bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional clearance of amino‐terminal pro‐brain natriuretic peptide from human plasma
Authors: Palmer Suetonia C. , Yandle Timothy G. , Nicholls M. Gary , Frampton Christopher M. , Richards A. Mark
Published: July 2009

Aims

Mechanisms for clearance of circulating amino‐terminal pro‐brain natriuretic peptide (NT‐proBNP) remain poorly understood and are relevant to the clinical utility of NT‐proBNP as a diagnostic and prognostic biomarker in cardiovascular disorders. We sought to determine site(s) of production and clearance of plasma NT‐proBNP in the human circulation.

Methods and results

In 120 subjects undergoing clinically indicated cardiac catheterization, blood samples were collected from arterial and multiple venous sites to measure transorgan gradients of plasma NT‐proBNP. Clearance of plasma NT‐proBNP occurred across kidney, liver, musculoskeletal, and head and neck tissues. Proportions of calculated total body NT‐proBNP clearance were 55–65% across the kidney, 20–25% across the liver, 10–15% across musculoskeletal tissue, and 5–10% across the head and neck. Renal fractional extraction of NT‐proBNP was unrelated to estimated glomerular filtration rate. Transorgan gradients, reflecting both renal and extra‐renal NT‐proBNP degradation, were correlated across multiple clearance sites within an individual.

Conclusion

Plasma NT‐proBNP is cleared by multiple tissues in the human circulation with ~55–65% of total clearance occurring in renal tissue. These data provide the first evidence for extra‐glomerular clearance of NT‐proBNP and suggest a common multisite clearance mechanism subject to generalized regulation. Renal NT‐proBNP extraction was sustained in the face of even moderate levels of kidney dysfunction.
Simultaneous Measurement of Cardiac Troponin I, B-type Natriuretic Peptide, and C-reactive Protein for the Prediction of Long-term Cardiac Outcome after Cardiac Surgery
Authors: Fellahi Jean-Luc , Hanouz Jean-Luc , Le Manach Yannick , Gué Xavier , Monier Emmanuel , Guillou Louis , Riou Bruno
Published: July 2009

Background

Simultaneous assessment of cardiac troponin I, B-type natriuretic peptide, and C-reactive protein has been found to provide unique prognostic information in acute coronary syndromes. The current study addressed the prognostic implication of a multiple-marker approach in cardiac surgery.

Methods

Two hundred twenty-four patients undergoing cardiac surgery were included and followed up within 12 months after surgery. Serial blood samples were drawn in all patients the day before surgery, at the end of surgery, and 6, 24, and 120 h after surgery. Major adverse cardiac events within 12 months after surgery were chosen as study endpoints and were defined as malignant ventricular arrhythmia, myocardial infarction, congestive heart failure, the need for myocardial revascularization, and/or death from cardiac cause. Predictive ability of each cardiac biomarker was assessed using logistic regression.

Results

Accuracies of C-reactive protein, cardiac troponin I, and B-type natriuretic peptide, considered as continuous variables, to predict the occurrence of major adverse cardiac events were limited (area under receiver operating characteristic curve: 0.54 [0.47-0.60], P = 0.42; 0.62 [0.55-0.68], P = 0.01; and 0.68 [0.61-0.74], P < 0.001, respectively). When biomarkers were considered as 75% specificity dichotomized variables, elevated C-reactive protein (> 180 mg/l), cardiac troponin I (> 3.5 ng/ml), and B-type natriuretic peptide (> 880 pg/ml) were independent predictors of major adverse cardiac events (odds ratio: 2.14 [1.03-4.49], P = 0.043; 2.37 [1.25-5.64], P = 0.011; and 2.65 [1.16-4.85], P = 0.018, respectively) in a multivariate model including the European System for Cardiac Operative Risk Evaluation score.

Conclusions

Simultaneous measurement of cardiac troponin I, B-type natriuretic peptide, and C-reactive protein improves the risk assessment of long-term adverse cardiac outcome after cardiac surgery.
Expression of Signal Transduction Genes Differs after Hypoxic or Isoflurane Preconditioning of Rat Hippocampal Slice Cultures
Authors: Bickler Philip E. , Fahlman Christian S.
Published: July 2009

Background

Preconditioning neurons with noninjurious hypoxia (hypoxic preconditioning, HPC) or the anesthetic isoflurane (APC) induces tolerance of severe ischemic stress. The mechanisms of both types of preconditioning in the hippocampus require moderate increases in intracellular Ca and activation of protein kinase signaling. The authors hypothesized that the expression of signal transduction genes would be similar after APC and HPC.

Methods

Hippocampal slice cultures prepared from 9-day-old rats were preconditioned with hypoxia (5 min of 95% nitrogen/5% carbon dioxide) or 1% isoflurane in air/5% carbon dioxide for 1 h. A day later, cultures were subjected to 10 min oxygen and glucose deprivation (simulated ischemia). Intracellular Ca, measured in CA1 neurons at the completion of preconditioning, and cell death in CA1, CA3, and dentate regions was assessed 48 h after simulated ischemia. Message RNA encoding 119 signal transduction genes was quantified with rat complimentary DNA microarrays from pre-oxygen-glucose deprivation samples.

Results

Both APC and HPC increased intracellular Ca approximately 50 nm and decreased CA1, CA3, and dentate neuron death by about 50% after simulated ischemia. Many signaling genes were increased after preconditioning, with hypoxia increasing more apoptosis/survival genes (8 of 10) than isoflurane (0 of 10). In contrast, isoflurane increased more cell cycle/development/growth genes than did hypoxia (8 of 14 genes, vs. 1 of 14).

Conclusions

Despite sharing similar upstream signaling and neuroprotective outcomes, the genomic response to APC and HPC is different. Increased expression of antiapoptosis genes after HPC and cell development genes after APC has implications both for neuroprotection and long-term effects of anesthetics.
Beneficial Effect of Propofol on Arterial Adenosine Triphosphate-sensitive K+Channel Function Impaired by Thromboxane
Authors: Haba Masanori , Kinoshita Hiroyuki , Matsuda Naoyuki , Azma Toshiharu , Hama-Tomioka Keiko , Hatakeyama Noboru , Yamazaki Mitsuaki , Hatano Yoshio
Published: July 2009

Background

It is not known whether thromboxane A2 impairs adenosine triphosphate (ATP)-sensitive K channel function via increased production of superoxide in blood vessels and whether propofol as a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor restores this modification.

Methods

Rat aortas without endothelium were used for isometric force recording, measurements of membrane potential, and superoxide production and Western immunoblotting. Vasorelaxation to an ATP-sensitive K channel opener levcromakalim was obtained during contraction to phenylephrine (3 x 10(-7) M) or a thromboxane A2 analogue U46619 (3 x 10(-7) M). In some experiments, aortas were incubated with an ATP-sensitive K channel antagonist glibenclamide, a superoxide inhibitor Tiron, a nonselective NADPH oxidase inhibitor apocynin, a hydrogen peroxide scavenger catalase, a xanthine oxidase inhibitor allopurinol, a thromboxane receptor antagonist SQ29548 or propofol (3 x 10(-7) to 3 x 10(-6) M).

Results

Levcromakalim-induced vasorelaxation was abolished by glibenclamide in rings contracted with either vasoconstrictor agent. Tiron, apocynin, and propofol, but not catalase, augmented the vasodilator response as well as the hyperpolarization by levcromakalim in aortas contracted with U46619. Tiron, apocynin, SQ29548, and propofol, but not allopurinol, similarly reduced in situ levels of superoxide within aortic vascular smooth muscle exposed to U46619. Protein expression of a NADPH oxidase subunit p47phox increased in these arteries, and this augmentation was abolished by propofol.

Conclusions

Thromboxane receptor activation induces vascular oxidative stress via NADPH oxidase, resulting in the impairment of ATP-sensitive K channel function. Propofol reduces this stress via inhibition of a NADPH oxidase subunit p47phox and, therefore, restores ATP-sensitive K channel function.
Influence of Vancomycin on Renal Function in Critically Ill Patients after Cardiac Surgery
Authors: Hutschala Doris , Kinstner Christian , Skhirdladze Keso , Thalhammer Florian , Müller Markus , Tschernko Edda
Published: July 2009

Background

Vancomycin is frequently used in clinical practice to treat severe wound and systemic infections caused by Gram-positive bacteria after cardiac surgery. The drug is excreted almost entirely by glomerular filtration and might exhibit nephrotoxic side effects. This study compared the nephrotoxic impact of vancomycin during continuous versus intermittent administration.

Methods

The authors analyzed 149 patients admitted to the intensive care unit during a 5-yr period. All patients were treated at the intensive care unit after elective open heart surgery. Thirty patients received a dosage of 1325 +/- 603 mg/d vancomycin (range 300-3400 mg/d) by intermittent infusion, and 119 patients received a mean dosage of 1935 +/- 688 mg/d (range 352-3411 mg/d) by continuous infusion.

Results

Nephrotoxicity occurred in 11 patients (36.7%) in the intermittent treatment group and in 33 patients (27.7%) in the continuous treatment group (P = 0.3; 95% CI = 0.283). Continuous veno-venous hemofiltration after vancomycin administration was required for 9 patients (9 of 30; 30%) in the intermittent treatment group and for 28 (28 of 119; 23.5%) in the continuous treatment group (P = 0.053; 95% CI = 0.256). A change of one unit (1 mg/l) in vancomycin serum concentration (DeltaVancoC) induced an average change of 0.04 mg/dl in creatinine (DeltaCrea) in the intermittent treatment group versus 0.006 mg/dl in the continuous treatment group (P < 0.001).

Conclusions

The data show that both the intermittent and also the continuous application modality of vancomycin are associated with deterioration of renal function in critically ill patients after cardiac surgery. However, continuous infusion showed the tendency to be less nephrotoxic than the intermittent infusion of vancomycin.
Oxygen Tissue Saturation Is Lower in Nonsurvivors than in Survivors after Early Resuscitation of Septic Shock
Authors: Leone Marc , Blidi Sami , Antonini François , Meyssignac Bertrand , Bordon Sébastien , Garcin Frédéric , Charvet Aude , Blasco Valéry , Albanèse Jacques , Martin Claude
Published: July 2009

Background

Growing evidence suggests that the microvascular dysfunction is the key element of the pathogenesis of septic shock. This study's purpose was to explore whether the outcome of septic shock patients after early resuscitation using early goal-directed therapy is related to their muscle tissue oxygenation.

Methods

Tissue oxygen saturation (Sto2) was monitored in septic shock patients using a tissue spectrometer (InSpectra Model 325; Hutchinson Technology, Hutchinson, MN). For the purpose of this retrospective study, the Sto2 values were collected at the first measurement done after the macrohemodynamic variables (mean arterial pressure, urine output, central venous saturation in oxygen) were optimized.

Results

After the hemodynamic variables were corrected, no difference was observed between the nonsurvivors and survivors, with the exception of pulse oximetry saturation (94% [92-97%] vs. 97% [94-99%], P = 0.04). The Sto2 values were significantly lower in the nonsurvivors than in the survivors (73% [68-82%] vs. 84% [81-90%], P = 0.02). No correlations were found between the Sto2 and Spo2 (P = 0.7).

Conclusions

In septic shock patients, tissue oxygen saturation below 78% is associated with increased mortality at day 28. Further investigations are required to determine whether the correction of an impaired level of tissue oxygen saturation may improve the outcome of these patients.
Clonidine as an Adjuvant to Local Anesthetics for Peripheral Nerve and Plexus Blocks
Authors: Pöpping Daniel M. , Elia Nadia , Marret Emmanuel , Wenk Manuel , Tramèr Martin R. , Warner David S. , Warner Mark A.
Published: July 2009

The effect of adding clonidine to local anesthetics for nerve or plexus blocks remains unclear. The authors searched for randomized placebo-controlled trials testing the impact of adding clonidine to local anesthetics for peripheral single-injection nerve or plexus blocks in adults undergoing any surgery (except eye) without general anesthesia. Twenty trials (1,054 patients, 573 received clonidine) published 1992-2006 tested plexus (14 brachial, 1 cervical) and nerve blocks (2 sciatic/femoral, 1 midhumeral, 1 ilioinguinal/iliohypogastric, 1 ankle). Clonidine doses ranged from 30 to 300 microg; most patients received 150 microg. Clonidine prolonged the duration of postoperative analgesia (weighted mean difference 122 min; 95% confidence interval [CI] 74-169), sensory block (weighted mean difference 74 min; 95% CI 37-111), and motor block (weighted mean difference 141 min; 95% CI 82-199). In a subgroup of patients receiving an axillary plexus block, these effects were independent of whether clonidine was added to an intermediate or a long-acting local anesthetic. Clonidine increased the risk of arterial hypotension (odds ratio 3.61; 95% CI 1.52-8.55; number-needed-to-harm 11), orthostatic hypotension or fainting (odds ratio 5.07; 95% CI 1.20-21.4; number-needed-to-harm 10), bradycardia (odds ratio 3.09; 95% CI 1.10-8.64; number-needed-to-harm 13), and sedation (odds ratio 2.28; 95% CI 1.15-4.51; number-needed-to-harm 5). There was a lack of evidence of dose-responsiveness for beneficial or harmful effects. Clonidine added to intermediate or long-acting local anesthetics for single-shot peripheral nerve or plexus blocks prolongs duration of analgesia and motor block by about 2 h. The increased risk of hypotension, fainting, and sedation may limit its usefulness. Dose-responsiveness remains unclear.
Lumbar Sympathetic Blockade in Children with Complex Regional Pain Syndromes
Authors: Meier Petra M. , Zurakowski David , Berde Charles B. , Sethna Navil F.
Published: July 2009

Background

Sympathetic blockade is used in the management of complex regional pain syndromes in children, but there are no data on the efficacy or mechanism(s) by which it produces pain relief. The purpose of this study is to compare the efficacy of lidocaine administered by lumbar sympathetic to IV route.

Methods

Under general anesthesia, children with unilateral lower limb complex regional pain syndromes received catheters along the lumbar sympathetic chain. In a double-blind placebo-controlled crossover design, patients received IV lidocaine and lumbar sympathetic saline or lumbar sympathetic lidocaine and IV saline. Spontaneous and evoked pain ratings and sensory thresholds were assessed before and after these two lidocaine/saline doses and between routes of lumbar sympathetic blockade and IV.

Results

Twenty-three patients, ages 10-18 yr, were enrolled. There was evidence for reduction of mean pain intensity of allodynia to brush (mean -1.4, 95% confidence interval [CI] -2.5 to -0.3) and to pinprick temporal summation (mean -1.3, 95% CI -2.5 to -0.2) with lidocaine treatment via the lumbar sympathetic blockade compared to IV route. Lumbar sympathetic blockade also produced significant reduction in pain intensity compared to pretreatment values of allodynia to brush, pinprick and pinprick temporal summation and verbal pain scores. IV lidocaine did not produce significant changes in spontaneous and evoked pain intensity measurements compared to pretreatment values. There were no carryover effects as assessed by route-by-period interaction.

Conclusions

Under the conditions of this study, the results provide some direct evidence that a component of pain may be mediated by abnormal sympathetic efferent activity.
Prognostic Value of Brain Natriuretic Peptide in Noncardiac Surgery
Authors: Ryding Alisdair D. S. , Kumar Saurabh , Worthington Angela M. , Burgess David
Published: July 2009

Background

The prognostic role of brain natriuretic peptide (BNP) measurement before noncardiac surgery is unclear. The authors therefore performed a meta-analysis of studies in patients undergoing noncardiac surgery to assess the prognostic value of elevated BNP or N-terminal pro-BNP (NT-proBNP) levels in predicting mortality and major adverse cardiovascular events (MACE) (cardiac death or nonfatal myocardial infarction).

Methods

Unrestricted searches of MEDLINE and EMBASE bibliographic databases were performed using the terms "brain natriuretic peptide," "b-type natriuretic peptide," "BNP," "NT-proBNP," and "surgery." In addition, review articles, bibliographies, and abstracts of scientific meetings were manually searched. The meta-analysis included prospective studies that reported on the association of BNP or NT-proBNP and postoperative major adverse cardiovascular event (MACE) or mortality. The study endpoints were MACE, all-cause mortality, and cardiac mortality at short-term (less than 43 days after surgery) and longer-term (more than 6 months) follow-up. A random-effects model was used to pool study results; funnel-plot inspection was done to evaluate publication bias; Cochrane chi-square test and I testing was used to test for heterogeneity.

Results

Data from 15 publications (4,856 patients) were included in the analysis. Preoperative BNP elevation was associated with an increased risk of short-term MACE (OR 19.77; 95% confidence interval [CI] 13.18-29.65; P < 0.0001), all-cause mortality (OR 9.28; 95% CI 3.51-24.56; P < 0.0001), and cardiac death (OR 23.88; 95% CI 9.43-60.43; P < 0.00001). Results were consistent for both BNP and NT-proBNP. Preoperative BNP elevation was also associated with an increased risk of long-term MACE (OR 17.70; 95% CI 3.11-100.80; P < 0.0001) and all-cause mortality (OR 4.77; 95% CI 2.99-7.46; P < 0.00001).

Conclusions

Elevated BNP and NT-proBNP levels identify patients undergoing major noncardiac surgery at high risk of cardiac mortality, all-cause mortality, and MACE.
Desflurane Selectively Suppresses Long-latency Cortical Neuronal Response to Flash in the Rat
Authors: Hudetz Anthony G. , Vizuete Jeannette A. , Imas Olga A.
Published: July 2009

Background

The effect of inhalational anesthetics on sensory-evoked unit activity in the cerebral cortex has been controversial. Desflurane has desirable properties for in vivo neurophysiologic studies, but its effect on cortical neuronal activity and neuronal responsiveness is not known. The authors studied the effect of desflurane on resting and visual evoked unit activity in rat visual cortex in vivo.

Methods

Desflurane was administered to adult albino rats at steady-state concentrations at 2%, 4%, 6%, and 8%. Flashes from a light emitting diode were delivered to the left eye at 5-s intervals. Extracellular unit activity within the right visual cortex was recorded using a 49-electrode array. Individual units were identified using principal components analysis.

Results

At 2% desflurane, 578 active units were found. Of these, 75% increased their firing rate in response to flash. Most responses contained early (0-100 ms) and late (150-1000 ms) components. With increasing desflurane concentration, the number of units active at baseline decreased (-13%), the number of early-responding units increased (+31%), and number of late-responding units decreased (-15%). Simultaneously, baseline firing rate decreased (-77%), the early response was unchanged, and the late response decreased (-60%).

Conclusions

The results indicate that visual cortex neurons remain responsive to flash stimulation under desflurane anesthesia, but the long-latency component of their response is attenuated in a concentration-dependent manner. Suppression of the long-latency response may be related to a loss of corticocortical feedback and loss of consciousness.
Moderate Exposure to Allogeneic Blood Products Is Not Associated with Reduced Long-term Survival after Surgery for Coronary Artery Disease
Authors: Weightman William M. , Gibbs Neville M. , Sheminant Matthew R. , Newman Mark A. J. , Grey Dianne E.
Published: July 2009

Background

It has been suggested that blood transfusion has an adverse effect on long-term health, mainly through immune modulation and tumor promotion. To further assess this concern, the authors have performed a prospective observational study with the hypothesis that after taking perioperative risk factors relevant to long-term survival into account, patients undergoing coronary artery surgery who receive a perioperative allogeneic blood transfusion have worse long-term survival than those who do not.

Methods

The health outcomes of 1,841 consecutive subjects who had isolated nonemergency first-time coronary artery surgery and who survived more than 60 days after surgery were determined by record linkage. The association between length of survival, blood products transfused, and risk factors for long-term survival at entry to the study were determined by Cox proportional hazards regression.

Results

A total of 1,062 subjects were transfused. Of these, 266 subjects died during a mean follow-up of 8.1 yr. Of subjects who were transfused, 27% had a new malignant condition recorded on the death certificate, compared with 43% who were not transfused. Older age, cerebrovascular disease, use of a mammary graft, chronic pulmonary disease, renal dysfunction, reduced left ventricular function, and preoperative anemia were predictive of reduced long-term survival. There was no association between transfusion of blood products and long-term survival.

Conclusions

Patients who have undergone coronary artery surgery and who have received moderate amounts of blood as part of responsible and conservative management should be reassured that they are unlikely to experience a reduction in long-term survival.
Intravenous Infusion Tests Have Limited Utility for Selecting Long-term Drug Therapy in Patients with Chronic Pain
Authors: Cohen Steven P. , Kapoor Shruti G. , Rathmell James P.
Published: July 2009

Since the first description in the early 1990s, the scope of intravenous infusions tests has expanded to encompass multiple drug classes and indications. Purported advantages of these tests include elucidating mechanisms of pain, providing temporary relief of symptoms, and usefulness as prognostic tools in guiding drug therapy. In an attempt to discern the value of these tests, the authors conducted a systematic review to explore the rationale and evidence behind the following intravenous infusion tests: lidocaine, ketamine, opioid, and phentolamine. The studies evaluating all intravenous infusion tests were characterized by lack of standardization, wide variations in outcome measures, and methodological flaws. The strongest evidence found was for the intravenous lidocaine test, with the phentolamine test characterized by the least convincing data. Whereas intravenous opioid infusions are the most conceptually appealing test, their greatest utility may be in predicting poor responders to sustained-release formulations.
Supraclavicular Approach Is an Easy and Safe Method of Subclavian Vein Catheterization Even in Mechanically Ventilated Patients
Authors: Czarnik Tomasz , Gawda Ryszard , Perkowski Tadeusz , Weron Rafal
Published: July 2009

Background

Central venous catheters are commonly inserted for hemodynamic monitoring, volume monitoring, administration of medications, long-term total parenteral nutrition, access for renal replacement therapy, cardiopulmonary resuscitation, and difficult peripheral catheterization. The primary outcome of this study was to define venipuncture, catheterization and entire procedure success rates, and finally complication rate of subclavian venous catheterization via the supraclavicular approach with special focus on mechanically ventilated patients. The secondary outcome was to potentially make recommendations regarding this technique of central venous catheterization in mechanically ventilated patients.

Methods

The methodology of this prospective cohort study included subclavian venous catheterization via the supraclavicular approach. The technique of cannulation was the same for both the right and left sides, but the right claviculosternocleidomastoid angle was the preferred catheterization site. All procedures were performed by the first three authors, each of whom had different levels of experience. Each physician had performed at least 20 procedures before starting the study.

Results

In the majority of patients, venipuncture occurred during the first attempt. In 362 patients, catheterization attempts were performed, in whom 311 catheterizations (85.6%) were successful during the first attempt. The overall subclavian venous catheterization via supraclavicular approach procedure complication rate reached 1.7% (95% confidence interval 0.6-3.6%). The overall subclavian venous catheterization via the supraclavicular approach procedure success rate reached 88.9% (95% confidence interval 85.1-91.9%, n = 359).

Conclusions

Subclavian venous catheterization via the supraclavicular approach is an excellent method of central venous access in mechanically ventilated patients. The procedure success rate and the significant complication rate are comparable to other techniques of central venous catheterization.
General Anesthesia Increases Temporal Precision and Decreases Power of the Brainstem Auditory-evoked Response-related Segments of the Electroencephalogram
Authors: Scheller Bertram C. A. , Daunderer Michael , Pipa Gordon
Published: July 2009

Background

Brainstem auditory-evoked responses (BAEP) have been reported to be unchanged in the presence of drugs used for induction and maintenance of general anesthesia. The aim of this study was to investigate if the signal segments after the auditory stimulus that are used to average the evoked response change under the influence of general anesthesia.

Methods

BAEPs of 156 patients scheduled for elective surgery under general anesthesia were investigated. Anesthetic regimen was randomized as a combination of one of four hypnotic drugs supplemented by one of four opioids. Signal segments after the auditory stimulus were obtained at six different periods of anesthesia. Power and phase properties of wavelet-filtered single-sweep auditory-evoked activity accounting for the waveform of the averaged BAEP wave V and the stability of amplitude and latency of the averaged BAEP wave V over periods were analyzed.

Results

Amplitude and latency of wave V change slightly with no significant difference between the periods. During anesthesia, however, the power of single sweeps is significantly reduced, whereas phase-locking properties of the according signal segments are significantly enhanced. This effect is independent of the anesthetic or opioid used.

Conclusions

General anesthesia affects phase and power of the segments of the electroencephalogram related to BAEP wave V. This study's results support the idea that temporally precise responses from a large number of neurons in the brainstem might play a crucial role in encoding and passing sensory information to higher subcortical and cortical areas of the brain.
Anesthesia for Cesarean Delivery and Learning Disabilities in a Population-based Birth Cohort
Authors: Sprung Juraj , Flick Randall P. , Wilder Robert T. , Katusic Slavica K. , Pike Tasha L. , Dingli Mariella , Gleich Stephen J. , Schroeder Darrell R. , Barbaresi William J. , Hanson Andrew C. , Warner David O.
Published: July 2009

Background

Anesthetics administered to immature brains may cause histopathological changes and long-term behavioral abnormalities. The association between perinatal exposure to anesthetics during Cesarean delivery (CD) and development of learning disabilities (LD) was determined in a population-based birth cohort.

Methods

The educational and medical records of all children born to mothers residing in five townships of Olmsted County, Minnesota from 1976-1982 and remaining in the community at age 5 were reviewed to identify those with LDs. Cox proportional hazards regression was used to compare rates of LD between children delivered vaginally and via CD (with general or regional anesthesia).

Results

Of the 5,320 children in this cohort, 497 were delivered via CD (under general anesthesia n = 193, and regional anesthesia n = 304). The incidence of LD depended on mode of delivery (P = 0.050, adjusted for sex, birth weight, gestational age, exposure to anesthesia before age 4 yr, and maternal education). LD risk was similar in children delivered by vagina or CD with general anesthesia, but was reduced in children receiving CD with regional anesthesia (hazard ratio = 0.64, 95% confidence interval 0.44 to 0.92; P = 0.017 for comparison of CD under regional anesthesia compared to vaginal delivery).

Conclusion

Children exposed to general or regional anesthesia during CD are not more likely to develop LD compared to children delivered vaginally, suggesting that brief perinatal exposure to anesthetic drugs does not adversely affect long-term neurodevelopmental outcomes. The risk of LD may be lower in children delivered by CD whose mothers received regional anesthesia.
Depletion of Calcium Stores in Injured Sensory Neurons
Authors: Gemes Geza , Rigaud Marcel , Weyker Paul D. , Abram Stephen E. , Weihrauch Dorothee , Poroli Mark , Zoga Vasiliki , Hogan Quinn H.
Published: July 2009

Background

Painful nerve injury leads to disrupted Ca signaling in primary sensory neurons, including decreased endoplasmic reticulum (ER) Ca storage. This study examines potential causes and functional consequences of Ca store limitation after injury.

Methods

Neurons were dissociated from axotomized fifth lumbar (L5) and the adjacent L4 dorsal root ganglia after L5 spinal nerve ligation that produced hyperalgesia, and they were compared to neurons from control animals. Intracellular Ca levels were measured with Fura-2 microfluorometry, and ER was labeled with probes or antibodies. Ultrastructural morphology was analyzed by electron microscopy of nondissociated dorsal root ganglia, and intracellular electrophysiological recordings were obtained from intact ganglia.

Results

Live neuron staining with BODIPY FL-X thapsigargin (Invitrogen, Carlsbad, CA) revealed a 40% decrease in sarco-endoplasmic reticulum Ca-ATPase binding in axotomized L5 neurons and a 34% decrease in L4 neurons. Immunocytochemical labeling for the ER Ca-binding protein calreticulin was unaffected by injury. Total length of ER profiles in electron micrographs was reduced by 53% in small axotomized L5 neurons, but it was increased in L4 neurons. Cisternal stacks of ER and aggregation of ribosomes occurred less frequently in axotomized neurons. Ca-induced Ca release, examined by microfluorometry with dantrolene, was eliminated in axotomized neurons. Pharmacologic blockade of Ca-induced Ca release with dantrolene produced hyperexcitability in control neurons, confirming its functional importance.

Conclusions

After axotomy, ER Ca stores are reduced by anatomic loss and possibly diminished sarco-endoplasmic reticulum Ca-ATPase. The resulting disruption of Ca-induced Ca release and protein synthesis may contribute to the generation of neuropathic pain.
Methoxycarbonyl-etomidate
Authors: Cotten Joseph F. , Husain S Shaukat , Forman Stuart A. , Miller Keith W. , Kelly Elizabeth W. , Nguyen Hieu H. , Raines Douglas E.
Published: July 2009

Background

Etomidate is a rapidly acting sedative-hypnotic that provides hemodynamic stability. It causes prolonged suppression of adrenocortical steroid synthesis; therefore, its clinical utility and safety are limited. The authors describe the results of studies to define the pharmacology of (R)-3-methoxy-3-oxopropyl1-(1-phenylethyl)-1H-imidazole-5-carboxylate (MOC-etomidate), the first etomidate analogue designed to be susceptible to ultra-rapid metabolism.

Methods

The gamma-aminobutyric acid type A receptor activities of MOC-etomidate and etomidate were compared by using electrophysiological techniques in human alpha1beta2gamma2l receptors. MOC-etomidate's hypnotic concentration was determined in tadpoles by using a loss of righting reflex assay. Its in vitro metabolic half-life was measured in human liver S9 fraction, and the resulting metabolite was provisionally identified by using high-performance liquid chromatography/mass spectrometry techniques. The hypnotic and hemodynamic actions of MOC-etomidate, etomidate, and propofol were defined in rats. The abilities of MOC-etomidate and etomidate to inhibit corticosterone production were assessed in rats.

Results

MOC-etomidate potently enhanced gamma-aminobutyric acid type A receptor function and produced loss of righting reflex in tadpoles. Metabolism in human liver S9 fraction was first-order, with an in vitro half-life of 4.4 min versus more than 40 min for etomidate. MOC-etomidate's only detectable metabolite was a carboxylic acid. In rats, MOC-etomidate produced rapid loss of righting reflex that was extremely brief and caused minimal hemodynamic changes. Unlike etomidate, MOC-etomidate produced no adrenocortical suppression 30 min after administration.

Conclusions

MOC-etomidate is an etomidate analogue that retains etomidate's important favorable pharmacological properties. However, it is rapidly metabolized, ultra-short-acting, and does not produce prolonged adrenocortical suppression after bolus administration.
Performance Improvement System and Postoperative Corneal Injuries
Authors: Martin David P. , Weingarten Toby N. , Gunn Paul W. , Lee KunMoo , Mahr Michael A. , Schroeder Darrell R. , Sprung Juraj
Published: July 2009

Background

The authors' department conducted a performance improvement initiative aimed to reduce the rate of perioperative corneal injuries. This study reports the effects of the initiative and examines the risk factors for corneal injury.

Method

The rate of corneal injuries during nonophthalmologic procedures under anesthesia was compared between the two time periods: preinitiative baseline (August 1, 2005-December 31, 2005) and initiative period (January 1, 2006-April 30, 2007). To examine the risk factors for corneal injury, a nested case-control study with a 2:1 matched-set design was separately performed and included cases between January 1, 2006 and July 31, 2008.

Results

During the baseline period, the corneal injury rate was 1.51 per 1,000, and it decreased to 0.79 per 1,000 during the performance initiative (P = 0.008). Independent risk factors were longer anesthetics (odds ratio = 1.2, 95% confidence interval (CI) 1.1-1.3 per 30 min), lower American Society of Anesthesiologists physical status (odds ratio 0.5, 95% CI 0.3-0.8 for American Society of Anesthesiologists physical status 3-4 vs. 1-2), and student nurse anesthetist as a primary anesthesia provider (odds ratio 2.6, 95% CI 1.3-5.0).

Conclusion

Corneal injury rate in our institution was significantly reduced and remains at low levels long after initiation of perioperative eye care improvement initiative. The higher rate of corneal injuries among student nurse anesthetists highlights the importance of standardizing education and supervision among all anesthesia providers. We believe that our model of performance improvement initiative can be used to improve other perioperative outcomes.
Celiac Disease Revealed in 3% of Swedish 12‐year‐olds Born During an Epidemic
Authors: Myléus Anna , Ivarsson Anneli , Webb Charlotta , Danielsson Lars , Hernell Olle , Högberg Lotta , Karlsson Eva , Lagerqvist Carina , Norström Fredrik , Rosén Anna , Sandström Olof , Stenhammar Lars , Stenlund Hans , Wall Stig , Carlsson Annelie
Published: July 2009

Objective:

Sweden experienced a marked epidemic of celiac disease between 1984 and 1996 in children younger than 2 years of age, partly explained by changes in infant feeding. The objective of this study was to determine the prevalence of celiac disease in 12‐year‐olds born during the epidemic (1993), including both symptomatic and screening detected cases.

Patients and Methods:

All sixth‐grade children in participating schools were invited (n = 10,041). Symptomatic and, therefore, previously diagnosed celiac disease cases were ascertained through the National Swedish Childhood Celiac Disease Register and/or medical records. All serum samples were analyzed for antihuman tissue transglutaminase (tTG)‐IgA (Celikey), and serum‐IgA, and some for tTG‐IgG and endomysial antibodies. A small intestinal biopsy was recommended for all children with suspected undiagnosed celiac disease.

Results:

Participation was accepted by 7567 families (75%). Previously diagnosed celiac disease was found in 67 children; 8.9/1000 (95% confidence interval [CI] 6.7–11). In another 192 children, a small intestinal biopsy was recommended and was performed in 180. Celiac disease was verified in 145 children, 20/1000 (95% CI 17–23). The total prevalence was 29/1000 (95% CI 25–33).

Conclusions:

The celiac disease prevalence of 29/1000 (3%)—with two thirds of cases undiagnosed before screening—is 3‐fold higher than the usually suggested prevalence of 1%. When these 12‐year‐olds were infants, the prevailing feeding practice was to introduce gluten abruptly, often without ongoing breast‐feeding, which might have contributed to this unexpectedly high prevalence.
Flexible Upper Videoendoscopy Through a Modified Endoscopy Mask in Infants and Young Children
Authors: Somri Mostafa , Gaitini Louis , Yanovski Boris , Tome Riad , Resnikov Igor , Karsh Karam , Shaoul Ron
Published: July 2009

Esophagogastroduodenoscopy (EGD) is considered an essential diagnostic and therapeutic procedure in the pediatric population. Although generally safe, EGD has the potential for airway complications. We routinely use general anesthesia to carry out EGD in patients younger than 10 years. In the past, these patients received oxygen either through a nasal cannula or were intubated; both modalities have drawbacks and may be associated with complications. Here we report our experience using a modified endoscopy mask, devised primarily for bronchoscopy, for upper endoscopy in children under general anesthesia.

Results:

Two hundred forty children (122 boys and 118 girls) participated in the study. Age range was 7 to 135 months (mean 60.7 ± 34.4 months). All patients maintained a stable hemodynamic status throughout the procedure. Ventilation was satisfactory in 230 patients. It was difficult in 9 patients, and external airway maneuvers had to be applied. Ventilation was impossible in only 1 patient (10 months old), and endotracheal intubation was performed. There were no procedure‐related complications.

Conclusion:

The modified endoscopy mask is efficient and safe and should be recommended for routine use for upper endoscopy under general anesthesia in children older than 6 months.
Defining Eosinophilic Colitis in Children: Insights From a Retrospective Case Series
Authors: Behjati Sam , Zilbauer Matthias , Heuschkel Robert , Phillips Alan , Salvestrini Camilla , Torrente Franco , Bates Alan W
Published: July 2009

Objectives:

Although it is a well‐described syndrome in infants, eosinophilic colitis is a loosely defined and poorly understood diagnosis in older children. The aims of this case series were to characterise colonic eosinophilia in children and to determine whether it represents a distinct clinicopathological condition.

Methods:

We retrospectively reviewed symptomatic children older than 12 months with the principal diagnosis of colonic eosinophilia who presented between January 2000 and February 2007 (n = 38) and a further 10 children whose colonic biopsies were reported as histologically normal. The eosinophil density in all available gastrointestinal biopsies (n = 620) of these children was determined using a validated quantitative morphometric method. Patients were subdivided according to mean colonic eosinophil levels into 3 groups (marked, moderate, or minimal colonic eosinophilia). The following patient information was obtained and compared among patient groups: symptoms prompting endoscopy, atopic history, outcome, serum C‐reactive protein and total immunoglobulin E (IgE) levels, erythrocyte sedimentation rate, blood eosinophil count, and endoscopic findings.

Results:

In all 3 patient groups, there was a colonic gradient of decreasing eosinophil density from caecum to rectum. Upper gastrointestinal tract biopsies did not exhibit eosinophilia. Although a significant association (P = 0.03) between abnormal total IgE levels and moderate or severe colonic eosinophilia was found, there was no significant difference (P > 0.05) in other patient characteristics. Furthermore, follow‐up data did not show a consistent relation between eosinophil density and progression of symptoms.

Conclusions:

We find no association between “eosinophilic colitis,” defined as a histologically demonstrated marked colonic eosinophilia, and symptoms, history of atopy, inflammatory markers, or clinical outcome.
Gastrostomy Placement Improves Height and Weight Gain in Girls With Rett Syndrome
Authors: Motil Kathleen J , Morrissey Matthew , Caeg Erwin , Barrish Judy O , Glaze Daniel G
Published: July 2009

Background:

Growth failure and undernutrition complicate the clinical course of girls with Rett syndrome (RTT). These abnormalities are, in part, the consequence of oral motor dysfunction and inadequate dietary intake.

Objective:

To determine whether gastrostomy placement for nutritional therapy alters the natural history of growth failure and undernutrition in RTT.

Hypothesis:

We hypothesized that gastrostomy placement for nutritional therapy reverses the decline in height, weight, and body mass index (BMI) z scores in RTT.

Methods:

Standard stadiometric and anthropometric measures were obtained to derive height, weight, and BMI z scores and estimates of fat‐free mass (FFM) and body fat in a cohort of girls (n = 92) with RTT before and after gastrostomy placement. Methyl‐CpG‐binding protein 2 (MECP2) mutations and the presence or absence of a fundoplication were recorded.

Results:

The differences in height (n = 73), weight (n = 81), and BMI (n = 81) z score slopes before and after gastrostomy placement were 1.31 + 2.06 (P < 0.001), 2.38 ± 3.18 (P < 0.001), and 3.25 ± 3.32 (P < 0.001), respectively. FFM and body fat (n = 43) increased after gastrostomy by 41 ± 27 g/cm height (P < 0.001) and 7.5% ± 5.7% body weight (P < 0.001), respectively. The differences in height, weight, and BMI z score slopes were similar regardless of the age at which the gastrostomy was placed. The differences in height, weight, and BMI z score slopes, as well as the change in FFM and body fat deposition after gastrostomy placement, did not differ between those who did or did not have a fundoplication and among the classes of MECP2 mutations.

Conclusion:

Gastrostomy placement for aggressive nutritional therapy favorably altered the natural history of growth failure and undernutrition in RTT, but did not restore height and weight z scores to birth values, regardless of the age at which surgery occurred and in the presence or absence of a fundoplication.
Headache in Pediatric Patients With Celiac Disease and Its Prevalence as a Diagnostic Clue
Authors: Lionetti Elena , Francavilla Ruggiero , Maiuri Luigi , Ruggieri Martino , Spina Massimo , Pavone Piero , Francavilla Teresa , Magistà Anna Maria , Pavone Lorenzo
Published: July 2009

Objectives:

To establish the prevalence of headache in children with celiac disease (CD), the response to a gluten‐free diet, and the prevalence of CD in children affected by headache.

Methods:

This hospital‐based study included 2 steps. In the retrospective part, 354 children with CD answered a questionnaire investigating the presence of headache before and after the gluten‐free diet. The same questionnaire was administered to 200 healthy children matched for sex and age. In the prospective part, 79 children affected by headache were screened for CD by antitransglutaminase IgA. Diagnosis of CD was confirmed by duodenal biopsy; before starting a gluten‐free diet patients underwent a brain positron emission tomography study. After 6 months of follow‐up children were reevaluated for the presence of headache.

Results:

Overall, 88 patients with CD complained of headaches before the diagnosis of CD as compared with 16 in the control group (24.8% vs 8%, P < 0.001). After the institution of a gluten‐free diet, the headaches significantly improved in 68 children (77.3%), of whom 24 (27.3%) were headache‐free during the study period. Four of 79 (5%) headache patients were found to have CD compared with 0.6% of the general population (P = 0.005). The brain positron emission tomography studies did not show any anomalies. During the follow‐up, headaches improved in all 4 children with CD.

Conclusions:

We recorded—in our geographical area—a high frequency of headaches in patients with CD and vice versa with a beneficial effect of a gluten‐free diet. Screening for CD could be advised in the diagnostic work‐up of patients with headache.
Prebiotics Improve Gastric Motility and Gastric Electrical Activity in Preterm Newborns
Authors: Indrio Flavia , Riezzo Giuseppe , Raimondi Francesco , Francavilla Ruggiero , Montagna Osvaldo , Valenzano Maria Luigia , Cavallo Luciano , Boehm Günther
Published: July 2009

The aim of this double‐blind, randomized, placebo‐controlled study was to evaluate the effect of a prebiotic mixture on gastric motility in preterm newborns. After a feeding period of 15 days, gastric electrical activity was measured by electrogastrography, and the gastric emptying time was studied by ultrasound technique. No difference was seen in the daily increase of body weight, and no adverse events have been reported. The percentage of time in which propagation was detected in the electrogastrography signal was twice in newborns receiving formula with prebiotics with respect to placebo, and the gastric half‐emptying time was 30% faster in the prebiotic group than the placebo group. Prebiotic oligosaccharides can modulate the electrical activity and the gastric emptying and may improve the intestinal tolerance of enteral feeding in preterm infants.
Risk of Capsule Endoscope Retention in Pediatric Patients: A Large Single‐center Experience and Review of the Literature
Authors: Atay Orhan , Mahajan Lori , Kay Marsha , Mohr Franziska , Kaplan Barbara , Wyllie Robert
Published: July 2009

Objectives:

Capsule retention is a potential complication of capsule endoscopy (CE). The aims of our study were to determine the incidence of capsule retention in pediatric patients undergoing CE and to identify potential risk factors for capsule retention.

Materials and Methods:

We performed an institutional review board–approved retrospective chart review of pediatric patients undergoing CE studies at a single center. Data collected included patient age, sex, prior diagnosis of inflammatory bowel disease (IBD), CE indication, prior small bowel series results, study result, and complications.

Results:

Two hundred seven CE procedures were performed in pediatric patients during the study period. Capsule retention occurred in 3 (1.4%) of the 207 studies. All 3 patients had known Crohn disease (CD). The risk of capsule retention in pediatric patients with known IBD was 5.2% (3/58). The risk of capsule retention for patients with suspected IBD and all other indications was 0%. If small bowel disease was identified on upper gastrointestinal series in patients with known CD, then the risk of capsule retention was 37.5% (3/8). Only 7 patients with known IBD had a body mass index (BMI) below the 5th percentile. Of these 7 patients, 3 (43%) had capsule retention.

Conclusions:

Red flags for potential CE retention identified in our study include known IBD (5.2% retention risk), previous small bowel follow‐through demonstrating small bowel CD (37.5% retention risk), and BMI <5th percentile with known IBD (43% retention risk). Caution is advised in these pediatric patients before capsule ingestion.