. Patients kept at 33°C had preserved ability of immune cells to respond to LPS and LTA compared to patients kept at 36°C. These differences disappeared over time. HLA-DR expression did not differ between 33°C and 36°C.Patients after cardiac arrest have a modest systemic inflammatory response compared to healthy controls, associated with lower HLA-DR expression and attenuated immune response to Gram-negative and Gram-positive antigens, the latter indicative of an impaired immune response to bacteria. Patients with a body temperature of 33°C did not differ from patients with a body temperature of 36°C, suggesting induced hypothermia does not affect immune response in patients with cardiac arrest.Trail registration: ClinicalTrials.gov NCT01020916, registered November 25, 2009.