bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the
O
-GlcNAc proteome: Direct identification of
O
-GlcNAc-modified proteins from the brain
Authors: Khidekel Nelly , Ficarro Scott B. , Peters Eric C. , Hsieh-Wilson Linda C.
Published: August 2004

The covalent modification of intracellular proteins by
O
-linked β-
N
-acetylglucosamine (
O
-GlcNAc) is emerging as a crucial regulatory posttranslational modification akin to phosphorylation. Numerous studies point to the significance of
O
-GlcNAc in cellular processes such as nutrient sensing, protein degradation, and gene expression. Despite its importance, the breadth and functional roles of
O
-GlcNAc are only beginning to be elucidated. Advances in our understanding will require the development of new strategies for the detection and study of
O
-GlcNAc-modified proteins
in vivo
. Herein we report the direct, high-throughput analysis of
O
-GlcNAc-glycosylated proteins from the mammalian brain. The proteins were identified by using a chemoenzymatic approach that exploits an engineered galactosyltransferase enzyme to selectively label
O
-GlcNAc proteins with a ketone-biotin tag. The tag permits enrichment of low-abundance
O
-GlcNAc species from complex mixtures and localization of the modification to short amino acid sequences. Using this approach, we discovered 25
O
-GlcNAc-glycosylated proteins from the brain, including regulatory proteins associated with gene expression, neuronal signaling, and synaptic plasticity. The functional diversity represented by this set of proteins suggests an expanded role for
O
-GlcNAc in regulating neuronal function. Moreover, the chemoenzymatic strategy described here should prove valuable for identifying
O
-GlcNAc-modified proteins in various tissues and facilitate studies of the physiological significance of
O
-GlcNAc across the proteome.
Enhanced neurogenesis in Alzheimer's disease transgenic (PDGF-APP
Sw,Ind
) mice
Authors: Jin Kunlin , Galvan Veronica , Xie Lin , Mao Xiao Ou , Gorostiza Olivia F. , Bredesen Dale E. , Greenberg David A.
Published: August 2004

Neurogenesis continues in the adult brain and is increased in certain pathological states. We reported recently that neurogenesis is enhanced in hippocampus of patients with Alzheimer's disease (AD). We now report that the effect of AD on neurogenesis can be reproduced in a transgenic mouse model. PDGF-APP
Sw,Ind
mice, which express the Swedish and Indiana amyloid precursor protein mutations, show increased incorporation of BrdUrd and expression of immature neuronal markers in two neuroproliferative regions: the dentate gyrus and subventricular zone. These changes, consisting of ≈2-fold increases in the number of BrdUrd-labeled cells, were observed at age 3 months, when neuronal loss and amyloid deposition are not detected. Because enhanced neurogenesis occurs in both AD and an animal model of AD, it seems to be caused by the disease itself and not by confounding clinical factors. As neurogenesis is increased in PDGF-APP
Sw,Ind
mice in the absence of neuronal loss, it must be triggered by more subtle disease manifestations, such as impaired neurotransmission. Enhanced neurogenesis in AD and animal models of AD suggests that neurogenesis may be a compensatory response and that measures to enhance neurogenesis further could have therapeutic potential.
Changes in connectivity profiles define functionally distinct regions in human medial frontal cortex
Authors: Johansen-Berg H. , Behrens T. E. J. , Robson M. D. , Drobnjak I. , Rushworth M. F. S. , Brady J. M. , Smith S. M. , Higham D. J. , Matthews P. M.
Published: August 2004

A fundamental issue in neuroscience is the relation between structure and function. However, gross landmarks do not correspond well to microstructural borders and cytoarchitecture cannot be visualized in a living brain used for functional studies. Here, we used diffusion-weighted and functional MRI to test structure-function relations directly. Distinct neocortical regions were defined as volumes having similar connectivity profiles and borders identified where connectivity changed. Without using prior information, we found an abrupt profile change where the border between supplementary motor area (SMA) and pre-SMA is expected. Consistent with this anatomical assignment, putative SMA and pre-SMA connected to motor and prefrontal regions, respectively. Excellent spatial correlations were found between volumes defined by using connectivity alone and volumes activated during tasks designed to involve SMA or pre-SMA selectively. This finding demonstrates a strong relationship between structure and function in medial frontal cortex and offers a strategy for testing such correspondences elsewhere in the brain.
RELMβ/FIZZ2 is a goblet cell-specific immune-effector molecule in the gastrointestinal tract
Authors: Artis David , Wang Mei Lun , Keilbaugh Sue A. , He Weimian , Brenes Mario , Swain Gary P. , Knight Pamela A. , Donaldson Deborah D. , Lazar Mitchell A. , Miller Hugh R. P. , Schad Gerhard A. , Scott Phillip , Wu Gary D.
Published: August 2004

Gastrointestinal (GI) nematode infections are an important public health and economic concern. Experimental studies have shown that resistance to infection requires CD4
+
T helper type 2 (Th2) cytokine responses characterized by the production of IL-4 and IL-13. However, despite >30 years of research, it is unclear how the immune system mediates the expulsion of worms from the GI tract. Here, we demonstrate that a recently described intestinal goblet cell-specific protein, RELMβ/FIZZ2, is induced after exposure to three phylogenetically distinct GI nematode pathogens. Maximal expression of RELMβ was coincident with the production of Th2 cytokines and host protective immunity, whereas production of the Th1 cytokine, IFN-γ, inhibited RELMβ expression and led to chronic infection. Furthermore, whereas induction of RELMβ was equivalent in nematode-infected wild-type and IL-4-deficient mice, IL-4 receptor-deficient mice showed minimal RELMβ induction and developed persistent infections, demonstrating a direct role for IL-13 in optimal expression of RELMβ. Finally, we show that RELMβ binds to components of the nematode chemosensory apparatus and inhibits chemotaxic function of a parasitic nematode
in vitro
. Together, these results suggest that intestinal goblet cell-derived RELMβ may be a novel Th2 cytokine-induced immune-effector molecule in resistance to GI nematode infection.
Universality in intermediary metabolism
Authors: Smith Eric , Morowitz Harold J.
Published: August 2004

We analyze the stoichiometry, energetics, and reaction concentration dependence of the reductive tricarboxylic acid (rTCA) cycle as a universal and possibly primordial metabolic core. The rTCA reaction sequence is a network-autocatalytic cycle along the relaxation pathway for redox couples in nonequilibrium reducing environments, which provides starting organic compounds for the synthesis of all major classes of biomolecules. The concentration dependence of its reactions suggests it as a precellular bulk process. We propose that rTCA is statistically favored among competing redox relaxation pathways under early-earth conditions and that this feature drove its emergence and also accounts for its evolutionary robustness and universality. The ability to enhance the rate of core reactions creates an energetic basis for selection of subsequent layers of biological complexity.
Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration
Authors: Cordeiro M. Francesca , Guo Li , Luong Vy , Harding Glen , Wang Wei , Jones Helen E. , Moss Stephen E. , Sillito Adam M. , Fitzke Frederick W.
Published: August 2004

Apoptotic nerve cell death is implicated in the pathogenesis of several devastating neurodegenerative conditions, including glaucoma and Alzheimer's and Parkinson's diseases. We have devised a noninvasive real-time imaging technique using confocal laser-scanning ophthalmoscopy to visualize single nerve cell apoptosis
in vivo
, which allows longitudinal study of disease processes that has not previously been possible. Our method utilizes the unique optical properties of the eye, which allow direct microscopic observation of nerve cells in the retina. We have been able to image changes occurring in nerve cell apoptosis over hours, days, and months and show that effects depend on the magnitude of the initial apoptotic inducer in several models of neurodegenerative disease in rat and primate. This technology enables the direct observation of single nerve cell apoptosis in experimental neurodegeneration, providing the opportunity for detailed investigation of fundamental disease mechanisms and the evaluation of interventions with potential clinical applications, together with the possibility of taking this method through to patients.
Activated Polymorphonuclear Leukocytes Rapidly Synthesize Retinoic Acid Receptor-α
Authors: Yost Christian C. , Denis Melvin M. , Lindemann Stephan , Rubner Frederick J. , Marathe Gopal K. , Buerke Michael , McIntyre Thomas M. , Weyrich Andrew S. , Zimmerman Guy A.
Published: August 2004

In addition to releasing preformed granular proteins, polymorphonuclear leukocytes (PMNs) synthesize chemokines and other factors under transcriptional control. Here we demonstrate that PMNs express an inducible transcriptional modulator by signal-dependent activation of specialized mechanisms that regulate messenger RNA (mRNA) translation. HL-60 myelocytic cells differentiated to surrogate PMNs respond to activation by platelet activating factor by initiating translation and with appearance of specific mRNA transcripts in polyribosomes. cDNA array analysis of the polyribosome fraction demonstrated that retinoic acid receptor (RAR)-α, a transcription factor that controls the expression of multiple genes, is one of the polyribosome-associated transcripts. Quiescent surrogate HL60 PMNs and primary human PMNs contain constitutive message for RAR-α but little or no protein. RAR-α protein is rapidly synthesized in response to platelet activating factor under the control of a specialized translational regulator, mammalian target of rapamycin, and is blocked by the therapeutic macrolide rapamycin, events consistent with features of the 5′ untranslated region of the transcript. Newly synthesized RAR-α modulates production of interleukin-8. Rapid expression of a transcription factor under translational control is a previously unrecognized mechanism in human PMNs that indicates unexpected diversity in gene regulation in this critical innate immune effector cell.
Theophylline Restores Histone Deacetylase Activity and Steroid Responses in COPD Macrophages
Authors: Cosio Borja G. , Tsaprouni Loukia , Ito Kazuhiro , Jazrawi Elen , Adcock Ian M. , Barnes Peter J.
Published: August 2004

Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease of the lungs with little or no response to glucocorticoids and a high level of oxidative stress. Histone deacetylase (HDAC) activity is reduced in cells of cigarette smokers, and low concentrations of theophylline can increase HDAC activity. We measured the effect of theophylline on HDAC activity and inflammatory gene expression in alveolar macrophages (AM) from patients with COPD. AM from normal smokers showed a decrease in HDAC activity compared with normal control subjects, and this was further reduced in COPD patients (51% decrease, P < 0.01). COPD AMs also showed increased basal release of IL-8 and TNF-α, which was poorly suppressed by dexamethasone. Theophylline induced a sixfold increase in HDAC activity in COPD AM lysates and significantly enhanced dexamethasone suppression of induced IL-8 release, an effect that was blocked by the HDAC inhibitor trichostatin A. Therefore, theophylline might restore steroid responsiveness in COPD patients.
Amphiphysin IIm Is Required for Survival of Chlamydia pneumoniae in Macrophages
Authors: Gold Elizabeth S. , Simmons Randi M. , Petersen Timothy W. , Campbell Lee Ann , Kuo Cho-Chou , Aderem Alan
Published: August 2004

Macrophages play a critical role in both innate and acquired immunity because of their unique ability to internalize, kill, and degrade bacterial pathogens through the process of phagocytosis. The adaptor protein, amphiphysin IIm, participates in phagocytosis and is transiently associated with early phagosomes. Certain pathogens, including Chlamydia pneumoniae, have evolved mechanisms to subvert macrophage phagosome maturation and, thus, are able to survive within these cells. We report here that, although amphiphysin IIm is usually only transiently associated with the phagosome, it is indefinitely retained on vacuoles containing C. pneumoniae. Under these wild-type conditions, C. pneumoniae do not elicit significant nitric oxide (NO) production and are not killed. Abrogation of amphiphysin IIm function results in C. pneumoniae–induced NO production and in the sterilization of the vacuole. The data suggest that C. pneumoniae retains amphiphysin IIm on the vacuole to survive within the macrophage.
The Same IκBα Mutation in Two Related Individuals Leads to Completely Different Clinical Syndromes
Authors: Janssen Riny , van Wengen Annelies , Hoeve Marieke A. , ten Dam Monique , van der Burg Miriam , van Dongen Jacques , van de Vosse Esther , van Tol Maarten , Bredius Robbert , Ottenhoff Tom H. , Weemaes Corry , van Dissel Jaap T. , Lankester Arjan
Published: August 2004

Both innate and adaptive immune responses are dependent on activation of nuclear factor κB (NF-κB), induced upon binding of pathogen-associated molecular patterns to Toll-like receptors (TLRs). In murine models, defects in NF-κB pathway are often lethal and viable knockout mice have severe immune defects. Similarly, defects in the human NF-κB pathway described to date lead to severe clinical disease. Here, we describe a patient with a hyper immunoglobulin M–like immunodeficiency syndrome and ectodermal dysplasia. Monocytes did not produce interleukin 12p40 upon stimulation with various TLR stimuli and nuclear translocation of NF-κB was impaired. T cell receptor–mediated proliferation was also impaired. A heterozygous mutation was found at serine 32 in IκBα. Interestingly, his father has the same mutation but displays complex mosaicism. He does not display features of ectodermal dysplasia and did not suffer from serious infections with the exception of a relapsing Salmonella typhimurium infection. His monocyte function was impaired, whereas T cell function was relatively normal. Consistent with this, his T cells almost exclusively displayed the wild-type allele, whereas both alleles were present in his monocytes. We propose that the T and B cell compartment of the mosaic father arose as a result of selection of wild-type cells and that this underlies the widely different clinical phenotype.
Inhibition of T Cell Receptor Signal Transduction by Tyrosine Kinase–interacting Protein of Herpesvirus saimiri
Authors: Cho Nam-Hyuk , Feng Pinghui , Lee Sun-Hwa , Lee Bok-Soo , Liang Xiaozhen , Chang Heesoon , Jung Jae U.
Published: August 2004

T cells play a central role in orchestrating immunity against pathogens, particularly viruses. Thus, impairing T cell activation is an important strategy employed by viruses to escape host immune control. The tyrosine kinase–interacting protein (Tip) of the T lymphotropic Herpesvirus saimiri (HVS) is constitutively present in lipid rafts and interacts with cellular Lck tyrosine kinase and p80 endosomal protein. Here we demonstrate that, due to the sequestration of Lck by HVS Tip, T cell receptor (TCR) stimulation fails to activate ZAP70 tyrosine kinase and to initiate downstream signaling events. TCR ζ chains in Tip-expressing T cells were initially phosphorylated to recruit ZAP70 molecule upon TCR stimulation, but the recruited ZAP70 kinase was not subsequently phosphorylated, resulting in TCR complexes that were stably associated with inactive ZAP70 kinase. Consequently, Tip expression not only markedly inhibited TCR-mediated intracellular signal transduction but also blocked TCR engagement with major histocompatibility complexes on the antigen-presenting cells and immunological synapse formation. These results demonstrate that a lymphotropic herpesvirus has evolved a novel mechanism to deregulate T cell activation to disarm host immune surveillance. This process contributes to the establishment and maintenance of viral latency.
A trilinear restriction problem for the paraboloid in ℝ³
Authors: Bennett Jonathan
Published: August 2004

We establish a sharp trilinear inequality for the extension operator associated to the paraboloid in

R

3

\mathbb {R}^{3}

. Our proof relies on a recent generalisation of the classical Loomis–Whitney inequality.
Spontaneous Ventilation with Halothane in Children
Authors: Reignier Jean , Ameur Mondher Ben , Ecoffey Claude
Published: August 2004

Background

It has been reported that, in children breathing spontaneously via an endotracheal tube, halothane depresses ventilation with paradoxic inspiratory movement. Endotracheal tubes have a higher airflow resistance than do laryngeal mask airways (LMAs). Therefore, the aim of this study was to compare spontaneous ventilation via the LMA with that via the endotracheal tube in children anesthetized with halothane.

Methods

The authors studied two groups of 6-24-month-old children with no cardiorespiratory and neurologic disorders, undergoing elective minor surgery with halothane anesthesia: one group breathing via LMA (n = 10) and one group breathing via endotracheal tube (n = 10). They measured tidal volume, respiratory rate, minute ventilation, and end-tidal CO2. They assessed paradoxic inspiratory movement using amplitude index and phase delay index.

Results

Age and weight were similar in both groups. Mean +/- SD tidal volume (7.5 +/- 1.9 ml/kg in the LMA group vs. 5.3 +/- 1.1 ml/kg in the endotracheal tube group; P < 0.05) and minute ventilation (325 +/- 105 ml.min-1.kg-1 in the LMA group vs. 246 +/- 38 ml.min-1.kg-1 in the endotracheal tube group; P < 0.05) were lower in the endotracheal tube group. The phase delay index (18 +/- 11% in the LMA group vs. 41 +/- 19% in the endotracheal tube group; P < 0.05) and the amplitude index (25 +/- 43% in the LMA group vs. 74 +/- 72% in the endotracheal tube group; P < 0.05) were significantly smaller with the LMA than with the endotracheal tube.

Conclusions

In 6-24-month-old children anesthetized with halothane, paradoxic inspiratory movement is less when breathing through an LMA than through an endotracheal tube.
Pulse Width, Stimulus Intensity, Electrode Placement, and Polarity during Assessment of Neuromuscular Block
Authors: Brull Sorin J. , Silverman David G.
Published: August 2004

Background

Although the intensity of neurostimulation (i.e., charge) is a product of current intensity and pulse duration, the effects of the latter on the amplitude of evoked response and subjective discomfort are unknown. Therefore, the authors investigated the effects of current intensity and pulse width, and their interaction with electrode placement and polarity, on force translation (FTR), accelerography (ACG), and electromyography (EMG) at the adductor pollics muscle.

Methods

Ulnar stimulating electrodes were applied in one of two configurations: over the distal forearm and olecranon groove ("A") or 5 cm apart on the distal forearm ("B"). Stimuli for FTR and EMG with current intensities of 20, 40, 60, and 70 mA and pulse widths of 0.05, 0.1, 0.2, and 0.4 msec resulted in 16 different charges. These combinations were delivered in each of four orientations: "A-" ("A" configuration with negative electrode distal); "A+", "B-", and "B+" (n = 64 stimuli). Eight stimulus combinations (n = 32 stimuli) were used for ACG. For each monitoring technique, the effects of current intensity, pulse width, electrode polarity, and placement were analyzed with repeated measures ANOVA. Pain responses were scored on a 0-100-mm verbal analog scale and analyzed with ANOVA and Fisher's exact test.

Results

The evoked response amplitude varied directly with current intensity and pulse width. In both electrode placement configurations, the response was greater when the negative electrode was distal. The electrode positioning ("A" vs. "B") had less of an impact on evoked responses than did polarity, regardless of monitoring technique. The evoked pain varied directly with the amplitude of evoked neuromuscular response in all electrode position-polarity combinations.

Conclusions

The total current charge required for evoking a supramaximal neuromuscular response is much higher than previously appreciated, and electrode polarity is important in attaining a supramaximal plateau. Failure to attain (and maintain) a supramaximal stimulus allows changes in the effectiveness of neurostimulation, thus influencing the magnitude of the evoked neuromuscular response and confounding measurements of neuromuscular block.
Heparin-Protamine Complexes Cause Pulmonary Hypertension in Goats
Authors: Horiguchi Takashi , Enzan Keiji , Mitsuhata Hiromasa , Murata Makoto , Suzuki Masahiro
Published: August 2004

Background

Protamine reversal of heparin-induced anticoagulation causes thromboxane release followed by pulmonary vasoconstriction in sheep and pigs. The aim of this study was to determine whether heparin-protamine (H-P) complexes are causative agents of thromboxane release followed by pulmonary hypertension associated with protamine reversal of heparin.

Methods

We separated H-P complexes and non-heparin-protamine (non-H-P) complexes from heparinized defibrinated human plasma neutralized with protamine by chromatography and studied the changes in hemodynamics, airway pressure, and thromboxane B2 concentration after injection of H-P complexes or non-H-P complexes into seven goats. In addition, we studied whether these pulmonary responses were blocked in goats pretreated with cyclooxgenase inhibitor (Indomethacin, n = 5) or thromboxane synthetase inhibitor (OKY-046, n = 5).

Results

A very small dose of H-P complexes increased pulmonary arterial and peak airway pressures and was followed by thromboxane B2 release (from 12 [5.5-23] to 28 [16-44] mmHg, from 9.0 [7.5-15] to 12 [8-19] cmH2O, and from 0.85 [0.34-3.2] to 16.4 [1.4-39.3] ng.ml-1, respectively). On the other hand, animals that received non-H-P complexes showed no significant changes. Indomethacin totally blocked and OKY-046 partially blocked the increases in pulmonary arterial pressure and thromboxane B2 concentration.

Conclusions

H-P complexes play a major role in pulmonary hypertension after protamine reversal of heparin, and thromboxane A2 is a main mediator of the pulmonary hypertensive response to H-P complexes in goats.
Role of Pertussis Toxin-sensitive G-Proteins in the Analgesic and Anesthetic Actions of α2-Adrenergic Agonists in the Rat
Authors: Hayashi Yukio , Rabin Bradford C. , Guo Tian-Zhi , Maze Mervyn
Published: August 2004

Background

alpha 2 Adrenoceptors are coupled to G-proteins sensitive to pertussis toxin (PTX) in the locus coeruleus. At this site, the hypnotic response to dexmedetomidine, an alpha 2 agonist, can be blocked by pretreatment with PTX. G-proteins sensitive to PTX may also be involved in the transduction of anesthetic and analgesic responses to alpha 2 agonists at supraspinal or spinal sites. To address this question the effects of pretreatment with PTX administered intracerebroventricularly, intrathecally, or a combination of the two were examined on the MAC for halothane, and the anesthetic-sparing and analgesic effects of a systemically administered alpha 2 agonist, dexmedetomidine.

Methods

Rats were cannulated intracerebroventricularly, intrathecally, and with a combination of intracerebroventricular/intrathecal and treated with PTX (0 and 2.5 micrograms intracerebroventricularly; 0 or 0.5 microgram intrathecally; 0 + 0 or 2.5 + 0.5 intracerebroventricular-intrathecal)). After 7 days, either the analgesic (tail-flick latency) or the MAC-sparing effects of a calculated 50% effective dose of dexmedetomidine were measured. To confirm that intracerebroventricularly administered PTX was effective, ribosylation of G-proteins was assessed in periventricular brain tissue.

Results

The analgesic action of dexmedetomidine was blocked by PTX intrathecally but not by PTX via the intracerebroventricular route. The MAC-sparing action of dexmedetomidine was not blocked by PTX via the intrathecal or intracerebroventricular routes alone or in combination. Yet, intracerebroventricularly administered PTX effectively ribosylated the G-proteins.

Conclusions

Taken together with the authors' previous report, these data suggest that the hypnotic and the analgesic responses to dexmedetomidine are transduced via PTX-sensitive G-protein-coupled alpha 2 adrenoceptors but at separate sites (analgesic-spinal; hypnotic-locus coeruleus). Further studies are needed to localize the precise site(s) for the MAC-sparing effect of dexmedetomidine and to establish whether PTX-sensitive G-proteins are involved in this response.
Cost-effectiveness of Prophylactic Antiemetic Therapy with Ondansetron, Droperidol, or Placebo
Authors: Hill Robert P. , Lubarsky David A. , Phillips-Bute Barbara , Fortney Jennifer T. , Creed Mary R. , Glass Peter S. A. , Gan Tong J.
Published: August 2004

Background

In an era of growing economic constraints on healthcare delivery, anesthesiologists are increasingly expected to understand cost analysis and evaluate clinical practices. Postoperative nausea and vomiting (PONV) are distressing for patients and may increase costs in an ambulatory surgical unit. The authors compared the cost-effectiveness of four prophylactic intravenous regimens for PONV: 4 mg ondansetron, 0.625 mg droperidol, 1.25 mg droperidol, and placebo.

Methods

Adult surgical outpatients at high risk for PONV were studied. Study drugs were administered intravenously within 20 min of induction of nitrous oxide-isoflurane or enflurane anesthesia. A decision-tree analysis was used to group patients into 12 mutually exclusive subgroups based on treatment and outcome. Costs were calculated for the prevention and treatment of PONV. Cost-effectiveness analysis was performed for each group.

Results

Two thousand sixty-one patients were enrolled. Efficacy data for study drugs have been previously reported, and the database from that study was used for pharmacoeconomic analysis. The mean-median total cost per patient who received prophylactic treatment with 4 mg ondansetron, 0.625 mg droperidol, 1.25 mg droperidol, and placebo were $112 or $16.44, $109 or $0.63, $104 or $0.51, and $164 or $51.20, respectively (P = 0.001, active treatment groups vs. placebo). The use of a prophylactic antiemetic agent significantly increased patient satisfaction (P < 0.05). Personnel costs in managing PONV and unexpected hospital admission constitute major cost components in our analysis. Exclusion of nursing labor costs from the calculation did not alter the overall conclusions regarding the relative costs of antiemetic therapy.

Conclusion

The use of prophylactic antiemetic therapy in high-risk ambulatory surgical patients was more effective in preventing PONV and achieved greater patient satisfaction at a lower cost compared with placebo. The use of 1.25 mg droperidol intravenously was associated with greater effectiveness, lower costs, and similar patient satisfaction compared with 0.625 mg droperidol intravenously and 4 mg ondansetron intravenously.
Memory Formation during General Anesthesia for Emergency Cesarean Sections
Authors: Lubke Gitta H. , Kerssens Chantal , Gershon Raphael Y. , Sebel Peter S.
Published: August 2004

Background

Occurrence of explicit memory (i.e., conscious recall) has been reported especially after surgical procedures in which anesthesia is considered to be "light." In addition, previous research has shown that implicit memory (e.g., improved memory test performance in absence of conscious recall) decreases with increasing hypnotic state. The current study investigated explicit and implicit memory during emergency cesarean sections with consistently light levels of hypnotic state.

Method

Words were presented via headphones, and the bispectral index was recorded throughout surgery. Memory for the presented words was tested after recovery with a word-stem completion test. Using both parts of the process dissociation procedure allowed separation of explicit and implicit memory. In the "inclusion" part of the process dissociation procedure, patients are asked to complete word stems, if possible, with the corresponding words recalled from the intraoperative presentation. In the "exclusion" part, patients are instructed to avoid the words presented intraoperatively and to use other words instead. In the absence of recall, patients are asked to use the first word that comes to mind.

Results

The mean bispectral index during word presentation was 76.3 (+/-3.0). On average, the 24 patients were able to make correct inclusion-exclusion decisions: In the inclusion part, hit rates (i.e., the probability of responding with a word presented during surgery) were higher than base rates (0.37 vs. 0.31), whereas in the exclusion part hit rates were lower (0.23 vs. 0.28). Importantly, the patients made these inclusion-exclusion decisions without being able to consciously recall the words presented during surgery.

Conclusions

This study shows that if words are presented at relatively light levels of anesthesia, patients are able to control their inclusion-exclusion decisions. This weak form of explicit memory can occur in the absence of conscious recall.
Plasma Concentration of Fentanyl with Xenon to Block Somatic and Hemodynamic Responses to Surgical Incision
Authors: Nakata Yoshinori , Goto Takahisa , Saito Hayato , Ishiguro Yoshiki , Terui Katsuo , Kawakami Hiromasa , Tsuruta Yoshihiko , Niimi Yoshinari , Morita Shigeho
Published: August 2004

Background

Although anesthesia with xenon has been supplemented with fentanyl, its requirement has not been established. This study was conducted to determine the plasma concentrations of fentanyl necessary to suppress somatic and hemodynamic responses to surgical incision in 50% patients in the presence of 0.7 minimum alveolar concentration (MAC) xenon.

Methods

Twenty-five patients were allocated randomly to predetermined fentanyl concentration between 0.5 and 4.0 ng/ml during 0.7 MAC xenon anesthesia. Fentanyl was administered using a pharmacokinetic model-driven computer-assisted continuous infusion device. At surgical incision each patient was monitored for somatic and hemodynamic responses. A somatic response was defined as any purposeful bodily movement. A positive hemodynamic response was defined as a more than 15% increase in heart rate or mean arterial pressure more than the preincision value. The concentrations of fentanyl to prevent somatic and hemodynamic responses in 50% of patients were calculated using logistic regression.

Results

The concentration of fentanyl to prevent a somatic response to skin incision in 50% of patients in the presence of 0.7 MAC xenon was 0.72 +/- 0.07 ng/ml and to prevent a hemodynamic response was 0.94 +/- 0.06 ng/ml.

Conclusions

Comparing these results with previously published results in the presence of 70% nitrous oxide, the fentanyl requirement in xenon anesthesia is smaller than that in the equianesthetic nitrous oxide anesthesia.
Both EMLA and Placebo Cream Reduced Pain during Extracorporeal Piezoelectric Shock Wave Lithotripsy with the Piezolith 2300
Authors: Tritrakarn Thara , Lertakyamanee Jariya , Koompong Pisamorn , Soontrapa Suchai , Somprakit Pradit , Tantiwong Anupan , Jittapapai Sunee
Published: August 2004

Background

The objectives were to determine whether a eutectic mixture of local anesthetic (EMLA) or placebo cream reduces pain during extracorporeal piezoelectric shock wave lithotripsy (EPSWL), and to determine which of the components of the application (i.e., the occlusive dressing, the cream, or the local anesthetic) contributes to analgesia.

Methods

A randomized, double blind, crossover study (part 1) was performed in 12 patients who were scheduled for EPSWL procedures on an ambulatory basis who received the first treatment without any intervention and who had verbal pain scores of 70 or more (on a 0-to- 100 scale). For the next two treatments at 2-week intervals, patients were randomly assigned to receive either 10 g EMLA or 10 g placebo cream and then crossed over to receive the other. The cream and occlusive dressing were left in place and immersed in water throughout the procedure. Verbal numeric pain score was assessed at 5 min after receiving the maximal tolerable intensity of shock wave and at the end of the procedure. The study continued (part 2) in 202 ambulatory patients; 125 men and 77 women, American Society of Anesthesiologists physical status I and II, subjected to EPSWL were randomly allocated into five groups who received (1) nothing on the skin (control), (2) plastic occlusive dressing, (3) placebo cream and plastic occlusive dressing, (4) EMLA cream and plastic occlusive dressing, (5) EMLA cream and plastic occlusive dressing for 60 min to achieve cutaneous anesthesia, which was removed before EPSWL. Pain score was evaluated 10 min into the procedure and at the end of the procedure.

Result

Both parts of the study showed that patients who received either EMLA or placebo cream with dressing throughout the procedure experienced less pain and tolerated higher energy levels compared with the control. Patients who received only pre-EPSWL cutaneous anesthesia of EMLA and who received only the occlusive dressing did not have a reduction in pain score.

Conclusions

EMLA and placebo creams under occlusive dressing reduced pain during EPSWL. The presence of the cream itself as a coupling medium contributed to analgesia. This may be a useful, simple, safe, and economical adjuvant technique to reduce pain during immersion EPSWL.
Mechanisms of Nonimmunological Histamine and Tryptase Release from Human Cutaneous Mast Cells
Authors: Veien Mette , Szlam Fania , Holden Jeannine T. , Yamaguchi Koji , Denson Donald D. , Levy Jerrold H.
Published: August 2004

Background

If mast cells are stimulated they release multiple mediators that delineate markers for immunologic and nonimmunologic reactions; histamine and tryptase are the two best known. Although histamine can be assayed in plasma, it is a nonspecific marker with a very short half-life. Tryptase has a longer half-life, but its release has not been proven to be specific for anaphylaxis. The authors investigated the mechanisms of nonimmunologic histamine release from human cutaneous mast cells to understand the mechanisms of mediator release and to determine whether tryptase was specific for allergic mediated activation.

Methods

Dispersed mast cell suspensions isolated from neonatal foreskins underwent challenge with vancomycin, calcium ionophore A23187, morphine, and atracurium, and histamine tryptase release was measured. The effects of calcium and magnesium, along with phospholipase C and phospholipase A2 inhibitors, also were investigated.

Results

Tryptase and histamine both were released by the known nonimmunologic stimuli (pharmacologic agents used in the current study; r2 = 0.6). Furthermore, vancomycin- and atracurium-induced histamine release was calcium dependent. Phospholipase C and phospholipase A2 inhibitors decreased vancomycin-induced histamine release, but not calcium ionophore A23187-induced release.

Conclusions

Tryptase is not a specific marker of mast cell activation (ie., anaphylaxis), and signaling mechanisms for mast cell activation involve activation of phospholipase C and phospholipase A2 pathways that are also involved in other cellular activation mechanisms.
Direct Coronary Vasomotor Effects of Sevoflurane and Desflurane in In Situ Canine Hearts
Authors: Crystal George J. , Zhou Xiping , Gurevicius Juozas , Czinn Edward A. , Salem M. Ramez , Alam Syed , Piotrowski Agnieszka , Hu Guochang
Published: August 2004

Background

An extracorporeal system was used to investigate the direct coronary vasomotor effects of sevoflurane and desflurane in vivo. The role of the adenosine triphosphate-sensitive potassium channels (KATP channels) in these effects was evaluated.

Methods

Twenty-one open-chest, anesthetized (fentanyl-midazolam) dogs were studied. The left anterior descending coronary artery was perfused at controlled pressure (80 mmHg) with normal arterial blood or arterial blood equilibrated with either sevoflurane or desflurane. Series 1 (n = 16) was divided into two groups of equal size on the basis of whether sevoflurane (1.2, 2.4, and 4.8%) or desflurane (3.6, 7.2, and 14.4%) was studied. The concentrations for the anesthetics corresponded to 0.5, 1.0, and 2.0 minimum alveolar concentration (MAC), respectively. Coronary blood flow (CBF) was measured with an ultrasonic, transit-time transducer. Local coronary venous samples were obtained and used to evaluate changes in myocardial oxygen extraction (EO2). In series 2 (n = 5), changes in CBF by 1 MAC sevoflurane and desflurane were assessed before and during intracoronary infusion of the KATP channel inhibitor glibenclamide (100 microg/min).

Results

Intracoronary sevoflurane and desflurane caused concentration-dependent increases in CBF (and decreases in EO2) that were comparable. Glibenclamide blunted significantly the anesthetic-induced increases in CBF.

Conclusions

Sevoflurane and desflurane have comparable coronary vasodilative effects in in situ canine hearts. The KATP channels play a prominent role in these effects. When compared with data obtained previously in the same model, the coronary vasodilative effects of sevoflurane and desflurane are similar to those of enflurane and halothane but considerably smaller than that of isoflurane.
Comparison of Volatile Anesthetic Effects on Actin–Myosin Cross-bridge Cycling in Neonatal versus Adult Cardiac Muscle
Authors: Prakash Yedatore S. , Cody Mark J. , Hannon James D. , Housmans Philippe R. , Sieck Gary C.
Published: August 2004

Background

The neonatal myocardium is more sensitive to volatile anesthetics compared with adults. The greater myocardial sensitivity of neonates may be attributable to greater anesthetic effect on force regulation at the level of the cross-bridge. In the current study, the authors compared the effects of 1 and 2 minimum alveolar concentration (MAC) halothane and sevoflurane on cardiac muscle from 0- to 3-day-old (neonate) and 84-day-old (adult) rats.

Methods

Triton X-100-skinned muscle strips were maximally activated at pCa (negative logarithm of the Ca2+ concentration) of 4.0, and the following were measured in the presence or absence of anesthetic: Rate of force redevelopment after rapid shortening and restretching (ktr) and isometric stiffness at maximal activation and in rigor. The fraction of attached cross-bridges (alphafs) and apparent rate constants for cross-bridge attachment (fapp) and detachment (gapp) were calculated assuming a two-state model for cross-bridge cycling. Anesthetic-induced changes in the mean stiffness per cross-bridge were also estimated from values in rigor versus maximum activation in the presence or absence of anesthetic.

Results

Neonatal cardiac muscle displayed significantly smaller alphafs slower ktr and slower fapp compared with adult cardiac muscle; however, gapp was not significantly different. Halothane, and sevoflurane to a significantly lesser extent, decreased alphafs, fapp, and the mean force per cross-bridge and increased gapp to a greater extent in neonates.

Conclusions

These data indicate that weaker force production in neonatal cardiac muscle involves, at least in part, less efficient cross-bridge cycling kinetics. The authors conclude that the greater myocardial sensitivity of neonates to volatile anesthetics reflects, at least in part, a direct inhibition of cross-bridge cycling, especially the rates of cross-bridge attachment and detachment.
Jugular Venous Bulb Oxygen Saturation in Patients with Preexisting Diabetes Mellitus or Stroke during Normothermic Cardiopulmonary Bypass
Authors: Kadoi Yuji , Saito Shigeru , Kawahara Fuminori , Goto Fumio , Owada Ryo-ichi , Fujita Nao
Published: August 2004

Background

The authors hypothesized that patients with cerebrovascular abnormalities or metabolic disorders may experience abnormality in cerebral circulation more frequently than patients without these risks. The current study attempted to assess jugular venous bulb oxygen saturation (SjvO2) in patients with preexisting diabetes mellitus or stroke undergoing normothermic cardiopulmonary bypass.

Methods

Thirty-nine patients undergoing elective coronary artery bypass graft surgery were studied, including 19 age-matched control patients, 10 diabetic patients, and 9 patients with preexisting stroke A 4.0-French fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb to continuously monitor internal SjvO2. Hemodynamic parameters and arterial and jugular venous blood gases were measured at seven time points: (1) after the induction of anesthesia and before the start of surgery, (2) just after the beginning of cardiopulmonary bypass, (3) 20 min after the beginning of bypass, (4) 40 min after the beginning of bypass, (5) 60 min after the beginning of bypass, (6) just after the cessation of bypass, and (7) at the end of the operation.

Results

No significant differences were seen in mean arterial pressure, arterial carbon dioxide tension (PaCO2), or hemoglobin concentration among the three groups during the study. The SjvO2 value did not differ among the three groups after anesthesia induction and before surgery, just after the beginning of cardiopulmonary bypass, 60 min after the beginning of bypass, just after the end of bypass, or at the end of the operation. Significant differences between the control group and the diabetic and stroke groups were observed, however, at 20 min and 40 min after the beginning of bypass (at 20 min: control group 62.2 +/- 6.8%, diabetes group 48.4 +/- 5.1%, stroke group 45.9 +/- 6.3%; at 40 min: control group 62.6 +/- 5.2%, diabetes group 47.1 +/- 5.2%, stroke group 48.8 +/- 4.1% [values expressed as the mean +/- SD]; P < 0.05). Also, values in the diabetes and stroke groups were decreased at 20 min and 40 min after the beginning of bypass compared with before the start of surgery.

Conclusions

A reduced SjvO2 value was observed more frequently in patients with preexisting diabetes mellitus or stroke during normothermic cardiopulmonary bypass. It is possible that cerebral circulation during normothermic bypass is altered in patients with risk factors for cerebrovascular disorder.
Impact of Shorter-acting Neuromuscular Blocking Agents on Fast-track Recovery of the Cardiac Surgical Patient
Authors: Murphy Glenn S. , Szokol Joseph W. , Marymont Jesse H. , Avram Michael J. , Vender Jeffery S. , Rosengart Todd K.
Published: August 2004

Background

Residual paralysis associated with the use of long-acting muscle relaxants can delay recovery from anesthesia and surgery. The authors tested the hypothesis that use of shorter-acting neuromuscular blocking agents is associated with reductions in tracheal extubation times and intensive care unit (ICU) length of stay in patients undergoing cardiac surgery with cardiopulmonary bypass.

Methods

One hundred ten patients scheduled for elective coronary artery bypass grafting or single valve surgery were randomized prospectively to receive either pancuronium or rocuronium intraoperatively. Anesthetic management and muscle relaxant maintenance dosing were standardized. In the ICU, the time required to wean ventilatory support, the duration of tracheal intubation, and length of stay were recorded. Subjects were asked to quantify generalized muscle weakness as they awakened in the ICU and again after tracheal extubation.

Results

Complete data were collected on 51 patients in the pancuronium group and 52 patients in the rocuronium group. No differences were found between the groups in anesthetic, surgical, or ICU management. Significant increases in the duration of weaning of ventilatory support were observed in patients who received pancuronium (median, 180 min; range, 50-780 min) compared with the rocuronium group (median, 110 min; range, 45-250 min). Tracheal extubation was significantly delayed in the pancuronium group (median, 500 min; range, 240-1,305 min) compared with the rocuronium group (median, 350 min; range, 210-1,140 min). Subjects in the pancuronium group experienced more mild to severe weakness in the ICU. However, the choice of muscle relaxant did not influence ICU length of stay.

Conclusion

The use of shorter-acting neuromuscular blocking agents in patients undergoing cardiac surgery with cardiopulmonary bypass is associated with reductions in tracheal extubation times and symptoms of residual paresis.
Increasing Maternal Blood Pressure with Ephedrine Increases Uterine Artery Blood Flow Velocity during Uterine Contraction
Authors: Ducros Laurent , Bonnin Philippe , Cholley Bernard P. , Vicaut Eric , Benayed Moncef , Jacob Denis , Payen Didier
Published: August 2004

Background

During labor, ephedrine is widely used to prevent or to treat maternal arterial hypotension and restore uterine perfusion pressure to avoid intrapartum fetal asphyxia. However, the effects of ephedrine on uterine blood flow have not been studied during uterine contractions. The purpose of the study was to assess the effects of ephedrine on uterine artery velocities and resistance index using the Doppler technique during the active phase of labor.

Methods

Ten normotensive, healthy parturients with uncomplicated pregnancies at term received intravenous ephedrine during labor to increase mean arterial pressure up to a maximum of 20% above their baseline pressure. Peak systolic and end-diastolic Doppler flow velocities and resistance indices were measured in the uterine artery before and immediately after administration of bolus intravenous ephedrine and after ephedrine washout. Umbilical and fetal middle cerebral arterial resistance indices and fetal heart rate were also calculated.

Results

After ephedrine administration, mean arterial pressure increased by 17 +/- 4%. End-diastolic flow velocity in the uterine artery at peak amplitude of uterine contraction was restored to 74% of the value observed in the absence of contraction. The systolic velocity was totally restored, and the uterine resistance index was significantly decreased, compared with the values in the absence of contraction. Between uterine contractions, ephedrine induced similar but less marked effects. Fetal hemodynamic parameters were not altered by ephedrine administration.

Conclusions

Bolus administration of intravenous ephedrine reversed the dramatic decrease in diastolic uteroplacental blood flow velocity and the increase in resistance index during uterine contraction, without altering fetal hemodynamic parameters. This suggests that the increase in uterine perfusion pressure during labor could in part restore uterine blood flow to the placenta during uterine contraction.