bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of ovarian cancer in women with first‐degree relatives with cancer
Authors: SOEGAARD MARIE , FREDERIKSEN KIRSTEN , JENSEN ALLAN , HØGDALL ESTRID , HØGDALL CLAUS , BLAAKAER JAN , RAMUS SUSAN J. , GAYTHER SIMON A. , KJAER SUSANNE K.
Published: March 2009

Objective. To assess the risk of ovarian cancer in women with first‐degree relatives with cancer at one of the four most frequent hereditary sites based on validated cancer diagnoses and to examine the association according to age at diagnosis of ovarian cancer and histology. Design. Case–control study. Setting and population. First‐degree relatives of 554 women with invasive epithelial ovarian cancer and 1,564 controls were included. Methods. Analyses were performed using multiple logistic regression models. Results. Ovarian cancer in a first‐degree relative was significantly associated with increased risk of ovarian cancer (OR, 2.4; 95% CI, 1.4–4.1 (mother or sister)). Ovarian cancer in a first‐degree relative appeared to be a stronger risk factor for early‐onset (≤50 years) ovarian cancer than late‐onset (OR, 5.3; 95% CI, 2.0–14.1 vs. OR, 1.8; 95% CI, 1.0–3.4). The positive association with ovarian cancer family history tended to be with non‐mucinous tumors. Breast cancer in one first‐degree female relative was not significantly associated with risk of ovarian cancer. Conclusion. Ovarian cancer in a first‐degree relative is a very strong predictor of epithelial ovarian cancer, especially early‐onset ovarian cancer. Ovarian cancer in first‐degree relatives seems to be positively associated with especially non‐mucinous tumors.
MIST: Maximum Information Spanning Trees for dimension reduction of biological data sets
Authors: King Bracken M. , Tidor Bruce
Published: March 2009

Motivation: The study of complex biological relationships is aided by large and high-dimensional data sets whose analysis often involves dimension reduction to highlight representative or informative directions of variation. In principle, information theory provides a general framework for quantifying complex statistical relationships for dimension reduction. Unfortunately, direct estimation of high-dimensional information theoretic quantities, such as entropy and mutual information (MI), is often unreliable given the relatively small sample sizes available for biological problems. Here, we develop and evaluate a hierarchy of approximations for high-dimensional information theoretic statistics from associated low-order terms, which can be more reliably estimated from limited samples. Due to a relationship between this metric and the minimum spanning tree over a graph representation of the system, we refer to these approximations as MIST (Maximum Information Spanning Trees).

Results: The MIST approximations are examined in the context of synthetic networks with analytically computable entropies and using experimental gene expression data as a basis for the classification of multiple cancer types. The approximations result in significantly more accurate estimates of entropy and MI, and also correlate better with biological classification error than direct estimation and another low-order approximation, minimum-redundancy–maximum-relevance (mRMR).

Availability: Software to compute the entropy approximations described here is available as Supplementary Material.

Contact:  tidor@mit.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Predictors of Postoperative Acute Renal Failure after Noncardiac Surgery in Patients with Previously Normal Renal Function
Authors: Kheterpal Sachin , Tremper Kevin K. , Englesbe Michael J. , O’Reilly Michael , Shanks Amy M. , Fetterman Douglas M. , Rosenberg Andrew L. , Swartz Richard D.
Published: March 2009

Background

The authors investigated the incidence and risk factors for postoperative acute renal failure after major noncardiac surgery among patients with previously normal renal function.

Methods

Adult patients undergoing major noncardiac surgery with a preoperative calculated creatinine clearance of 80 ml/min or greater were included in a prospective, observational study at a single tertiary care university hospital. Patients were followed for the development of acute renal failure (defined as a calculated creatinine clearance of 50 ml/min or less) within the first 7 postoperative days. Patient preoperative characteristics and intraoperative anesthetic management were evaluated for associations with acute renal failure. Thirty-day, 60-day, and 1-yr all-cause mortality was also evaluated.

Results

A total of 65,043 cases between 2003 and 2006 were reviewed. Of these, 15,102 patients met the inclusion criteria; 121 patients developed acute renal failure (0.8%), and 14 required renal replacement therapy (0.1%). Seven independent preoperative predictors were identified (P < 0.05): age, emergent surgery, liver disease, body mass index, high-risk surgery, peripheral vascular occlusive disease, and chronic obstructive pulmonary disease necessitating chronic bronchodilator therapy. Several intraoperative management variables were independent predictors of acute renal failure: total vasopressor dose administered, use of a vasopressor infusion, and diuretic administration. Acute renal failure was associated with increased 30-day, 60-day, and 1-yr all-cause mortality.

Conclusions

Several preoperative predictors previously reported to be associated with acute renal failure after cardiac surgery were also found to be associated with acute renal failure after noncardiac surgery. The use of vasopressor and diuretics is also associated with acute renal failure.
Monitoring of Neuromuscular Blockade at the P6 Acupuncture Point Reduces the Incidence of Postoperative Nausea and Vomiting
Authors: Arnberger Michael , Stadelmann Karin , Alischer Petra , Ponert Regina , Melber Andrea , Greif Robert
Published: March 2009

Background

Electrical stimulation of the P6 acupuncture point reduces the incidence of postoperative nausea and vomiting (PONV). Neuromuscular blockade during general anesthesia can be monitored with electrical peripheral nerve stimulation at the wrist. The authors tested the effect of neuromuscular monitoring over the P6 acupuncture point on the reduction of PONV.

Methods

In this prospective, double-blinded, randomized control trial, the authors investigated, with institutional review board approval and informed consent, 220 women undergoing elective laparoscopic surgery anesthetized with fentanyl, sevoflurane, and rocuronium. During anesthesia, neuromuscular blockade was monitored by a conventional nerve stimulator at a frequency of 1 Hz over the ulnar nerve (n = 110, control group) or over the median nerve (n = 110, P6 group) stimulating at the P6 acupuncture point at the same time. The authors evaluated the incidence of nausea and vomiting during the first 24 h.

Results

No differences in demographic and morphometric data were found between both groups. The 24-h incidence of PONV was 45% in the P6 acupuncture group versus 61% in the control group (P = 0.022). Nausea decreased from 56% in the control group to 40% in the P6 group (P = 0.022), but emesis decreased only from 28% to 23% (P = 0.439). Nausea decreased substantially during the first 6 h of the observation period (P = 0.009). Fewer subjects in the acupuncture group required ondansetron as rescue therapy (27% vs. 39%; P = 0.086).

Conclusion

Intraoperative P6 acupuncture point stimulation with a conventional nerve stimulator during surgery significantly reduced the incidence of PONV over 24 h. The efficacy of P6 stimulation is similar to that of commonly used antiemetic drugs in the prevention of PONV.
Quantification of Epileptiform Electroencephalographic Activity during Sevoflurane Mask Induction
Authors: Särkelä Mika O. K. , Ermes Miikka J. , van Gils Mark J. , Yli-Hankala Arvi M. , Jäntti Ville H. , Vakkuri Anne P.
Published: March 2009

Background

Sevoflurane may induce epileptiform electroencephalographic activity leading to unstable Bispectral Index numbers, underestimating the hypnotic depth of anesthesia. The authors developed a method for the quantification of epileptiform electroencephalographic activity during sevoflurane anesthesia.

Methods

Electroencephalographic data from 60 patients under sevoflurane mask induction were used in the analysis. Electroencephalographic data were visually classified. A novel electroencephalogram-derived quantity, wavelet subband entropy (WSE), was developed. WSE variables were calculated from different frequency bands. Performance of the WSE in detection and quantification of epileptiform electroencephalographic activity and the ability of the WSE to recognize misleading Bispectral Index readings caused by epileptiform activity were evaluated.

Results

Two WSE variables were found to be sufficient for the quantification of epileptiform activity: WSE from the frequency bands 4-16 and 16-32 Hz. The lower frequency band was used for monophasic pattern monitoring, and the higher frequency band was used for spike activity monitoring. WSE values of the lower and higher bands followed the time evolution of epileptiform activity with prediction probabilities of 0.809 (SE, 0.007) and 0.804 (SE, 0.007), respectively. In deep anesthesia with epileptiform activity, WSE detected electroencephalographic patterns causing Bispectral Index readings greater than 60, with event sensitivity of 97.1%.

Conclusions

The developed method proved useful in detection and quantification of epileptiform electroencephalographic activity during sevoflurane anesthesia. In the future, it may improve the understanding of electroencephalogram-derived information by assisting in recognizing misleading readings of depth-of-anesthesia monitors. The method also may assist in minimizing the occurrence of epileptiform activity and seizures during sevoflurane anesthesia.
Echocardiographic Doppler Estimation of Pulmonary Artery Pressure in Critically Ill Patients with Severe Hypoxemia
Authors: Bouhemad Bélaïd , Ferrari Fabio , Leleu Kris , Arbelot Charlotte , Lu Qin , Rouby Jean-Jacques
Published: March 2009

Background

In spontaneously breathing cardiac patients, pulmonary artery pressure (PAP) can be accurately estimated from the transthoracic Doppler study of pulmonary artery and tricuspid regurgitation blood flows. In critically ill patients on mechanical ventilation for acute lung injury, the interposition of gas between the probe and the heart renders the transthoracic approach problematic. This study was aimed at determining whether the transesophageal approach could offer an alternative.

Methods

Fifty-one consecutive sedated and ventilated patients with severe hypoxemia (arterial oxygen tension/fraction of inspired oxygen < 300) were prospectively studied. Mean PAP measured from the pulmonary artery catheter was compared with several indices characterizing pulmonary artery blood flow assessed using transesophageal echocardiography: preejection time, acceleration time, ejection duration, preejection time on ejection duration ratio, and acceleration time on ejection duration ratio. In a subgroup of 20 patients, systolic PAP measured from the pulmonary artery catheter immediately before withdrawal was compared with Doppler study of regurgitation tricuspid flow performed immediately after pulmonary artery catheter withdrawal using either the transthoracic or the transesophageal approach.

Results

Weak and clinically irrelevant correlations were found between mean PAP and indices of pulmonary artery flow. A statistically significant and clinically relevant correlation was found between systolic PAP and regurgitation tricuspid flow. In 3 patients (14%), pulmonary artery pressure could not be assessed echocardiographically.

Conclusions

In hypoxemic patients on mechanical ventilation, mean PAP cannot be reliably estimated from indices characterizing pulmonary artery blood flow. Systolic PAP can be estimated from regurgitation tricuspid flow using either transthoracic or transesophageal approach.
On-demand Rather than Daily-routine Chest Radiography Prescription May Change Neither the Number Nor the Impact of Chest Computed Tomography and Ultrasound Studies in a Multidisciplinary Intensive Care Unit
Authors: Kröner Anke , Binnekade Jan M. , Graat Marleen E. , Vroom Margreeth B. , Stoker Jaap , Spronk Peter E. , Schultz Marcus J.
Published: March 2009

Background

Elimination of daily-routine chest radiographs (CXRs) may influence chest computed tomography (CT) and ultrasound practice in critically ill patients.

Methods

This was a retrospective cohort study including all patients admitted to a university-affiliated intensive care unit during two consecutive periods of 5 months, one before and one after elimination of daily-routine CXR. Chest CT and ultrasound studies were identified retrospectively by using the radiology department information system. Indications for and the diagnostic/therapeutic yield of chest CT and ultrasound studies were collected.

Results

Elimination of daily-routine CXR resulted in a decrease of CXRs per patient day from 1.1 +/- 0.3 to 0.6 +/- 0.4 (P < 0.05). Elimination did not affect duration of stay or mortality rates. Neither the number of chest CT studies nor the ratio of chest CT studies per patient day changed with the intervention: Before elimination of daily-routine CXR, 52 chest CT studies were obtained from 747 patients; after elimination, 54 CT studies were obtained from 743 patients. Similarly, chest ultrasound practice was not affected by the change of CXR strategy: Before and after elimination, 21 and 27 chest ultrasound studies were performed, respectively. Also, timing of chest CT and ultrasound studies was not different between the two study periods. During the two periods, 40 of 106 chest CT studies (38%) and 18 of 48 chest ultrasound studies (38%) resulted in a change in therapy. The combined therapeutic yield of chest CT and ultrasound studies did not change with elimination of daily-routine CXR.

Conclusions

Elimination of daily-routine CXRs may not affect chest CT and ultrasound practice in a multidisciplinary intensive care unit.
Type and Severity of Cognitive Decline in Older Adults after Noncardiac Surgery
Authors: Price Catherine C. , Garvan Cynthia W. , Monk Terri G.
Published: March 2009

Background

The authors investigated type and severity of cognitive decline in older adults immediately and 3 months after noncardiac surgery. Changes in instrumental activities of daily living were examined relative to type of cognitive decline.

Methods

Of the initial 417 older adults enrolled in the study, 337 surgery patients and 60 controls completed baseline, discharge, and/or 3-month postoperative cognitive and instrumental activities of daily living measures. Reliable change methods were used to examine three types of cognitive decline: memory, executive function, and combined executive function/memory. SD cutoffs were used to grade severity of change as mild, moderate or severe.

Results

At discharge, 186 (56%) patients experienced cognitive decline, with an equal distribution in type and severity. At 3 months after surgery, 231 patients (75.1%) experienced no cognitive decline, 42 (13.6%) showed only memory decline, 26 (8.4%) showed only executive function decline, and 9 (2.9%) showed decline in both executive and memory domains. Of those with cognitive decline, 36 (46.8%) had mild, 25 (32.5%) had moderate, and 16 (20.8%) had severe decline. The combined group had more severe impairment. Executive function or combined (memory and executive) deficits involved greater levels of functional (i.e., instrumental activities of daily living) impairment. The combined group was less educated than the unimpaired and memory groups.

Conclusion

Postsurgical cognitive presentation varies with time of testing. At 3 months after surgery, more older adults experienced memory decline, but only those with executive or combined cognitive decline had functional limitations. The findings have relevance for patients and caregivers. Future research should examine how perioperative factors influence neuronal systems.
A Rat Model of Radicular Pain Induced by Chronic Compression of Lumbar Dorsal Root Ganglion with SURGIFLO ™
Authors: Gu Xiaoping , Yang Liling , Wang Shuxing , Sung Backil , Lim Grewo , Mao Ji , Zeng Qing , Yang Chang , Mao Jianren
Published: March 2009

Background

Radicular pain is a common and debilitating clinical pain condition. To date, the mechanisms of radicular pain remain unclear, partly because of the lack of suitable preclinical models. The authors report a modified rat model of radicular pain that could mimic a subset of clinical radicular pain conditions induced by the soft tissue compression on dorsal root ganglion.

Methods

A rat model of radicular pain was produced by infiltrating the L5 intervertebral foramen with 60 microl of a hemostatic matrix (SURGIFLO; Johnson & Johnson, Somerville, NJ) resulting in chronic compression of lumbar dorsal root ganglion. Thermal hyperalgesia and mechanical allodynia were measured with or without epidural treatment with triamcinolone. Western blot was used to assess the expression of the NR1 subunit of the N-methyl-D-aspartate receptor and inhibitory factor kappabeta-alpha, an inflammatory marker, within the affected L5 dorsal root ganglion and spinal cord dorsal horn.

Results

Chronic compression of lumbar dorsal root ganglion resulted in: (1) persistent mechanical allodynia and thermal hyperalgesia up to 4 or 5 postoperative weeks and (2) up-regulation of the N-methyl-D-aspartate receptor and inhibitory factor kappabeta-alpha within the ipsilateral L5 dorsal root ganglion and spinal cord dorsal horn. Epidural administration of triamcinolone (6.25-100 microg) on postoperative day 3 dose-dependently attenuated both thermal hyperalgesia and mechanical allodynia in rats with chronic compression of lumbar dorsal root ganglion.

Conclusion

The data suggest that this modified rat model of chronic compression of lumbar dorsal root ganglion may be a useful tool to explore the mechanisms as well as new therapeutic options of radicular pain.
Equipment-related Electrocardiographic Artifacts
Authors: Patel Santosh I. , Souter Michael J. , Warner David S. , Warner Mark A.
Published: March 2009

Interference of the monitored or recorded electrocardiogram is common within operating room and intensive care unit environments. Artifactual signals, which corrupt the normal cardiac signal, may arise from internal or external sources. Electrical devices used in the clinical setting can induce artifacts by various different mechanisms. Newer diagnostic and therapeutic modalities may generate artifactual changes. These artifacts may be nonspecific or may resemble serious arrhythmia. Clinical signs, along with monitored waveforms from other simultaneously monitored parameters, may provide the clues to differentiate artifacts from true changes on the electrocardiogram. Simple measures, such as proper attention to basic principles of electrocardiographic measurement, can eliminate some artifacts. However, in persistent cases, expert help may be required to identify the precise source and minimize interference on the electrocardiogram. Technological advancements in processing the electrocardiographic signal may be useful to detect and eliminate artifacts. Ultimately, an improved understanding of the artifacts generated by equipment, and their identifying characteristics, is important to avoid misinterpretation, misdiagnosis, and iatrogenic complication.
A Randomized, Double-masked, Multicenter Comparison of the Safety of Continuous Intrathecal Labor Analgesia Using a 28-Gauge Catheter versus Continuous Epidural Labor Analgesia
Authors: Arkoosh Valerie A. , Palmer Craig M. , Yun Esther M. , Sharma Shiv K. , Bates James N. , Wissler Richard N. , Buxbaum Jodie L. , Nogami Wallace M. , Gracely Edward J.
Published: March 2009

Background

Continuous intrathecal labor analgesia produces rapid analgesia or anesthesia and allows substantial flexibility in medication choice. The US Food and Drug Administration, in 1992, removed intrathecal microcatheters (27-32 gauge) from clinical use after reports of neurologic injury in nonobstetric patients. This study examined the safety and efficacy of a 28-gauge intrathecal catheter for labor analgesia in a prospective, randomized, multicenter trial.

Methods

Laboring patients were randomly assigned to continuous intrathecal analgesia with a 28-gauge catheter (n = 329) or continuous epidural analgesia with a 20-gauge catheter (n = 100), using bupivacaine and sufentanil. The primary outcome was the incidence of neurologic complications, as determined by masked neurologic examinations at 24 and 48 h postpartum, plus telephone follow-up at 7-10 and 30 days after delivery. The secondary outcomes included adequacy of labor analgesia, maternal satisfaction, and neonatal status.

Results

No patient had a permanent neurologic change. The continuous intrathecal analgesia patients had better early analgesia, less motor blockade, more pruritus, and higher maternal satisfaction with pain relief at 24 h postpartum. The intrathecal catheter was significantly more difficult to remove. There were no significant differences between the two groups in neonatal status, post-dural puncture headache, hemodynamic stability, or obstetric outcomes.

Conclusions

Providing intrathecal labor analgesia with sufentanil and bupivacaine via a 28-gauge catheter has an incidence of neurologic complication less than 1%, and produces better initial pain relief and higher maternal satisfaction, but is associated with more technical difficulties and catheter failures compared with epidural analgesia.
The Common Inhalational Anesthetic Isoflurane Induces Apoptosis via Activation of Inositol 1,4,5-Trisphosphate Receptors
Authors: Wei Huafeng , Liang Ge , Yang Hui , Wang Qiujun , Hawkins Brian , Madesh Muniswamy , Wang Shouping , Eckenhoff Roderic G.
Published: March 2009

Background

Isoflurane induces cell apoptosis by an unknown mechanism. The authors hypothesized that isoflurane activates inositol 1,4,5-trisphosphate (IP3) receptors on the endoplasmic reticulum (ER) membrane, causing excessive calcium release, triggering apoptosis.

Methods

The authors determined isoflurane-induced cytotoxicity by measuring caspase-3 activity, lactate dehydrogenase release, MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) reduction, and imaging analysis of cell damage markers (annexin V and propidium iodide staining) in different cell types. The authors used the chicken B lymphocyte with a total knock-out of IP3 receptors, PC12 cells with elevated IP3 receptor activity (transfected with L286V presenilin 1), striatal cells with a knock-in of Q111 Huntingtin, and each cell line's corresponding wild-type controls. The authors also measured the isoflurane-evoked changes of calcium concentration in cytosol and/or mitochondria in these cells.

Results

Isoflurane induced apoptosis concentration- and time-dependently, and sequentially elevated cytosolic and then mitochondrial calcium in the chicken B-lymphocyte wild-type but not the IP3 receptor total knock-out cells. Thapsigargin, a calcium adenosine triphosphatase inhibitor on ER membranes, induced apoptosis and elevations of calcium in cytosol and mitochondria in both chicken B-lymphocyte wild-type and IP3 receptor total knock-out cells. Isoflurane induced significantly more neurotoxicity and greater calcium release from the ER in L286V PC12 and Q111 Huntingtin striatal cells than in their corresponding wild-type controls, both of which were significantly inhibited by the IP3 receptor antagonist xestospongin C.

Conclusion

These findings suggest that isoflurane activates the ER membrane IP3 receptor, producing excessive calcium release and triggering apoptosis. Neurons with enhanced IP3 receptor activity, as in certain cases of familial Alzheimer or Huntington disease, may be especially vulnerable to isoflurane cytotoxicity.
Postconditioning Prevents Reperfusion Injury by Activating δ-Opioid Receptors
Authors: Jang Youngho , Xi Jinkun , Wang Huihua , Mueller Robert A. , Norfleet Edward A. , Xu Zhelong
Published: March 2009

Background

While postconditioning has been proposed to protect the heart by targeting the mitochondrial permeability transition pore (mPTP), the detailed mechanism underlying this action is unknown. The authors hypothesized that postconditioning stimulates opioid receptors, which in turn protect the heart from reperfusion injury by targeting the mPTP.

Methods

Rat hearts (both in vivo and in vitro) were subjected to 30 min of ischemia and 2 h of reperfusion. Postconditioning was elicited by six cycles of 10-s reperfusion and 10-s ischemia. To measure nitric oxide concentration, cardiomyocytes loaded with 4-amino-5-methylamino-2',7'-difluorofluorescein were imaged using confocal microscopy. Mitochondrial membrane potential was determined by loading cardiomyocytes with tetramethylrhodamine ethyl ester.

Results

In open chest rats, postconditioning reduced infarct size, an effect that was reversed by both naloxone and naltrindole. The antiinfarct effect of postconditioning was also blocked by the mPTP opener atractyloside. In isolated hearts, postconditioning reduced infarct size. Morphine mimicked postconditioning to reduce infarct size, which was abolished by both naltrindole and atractyloside. N-nitro-l-arginine methyl ester and guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one blocked the action of morphine. Further experiments showed that morphine produces nitric oxide in cardiomyocytes by activating delta-opioid receptors. Moreover, morphine could prevent hydrogen peroxide-induced collapse of mitochondrial membrane potential in cardiomyocytes, which was reversed by naltrindole, N-nitro-l-arginine methyl ester, and the protein kinase G inhibitor KT5823.

Conclusions

Postconditioning protects the heart by targeting the mPTP through activation of delta-opioid receptors. The nitric oxide-cyclic guanosine monophosphate-protein kinase G pathway may account for the effect of postconditioning on the mPTP opening.
Intermitted Pharmacologic Pretreatment by Xenon, Isoflurane, Nitrous Oxide, and the Opioid Morphine Prevents Tumor Necrosis Factor α–induced Adhesion Molecule Expression in Human Umbilical Vein Endothelial Cells
Authors: Weber Nina C. , Kandler Jennis , Schlack Wolfgang , Grueber Yvonne , Fräßdorf Jan , Preckel Benedikt
Published: March 2009

Background

The barrier properties of the endothelium are of critical importance during pathophysiologic processes. These barrier properties depend on an intact cytoskeleton and are regulated by cell adhesion molecules. Tumor necrosis factor alpha (TNF-alpha) is known to induce cell adhesion molecule expression. In myocardium, the protective effect by xenon and isoflurane preconditioning was found to be linked to the cytoskeleton. The authors investigated the impact of different anesthetics and morphine on TNF-alpha-induced endothelial cell adhesion molecule expression.

Methods

Human umbilical vein endothelial cells were isolated from three different preparations. Cells were either left untreated or pretreated with xenon, nitrous oxide, isoflurane (each 0.43 minimum alveolar concentration), or morphine (100 ng/ml) and stimulated with 10 ng/ml TNF-alpha. Reverse-transcription polymerase chain reaction and fluorescence-activated cell sorting of intracellular cell adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin were performed. Transcriptional activity of nuclear factor kappaB was assessed by infrared electrophoretic mobility shift assay.

Results

Tumor necrosis factor alpha significantly induced messenger RNA (mRNA) and protein expression of cell adhesion molecules as well as transcriptional activity of nuclear factor kappaB. All four agents prevented TNF-alpha-induced mRNA and protein expression of intracellular cell adhesion molecule 1. Vascular cell adhesion molecule 1 expression was only blocked by the inhalational anesthetics and not by morphine. None of the four agents had an effect on TNF-alpha induced E-selectin expression. TNF-alpha-induced transcriptional activity of nuclear factor kappaB was decreased by all four agents.

Conclusion

These results suggest a protective effect of anesthetics on TNF-alpha-induced endothelial cell damage.
Effect of Dexmedetomidine on Cerebral Blood Flow Velocity, Cerebral Metabolic Rate, and Carbon Dioxide Response in Normal Humans
Authors: Drummond John C. , Dao Andrew V. , Roth David M. , Cheng Ching-Rong , Atwater Benjamin I. , Minokadeh Anushirvan , Pasco Leonardo C. , Patel Piyush M.
Published: March 2009

Background

Dexmedetomidine reduces cerebral blood flow (CBF) in humans and animals. In animal investigations, cerebral metabolic rate (CMR) was unchanged. Therefore, the authors hypothesized that dexmedetomidine would cause a decrease in the CBF/CMR ratio with even further reduction by superimposed hyperventilation. This reduction might be deleterious in patients with neurologic injuries.

Methods

Middle cerebral artery velocity (CBFV) was recorded continuously in six volunteers. CBFV, jugular bulb venous saturation (Sjvo2), CMR equivalent (CMRe), and CBFV/CMRe ratio were determined at six intervals before, during, and after administration of dexmedetomidine: (1) presedation; (2) presedation with hyperventilation; at steady state plasma levels of (3) 0.6 ng/ml and (4) 1.2 ng/ml; (5) 1.2 ng/ml with hyperventilation; and (6) 30 min after discontinuing dexmedetomidine. The slope of the arterial carbon dioxide tension (Paco2)-CBFV relation was determined presedation and at 1.2 ng/ml.

Results

CBFV and CMRe decreased in a dose-related manner. The CBFV/CMRe ratio was unchanged. The CBFV response to carbon dioxide decreased from 1.20 +/- 0.2 cm.s.mm Hg presedation to 0.40 +/- 0.15 cm.s.mm Hg at 1.2 ng/ml. Sjvo2 was statistically unchanged during hyperventilation at 1.2 ng/ml versus presedation (50 +/- 11 vs. 43 +/- 5%). Arousal for hyperventilation at 1.2 ng/ml resulted in increased CBFV (30 +/- 5 to 38 +/- 4) and Bispectral Index (43 +/- 10 to 94 +/- 3).

Conclusions

The predicted decrease in CBFV/CMRe ratio was not observed because of an unanticipated reduction of CMRe and a decrease in the slope of the Paco2-CBFV relation. CBFV and Bispectral Index increases during arousal for hyperventilation at 1.2 ng/ml suggest that CMR-CBF coupling is preserved during dexmedetomidine administration. Further evaluation of dexmedetomidine in patients with neurologic injuries seems justified.
Proteomics in Neuropathic Pain Research
Authors: Niederberger Ellen , Geisslinger Gerd , Warner David S. , Warner Mark A.
Published: March 2009

Neuropathic pain is often caused by nerve injury or dysfunction in the peripheral and central nervous system and is frequently associated with allodynia and hyperalgesia. The underlying molecular mechanisms of neuropathic pain are largely unknown, and therefore, pharmacologic treatment is insufficient in many cases. To elucidate translational and posttranslational modifications in the nervous system that arise after nerve injury, a number of proteomic studies have been performed using different animal neuropathy models. The results of these proteomic approaches are summarized in this review to provide a better overview of proteins that are involved into the pathogenesis of nerve injury and neuropathic pain. This might allow a better understanding of the pathophysiologic signaling pathways in this impairment, facilitate the discovery of specific biomarkers, and thus promote the development of novel pain therapies.
Concentration–Effect Relations, Prediction Probabilities (Pk), and Signal-to-noise Ratios of Different Electroencephalographic Parameters during Administration of Desflurane, Isoflurane, and Sevoflurane in Rats
Authors: Ihmsen Harald , Schywalsky Michael , Plettke Regina , Priller Michael , Walz Florian , Schwilden Helmut
Published: March 2009

Background

The authors investigated the suitability of different electroencephalographic parameters to quantify the anesthetic effect of desflurane, isoflurane, and sevoflurane in rats.

Methods

Ten male Sprague-Dawley rats were anesthetized in a randomized crossover design with maximum values of 11% desflurane, 2.1% isoflurane, and 3.5% sevoflurane. The electroencephalogram was recorded with implanted electrodes and a wireless telemetry system. Concentration-effect relations and signal-to-noise ratios were determined for the approximate entropy and for the median frequency and the spectral edge frequency, which were modified to account for spikes and burst suppression. The prediction probability Pk with respect to the response to a painful stimulus was determined.

Results

All drugs produced deep anesthesia with burst suppression and no response at the highest concentrations. The occurrence of spikes and burst suppression made a modification of median frequency and spectral edge frequency necessary to obtain Pk values greater than 0.5 and monotonic sigmoid concentration-effect relations. The Pk values were between 0.89 and 0.98, with significantly higher values for modified median frequency and spectral edge frequency during desflurane and sevoflurane. The signal-to-noise ratios were between 3.0 and 6.4 dB, with significantly better values for modified spectral edge frequency and approximate entropy during sevoflurane.

Conclusions

If modified for spikes and burst suppression, median frequency and spectral edge frequency as well as the unmodified approximate entropy were able to assess the anesthetic effect of desflurane, isoflurane, and sevoflurane in rats. For sevoflurane, the modified spectral edge frequency was best with regard to signal-to-noise ratio and prediction probability.
Brain Maturation of Preterm Newborn Babies: New Insights
Authors: Ramenghi Luca A , Fumagalli Monica , Bassi Laura , Groppo Michela , De Carli Agnese , Fanaro Silvia , Mosca Fabio
Published: March 2009

Preterm birth still results in a high number of neurodevelopmental sequelae, although major forms of brain lesions—such as periventricular leukomalacia and intraventricular hemorrhage—are significantly reduced in this population of babies compared with a few years ago. This paper focuses on the possible reasons for this phenomenon. Some brain lesions, such as those affecting the periventricular white matter and the cerebellum, may be underestimated if magnetic resonance imaging is not used. In addition, a functional neurological consequence is not necessarily due to a recognized brain lesion, but may simply derive from an abnormally or suboptimally developed brain structure. The quality of nutrition given to a preterm baby could play a crucial role in such cases. In fact, nutrition is known to affect brain function; a case in point is the improvement in visual function resulting from dietary essential fatty acids. Finally, research in this area should aim at both reducing potential hazards and improving the quality of perinatal care, including the quality of nutrition.
Protective Effects of L‐Arginine on Rat Terminal Ileum Subjected to Ischemia/Reperfusion
Authors: Sayan Hale , Ozacmak V Haktan , Altaner Semsi , Aktas R Gulhan , Arslan S Oktay
Published: March 2009

Objectives:

Studies have shown that nitric oxide (NO) may play a major role in sustaining mucosal integrity; however, NO has been also implicated in the pathogenesis of ischemia/reperfusion (I/R)–related tissue injury. We investigated the effects of L‐arginine andNG‐nitro L‐arginine methyl ester (L‐NAME) on the acetylcholine‐induced contractile response of ileum and the levels of malondialdehyde (MDA) and reduced glutathione (GSH). Histopathological changes were also evaluated in ileal preparations.

Materials and Methods:

Male Wistar Albino rats were subjected to mesenteric ischemia (30 min) followed by reperfusion (3 hours). Four groups were designed: sham‐operated control; I/R; I/R and L‐arginine pretreatment; and I/R and L‐NAME pretreatment. After reperfusion, ileum specimens were collected to determine the parameters mentioned above.

Results:

Following reperfusion, a significant decrease in acetylcholine‐induced contractile response, an increase in lipid peroxidation, a decrease in GSH content, and mucosal damage of the ileal preparations were observed. We showed that decreased contractility, increased lipid peroxidation, and reduced GSH content have been reversed by L‐arginine but not by L‐NAME. Mucosal injury was significantly lowered in the L‐arginine group.

Conclusions:

Treatment with L‐arginine exerted a protective effect in intestinal I/R injury, which was mediated in part by regulating MDA and GSH levels, consequently ameliorating impaired contractile response and mucosal injury.
Pilot Evaluation of an Instrument to Measure Quality of Life in British Children With Inflammatory Bowel Disease
Authors: Ogden Cassandra Anne , Abbott Janice , Aggett Peter , Derkx Bert H , Maity Santanu , Thomas Adrian G
Published: March 2009

The IMPACT questionnaire was developed in Canada to measure quality of life in children with inflammatory bowel disease (IBD). In the present study, 20 children with IBD completed 2 versions of the IMPACT questionnaire with a Likert scale or visual analog scale (VAS), 5 of whom expressed problems with language or phrasing. Difficult words included “restrictions,” “moderate,” “diarrhea,” “school break,” and the abbreviation “IBD.” Fifteen children preferred the Likert scale to the VAS (χ2 = 20, P < 0.01). Rewording the difficult words and using a Likert scale should facilitate completion of the IMPACT questionnaire in the United Kingdom. Further validation is needed to ensure that the instrument is reliable and valid.
Metabolic Syndrome and Insulin Resistance
Authors: Bagry Hema S. , Raghavendran Sreekrishna , Carli Franco , Warner David S. , Warner Mark A.
Published: March 2009

Metabolic syndrome represents a constellation of risk factors associated with increased incidence of cardiovascular disease and progression to diabetes mellitus. Insulin resistance, a state of decreased biologic response to physiologic concentrations of insulin, is a key component of this syndrome and seems to be the result of a primary defect at the skeletal muscle glucose transporter. Acute illness and the perioperative period are characterized by a state of insulin resistance that manifests as hyperglycemia and leads to various other metabolic and biochemical alterations that adversely affect end organ function. Hyperglycemia in acutely ill patients adversely affects outcome. Achieving euglycemia seems beneficial in certain clinical situations, but considerable disagreement exists regarding the target blood sugar levels, the duration of therapy, and the modality. Pharmacotherapy, exercise, and nutrition to improve insulin sensitivity seem promising but require further evaluation to confirm their efficacy for perioperative risk reduction. This review discusses the pathophysiology and the clinical implications of metabolic syndrome and insulin resistance in the acutely ill patient with an emphasis on perioperative modulation strategies.
Quantitation of the Effect of Nitrous Oxide on Rocuronium Infusion Requirements Using Closed-loop Feedback Control
Authors: Illman Hanna , Antila Heikki , Olkkola Klaus T.
Published: March 2009

Background

Nitrous oxide has a minor effect on the effective dose 50% values of bolus doses of rocuronium. The authors have studied the effect of nitrous oxide on the infusion requirements of rocuronium using closed-loop feedback control of rocuronium infusion.

Methods

The authors obtained institutional approval and informed consent to study 70 patients. The patients were given total intravenous anesthesia with propofol and remifentanil by target-controlled infusion and were randomly assigned to one of two groups, one receiving nitrous oxide with 30% oxygen (n = 35) and the other group receiving air with 30% oxygen (n = 35). The possible interaction of rocuronium with nitrous oxide was quantitated by determining the asymptotic steady state rate of infusion of rocuronium necessary to produce a constant 90% neuromuscular block. This was accomplished by applying nonlinear curve fitting to data on the cumulative dose requirement during the initial 90-min period after bolus administration of rocuronium.

Results

Patient characteristics and controller performance, i.e., the ability of the controller to maintain the neuromuscular block constant at the set point, did not differ significantly between the groups. The administration of nitrous oxide did not affect rocuronium infusion requirements. The mean steady state rates of infusion were 33.0 +/- 9.8 and 36.9 +/- 13.2 mg/h in the nitrous oxide-total intravenous anesthesia and air-total intravenous anesthesia groups, respectively.

Conclusions

Nitrous oxide does not affect the infusion requirements of rocuronium to a clinically significant degree.
Transient Hyperglycemia Affects the Extent of Ischemia-Reperfusion-induced Renal Injury in Rats
Authors: Hirose Ryutaro , Xu Fengyun , Dang Kim , Liu Tao , Behrends Matthias , Brakeman Paul R. , Wiener-Kronish Jeanine , Niemann Claus U.
Published: March 2009

Background

Chronic hyperglycemia is known to increase renal injury, particularly during ischemia-reperfusion episodes. The goal of this study was to examine whether transient hyperglycemia during or after renal ischemia-reperfusion increased renal dysfunction.

Methods

Male Lewis rats underwent sham operations or unilateral nephrectomies followed by contralateral renal ischemia-reperfusion. Hyperglycemic rats were given 25% dextrose to induce transient hyperglycemia lasting throughout the duration of ischemia (PI rats) or beginning 2 h after initiation of reperfusion (PR rats). Additional vehicle control rats received saline and underwent ischemia-reperfusion surgery as with PI and PR rats. Twenty-five minutes of mild renal ischemia followed by 24 h of reperfusion was induced by occluding the renal artery and vein.

Results

Terminal serum creatinine concentrations were significantly higher in the PI rats when compared with the PR or vehicle control rats. Histology demonstrated significantly increased necrosis in the PI rats relative to PR and control animals. Tissue analyses demonstrated significantly higher heat shock protein 70, heat shock protein 32, and cleaved caspase-3 protein levels in the PI rats. Oxidative stress generated through the xanthine pathway in the PI group was significantly increased compared with the oxidative stress in the PR and vehicle control rats. In contrast, vascular endothelial growth factor and erythropoietin were significantly decreased in the PI rats compared with the PR rats and controls.

Conclusions

Hyperglycemia that occurred during renal ischemia-reperfusion resulted in severe functional injury compared with normoglycemia or with hyperglycemia that occurred after reperfusion. Investigated molecular pathways are more profoundly affected by hyperglycemia that occurs before renal ischemia-reperfusion.
Alteration of the Piglet Diaphragm Contractility In Vivo and Its Recovery after Acute Hypercapnia
Authors: Jaber Samir , Jung Boris , Sebbane Mustapha , Ramonatxo Michèle , Capdevila Xavier , Mercier Jacques , Eledjam Jean-Jacques , Matecki Stefan
Published: March 2009

Background

The effects of hypercapnic acidosis on the diaphragm and its recovery to normocapnia have been poorly evaluated. The authors studied diaphragmatic contractility facing acute variations of arterial carbon dioxide tension (Paco2) and evaluated the contractile function at 60 min after normocapnia recovery.

Methods

Thirteen piglets weighing 15-20 kg were anesthetized, ventilated, and separated into two groups: a control group (n = 5) evaluated in normocapnia (time-control experiments) and a hypercapnia group (n = 8) in which animals were acutely and shortly exposed to five consecutive ranges of Paco2 (40, 50, 70, 90, and 110 mmHg). Then carbon dioxide insufflation was stopped. Diaphragmatic contractility was assessed by measuring transdiaphragmatic pressure variations obtained after bilateral transjugular phrenic nerve pacing at increased frequencies (20-120 Hz). For each level of arterial pressure of carbon dioxide, pressure-frequency curves were obtained in vivo by phrenic nerve pacing.

Results

In the hypercapnia group, mean +/- SD transdiaphragmatic pressure significantly decreased from 41 +/- 3 to 29 +/- 3 cm H2O (P < 0.05) between the first (40 mmHg) and fifth (116 mmHg) stages of capnia at the frequency of 100 Hz stimulation. The observed alteration of the contractile force was proportional to the level of Paco2 (r = 0.61, P < 0.01). Normocapnia recuperation allowed a partial recovery of the diaphragmatic contractile force (80% of the baseline value) at 60 min after carbon dioxide insufflation interruption.

Conclusion

A short exposure to respiratory acidosis decreased diaphragmatic contractility proportionally to the degree of hypercapnia, and this alteration was only partially reversed at 60 min after exposure.
Impact of Heart Failure on Patients Undergoing Major Noncardiac Surgery
Authors: Hammill Bradley G. , Curtis Lesley H. , Bennett-Guerrero Elliott , O'Connor Christopher M. , Jollis James G. , Schulman Kevin A. , Hernandez Adrian F.
Published: March 2009

Background

Changes in the demographics and epidemiology of patients with cardiovascular comorbidities who undergo major noncardiac surgery require an updated assessment of which patients are at greater risk of mortality or readmission. The authors evaluated short-term outcomes among patients with heart failure, coronary artery disease (CAD), or neither who underwent major noncardiac surgery.

Methods

Patients were aged 65 and older, had Medicare fee-for-service coverage, and underwent 1 of 13 major noncardiac procedures from 2000 through 2004, excluding patients with end-stage renal disease and patients who did not have at least 1 yr of Medicare fee-for-service eligibility before surgery. Main outcome measures were operative mortality and 30-day all-cause readmission.

Results

Of 159,327 procedures, 18% were performed in patients with heart failure and 34% were performed in patients with CAD. Adjusted hazard ratios of mortality and readmission for patients with heart failure, compared with patients with neither heart failure nor CAD, were 1.63 (95% confidence interval, 1.52-1.74) and 1.51 (95% confidence interval, 1.45-1.58), respectively. Adjusted hazard ratios of mortality and readmission for patients with CAD, compared with patients with neither heart failure nor CAD, were 1.08 (95% confidence interval, 1.01-1.16) and 1.16 (95% confidence interval, 1.12-1.20), respectively. These effects were statistically significant. Patients with heart failure were at significantly higher risk for both outcomes compared with patients with CAD.

Conclusions

Elderly patients with heart failure who undergo major surgical procedures have substantially higher risks of operative mortality and hospital readmission than other patients, including those with coronary disease, admitted for the same procedures. Improvements in perioperative care are needed for the growing population of patients with heart failure undergoing major noncardiac surgery.
Venous Function and Central Venous Pressure
Authors: Gelman Simon , Warner David S. , Warner Mark A.
Published: March 2009

The veins contain approximately 70% of total blood volume and are 30 times more compliant than arteries; therefore, changes in blood volume within the veins are associated with relatively small changes in venous pressure. The terms venous capacity, compliance, and stressed and unstressed volumes are defined. Decreases in flow into a vein are associated with decreases in intravenous pressure and volume, and vice versa. Changes in resistance in the small arteries and arterioles may affect venous return in opposite directions; this is explained by a two-compartment model: compliant (mainly splanchnic veins) and noncompliant (nonsplanchnic veins). Effects of intrathoracic and intraabdominal pressures on venous return and central venous pressure as well as the value of central venous pressure as a diagnostic variable are discussed.