bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Rapid Ischemic Preconditioning in a Rabbit Model of Spinal Cord Ischemia
Authors: Kakimoto Meiko , Kawaguchi Masahiko , Sakamoto Takanori , Inoue Satoki , Furuya Hitoshi , Nakamura Mitsutoshi , Konishi Noboru 
Published: November 2003

Background
Rapid ischemic preconditioning (IPC) has been shown to reduce cellular injury after subsequent cardiac and cerebral ischemia. However, the data on rapid IPC of the spinal cord is limited. The authors investigated whether pretreatment with sublethal ischemia of spinal cord can attenuate neuronal injury after spinal cord ischemia in rabbits.

Methods
Forty-seven male New Zealand white rabbits were randomly assigned to one of three groups (n = 15 or 16 each). In the IPC(-) group, the infrarenal aorta was occluded for 17 min to produce spinal cord ischemia. In the IPC(+) group, 5 min of aortic occlusion was performed 30 min before 17 min of spinal cord ischemia. In the sham group, the aorta was not occluded. Hind limb motor function was assessed at 3 h, 24 h, 4 days, and 7 days after reperfusion using Tarlov scoring (0 = paraplegia; 4 = normal). Animals were killed for histopathologic evaluation at 24 h or 7 days after reperfusion. The number of normal neurons in the anterior spinal cord (L4-L6) was counted.

Results
Neurologic scores were significantly higher in the IPC(+) group than the IPC(-) group at 3 and 24 h after reperfusion (P < 0.05). However, neurologic scores in the IPC(+) group gradually decreased and became similar to those in the IPC(-) group at 4 and 7 days after reperfusion. At 24 h after reperfusion, the numbers of normal neurons were significantly higher in the IPC (+) group than in the IPC(-) group (P < 0.05) and were similar between the IPC(+) and sham groups. At 7 days after reperfusion, there was no difference in the number of normal neurons between the IPC(+) and IPC(-) groups.

Conclusion
The results indicate that rapid IPC protects the spinal cord against neuronal damage 24 h but not 7 days after reperfusion in a rabbit model of spinal cord ischemia, suggesting that the efficacy of rapid IPC may be transient.
Selective Blockade of AT1 Receptor Attenuates Impairment of Hypotensive Autoregulation and Improves Cerebral Blood Flow after Brain Injury in the Newborn Pig
Authors: Baranov Dimitry , Armstead William M. 
Published: November 2003

Background
Fluid percussion injury (FPI) in piglets produces vasoconstriction of pial arteries (PAs), decreases in cerebral blood flow (CBF), and impairment of hypotensive autoregulation. Two types of angiotensin II receptors, AT1 and AT2, have been identified in the brain. This study characterized the effect of pretreatment with AT1- and AT2-selective antagonists on CBF and hypotensive autoregulation after FPI.

Methods
Fluid percussion injury was induced in chloralose-anesthetized newborn pigs equipped with closed cranial windows. CBF was determined by the radiolabeled microsphere technique.

Results
Moderate and severe hypotension (71 +/- 3, 53 +/- 2, and 40 +/- 1 mmHg for normotension, moderate hypotension, and severe hypotension, respectively) elicited PA dilation without changes in CBF in sham control piglets. The AT1 antagonist ZD 7155 partially restored impaired hypotension-induced PA dilation after FPI (19 +/- 1 and 34 +/- 1 vs. 5 +/- 1 and 7 +/- 1 vs. 12 +/- 1 and 20 +/- 3% for PA dilation during moderate and severe hypotension in sham control, FPI, and FPI + ZD 7155 animals, respectively). ZD 7155 also blunted the reductions in CBF during normotension and hypotension observed in untreated animals (43 +/- 4, 38 +/- 5, and 55 +/- 3 vs. 32 +/- 4, 19 +/- 2, and 27 +/- 5% CBF reductions during normotension, moderate hypotension, and severe hypotension in untreated and pretreated animals, respectively). The AT2 selective antagonist PD 123,319 did not restore hypotension-induced PA dilation and did not prevent decreases in CBF observed during normotension and moderate and severe hypotension after FPI.

Conclusion
These data indicate that blockade of the AT1 and not the AT2 receptor diminished the reduction in hypotensive PA dilation after FPI. AT1 blockade also blunted the decrease in CBF during normotension as well as the further decrease in CBF observed during hypotension after FPI. These data suggest that AT1 receptor activation by angiotensin II contributes to cerebrovascular dysregulation during hypotension after FPI.
Severe Hypotension Is Not Essential for Isoflurane Neuroprotection against Forebrain Ischemia in Mice
Authors: Homi H. Mayumi , Mixco Javier M. , Sheng Huaxin , Grocott Hilary P. , Pearlstein Robert D. , Warner David S. 
Published: November 2003

Background
Volatile anesthetics provide protection in experimental models of global cerebral ischemia. To date, all models evaluated have included profound systemic arterial hypotension as a component of the ischemic insult. This study was designed to determine if isoflurane protection persists in a global insult devoid of hypotension.

Methods
C57BL/6J mice having a high incidence of posterior communicating artery atresia were anesthetized with isoflurane (1.2%) or fentanyl/N2O and subjected to bilateral carotid artery occlusion for 15 min or 20 min with normotension (80-110 mmHg mean arterial pressure) or for 10 min with hypotension (35 mmHg mean arterial pressure). Three days later, neurologic function and histologic damage were assessed. Other mice underwent measurement of intraischemic cerebral blood flow (4-iodo-N-methyl-[14C]antipyrine autoradiography) or plasma norepinephrine.

Results
Isoflurane reduced the percentage of hippocampal CA1 dead neurons (e.g., 10 min bilateral carotid occlusion + hypotension: 43 +/- 18 (isoflurane) vs. 67 +/- 20 (fentanyl/N2O), P = 0.003; 20 min bilateral carotid occlusion + normotension: 49 +/- 27 (isoflurane) vs. 71 +/- 22 (fentanyl/N2O), P = 0.003). Isoflurane also reduced CA3 damage and improved neurologic function under all conditions. Intraischemic forebrain blood flow was similar during bilateral carotid occlusion plus normotension for the two anesthetic states. Plasma norepinephrine values were greater when hypotension was added to the ischemic insult.

Conclusions
Isoflurane resulted in improved neurologic function and reduced histologic damage regardless of the presence or absence of systemic hypotension during the ischemic insult. This indicates that beneficial effects of isoflurane are most likely attributable to direct effects at the neuronal level as opposed to indirect effects resulting from interactions with profound hypotension.
Arthroscopic Knee Surgery Does Not Modify Hyperalgesic Responses to Heat Injury
Authors: Werner Mads U. , Duun Preben , Kraemer Otto , Lassen Birgit , Kehlet Henrik 
Published: November 2003

Background
Experimental studies suggest that surgical injury may up- or down-regulate nociceptive function. Therefore, the aim of this clinical study was to evaluate the effect of elective arthroscopically assisted knee surgery on nociceptive responses to a heat injury.

Methods
Seventeen patients scheduled to undergo repair of the anterior cruciate ligament and 16 healthy controls were studied. The first burn injury was induced 6 days before surgery, and the second burn was induced 1 day after surgery with a contact thermode (12.5 cm2, 47 degrees C for 7 min) placed on the medial aspect of the calf contralateral to the surgical side. Ibuprofen and acetaminophen were given for 2 days before the first burn injury and again from the time of surgery. In the controls, the two burn injuries were separated by 7 days. Sensory variables included cumulated pain score during induction of the burn (visual analog scale), secondary hyperalgesia area, and mechanical and thermal pain perception and pain thresholds assessed before and 1 h after the burn injury.

Results
The heat injuries induced significant increases in pain perception (P < 0.001) and decreases in pain thresholds (P < 0.02). Baseline heat pain thresholds were higher during the second burn injury in patients (P < 0.001) and controls (P < 0.01). However, there were no significant differences in pain to heat injury (P > 0.8), secondary hyperalgesia areas (P > 0.1), mechanical and thermal pain perception (P > 0.1), or mechanical and thermal pain thresholds (P > 0.08) in the burn area before surgery compared to after surgery.

Conclusion
Arthroscopic knee surgery did not modify nociceptive responses to a contralaterally applied experimental burn injury.
Efficacy, Safety, and Pharmacokinetics of Levobupivacaine with and without Fentanyl after Continuous Epidural Infusion in Children
Authors: Lerman Jerrold , Nolan Judith , Eyres Rob , Schily Mark , Stoddart Peter , Bolton Christopher M. , Mazzeo Frank , Wolf Andrew R. 
Published: November 2003

Background
Levobupivacaine, the levo-enantiomer of bupivacaine, is as potent as bupivacaine but less toxic. Therefore, the authors investigated the efficacy, safety, and pharmacokinetics of perioperative epidural levobupivacaine with and without fentanyl in children.

Methods
After Research Ethics Board approval and informed written consent, 120 healthy children aged 6 months to 12 yr who were scheduled to undergo urologic or abdominal surgery were randomized in a double-blinded and concealed manner to receive one of four epidural solutions as a continuous infusion for 24 h: 0.125% levobupivacaine; 0.0625% levobupivacaine; 1 mug/ml fentanyl; or the combination, 0.0625 levobupivacaine and 1 mug/ml fentanyl. After induction of anesthesia and tracheal intubation, a lumbar epidural catheter was sited, a loading dose was administered (0.75 ml/kg levobupivacaine, 0.175%), and the epidural infusion was commenced. The primary endpoint was the need for rescue analgesia (morphine) in the first 10 h after surgery. Pain, motor strength, and side effects were recorded for 24 h. Venous blood was collected from 18 children to determine the plasma concentrations of levobupivacaine and/or fentanyl before and 2, 4, 8, 16, 24, and 26 or 30 h after the start of the epidural infusion.

Results
Of the 114 children who were analyzed for intention to treat, a similar number of children in each group reached the 10-h mark. The time to the first dose of morphine in the first 10 h was less in the plain fentanyl group (P < 0.044). All other effects were similar among the four groups. The plasma concentration of levobupivacaine increased during the infusion period, reaching a maximum of 0.76 +/- 0.11 mug/ml in the 0.125% group and 0.48 +/- 0.12 mug/ml in the 0.0625% group by 24 h. The plasma concentration of fentanyl also increased steadily, reaching a maximum concentration of 0.37 +/- 0.11 ng/ml by 24 h.

Conclusion
We conclude that 0.0625% levobupivacaine without fentanyl is an effective perioperative epidural solution in children when infused at a rate of 0.3 ml. kg-1. h-1. The plasma concentrations of 0.125% and 0.0625% levobupivacaine and fentanyl (1 mug/ml) at the end of a 24-h infusion are low.
Reporting of Ethical Approval and Informed Consent in Clinical Research Published in Leading Anesthesia Journals
Authors: Myles Paul S. , Tan Nicole 
Published: November 2003

Background
Ethical conduct in human research in anesthesia includes approval by an institutional review board (IRB) or ethics committee and informed consent. Evidence of these is sometimes lacking in journal publications.

Methods
The authors reviewed all publications involving human subjects in six leading anesthesia journals for the year 2001 (n = 1189). Rates of IRB approval and informed consent were examined and compared with potential predictors that included journal, type of publication, and patient demographics (age, sex, elective or emergency status). Rates were compared by use of chi-square and logistic regression.

Results
The authors found that IRB approval was documented in 71% of publications and consent was obtained in 66% of publications. Significant variation in IRB approval and consent was found among journals (P < 0.0005) and according to type of publication (P < 0.0005). Because publication type affected rates of IRB approval and consent (trials > mechanistic studies > observational studies > case reports), an analysis restricted to prospective studies also found a significant difference in IRB approval and consent among journals (P < 0.0005).

Conclusions
This study suggests that rates of IRB approval and informed consent vary among publications in anesthesia journals. Clearer guidelines (and author adherence) for all types of publication are needed, both as a protection for research subjects and to maintain public trust in the process.
IGF‐I Induced Phosphorylation of S6K1 and 4E‐BP1 in Heart is Impaired by Acute Alcohol Intoxication
Authors: Lang Charles H. , Kumar Vinayshree , Liu Xiaoli , Frost Robert A. , Vary Thomas C. 
Published: November 2003

Background: The purpose of the present study was to determine whether acute alcohol (EtOH) intoxication impairs the signal transduction pathway used to coordinate insulin‐like growth factor (IGF)‐I stimulation of myocardial protein synthesis.Methods: Rats were injected intraperitoneally with EtOH or saline. After 2.5 h, IGF‐I or saline was injected intravenously and the heart was excised at 2 min or 20 min. Additional rats were pretreated with RU486 or tumor necrosis factor (TNF) binding protein (BP) to assess the importance of elevations in glucocorticoids or TNF, respectively, as endogenous modulators of IGF‐I signal transduction.Results: EtOH did not alter the total amount or tyrosine phosphorylation of the IGF‐I receptor, IRS‐1 or PKB under basal or IGF‐stimulated conditions. However, EtOH attenuated the ability of IGF‐I to phosphorylate ribosomal S6 kinase (S6K)‐1 on residues T389 (∼62%) and T421/S424 (∼40%), and also reduced ribosomal protein S6 phosphorylation. Under basal conditions, EtOH altered the distribution of eukaryotic initiation factor (eIF) 4E, as evidenced by a decreased amount of the active eIF4E·eIF4G complex (53%), an increased amount of inactive eIF4E·4E‐BP1 complex (∼3‐fold), and decreased phosphorylation of 4E‐BP1 (56%). EtOH also impaired the ability of IGF‐I to reverse the above‐mentioned changes in the eIF4E system. Pretreatment of rats with RU486 or TNFBP was unable to attenuate the EtOH‐induced changes in either eIF4E distribution or the phosphorylation state of 4E‐BP1, S6K1 or S6.Conclusions: These data indicate that acute EtOH intoxication alters selected aspects of translational control in the heart under basal conditions. Furthermore, despite appropriate stimulation of IGF‐I receptor, IRS‐1 and PKB, EtOH impairs IGF‐I signaling via S6K1 and 4E‐BP1 pathways, and this defect is regulated in a glucocorticoid‐ and TNF‐independent manner. This IGF‐I resistance may represent a participating mechanism by which alcohol limits protein synthesis in heart.
The Effect of Chronic Binge Ethanol Consumption on the Primary Stage of SIV Infection in Rhesus Macaques
Authors: Bagby Gregory J. , Stoltz David A. , Zhang Ping , Kolls Jay K. , Brown Julie , Bohm Rudolf P. , Rockar Richard , Purcell Jeanette , Murphey‐Corb Michael , Nelson Steve 
Published: November 2003

Background: Alcohol abuse and infection with HIV individually compromise immune function, but the consequence of both conditions together is poorly understood owing to the difficulties of performing appropriate studies in human subjects. Simian immunodeficiency virus (SIV) infection of rhesus macaques is considered to closely model HIV disease in that the virus infects CD4+ cells and this infection leads to a similar AIDS state. This study was initiated to study the combined effects of chronic binge alcohol consumption on the primary stage of SIV infection.Methods: Rhesus macaques were administered alcohol or isocaloric sucrose via a permanently indwelling intragastric catheter 4 consecutive days per week for the duration of the study. Doses were individualized to achieve plasma alcohol concentrations of 50–60 mM over a 5‐hr period. After 3 months, animals were inoculated intravenously with 10,000 times the ID50 (50% infective dose) of SIVDeltaB670 at the conclusion of an alcohol session and followed for 2 months postinoculation.Results: At 1 week, plasma SIV RNA was greater than 60‐fold higher in alcohol‐consuming animals compared with sucrose controls. Likewise, alcohol consumption enhanced the SIV‐induced increase in cell cycling T lymphocytes (i.e., cells expressing Ki67 protein) in blood. These differences between alcohol‐ and sucrose‐treated animals were not sustained during the observation period. Peak viral load occurred 2 weeks post‐SIV inoculation at 7.6 ± 4.2 and 5.2 ± 3.1 × 106 copies/ml in alcohol‐ versus sucrose‐consuming animals, respectively. Blood CD4+ lymphocyte numbers were decreased 1 and 2 months after SIV inoculation to a similar degree in both sucrose‐control and alcohol‐treated animals.Conclusions: The consequence of the early rise in viral load and increase in lymphocyte turnover seen with excess alcohol consumption is unknown. We hypothesize that alcohol intoxication may increase the susceptibility of the host to HIV/SIV infection. This possibility needs to be explored further.
Genetic Analyses of Ethanol‐Induced Hyperglycemia
Authors: Risinger Fred O. 
Published: November 2003

Background: Genetic sensitivity to ethanol‐induced hyperglycemia was hypothesized to be related to sensitivity to ethanol‐induced hypothermia and conditioned taste aversion. These hypotheses were explored by characterizing blood glucose changes after ethanol exposure in BXD recombinant inbred mice.Methods: Adult male and female BXD recombinant inbred mice were acutely exposed to 4 g/kg of ethanol or saline with the order of exposure counterbalanced, and separated by a 1‐week interval. Tail blood samples and rectal temperatures were determined immediately before ethanol/saline exposure and 2 hr after exposure.Results: Substantial strain differences in ethanol‐induced hyperglycemia and hypothermia were noted. In addition, sex also determined sensitivity to ethanol‐induced hyperglycemia and interacted with strain. Correlational analyses using strain means indicated that ethanol‐induced hyperglycemia was genetically independent from ethanol‐induced hypothermia or conditioned taste aversion. Quantitative trait locus (QTL) analyses indicated provisional QTL for ethanol‐induced hyperglycemia on chromosomes 1, 3, 4, 6, 7, 9, 12, 14, and 18, which, in part, were sex specific.Conclusions: These findings indicate important sex differences in the glycemic response to ethanol. In addition, multiple genes likely control this response, independent from genes that are important for the thermic or aversive effects of ethanol.
A 5‐Year Prospective Evaluation of DSM‐IV Alcohol Dependence With and Without a Physiological Component
Authors: Schuckit M. A. , Danko G. P. , Smith T. L. , Hesselbrock V. , Kramer J. , Bucholz K. 
Published: November 2003

Background:The DSM‐III‐R removed tolerance and withdrawal as required elements for a diagnosis of alcohol dependence. Although this practice was continued in DSM‐IV, the more recent manual asked clinicians to note whether physiological aspects of withdrawal (tolerance and withdrawal) had ever been experienced. Few studies have determined the prognostic meaning of a history of a physiological component to DSM‐IV alcohol dependence.Methods:Face‐to‐face structured interviews were used to evaluate the course of alcohol, drug, and psychiatric problems during the subsequent 5 years for 1094 alcohol‐dependent men and women. These subjects had been classified into subgroups at the time of initial interview regarding evidence of tolerance or withdrawal, and all evaluations were based on DSM‐IV criteria. At baseline, the application of DSM‐IV diagnostic guidelines resulted in 649 (59.3%) individuals having a history of an alcohol withdrawal syndrome, with or without tolerance (group 1); 391 (35.7%) with histories of tolerance but not withdrawal (group 2); and 54 (4.9%) with no lifetime histories of tolerance or withdrawal (group 3).Results:During the 5‐year follow‐up, both the broad (group 1 plus 2 versus group 3) and narrow (group 1 versus group 2 plus group 3) definitions of physiological dependence were associated with more alcohol and drug problems. However, for most items, this differential primarily reflected differences between groups 1 and 3, with a less impressive effect by group 2. Although no group differences were noted for the rate of independent major depressive episodes, substance‐induced depressions did differentiate among groups, a finding also most closely related to the distinction between groups 1 and 3.Conclusions:These data support the prognostic importance of noting the presence of a physiological component in alcohol dependence and indicate the potential relevance of limiting the definition of a physiological component to withdrawal.
Severe Alcoholic Hepatitis Successfully Treated by Leukocytapheresis: A Case Report
Authors: Tsuji Yoshiyasu , Kumashiro Ryukichi , Ishii Kunihide , Arinaga Teruko , Sakamoto Yoshihiro , Tanabe Ryo , Ogata Kei , Koga Yuriko , Ide Tatsuya , Ono Naofumi , Tanaka Eisuke , Abe Hirohiko , Sata Michio 
Published: November 2003

Background: The prognosis of severe alcoholic hepatitis is poor, and there is no established method for a cure.Methods: A 34‐year‐old man was admitted to Kurume University Hospital because of severe liver dysfunction due to excess alcohol intake. He was treated with prednisolone and two sessions of granulocyte and monocyte adsorption apheresis (GCAP) using an Adacolumn, which removes leukocytes—especially granulocytes and monocytes—from the peripheral blood. We evaluated the changes in the serum levels of interleukin‐6, interleukin‐8, tumor necrosis factor‐α, and soluble intercellular adhesion molecule‐1, as well as the conventional liver tests and peripheral white blood cell count.Results: Prednisolone was effective in the short term but resulted in an increase in C‐reactive protein (CRP), peripheral leukocytes, and serum total bilirubin. GCAP performed on the 34th and 41th hospital days produced decreases in the white blood cell count, total bilirubin, and intercellular adhesion molecule‐1. The patient survived, despite the expected poor prognosis on admission.Conclusions: GCAP is recommended as a potential therapeutic option for severe alcoholic hepatitis.