bluuebunny/crossref_metadata_2025 huggingface dataset:
Contributions of Anesthesiology to the Surgical Treatment of Cerebrovascular Disease
Authors: Collard Charles D. , Anton James M. , Cooper John R. , Giesecke N Martin , Warner David S.
Published: March 2009

Increased tolerance to cerebral ischemia produced by general anesthesia during temporary carotid occlusion. By B. A. Wells, A. S. Keats, and D. A. Cooley. Surgery 1963; 54:216-23. Local anesthesia with little or no preoperative sedation is currently recommended as the anesthetic of choice for temporary carotid occlusion during carotid endarterectomy. Purported advantages include minimal circulatory and respiratory changes from the local anesthetic, and constant verbal contact can be maintained with the patient so that neurologic changes are promptly recognized. However, local anesthesia may not be satisfactory in uncooperative or semiconscious patients. We therefore undertook a trial of general anesthesia in 56 consecutive patients undergoing carotid endarterectomy. Patients were induced in standardized fashion using intravenous thiopental (100-400 mg), atropine (0.2 mg), and succinylcholine (40-80 mg). Cyclopropane, along with deliberate hypercapnia and hypertension, was used for anesthesia maintenance. All patients tolerated carotid occlusion for periods of up to 30 min during general anesthesia without shunt, bypass, or hypothermia. Except for one patient, electroencephalogram evidence of cerebral ischemia was not apparent during occlusion, and no patient suffered postoperative neurologic sequela. Twenty percent of patients who had their carotid arteries occluded preoperatively for 30-60 s without general anesthesia suffered convulsions. These data suggest that general anesthesia increased the tolerance to cerebral ischemia. Potential mechanisms involved might include: 1) decreased cerebral metabolic rate for oxygen; 2) increased cerebral blood flow from hypercapnia; 3) increased arterial oxygen tension; and 4) recruitment of new routes of collateral circulation.
Isoflurane Differentially Modulates Inhibitory and Excitatory Synaptic Transmission to the Solitary Tract Nucleus
Authors: Peters James H. , McDougall Stuart J. , Mendelowitz David , Koop Dennis R. , Andresen Michael C.
Published: March 2009

Background

Isoflurane anesthesia produces cardiovascular and respiratory depression, although the specific mechanisms are not fully understood. Cranial visceral afferents, which innervate the heart and lungs, synapse centrally onto neurons within the medial portion of the nucleus tractus solitarius (NTS). Isoflurane modulation of afferent to NTS synaptic communication may underlie compromised cardiorespiratory reflex function.

Methods

Adult rat hindbrain slice preparations containing the solitary tract (ST) and NTS were used. Shocks to ST afferents evoked excitatory postsynaptic currents with low-variability (SEM <200 mus) latencies identifying neurons as second order. ST-evoked and miniature excitatory postsynaptic currents as well as miniature inhibitory postsynaptic currents were measured during isoflurane exposure. Perfusion bath samples were taken in each experiment to measure isoflurane concentrations by gas chromatography-mass spectrometry.

Results

Isoflurane dose-dependently increased the decay-time constant of miniature inhibitory postsynaptic currents. At greater than 300 mum isoflurane, the amplitude of miniature inhibitory postsynaptic currents was decreased, but the frequency of events remained unaffected, whereas at equivalent isoflurane concentrations, the frequency of miniature excitatory postsynaptic currents was decreased. ST-evoked excitatory postsynaptic current amplitudes decreased without altering event kinetics. Isoflurane at greater than 300 mum increased the latency to onset and rate of synaptic failures of ST-evoked excitatory postsynaptic currents.

Conclusions

In second-order NTS neurons, isoflurane enhances phasic inhibitory transmission via postsynaptic gamma-aminobutyric acid type A receptors while suppressing excitatory transmission through presynaptic mechanisms. These results suggest that isoflurane acts through multiple distinct mechanisms to inhibit neurotransmission within the NTS, which would underlie suppression of homeostatic reflexes.
Motor and Somatosensory Evoked Potentials
Authors: Shine Timothy S.J. , Harrison Barry A. , De Ruyter Martin L. , Crook Julia E. , Heckman Michael , Daube Jasper R. , Stapelfeldt Wolf H. , Cherry Kenneth J. , Gloviczki Peter , Bower Thomas C. , Murray Michael J.
Published: March 2009

Background

Paraplegia is a devastating complication for patients undergoing repair of thoracoabdominal aortic aneurysms. A monitor to detect spinal cord ischemia is necessary if anesthesiologists are to intervene to protect the spinal cord during aortic aneurysm clamping.

Methods

The medical records of 60 patients who underwent thoracoabdominal aortic aneurysm repair with regional lumbar epidural cooling with evoked potential monitoring were reviewed. The authors analyzed latency and amplitude of motor evoked potentials, somatosensory evoked potentials, and H reflexes before cooling and clamping, after cooling and before clamping, during clamping, and after release of aortic cross clamp.

Results

Twenty minutes after the aortic cross clamp was placed, motor evoked potentials had 88% sensitivity and 65% specificity in predicting spinal cord ischemia. The negative predictive value of motor evoked potentials at 20 min after aortic cross clamping was 96%.

Conclusions

Rapid loss of motor evoked potentials or H reflexes after application of the aortic cross clamp identifies a subgroup of patients who are at high risk of developing spinal cord ischemia and in whom aggressive anesthetic and surgical interventions may be justified.
Acceleromyography for Use in Scientific and Clinical Practice
Authors: Claudius Casper , Viby-Mogensen Jørgen , Warner David S. , Warner Mark A.
Published: March 2009

This systematic review describes the evidence on the use of acceleromyography for perioperative neuromuscular monitoring in clinical practice and research. The review documents that although acceleromyography is widely used in research, it cannot be used interchangeably with mechanomyography and electromyography for construction of dose-response curves or for recording different pharmacodynamic variables after injection of a neuromuscular blocking agent. Some studies indicate that it may be beneficial to use a preload to increase the precision of acceleromyography, and to "normalize" the train-of-four ratio to decrease the bias in relation to mechanomyography and electromyography. However, currently the evidence is insufficient to support the routine clinical use of preload and "normalization." In contrast, there is good evidence that acceleromyography improves detection of postoperative residual paralysis. A train-of-four ratio of 1.0 predicts with a high predictive value recovery of pulmonary and upper airway function from neuromuscular blockade.
Obesity-induced Insulin Resistance and Hyperglycemia
Authors: Martyn J A. Jeevendra , Kaneki Masao , Yasuhara Shingo , Warner David S. , Warner Mark A.
Published: March 2009

Obesity is a major cause of type 2 diabetes, clinically evidenced as hyperglycemia. The altered glucose homeostasis is caused by faulty signal transduction via the insulin signaling proteins, which results in decreased glucose uptake by the muscle, altered lipogenesis, and increased glucose output by the liver. The etiology of this derangement in insulin signaling is related to a chronic inflammatory state, leading to the induction of inducible nitric oxide synthase and release of high levels of nitric oxide and reactive nitrogen species, which together cause posttranslational modifications in the signaling proteins. There are substantial differences in the molecular mechanisms of insulin resistance in muscle versus liver. Hormones and cytokines from adipocytes can enhance or inhibit both glycemic sensing and insulin signaling. The role of the central nervous system in glucose homeostasis also has been established. Multipronged therapies aimed at rectifying obesity-induced anomalies in both central nervous system and peripheral tissues may prove to be beneficial.
Oxygen and Life on Earth
Authors: Lindahl Sten G. E.
Published: March 2009

The advent of oxygenic photosynthesis and the accumulation of oxygen in our atmosphere opened up new possibilities for the development of life on Earth. The availability of oxygen, the most capable electron acceptor on our planet, allowed the development of highly efficient energy production from oxidative phosphorylation, which shaped the evolutionary development of aerobic life forms from the first multicellular organisms to the vertebrates.
Comparison of Thoracic Epidural Pressure in the Sitting and Lateral Decubitus Positions
Authors: Gil Nam Su , Lee Jong-Hwan , Yoon Seung Z. , Jeon Yunseok , Lim Young Jin , Bahk Jae Hyon
Published: March 2009

Background

The hanging drop technique identifies the epidural space using the negative pressure of this space. Although the hanging drop technique is popular at the thoracic level, there is still controversy on the negative epidural pressure at this level. The authors hypothesized that the epidural pressure is more consistently negative in the sitting position than in the lateral decubitus position at the thoracic level.

Methods

This study compared the epidural pressures of 28 awake patients in the sitting (sitting group, n = 14) or lateral decubitus (lateral group, n = 14) position. The T5-T6 epidural pressure was measured using a closed pressure measurement system connected to a Tuohy needle.

Results

All of the thoracic epidural pressures in the sitting group were negative (median, -5 mmHg; range, -18 to -1; mean, -7.2; SD, 6.3), in contrast to the lateral group (median, 5 mmHg; range, -4 to 13; mean, 5.1; SD, 4.4). The thoracic epidural pressure in the sitting group was significantly lower than in the lateral group (P < 0.001).

Conclusions

The thoracic epidural pressure is more negative in the sitting position than in the lateral decubitus position. These results suggest that the patient should be sitting when the hanging drop technique is used to identify the epidural space.
Electrophysiologic Characteristics of Large Neurons in Dorsal Root Ganglia during Development and after Hind Paw Incision in the Rat
Authors: Ririe Douglas G. , Liu Baogang , Clayton Bridgette , Tong Chuanyao , Eisenach James C.
Published: March 2009

Background

Withdrawal thresholds in the paw are lower in younger animals, and incision further reduces these thresholds. The authors hypothesized that these differences result in part from changes in intrinsic electrophysiologic properties of large neurons.

Methods

Using isolated whole dorsal root ganglion, current clamping was performed to determine the electrophysiologic properties of large neurons before and after incision in animals aged 1 and 4 weeks. Mechanical withdrawal thresholds were used to follow paw sensitivity.

Results

After paw incision, withdrawal thresholds decreased to a similar degree at both ages, but returned to control threshold at 72 h only in the 1-week-old animals. The resting membrane potential was less negative and the rheobase and the resistance of the membrane were lower at baseline in the 1-week-old animals (P < 0.05). After incision, the membrane potential became more depolarized and the rheobase was less in both ages. These changes remained 72 h after the incision in both ages.

Conclusion

These findings suggest that lower mechanical thresholds in the younger animals may be partially attributed to the intrinsic electrophysiologic properties of the larger-diameter afferent neurons. The lack of resolution of the electrophysiologic changes in the young despite the resolution of the withdrawal response suggests that continued input from large fibers into the central nervous system may occur at this age despite the apparent resolution of behavioral changes. Further studies are needed to determine the etiology of these differences, their impact in the central nervous system, and whether theses changes can be prevented.
Successful Transtracheal Lung Ventilation Using a Manual Respiration Valve
Authors: Meissner Konrad , Iber Thomas , Roesner Jan-Patrick , Mutz Christian , Wagner Hans-Erich , Layher Christina , Bartels Utz , Gründling Matthias , Usichenko Taras I. , Wendt Michael , Lehmann Christian , Pavlovic Dragan
Published: March 2009

Background

Lung ventilation through a thin transtracheal cannula may be attempted in patients with laryngeal stenosis or "cannot intubate, cannot ventilate" situations. It may be impossible to achieve sufficient ventilation if the lungs are spontaneously emptying only through the thin transtracheal cannula, which imposes high resistance to airflow, resulting in dangerous hyperinflation. Therefore, the authors describe the use of a manual respiration valve that serves as a bidirectional pump providing not only inflation but also active deflation of the lungs in case of emergency transtracheal lung ventilation.

Methods

The effectiveness of such a valve was tested in vitro using mechanical lungs in combination with two different cannula sizes and various gas flows. The valve was then tested in five pigs using a transtracheal 16-gauge cannula with three different combinations of inspiratory/expiratory times and gas flows and an occluded upper airway.

Results

In the mechanical lungs, the valve permitted higher minute volumes compared with spontaneous lung emptying. In vivo, the arterial oxygen and carbon dioxide partial pressures increased initially and then remained stable over 1 h (arterial oxygen tension, 470.8 +/- 86.8; arterial carbon dioxide tension, 63.0 +/- 7.2 mmHg). The inspiratory pressures measured in the trachea remained below 10 cm H2O and did not substantially influence central venous and pulmonary artery pressures. Mean arterial pressure and cardiac output were unaffected by the ventilation maneuvers.

Conclusions

This study demonstrated in vitro and in vivo in adult pigs that satisfactory lung ventilation can be assured with transtracheal ventilation through a 16-gauge cannula for a prolonged period of time if combined with a bidirectional manual respiration valve.
Enhancement of Spinal N -Methyl-d-aspartate Receptor Function by Remifentanil Action at δ-Opioid Receptors as a Mechanism for Acute Opioid-induced Hyperalgesia or Tolerance
Authors: Zhao Min , Joo Daisy T.
Published: March 2009

Background

Intraoperative remifentanil infusions have been associated with postoperative opioid-induced hyperalgesia and tolerance. Using a previously identified subpopulation of spinal neurons that displays an augmentation in N-methyl-D-aspartate (NMDA) receptor current after chronic morphine, investigations were undertaken to determine whether remifentanil induces acute increases in NMDA responses that are concentration dependent and receptor subtype dependent.

Methods

Electrophysiologic recordings of NMDA current were made from cultured rat dorsal horn neurons treated with remifentanil at various concentrations for 60 min. Selective mu- or delta-opioid receptor inhibitors and agonists were used to determine the site of action of remifentanil.

Results

Remifentanil at 4, 6, and 8 nM, but not higher or lower concentrations, caused significant mean increases in NMDA peak current amplitude of 37.30% (P < 0.001), 30.19% (P < 0.001), and 23.52% (P = 0.025), respectively, over control conditions. This occurred by 36 min of remifentanil perfusion and persisted throughout its washout. Inhibition by 100 nM naloxone or 1 nM naltrindole attenuated the remifentanil-induced NMDA response increase. Selective delta-opioid agonists [D-Pen(2), D-Pen(5)]enkephalin and deltorphin II displayed a similar bell-shaped concentration-response relation for the enhancement of NMDA responses, and 10 nM deltorphin II occluded the effects of 4 nM remifentanil on NMDA responses.

Conclusions

Clinically relevant concentrations of remifentanil induce rapid, persistent increases in NMDA responses that mirror the development of remifentanil-induced hyperalgesia and tolerance. NMDA enhancement by remifentanil is dependent on the activation of both mu- and delta-opioid receptors and is inducible solely by delta-opioid receptor activation. Therefore, selective delta-opioid inhibition may attenuate acute paradoxical increases in pain and tolerance to opioids.
Anesthetic Technique for Radical Prostatectomy Surgery Affects Cancer Recurrence
Authors: Biki Barbara , Mascha Edward , Moriarty Denis C. , Fitzpatrick John M. , Sessler Daniel I. , Buggy Donal J.
Published: March 2009

Background

Regional anesthesia and analgesia attenuate or prevent perioperative factors that favor minimal residual disease after removal of the primary carcinoma. Therefore, the authors evaluated prostate cancer recurrence in patients who received either general anesthesia with epidural anesthesia/analgesia or general anesthesia with postoperative opioid analgesia.

Methods

In a retrospective review of medical records, patients with invasive prostatic carcinoma who underwent open radical prostatectomy between January 1994 and December 2003 and had either general anesthesia-epidural analgesia or general anesthesia-opioid analgesia were evaluated through October 2006. The endpoint was an increase in postoperative prostate-specific antigen.

Results

After adjusting for tumor size, Gleason score, preoperative prostate-specific antigen, margin, and date of surgery, the epidural plus general anesthesia group had an estimated 57% (95% confidence interval, 17-78%) lower risk of recurrence compared with the general anesthesia plus opioids group, with a corresponding hazard ratio of 0.43 (95% confidence interval, 0.22-0.83; P = 0.012) in a multivariable Cox regression model. Gleason score and tumor size (percent of prostate involved) were also independent predictors of recurrence (hazards ratios of 1.19 [1.08, 1.52], P = 0.004, and 1.17 [1.03, 1.34] for 10% size difference, P = 0.01, respectively). A similar association between epidural use and recurrence was obtained by comparing patients matched on the propensity to receive epidural versus general anesthesia.

Conclusions

Open prostatectomy surgery with general anesthesia, substituting epidural analgesia for postoperative opioids, was associated with substantially less risk of biochemical cancer recurrence. Prospective randomized trials to evaluate this association seem warranted.
Reversal of Profound, High-dose Rocuronium-induced Neuromuscular Blockade by Sugammadex at Two Different Time Points: An International, Multicenter, Randomized, Dose-finding, Safety Assessor-blinded, Phase II Trial
Authors: Pühringer Friedrich K. , Rex Christopher , Sielenkämper Andreas W. , Claudius Casper , Larsen Per Bo , Prins Martine E. , Eikermann Matthias , Khuenl-Brady Karin S.
Published: March 2009

Background

Sugammadex (Org 25969), a novel, selective relaxant binding agent, was specifically designed to rapidly reverse rocuronium-induced neuromuscular blockade. The efficacy and safety of sugammadex for the reversal of profound, high-dose rocuronium-induced neuromuscular blockade was evaluated.

Methods

A total of 176 adult patients were randomly assigned to receive sugammadex (2, 4, 8, 12, or 16 mg/kg) or placebo at 3 or 15 min after high-dose rocuronium (1.0 or 1.2 mg/kg) during propofol anesthesia. The primary endpoint was time to recovery of the train-of-four ratio to 0.9. Neuromuscular monitoring was performed using acceleromyography.

Results

Sugammadex administered 3 or 15 min after injection of 1 mg/kg rocuronium decreased the median recovery time of the train-of-four ratio to 0.9 in a dose-dependent manner from 111.1 min and 91.0 min (placebo) to 1.6 min and 0.9 min (16 mg/kg sugammadex), respectively. After 1.2 mg/kg rocuronium, sugammadex decreased time to recovery of train-of-four from 124.3 min (3-min group) and 94.2 min (15-min group) to 1.3 min and 1.9 min with 16 mg/kg sugammadex, respectively. There was no clinical evidence of reoccurrence of neuromuscular blockade or residual neuromuscular blockade. Exploratory analysis revealed that prolongation of the corrected QT interval considered as possibly related to sugammadex occurred in one patient. Another two patients developed markedly abnormal arterial blood pressure after sugammadex that lasted approximately 15 min.

Conclusion

Sugammadex provides a rapid and dose-dependent reversal of profound neuromuscular blockade induced by high-dose rocuronium (1.0 or 1.2 mg/kg) in adult surgical patients.
Remifentanil Modifies the Relation of Electroencephalographic Spectral Changes and Clinical Endpoints in Propofol Anesthesia
Authors: Kortelainen Jukka , Koskinen Miika , Mustola Seppo , Seppänen Tapio
Published: March 2009

Background

Depth-of-anesthesia monitoring with the electroencephalogram has become widely used in anesthesia practice. Generally, the methods presented are based on the spectral changes of the electroencephalogram. In this study, the authors evaluate the influence of remifentanil on the relation of timely occurrence of clinical endpoints and the spectral behavior of the electroencephalogram.

Methods

Twenty-seven patients scheduled to undergo a surgical procedure were randomly assigned to three groups. Patients blindly received equal volumes of saline or remifentanil (7.5 or 30 microg.kg.h) 1 min before induction of anesthesia with infusion of propofol (30 mg.kg.h). The occurrence of loss of counting, loss of obeying verbal command, and loss of reaction to tetanic stimulation was assessed. The electroencephalogram was recorded from electrode Fz referenced to the common average, and an iterative algorithm was applied to solve the underlying frequency progression pattern. The positions of the clinical endpoints on the pattern were analyzed.

Results

The administration of remifentanil during induction of anesthesia with propofol led to an earlier occurrence of the clinical endpoints on the frequency progression pattern. A significant difference (P < 0.05) was observed between the saline and high-dose patient groups in all three endpoints. The effect of remifentanil was proportional to the infusion rate.

Conclusions

The infusion of remifentanil during propofol anesthesia significantly modifies the mutual relations of the electroencephalographic spectral characteristics and the endpoints in a predictable and quantifiable manner. This finding suggests that the electroencephalographic phenomena and the endpoints may not be identical but rather to some extent separate manifestations of hypnotic drug effect.
Effects of Heme Oxygenase 1 on Brain Edema and Neurologic Outcome after Cardiopulmonary Resuscitation in Rats
Authors: Zhang Bing , Wei Xia , Cui Xiaoguang , Kobayashi Tsutomu , Li Wenzhi
Published: March 2009

Background

Heme oxygenase 1 (HO-1) has been shown to attenuate neuronal injury. Therefore, the authors examined whether HO-1 would reduce the brain damage caused by cardiac arrest.

Methods

Rats anesthetized with halothane were subjected to 8 min of cardiac arrest by asphyxia without any pretreatment (control group) or pretreated with an inducer of HO-1 (hemin group) or with an inhibitor of HO-1 (tin protoporphyrin group). Then, the animals were resuscitated with a standardized method. Brain water content (1 and 6 h after resuscitation), neurologic deficit score, viable neuronal counts, and caspase-3 immunostaining in the hippocampus (4 and 14 days) were evaluated.

Results

Water content in the hemin group was significantly reduced (mean +/- SD: 83.1 +/- 1.9% for 1 h after resuscitation; P = 0.03) and significantly greater in the tin protoporphyrin group (91.1 +/- 2.0% for 1 h after resuscitation; P = 0.035) when compared with the control group (88.2 +/- 2.4%). Water content of the cortex was nearly the same as that of the hippocampus. Neurologic deficit scores and neuronal survival were significantly better in the hemin group than in the control group on the 4th and 14th days. In rats that survived for 4 days, the amount of caspase 3-positive neurons was 27 +/- 7 in the control group, whereas the value was 14 +/- 6 in the hemin group (P < 0.05).

Conclusions

In rats resuscitated from cardiac arrest, induction of HO-1 by hemin reduced brain edema, improved neurologic outcome, and protected neurons against apoptosis.
Temperature Monitoring and Perioperative Thermoregulation
Authors: Sessler Daniel I. , Warner David S. , Warner Mark A.
Published: March 2009

Most clinically available thermometers accurately report the temperature of whatever tissue is being measured. The difficulty is that no reliably core-temperature-measuring sites are completely noninvasive and easy to use-especially in patients not undergoing general anesthesia. Nonetheless, temperature can be reliably measured in most patients. Body temperature should be measured in patients undergoing general anesthesia exceeding 30 min in duration and in patients undergoing major operations during neuraxial anesthesia. Core body temperature is normally tightly regulated. All general anesthetics produce a profound dose-dependent reduction in the core temperature, triggering cold defenses, including arteriovenous shunt vasoconstriction and shivering. Anesthetic-induced impairment of normal thermoregulatory control, with the resulting core-to-peripheral redistribution of body heat, is the primary cause of hypothermia in most patients. Neuraxial anesthesia also impairs thermoregulatory control, although to a lesser extent than does general anesthesia. Prolonged epidural analgesia is associated with hyperthermia whose cause remains unknown.
Low-dose Propofol–induced Amnesia Is Not due to a Failure of Encoding
Authors: Veselis Robert A. , Pryor Kane O. , Reinsel Ruth A. , Mehta Meghana , Pan Hong , Johnson Ray
Published: March 2009

Background

Propofol may produce amnesia by affecting encoding. The hypothesis that propofol weakens encoding was tested by measuring regional cerebral blood flow during verbal encoding.

Methods

Seventeen volunteer participants (12 men; aged 30.4 +/- 6.5 yr) had regional cerebral blood flow measured using H2O positron emission tomography during complex and simple encoding tasks (deep vs. shallow level of processing) to identify a region of interest in the left inferior prefrontal cortex (LIPFC). The effect of either propofol (n = 6, 0.9 microg/ml target concentration), placebo with a divided attention task (n = 5), or thiopental at sedative doses (n = 6, 3 microg/ml) on regional cerebral blood flow activation in the LIPFC was tested. The divided attention task was expected to decrease activation in the LIPFC.

Results

Propofol did not impair encoding performance or reaction times, but impaired recognition memory of deeply encoded words 4 h later (median recognition of 35% [interquartile range, 17-54%] of words presented during propofol vs. 65% [38-91%] before drug; P < 0.05). Statistical parametric mapping analysis identified a region of interest of 6.6 cm in the LIPFC (T = 7.44, P = 0.014). Regional cerebral blood flow response to deep encoding was present in this region of interest in each group before drug (T > 4.41, P < 0.04). During drug infusion, only the propofol group continued to have borderline significant activation in this region (T = 4.00, P = 0.063).

Conclusions

If the amnesic effect of propofol were solely due to effects on encoding, activation in the LIPFC should be minimal. Because LIPFC activation was not totally eliminated by propofol, the amnesic action of propofol must be present in other brain regions and/or affect other memory processes.
Droperidol and Ondansetron-induced QT Interval Prolongation
Authors: Charbit Beny , Alvarez Jean Claude , Dasque Eric , Abe Emuri , Démolis Jean Louis , Funck-Brentano Christian
Published: March 2009

Background

Droperidol and ondansetron have previously been found to prolong the QT interval in the treatment of postoperative nausea and vomiting. However, this adverse effect has never been confirmed and compared with both drugs under controlled conditions. The objective was to study the effects of droperidol and ondansetron alone or in combination on QT interval duration in healthy subjects.

Methods

Sixteen healthy volunteers, eight males and eight females, were enrolled in this prospective, double-blind, randomized, placebo-controlled study. Subjects received 1 mg droperidol, 4 mg ondansetron, 1 mg droperidol plus 4 mg ondansetron, or a placebo, intravenously in a crossover design. Fridericia-corrected QT interval (QTcF) and plasma concentrations were measured repeatedly during 10 h at each study period. The primary endpoint was the maximal placebo time-matched and baseline-subtracted QTcF prolongation (DeltaDeltaQTcF).

Results

Compared with placebo, both droperidol and ondansetron significantly prolonged the QTcF interval. DeltaDeltaQTcF prolongation was 25 +/- 8 ms after droperidol, significantly greater than the 17 +/- 10-ms prolongation with ondansetron (P = 0.014). The combination of droperidol and ondansetron significantly increased the mean maximal DeltaDeltaQTcF by 28 +/- 10 ms. The combination induced greater QTcF prolongation compared with ondansetron alone (P = 0.001), but not with droperidol alone (P = 0.33). There was no significant pharmacokinetic interaction between droperidol and ondansetron.

Conclusions

Under controlled conditions, both droperidol and ondansetron either alone or in combination induced significant marked QTc interval prolongation. However, the combination of both drugs did not significantly increase QTc prolongation compared with that induced by droperidol alone.
Frequency and Clinical Correlations of Granulomas in Children With Crohn Disease
Authors: De Matos Vera , Russo Pierre A , Cohen Aaron B , Mamula Petar , Baldassano Robert N , Piccoli David A
Published: March 2009

Background:

Granulomas are pathognomonic findings of Crohn disease (CD); however, their occurrence and clinical significance are not well characterized. Our aim was to determine the frequency and distribution of granulomas in untreated and treated patients with CD and their relation to age and disease severity.

Patients and Methods:

Records from patients with CD undergoing colonoscopy with terminal ileum biopsy over 7 years were reviewed. Clinical information and laboratory, pathology, and radiology results were recorded. The frequency and distribution of granulomas were determined.

Results:

From 376 patients with CD, 75% underwent concurrent esophagogastroduodenoscopy and colonoscopy. Of those, 65% (184/282) were untreated. Granulomas were identified in 48% (136/282) of all patients and in 61% (112/184) of untreated patients and 24.5% (24/98) of treated patients (P < 0.0005). The upper tract and terminal ileum biopsies were essential to the identification of 42% of patients with granulomas. The presence of granulomas at diagnosis was related to anti‐Saccharomyces cerevisiae antibodies, hypoalbuminemia, perianal disease, and gastritis at presentation (P = 0.03, P = 0.008, P = 0.03, and P = 0.001), respectively, and to perianal disease and infliximab treatment at the latest visit (P = 0.02 and P = 0.01), respectively. Granulomas were not related to age, sex, ethnicity, weight and height z scores, hemoglobin, C‐reactive protein, erythrocyte sedimentation rate, CARD15/NOD2 mutations, abdominal surgery, or stricturing or fistulizing disease.

Conclusions:

Granulomas were identified in 61% of fully investigated pediatric patients with CD at diagnosis, including a substantial proportion of patients in whom colonoscopy to the cecum would have been insufficient for diagnosis. Granulomas were more frequent in untreated patients (P < 0.0005), and their prevalence was not affected by age. The presence of granulomas at diagnosis was associated with perianal disease, gastritis, hypoalbuminemia, anti–Saccharomyces cerevisiae antibodies, and infliximab treatment.
Measuring Quality of Life in Pediatric Patients With Inflammatory Bowel Disease: Psychometric and Clinical Characteristics
Authors: Perrin James M , Kuhlthau Karen , Chughtai Aziz , Romm Diane , Kirschner Barbara S , Ferry George D , Cohen Stanley A , Gold Benjamin D , Heyman Melvin B , Baldassano Robert N , Winter Harland S
Published: March 2009

Objective:

To extend development of a pediatric inflammatory bowel disease (IBD) health‐related quality of life (HRQoL) measure by determining its factor structure and associations of factors with generic HRQoL measures and clinical variables.

Patients and Methods:

Cross‐sectional survey of children and adolescents ages 8 years to 18 years and their parents attending any of 6 US IBD centers, recruited from either existing registry of age‐eligible subjects or visits to participating centers. The survey included generic (Pediatric Quality of Life Inventory) and IBD‐specific (Impact Questionnaire) quality of life measures, disease activity, and other clinical indicators. We carried out factor analysis of Impact responses, comparing resulting factors with results on the generic HRQoL and the clinical measures.

Results:

We included 220 subjects (161 with Crohn disease and 59 with ulcerative colitis). Initial confirmatory factor analysis did not support the 6 proposed Impact domains. Exploratory factor analysis indicated 4 factors with good to excellent reliability for IBD responses: general well‐being and symptoms, emotional functioning, social interactions, and body image. Two items did not load well on any factor. The 4 factors correlated well with the Pediatric Quality of Life Inventory and subscales. Children with higher disease activity scores and other indicators of clinical activity reported lower HRQoL.

Conclusions:

This study provides further characteristics of a HRQoL measure specific to pediatric IBD and indicates ways to score the measure based on the resulting factor structure. The measure correlates appropriately with generic HRQoL measures and clinical severity indicators.
Gallbladder Motility in Children With Chronic Constipation
Authors: Neto Magno Cardoso Veras , Yamada Roberto Massao , da Costa Pinto Elizete Aparecida Lomazi
Published: March 2009

Objective:

The aim of this study was to evaluate gallbladder motility in constipated children.

Patients and Methods:

A cross‐sectional study was conducted on pediatric patients with refractory constipation examined in a pediatric gastroenterology unit of a teaching hospital between January 2005 and August 2006. All of the patients seen during the period were included (age range, 2–16 years). The control group, matched for sex and age, was selected among patients seen at the same basic health units where patients were seen before being referred to pediatric gastroenterologists. A gallbladder contractility index was calculated based on fasting and postprandial gallbladder areas, using an ultrasonographic method. Ultrasonography studies were performed prospectively and blindly by the same physician. Measurements obtained in patients were compared with those obtained in controls.

Results:

A total of 132 constipated children and the same number of healthy controls were included in the study. Median and mean fasting gallbladder areas were similar in patients and controls. Postprandial gallbladder areas were larger in the patient group, mean ± SD = 594.8 ± 206.4 mm2, median, 562.5 mm2, than in the control group, mean ± SD = 541.1 ± 156.1 mm2, median, 530.5 mm2; P = .031. Logistic regression showed that the risk of a contractility index <25% was 5.2 times greater in patients (odds ratio [OR] 5.2; 95% confidence interval [CI] 2.5–10.81) than in controls. Age was found to be a protective factor (OR 0.79; 95% CI 0.71–0.88).

Conclusions:

Gallbladder motility disorder was identified in a group of children with severe constipation. This finding may contribute to the understanding of functional constipation in children.
Clinical and Laboratory Predictors of Esophageal Varices in Children and Adolescents With Portal Hypertension Syndrome
Authors: Fagundes Eleonora Druve Tavares , Ferreira Alexandre Rodrigues , Roquete Mariza Leitão Valadares , Penna Francisco José , Goulart Eugênio Marcos Andrade , Filho Paulo Pimenta Figueiredo , Bittencourt Paulo Fernando Souto , Carvalho Simone Diniz , Albuquerque Walton
Published: March 2009

Objectives:

To determine the clinical and laboratory parameters that may predict the presence of esophageal varices in children and adolescents with portal hypertension.

Patients and Methods:

Overall, 111 patients with portal hypertension and no previous history of digestive bleeding underwent esophagogastroduodenoscopy for detection of esophageal varices. A univariate analysis initially was carried out, followed by a logistic regression analysis to identify the independent variables associated with the presence of esophageal varices. Sensitivity and specificity rates, positive predictive value, negative predictive value, and the accuracy of the predictive variables identified among cirrhotic patients were calculated with the esophagogastroduodenoscopy as the reference test.

Results:

Sixty percent of patients had esophageal varices on the first esophagogastroduodenoscopy. Patients with portal vein thrombosis and congenital hepatic fibrosis were 6.15‐fold more likely to have esophageal varices than cirrhotic patients. When we analyzed 85 cirrhotic patients alone, splenomegaly and hypoalbuminemia remained significant indicators of esophageal varices. Only spleen enlargement showed appropriate sensitivity and negative predictive value (97.7% and 91.7%, respectively) to be used as a screening test for esophageal varices among cirrhotic patients.

Conclusions:

In reference services and research protocols, endoscopic screening should be performed in all patients with portal vein thrombosis and congenital hepatic fibrosis. Among cirrhotic patients, the indication should be conditioned to clinical evidence of splenomegaly or hypoalbuminemia. For clinicians, the recommendation is to emphasize the orientations given to guardians of patients with portal vein thrombosis and congenital hepatic fibrosis as to the risk of digestive bleeding. Cirrhotic patients with hypoalbuminemia and splenomegaly should receive the same orientations.
Body Perception: Do Parents, Their Children, and Their Children's Physicians Perceive Body Image Differently?
Authors: Chaimovitz R , Issenman R , Moffat T , Persad R
Published: March 2009

Objectives:

To compare children's, parents' and physicians' perceptions of children's body size.

Patients and Methods:

We administered a structured questionnaire of body size perception using a descriptive Likert scale keyed to body image figures to children ages 12 to 18 years. The same scale was given to parents of children ages 5 to 18 years. The sample consisted of 91 children and their parents being seen in the Pediatric Gastroenterology Clinic for concerns unrelated to overweight. Weight and height of the children were measured, and body mass index (BMI) was calculated. The children's BMI percentiles were categorized as underweight (<15th), normal (15th–85th), overweight (85th–95th), and obese (95th and above). The attending physician independently completed the body image and description scale and indicated the figure that most accurately represented the patient without reference to BMI standards. Accuracy of the patients', parents', and doctors' estimates were statistically compared.

Results:

The sample population consisted of 6.4% underweight, 70.5% normal weight, 7.7% overweight, and 15.4% obese. Forty‐four percent of parents underestimated children's body size using word descriptions and 47% underestimated using figures. Forty percent of the children underestimated their own body size using descriptions and 43% underestimated using figures. The physicians in this study had a higher percentage of correct estimates; however, they underestimated 33% of the patients using both word descriptions and figures. Some obese children were not recognized, and several average children were perceived as underweight.

Conclusions:

Many children underestimated their degree of overweight. Their parents and even their attending physicians shared this misperception. This study demonstrates the need to further educate physicians to recognize obesity and overweight so that they can counsel children and their families.
Prevalence of Celiac Disease in Egyptian Children Disputes the East–West Agriculture‐dependent Spread of the Disease
Authors: Abu‐Zekry M , Kryszak D , Diab M , Catassi C , Fasano A
Published: March 2009

Objectives:

Celiac disease (CD) seems to be a common disorder in north Africa; however, to our knowledge no data are yet available on its prevalence in Egypt. This study was undertaken to investigate the frequency of CD in Egyptian children.

Patients and Methods:

We investigated a sample of the general pediatric population (1500 individuals, 656 girls and 844 boys, age range 7 months to 18 years, median age 8.0 years) (group A); 150 children (age range 6 months to 13 years, median age 16 months) admitted for diarrhea or failure to thrive (group B); and 250 children and adolescents with type 1 diabetes (group C). The screening test was serum class A anti‐transglutaminase (anti‐tTG) antibody; immunoglobulin A (IgA) antiendomysium, total IgA, and IgG anti‐tTG, and small bowel biopsy was performed for confirmation of diagnosis.

Results:

In group A, 8 of 1500 children fulfilled the criteria for CD diagnosis; the prevalence of CD was at least 1 in 187 individuals (0.53%; 95% CI 0.17%–0.89%). In group B, 7 of 150 children had CD (4.7%, 95% CI 1.4–7.9). In group C, 16 of 250 sera showed positive results to both the IgA anti‐tTG and the IgA antiendomysium test (6.4%; 95% CI 3.4–9.4).

Conclusions:

Celiac disease is a frequent disorder among Egyptian children, both in the general population and in at‐risk groups. Therefore, our data do not support the theory of a Middle East–Europe CD prevalence gradient secondary to the pattern of agriculture spreading from the so‐called Fertile Crescent.
Neuromotor Markers of Esophageal Motility in Feeding Intolerant Infants With Gastroschisis
Authors: Jadcherla Sudarshan Rao , Gupta Alankar , Stoner Erin , Fernandez Soledad , Caniano Donna , Rudolph Colin D
Published: March 2009

Background:

Feeding problems in neonates with gastroschisis are commonly attributed to foregut dysmotility. However, the dysmotility mechanisms are not well understood.

Objective:

Our aim was to differentiate the pharyngoesophageal motility characteristics in neonates with gastroschisis compared with the controls. Specifically, the characteristics of swallowing, upper esophageal sphincter (UES), esophageal body, and lower esophageal sphincter (LES) were evaluated during basal state and upon provocation.

Patients and Methods:

Surgically repaired and recovered study infants with persistent feeding difficulties (n = 8; 36 ± 2 weeks gestational age) and controls (n = 8; 38 ± 2 weeks gestational age) were evaluated at 40 ± 2 weeks and 42 ± 2.5 weeks postmenstrual age, respectively. The basal and adaptive pharyngoesophageal motility characteristics were evaluated using a specially designed esophageal motility catheter with UES and LES sleeves and pneumohydraulic micromanometric water perfusion system at the crib side. Analysis of variance, chi‐square, and t tests were applied; data are shown as mean ± standard deviation, and P < 0.05 was considered significant.

Results:

Birth weight was less in gastroschisis (P < 0.03, vs controls) and length was less at motility study (P < 0.01, vs controls). The study group (vs controls) needed prolonged respiratory support (21 ± 23 vs 1 ± 2 days; P < 0.001) and prolonged gavage feeding (167 ± 100 vs 9 ± 16 days; P < 0.01). Compared with the controls, the gastroschisis group had lower frequency (P < 0.05) and poor propagation of spontaneous swallows (P < 0.001), UES relaxation time was shorter (P < 0.05), rate of relaxation was faster (P < 0.001), and esophageal peristaltic propagation velocity was slower (P < 0.05). Upon esophageal provocation with air and liquids, frequency occurrence of the esophageal reflexes was low (P < 0.05) with respect to primary peristalsis, secondary peristalsis, UES contractile reflex, and LES relaxation reflex.

Conclusions:

In gastroschisis feeding milestones and respiratory milestones were delayed, basal pharyngoesophageal peristaltic failure was common, adaptive peristaltic reflexes were less frequent and failed to occur, and frequency occurrences of UES and LES responses were impaired. These neuromotor markers may provide clues to define the esophageal motor function abnormalities in infants with an abnormality thought to be limited to the intestine.
Taurolidine and Catheter‐related Bloodstream Infection: A Systematic Review of the Literature
Authors: Bradshaw Joanne H , Puntis John WL
Published: March 2009

Background:

Catheter‐related bloodstream infection remains the most common serious complication associated with long‐term parenteral nutrition. Taurolock (Bio‐Implant HealthCare, Winsen, Germany), which contains taurolidine, is being marketed as a central venous catheter lock solution for decreasing the risk of catheter sepsis.

Aim:

To review available literature and examine the evidence for efficacy of taurolidine in prevention of central venous catheter–related infection.

Materials and Methods:

Search of MEDLINE, Embase, and the Internet for all studies involving use of taurolidine to prevent central venous catheter infection.

Results:

Six in vitro and 11 in vivo studies were assessed. Although in vivo studies suggest a possible useful role for taurolidine, the evidence base from clinical studies is poor, with much of it observational or of poor methodology.

Conclusions:

The evidence is insufficient to warrant routine use of taurolidine. However, results of in vitro studies are encouraging and further adequately powered and well‐designed randomized trials are required.
Could the Savory Taste of Snacks Be a Further Risk Factor for Overweight in Children?
Authors: Maffeis C , Grezzani A , Perrone L , Del Giudice E Miraglia , Saggese G , Tatò L
Published: March 2009

Introduction:

The quantity, type and composition of snack foods may play a role in the development and maintenance of obesity in children. A high consumption of energy‐dense snacks may promote fat gain.

Aims:

To assess the type and number of snacks consumed weekly by a large sample of 8‐ to 10‐year‐old children, as well as to assess its relationship with body size.

Results:

The children consumed on average 4 snacks per day. There was no statistical difference in the number of servings per day between obese and nonobese children. However, the mean energy density of the foods consumed was significantly higher for obese and overweight children than for normal weight children [6.8 (0.3) kJ/g, 6.8 (0.16) kJ/g, and 6.3 (0.08) kJ/g, respectively; P < 0.05]. Logistic regression analysis showed that the energy density of the snacks (kJ/g), their savory taste (servings/week), television viewing (hours/day) and sports activity (hours/week) independently contributed to predict obesity in children. However, when the parents' body mass index was included among the independent variables of the regression, only salty foods and sports activity showed an independent association with childhood obesity.

Conclusions:

Parents' eating habits and lifestyle influence those of their children, as suggested by the association between parents' obesity and their children's energy‐dense food intake at snacktime, the savory taste of snacks and sedentary behavior. However, regardless of parents' body mass index, the preference for savory snacks seems to be associated with overweight in prepubertal children.