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- Two case studies and a review of paroxysmal cold hemoglobinuria. [Journal Article]
- Lab Med 2014; 45(3):253-8.
Paroxysmal cold hemoglobinuria (PCH) is an acquired hemolytic anemia caused by immunoglobulin G (IgG) antibodies that sensitize red blood cells (RBCs) at cold temperatures by fixing complement to the RBCs causing intravascular hemolysis on rewarming. PCH usually appears in young children as recurrent high fevers, chills, and passage of red-brown urine. The diagnostic test for PCH is the Donath-Landsteiner test, an in vitro assay for biphasic hemolysis. Herein, we present 2 cases of PCH that occurred within 12 months of each other. We quickly diagnosed the second case and treated the patient successfully, in part due to our recognition of its characteristics based on the first case. PCH is a hemolytic anemia for which there is a specific diagnostic test; the timely recognition of this entity by physicians and laboratory staff will allow prompt, supportive therapy and will raise the odds of quick resolution of hemolysis.
- Plasma proteomic changes during hypothermic and normothermic cardiopulmonary bypass in aortic surgeries. [JOURNAL ARTICLE]
- Int J Mol Med 2014 Jul 15.
Deep hypothermic circulatory arrest (DHCA) is a protective method against brain ischemia in aortic surgery. However, the possible effects of DHCA on the plasma proteins remain to be determined. In the present study, we used novel high‑throughput technology to compare the plasma proteomes during DHCA (22˚C) with selective cerebral perfusion (SCP, n=7) to those during normothermic cardiopulmonary bypass (CPB, n=7). Three plasma samples per patient were obtained during CPB: T1, prior to cooling; T2, during hypothermia; T3, after rewarming for the DHCA group and three corresponding points for the normothermic group. A proteomic analysis was performed using isobaric tag for relative and absolute quantification (iTRAQ) labeling tandem mass spectrometry to assess quantitative protein changes. In total, the analysis identified 262 proteins. The bioinformatics analysis revealed a significant upregulation of complement activation at T2 in normothermic CPB, which was suppressed in DHCA. These findings were confirmed by the changes of the terminal complement complex (SC5b‑9) levels. At T3, however, the level of SC5b‑9 showed a greater increase in DHCA compared to normothermic CPB, while 48 proteins were significantly downregulated in DHCA. The results demonstrated that DHCA and rewarming potentially exert a significant effect on the plasma proteome in patients undergoing aortic surgery.
- Induced Hypothermia During Resuscitation From Hemorrhagic Shock Attenuates Microvascular Inflammation In The Rat Mesenteric Microcirculation. [JOURNAL ARTICLE]
- Shock 2014 Jul 18.
Microvascular inflammation occurs during resuscitation following hemorrhagic shock, causing multiple organ dysfunction and mortality. Pre-clinical evidence suggests that hypothermia may have some benefit in selected patients by decreasing this inflammation, but this effect has not been extensively studied.Intravital microscopy was used to visualize mesenteric venules of anesthetized rats in real time to evaluate leukocyte adherence and mast cell degranulation. Animals were randomly allocated to normotensive or hypotensive groups, and further subdivided into hypothermic and normothermic resuscitation (N=6 per group). Animals in the shock groups underwent mean arterial blood pressure reduction to 40-45 mmHg for 1 hour via blood withdrawal. During the first two hours following resuscitation by infusion of shed blood plus double that volume of normal saline, rectal temperature of the hypothermic groups were maintained at 32-34°C, while the normothermic groups were maintained between 36-38°C. The hypothermic group was then rewarmed for the final two hours of resuscitation.Leukocyte adherence was significantly lower after 2 hours of hypothermic resuscitation compared with normothermic resuscitation: (2.8±0.8 vs 8.3±1.3 adherent leukocytes, p=0.004). Following rewarming, leukocyte adherence remained significantly different between hypothermic and normothermic shock groups: (4.7±1.2 vs 9.5±1.6 adherent leukocytes, p=0.038). Mast cell degranulation index (MDI) was significantly decreased in the hypothermic (1.02±0.04 MDI) vs normothermic (1.22±0.07 MDI) shock groups (p=0.038) after the experiment.Induced hypothermia during resuscitation following hemorrhagic shock attenuates microvascular inflammation in rat mesentery. Furthermore, this decrease in inflammation is carried over after rewarming takes place.
- Extracorporeal-Assisted Rewarming in the Management of Accidental Deep Hypothermic Cardiac Arrest: A Systematic Review of the Literature. [REVIEW]
- Heart Lung Circ 2014 Jun 27.
A systematic review of the literature surrounding the use of Extra-Corporeal Assisted Rewarming (ECAR) in patients presenting with deep hypothermia or hypothermic cardiac arrest was undertaken using a structured protocol. Thirty-one papers were deemed suitable for review, 13 of these were of sufficient quality to permit systematic data analysis. The primary outcome measure was survival to hospital discharge. The secondary outcome measure was functional neurological status at last follow-up. Analysis revealed a 67.7% survival to discharge and a 61.5% rate of good neurological recovery for patients presenting with pure hypothermic cardiac arrest. This was in marked contrast to a 23.4% survival and a 9.4% rate of good neurological outcome in those presenting with a mixed hypoxic/hypothermic arrest. Other data revealed a survival benefit for patients presenting with deep hypothermia without cardiac arrest treated with ECAR compared to those treated with conventional rewarming techniques. Hypoxic arrest, serum potassium >10mmol/L and presenting rhythm of asystole were found likely be significant predictors of poor outcome. Innovative reperfusion and rewarming strategies are also reviewed.
- Hand temperature responses to local cooling after a 10-day confinement to normobaric hypoxia with and without exercise. [JOURNAL ARTICLE]
- Scand J Med Sci Sports 2014 Jul 15.
The study examined the effects of a 10-day normobaric hypoxic confinement (FiO2 : 0.14), with [hypoxic exercise training (HT); n = 8)] or without [hypoxic ambulatory (HA; n = 6)] exercise, on the hand temperature responses during and after local cold stress. Before and after the confinement, subjects immersed their right hand for 30 min in 8 °C water [cold water immersion (CWI)], followed by a 15-min spontaneous rewarming (RW), while breathing either room air (AIR), or a hypoxic gas mixture (HYPO). The hand temperature responses were monitored with thermocouples and infrared thermography. The confinement did not influence the hand temperature responses of the HA group during the AIR and HYPO CWI and the HYPO RW phases; but it impaired the AIR RW response (-1.3 °C; P = 0.05). After the confinement, the hand temperature responses were unaltered in the HT group throughout the AIR trial. However, the average hand temperature was increased during the HYPO CWI (+0.5 °C; P ≤ 0.05) and RW (+2.4 °C; P ≤ 0.001) phases. Accordingly, present findings suggest that prolonged exposure to normobaric hypoxia per se does not alter the hand temperature responses to local cooling; yet, it impairs the normoxic RW response. Conversely, the combined stimuli of continuous hypoxia and exercise enhance the finger cold-induced vasodilatation and hand RW responses, specifically, under hypoxic conditions.
- Hyperglycemia and Insulin Resistance in Cardiac Arrest Patients Treated with Moderate Hypothermia. [JOURNAL ARTICLE]
- J Clin Endocrinol Metab 2014 Jul 17.:jc20141449.
Context: It is unknown whether the hyperglycemia that follows cardiac arrest and during therapeutic hypothermia (TH) is due to the arrest or the TH, whether it is associated with adverse outcomes or whether its treatment affects outcomes. Objective: To determine the effects of TH on blood glucose (BG) levels in post-cardiac arrest patients and the effects of hyperglycemia on mortality. Design: Chart review of 62 patients undergoing TH after cardiac arrest between September, 2005 and April, 2008. BG levels from 72 hours before arrest to 48 hours after TH and IV insulin infusion rates were analyzed and correlated with survival to discharge from hospital. Setting: Tertiary, university referral center. Patients: Patients undergoing TH after cardiac arrest. Interventions: TH consisted of cooling as rapidly as possible to 33°C, holding that temperature for 24 hours, and then controlled rewarming to 37°C over 8 or 16 hours. Hyperglycemia was managed with intravenous insulin drip protocols. Main Outcome Measure: The relationship of cardiac arrest and hypothermia to hyperglycemia with a key secondary outcome being the relationship of hyperglycemia to survival to discharge. Results: Analysis of glucose patterns showed no independent effect of TH on BG levels. Mean BG levels between cardiac arrest and the initiation of hypothermia were higher in Non-survivors (253 ± 112 mg/dL, n=48) than in Survivors (192 ± 69 mg/dL, n=24, p=0.016). BG, insulin infusion rates and insulin resistance during hypothermia, during rewarming, and 24-48 hours after hypothermia were not significantly different between the two groups. Conclusions: In patients treated with TH, the TH had no independent effect on BG levels. Mortality was associated with increased BG levels after cardiac arrest but before initiation of TH or an insulin drip. Likely, it is the severity of stress from the cardiac arrest that causes the hyperglycemia in these patients.
- The Effects of Local and General Hypothermia on Temperature Profiles of the Central Nervous System Following Spinal Cord Injury in Rats. [JOURNAL ARTICLE]
- Ther Hypothermia Temp Manag 2014 Jul 14.
Local and general hypothermia are used to treat spinal cord injury (SCI), as well as other neurological traumas. While hypothermia is known to provide significant therapeutic benefits due to its neuroprotective nature, it is unclear how the treatment may affect healthy tissues or whether it may cause undesired temperature changes in areas of the body that are not the targets of treatment. We performed 2-hour moderate general hypothermia (32°C core) or local hypothermia (30°C spinal cord) on rats that had received either a moderate contusive SCI or laminectomy (control) while monitoring temperatures at three sites: the core, spinal cord, and cortex. First, we identified that injured rats that received general hypothermia exhibited larger temperature drops at the spinal cord (-3.65°C, 95% confidence intervals [CIs] -3.72, -3.58) and cortex (-3.64°C, CIs -3.73, -3.55) than uninjured rats (spinal cord: -3.17°C, CIs -3.24, -3.10; cortex: -3.26°C, CIs -3.34, -3.17). This was found due to elevated baseline temperatures in the injured group, which could be due to inflammation. Second, both general hypothermia and local hypothermia caused a significant reduction in the cortical temperature (-3.64°C and -1.18°C, respectively), although local hypothermia caused a significantly lower drop in cortical temperature than general hypothermia (p<0.001). Lastly, the rates of rewarming of the cord were not significantly different among the methods or injury groups that were tested; the mean rate of rewarming was 0.13±0.1°C/min. In conclusion, local hypothermia may be more suitable for longer durations of hypothermia treatment for SCI to reduce temperature changes in healthy tissues, including the cortex.
- Brain hypothermia therapy for status epilepticus in childhood. [Journal Article]
- Eur Rev Med Pharmacol Sci 2014 Jul; 18(13):1883-8.
At the Dokkyo Medical University Hospital, we introduced a brain hypothermia therapy protocol for treating childhood status epilepticus and acute encephalitis/encephalopathy in 2004.This protocol focuses on infants with a minimum age of six months or 7.5 kg in weight. Applicable diseases include acute encephalitis/encephalopathy occurring from status epilepticus or seizures lasting for 30 minutes or longer, in cases such as near drowning, hypoxic-ischemic encephalopathy, post-resuscitation encephalopathy, cardio-respiratory arrest, severe head injury, or other diagnoses in which the pediatric neurologist recognizes the possibility of neurological complications. Brain hypothermia therapy is managed within the intensive care unit (ICU).The target body temperature is a bladder or rectum temperature of 34.0 to 35.0 degrees. This body temperature is reduced to the target temperature within six hours of the seizures. Hypothermia is maintained for 48 hours and concomitant steroid pulse therapy may be used at appropriate times. Sodium thiopental is used to sedate and rewarming is carried out at 0.5 degrees per 12 hours. Osmotic diuretics, muscle relaxants and circulatory antagonists may be concomitantly used at appropriate times.This paper reviews the brain hypothermia therapy protocol.
- Development of a PVS2 droplet vitrification method for potato cryopreservation. [Journal Article, Research Support, Non-U.S. Gov't]
- Cryo Letters 2014 May-Jun; 35(3):255-66.
CIP maintains the largest in vitro clonal potato collection in the world, comprising 4,013 landraces and 3,353 improved accessions. The in vitro technology is more efficient and secure than conservation in the field, allowing in vitro plantlets to be stored for approximately 2 years without sub-culture. This method however is not ideal for the long-term germplasm conservation because it is labor consuming, costly, and carries risks of losing accessions due to human error, such as contamination and mislabeling during sub-culturing.To improve the potato cryopreservation procedure based on the droplet PVS2 vitrification.The improved method is as follows: excision of 1.8-2.5 mm apical shoot tips from 3 weeks old cultures; 15 min exposure to a loading solution and 50 min to PVS2 (at 0 degree C); ultra-rapid cooling on aluminum foil strips (0.5 x 2 cm) in LN; rewarming (20 min) in 1.2 M sucrose MS liquid medium; post-cryo culture in the dark on potato meristem medium with progressively decreased sucrose levels (daily transfers from 0.3, to 0.2, to 0.1 M and maintained on 0.07 M). This method was compared with those previously applied by IPK (Germany) and CIP potato genebanks.Survival and recovery were higher using the PVS2 droplet method. Cultivars from several species, one frost tolerant (Solanum juzecpzukii, cv. Pinaza) and two drought tolerant (S. tuberosum subsp andigena, cv Ccompis, and Solanum spp, cv Desiree) responded similarly.The improved method is recommended for the long term conservation of diverse potato germplasm.
- Cryopreservation of Passiflora pohlii nodal segments and assessment of genetic stability of regenerated plants. [JOURNAL ARTICLE]
- Cryo Letters 2014 May/June; 35(3):204-215.
Passiflora pohlii is a wild species native to Brazil, with a potential agronomic interest due to its tolerance to soil-borne pathogens that cause damage to the passion fruit culture, and could be used in breeding. Because this species occurs in impacted regions, the goal of this study was the development of in vitro conservation strategies, using nodal segments from axenic plants. Encapsulation-vitrification and vitrification techniques were tested for cryopreservation of nodal segments. The highest recovery (65%) was obtained with the vitrification technique using treatment with the PVS3 vitrification solution from 30 to 120 min. Post-rewarming recovery was achieved on MSM medium supplemented with 30.8 μM BAP with incubation in the dark for 30 days before transfer in the presence of light. No differences were detected between control and cryopreserved materials as assayed by RAPD and ISSR.