bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Alzheimer and Inflammation Biomarkers after Anesthesia and Surgery
Authors: Tang Junxia X. , Baranov Dimitry , Hammond Mary , Shaw Leslie M. , Eckenhoff Maryellen F. , Eckenhoff Roderic G.
Published: October 2011

Background

The prevalence of postoperative cognitive disturbance, coupled with growing in vitro, cell, and animal evidence suggesting anesthetic effects on neurodegeneration, calls for additional study of the interaction between surgical care and Alzheimer neuropathology. The authors studied human cerebrospinal fluid (CSF) biomarkers during surgery.

Methods

Eleven patients undergoing idiopathic nasal CSF leak correction were admitted to this Institutional Review Board-approved study. Lumbar subarachnoid catheters were placed before the procedure. Anesthesia was total intravenous propofol or remifentanil or inhalational sevoflurane, depending on provider choice. CSF samples were taken after catheter placement (base), at procedure end (0 h), and then at 6, 24, and 48 h. CSF was analyzed using xMAP Luminex immunoassay (Luminex, Austin, TX).

Results

Of the 11 patients (age range, 53 ± 6 yr), 8 were women; 4 received intravenous anesthesia, 6 sevoflurane, and 1 mixed. Procedures lasted 6.4 ± 2 h. Mean CSF amyloid-β(1-42) remained unchanged, but total-tau and phosphorylated-tau181P increased progressively until at least 48 h. Total-tau, phosphorylated-tau, or amyloid-β(1-42) concentrations were not different between anesthetic groups. CSF interleukin-10, S100Beta, and tumor necrosis factor α were increased similarly in both anesthetic groups at 24 h, but interleukin-6 was increased more in the inhalational group.

Conclusion

These data indicate a robust neuroinflammatory response, including not only the usual markers (interleukin-6, tumor necrosis factor α, interleukin-10), but also S100Beta and tau, markers of injury. The total-tau/amyloid-β(1-42) ratio increased in a pattern consistent with Alzheimer disease, largely because of an increase in total-tau rather than a decline in amyloid-β(1-42). The differences in CSF interleukin-6 concentrations suggest that anesthetic management may make a difference in neuroinflammatory response.
Cysteinyl Leukotrienes Impair Hypoxic Pulmonary Vasoconstriction in Endotoxemic Mice
Authors: Petersen Bodil , Austen K. Frank , Bloch Kenneth D. , Hotta Yukako , Ichinose Fumito , Kanaoka Yoshihide , Zapol Warren M.
Published: October 2011

Background

Sepsis impairs hypoxic pulmonary vasoconstriction (HPV) in patients and animal models, contributing to systemic hypoxemia. Concentrations of cysteinyl leukotrienes are increased in the bronchoalveolar lavage fluid of patients with sepsis, but the contribution of cysteinyl leukotrienes to the impairment of HPV is unknown.

Methods

Wild-type mice, mice deficient in leukotriene C(4) synthase, the enzyme responsible for cysteinyl leukotriene synthesis, and mice deficient in cysteinyl leukotriene receptor 1 were studied 18 h after challenge with either saline or endotoxin. HPV was measured by the increase in left pulmonary vascular resistance induced by left mainstem bronchus occlusion. Concentrations of cysteinyl leukotrienes were determined in the bronchoalveolar lavage fluid.

Results

In the bronchoalveolar lavage fluid of all three strains, cysteinyl leukotrienes were not detectable after saline challenge; whereas endotoxin challenge increased cysteinyl leukotriene concentrations in wild-type mice and mice deficient in cysteinyl leukotriene receptor 1, but not in mice deficient in leukotriene C(4) synthase. HPV did not differ among the three mouse strains after saline challenge (120 ± 26, 114 ± 16, and 115 ± 24%, respectively; mean ± SD). Endotoxin challenge markedly impaired HPV in wild-type mice (41 ± 20%) but only marginally in mice deficient in leukotriene C(4) synthase (96 ± 16%, P < 0.05 vs. wild-type mice), thereby preserving systemic oxygenation. Although endotoxin modestly decreased HPV in mice deficient in cysteinyl leukotriene receptor 1 (80 ± 29%, P < 0.05 vs. saline challenge), the magnitude of impairment was markedly less than in endotoxin-challenged wild-type mice.

Conclusion

Cysteinyl leukotrienes importantly contribute to endotoxin-induced impairment of HPV in part via a cysteinyl leukotriene receptor 1-dependent mechanism.
A Single Subanesthetic Dose of Ketamine Relieves Depression-like Behaviors Induced by Neuropathic Pain in Rats
Authors: Wang Jing , Goffer Yossef , Xu Duo , Tukey David S. , Shamir D. B. , Eberle Sarah E. , Zou Anthony H. , Blanck Thomas J. J. , Ziff Edward B.
Published: October 2011

Background

Chronic pain is associated with depression. In rodents, pain is often assessed by sensory hypersensitivity, which does not sufficiently measure affective responses. Low-dose ketamine has been used to treat both pain and depression, but it is not clear whether ketamine can relieve depression associated with chronic pain and whether this antidepressant effect depends on its antinociceptive properties.

Methods

The authors examined whether the spared nerve injury model of neuropathic pain induces depressive behavior in rats, using sucrose preference test and forced swim test, and tested whether a subanesthetic dose of ketamine treats spared nerve injury-induced depression.

Results

Spared nerve injury-treated rats, compared with control rats, showed decreased sucrose preference (0.719 ± 0.068 (mean ± SEM) vs. 0.946 ± 0.010) and enhanced immobility in the forced swim test (107.3 ± 14.6s vs. 56.2 ± 12.5s). Further, sham-operated rats demonstrated depressive behaviors in the acute postoperative period (0.790 ± 0.062 on postoperative day 2). A single subanesthetic dose of ketamine (10 mg/kg) did not alter spared nerve injury-induced hypersensitivity; however, it treated spared nerve injury-associated depression-like behaviors (0.896 ± 0.020 for ketamine vs. 0.663 ± 0.080 for control rats 1 day after administration; 0.858 ± 0.017 for ketamine vs. 0.683 ± 0.077 for control rats 5 days after administration).

Conclusions

Chronic neuropathic pain leads to depression-like behaviors. The postoperative period also confers vulnerability to depression, possibly due to acute pain. Sucrose preference test and forced swim test may be used to compliment sensory tests for assessment of pain in animal studies. Low-dose ketamine can treat depression-like behaviors induced by chronic neuropathic pain.
Role of the O-linked β-N -acetylglucosamine in the Cardioprotection Induced by Isoflurane
Authors: Hirose Kayo , Tsutsumi Yasuo M. , Tsutsumi Rie , Shono Masayuki , Katayama Erika , Kinoshita Michiko , Tanaka Katsuya , Oshita Shuzo
Published: October 2011

Background

Cardiac protection by volatile anesthetic-induced preconditioning and ischemic preconditioning have similar signaling pathways. Recently, it was reported that augmentation of protein modified with O-linked β-N-acetylglucosamine (O-GlcNAc) contributes to cardiac protection. This study investigated the role of O-GlcNAc in cardiac protection induced by anesthetic-induced preconditioning.

Methods

O-GlcNAc-modified proteins were visualized by immunoblotting. Tolerance against ischemia or reperfusion was tested in vivo (n = 8) and in vitro (n = 6). The opening of the mitochondrial permeability transition pore (mPTP) upon oxidative stress was examined in myocytes treated with calcein AM (n = 5). Coimmunoprecipitation and enzymatic labeling were performed to detect the mitochondrial protein responsible for the mPTP opening.

Results

Isoflurane treatment and the consequent augmentation of O-GlcNAc concentrations reduced the infarct size (26 ± 5% [mean ± SD], P < 0.001) compared with the control. The protective effect of O-GlcNAc was eliminated in the group pretreated with the O-GlcNAc transferase inhibitor alloxan (39 ± 5%, P < 0.001). Myocyte survival also showed the same result in vitro. Formation of the mPTP was abrogated in the isoflurane-treated cells (86 ± 4%, P < 0.001) compared with the control and alloxan-plus-isoflurane-treated cells (57 ± 7%, P < 0.001). Coimmunoprecipitation and enzymatic labeling studies revealed that the O-GlcNAc-modified, voltage-dependent anion channel restained the mPTP opening.

Conclusions

Isoflurane induced O-GlcNAc modification of mitochondrial voltage-dependent anion channel. This modification inhibited the opening of the mPTP and conferred resistance to ischemia-reperfusion stress.
Potential Adverse Ultrasound-related Biological Effects
Authors: Shankar Hariharan , Pagel Paul S. , Warner David S.
Published: October 2011

Ultrasound energy exerts important cellular, genetic, thermal, and mechanical effects. Concern about the safety of ultrasound prompted several agencies to devise regulatory limits on the machine output intensities. The visual display of thermal and mechanical indices during ultrasound imaging provides an aid to limit the output of the machine. Despite many animal studies, no human investigations conducted to date have documented major physiologic consequences of ultrasound exposed during imaging. To date, ultrasound imaging appears to be safe for use in regional anesthesia and pain medicine interventions, and adherence to limiting the output of ultrasound machines as outlined by the Food and Drug Administration may avoid complications in the future. This article reviews ultrasound-related biologic effects, the role of the regulatory agencies in ensuring safety with the use of ultrasound, and the limitations and implications of ultrasound use in humans.
Identical de novo Mutation in the Type 1 Ryanodine Receptor Gene Associated with Fatal, Stress-induced Malignant Hyperthermia in Two Unrelated Families
Authors: Groom Linda , Muldoon Sheila M. , Tang Zhen Zhi , Brandom Barbara W. , Bayarsaikhan Munkhuu , Bina Saiid , Lee Hee-Suk , Qiu Xing , Sambuughin Nyamkhishig , Dirksen Robert T.
Published: October 2011

Background

Mutations in the type 1 ryanodine receptor gene (RYR1) result in malignant hyperthermia, a pharmacogenetic disorder typically triggered by administration of anesthetics. However, cases of sudden death during exertion, heat challenge, and febrile illness in the absence of triggering drugs have been reported. The underlying causes of such drug-free fatal "awake" episodes are unknown.

Methods

De novo R3983C variant in RYR1 was identified in two unrelated children who experienced fatal, nonanesthetic awake episodes associated with febrile illness and heat stress. One of the children also had a second novel, maternally inherited D4505H variant located on a separate haplotype. Effects of all possible heterotypic expression conditions on RYR1 sensitivity to caffeine-induced Ca release were determined in expressing RYR1-null myotubes.

Results

Compared with wild-type RYR1 alone (EC50 = 2.85 ± 0.49 mM), average (± SEM) caffeine sensitivity of Ca release was modestly increased after coexpression with either R3983C (EC50 = 2.00 ± 0.39 mM) or D4505H (EC50 = 1.64 ± 0.24 mM). Remarkably, coexpression of wild-type RYR1 with the double mutant in cis (R3983C-D4505H) produced a significantly stronger sensitization of caffeine-induced Ca release (EC50 = 0.64 ± 0.17 mM) compared with that observed after coexpression of the two variants on separate subunits (EC50 = 1.53 ± 0.18 mM).

Conclusions

The R3983C mutation potentiates D4505H-mediated sensitization of caffeine-induced RYR1 Ca release when the mutations are in cis (on the same subunit) but not when present on separate subunits. Nevertheless, coexpression of the two variants on separate subunits still resulted in a ∼2-fold increase in caffeine sensitivity, consistent with the observed awake episodes and heat sensitivity.
First-line Therapy with Coagulation Factor Concentrates Combined with Point-of-Care Coagulation Testing Is Associated with Decreased Allogeneic Blood Transfusion in Cardiovascular Surgery
Authors: Görlinger Klaus , Dirkmann Daniel , Hanke Alexander A. , Kamler Markus , Kottenberg Eva , Thielmann Matthias , Jakob Heinz , Peters Jürgen
Published: October 2011

Introduction

Blood transfusion is associated with increased morbidity and mortality. We developed and implemented an algorithm for coagulation management in cardiovascular surgery based on first-line administration of coagulation factor concentrates combined with point-of-care thromboelastometry/impedance aggregometry.

Methods

In a retrospective cohort study including 3,865 patients, we analyzed the incidence of intraoperative allogeneic blood transfusions (primary endpoints) before and after algorithm implementation.

Results

Following algorithm implementation, the incidence of any allogeneic blood transfusion (52.5 vs. 42.2%; P < 0.0001), packed red blood cells (49.7 vs. 40.4%; P < 0.0001), and fresh frozen plasma (19.4 vs. 1.1%; P < 0.0001) decreased, whereas platelet transfusion increased (10.1 vs. 13.0%; P = 0.0041). Yearly transfusion of packed red blood cells (3,276 vs. 2,959 units; P < 0.0001) and fresh frozen plasma (1986 vs. 102 units; P < 0.0001) decreased, as did the median number of packed red blood cells and fresh frozen plasma per patient. The incidence of fibrinogen concentrate (3.73 vs. 10.01%; P < 0.0001) and prothrombin complex concentrate administration (4.42 vs. 8.9%; P < 0.0001) increased, as did their amount administered per year (179 vs. 702 g; P = 0.0008 and 162 × 10³ U vs. 388 × 10³ U; P = 0.0184, respectively). Despite a switch from aprotinin to tranexamic acid, an increase in use of dual antiplatelet therapy (2.7 vs. 13.7%; P < 0.0001), patients' age, proportion of females, emergency cases, and more complex surgery, the incidence of massive transfusion [(≥10 units packed red blood cells), (2.5 vs. 1.26%; P = 0.0057)] and unplanned reexploration (4.19 vs. 2.24%; P = 0.0007) decreased. Composite thrombotic/thromboembolic events (3.19 vs. 1.77%; P = 0.0115) decreased, but in-hospital mortality did not change (5.24 vs. 5.22%; P = 0.98).

Conclusions

First-line administration of coagulation factor concentrates combined with point-of-care testing was associated with decreased incidence of blood transfusion and thrombotic/thromboembolic events.
Definition of mortality for trauma center performance evaluation: A comparative study*
Authors: Moore Lynne , Turgeon Alexis F. , Émond Marcel , Le Sage Natalie , Lavoie André
Published: October 2011

Objective:

Mortality is widely used as a performance indicator to evaluate the quality of trauma care, but there is no consensus on the most appropriate definition. Our objective was to evaluate the influence of the definition of mortality in terms of the place (in-hospital or postdischarge) and time (30 days and 3, 6, and 12 months) of death on the results of trauma center performance evaluations according to the patients' ages.

Design:

Multicenter retrospective cohort study.

Setting:

Inclusive Canadian provincial trauma system.

Patients:

Adults admitted between 1999 and 2006 with a maximum abbreviated injury severity score ≥3 (n = 47,261).

Interventions:

None.

Measurements and Main Results:

Trauma registry data were linked to vital statistics data to obtain mortality up to 12 months postadmission. Observed mortality was compared to that expected according to provincial population mortality rates. Trauma center performance was evaluated with risk-adjusted mortality estimates. Agreement between performance results based on different definitions of mortality was evaluated with correlation coefficients; >.9 was considered acceptable. Analyses were stratified by predefined age categories (16–64, 65–84, and ≥85 yrs). A total of 3,338 patients (7%) died in-hospital, and 1,794 patients (4%) died postdischarge. Among patients 16–64 yrs old, 30-day hospital mortality represented 83% of all deaths and correlation coefficients across all definitions of mortality were >.9. In patients 65–84 yrs old, 30-day hospital mortality represented 52% of all deaths, observed mortality reached expected rates at around 6 months, and agreement across mortality definitions was low.

Conclusions:

We observed an important variation in performance evaluation results across definitions of mortality, specifically in patients aged ≥65 yrs. Half of the deaths among elders occurred later than 30 days following admission, including a significant number postdischarge. Results suggest that if performance evaluations include elderly patients, data on postdischarge mortality up to 6 months following admission are required.
Effect of Demyelinating Ulnar Nerve Injury on Strength and Fatigue
Authors: Allen Matti D , Doherty Timothy J
Published: October 2011

Objectives:

Conduction block (CB) from focal neuropathy is often associated with weakness and fatigue in affected muscles. Ulnar neuropathy at the elbow (UNE) provides an excellent model to examine the relationships between electrophysiologically defined CB and quantitative measurement of weakness and fatigue.

Methods:

Eight healthy control subjects (47 ± 14 years) and nine patients (53 ± 3 years) with clinical and electrophysiological features of UNE with CB were studied. All underwent bilateral, ulnar motor nerve conduction studies recording from the first dorsal interosseous muscle as well as quantitative measurement of strength and fatigue of the first dorsal interosseous with a custom dynamometer.

Results:

Strength and fatigue were similar in the dominant and nondominant hands of control subjects and unaffected limb in patients. Varying degrees of conduction block (14-62%, mean 36%) and conduction slowing (31 m/s ± 7) were observed in those with UNE. CB was associated with significant reductions in strength (42%) and fatigue (23%) on a timed fatigue task. The reductions in strength (r = 0.74) and fatigue (r = 0.60) were strongly correlated with the degree of CB.

Conclusions:

CB in UNE defined by electrophysiological criteria was strongly correlated with weakness and fatigue in the first dorsal interosseous. Fatigue may be simply related to the reduction in strength, but activity or frequency dependent CB may also contribute.
Inter‐ and Intraobserver Agreement in 24‐hour Combined Multiple Intraluminal Impedance and pH Measurement in Children
Authors: Pilic Denisa , Höfs Carolin , Weitmann Sandra , Nöh Frank , Fröhlich Thorsten , Skopnik Heino , Köhler Henrik , Wenzl Tobias G. , Schmidt‐Choudhury Anjona
Published: October 2011

Objectives:

Assessment of intra‐ and interobserver agreement in multiple intraluminal impedance (MII) measurement between investigators from different institutions.

Methods:

Twenty‐four 18‐ to 24‐hour MII tracings were randomly chosen from 4 different institutions (6 per center). Software‐aided automatic analysis was performed. Each result was validated by 2 independent investigators from the 4 different centers (4 investigator combinations). For intraobserver agreement, 6 measurements were analyzed twice by the same investigator. Agreement between investigators was calculated using the Cohen kappa coefficient.

Results:

Interobserver agreement: 13 measurements showed a perfect agreement (kappa >0.8); 9 had a substantial (kappa 0.61–0.8), 1 a moderate (kappa coefficient 0.41 to 0.6), and 1 a fair agreement (kappa coefficient 0.11–0.4). Median kappa value was 0.83. Intraobserver agreement: 5 tracings showed perfect and 1 showed a substantial agreement. The median kappa value was 0.88.

Conclusions:

Most measurements showed substantial to perfect intra‐ and interobserver agreement. Still, we found a few outliers presumably caused by poorer signal quality in some tracings rather than being observer dependent. An improvement of analysis results may be achieved by using a standard analysis protocol, a standardized method for judging tracing quality, better training options for method users, and more interaction between investigators from different institutions.
Evaluation of Guidelines for Management of Familial Adenomatous Polyposis in a Multicenter Pediatric Cohort
Authors: Munck Anne , Gargouri Lamia , Alberti Corinne , Viala Jerome , Peuchmaur Michel , Lenaerts Catherine , Michaud Laurent , Lamireau Thierry , Mougenot Jean Francois , Dabadie Alain , Maurage Chantal , Lachaux Alain , Scaillon Michele , Languepin Jane , Spyckerelle Claire , Meyer Martine , Olschwang Sylvianne
Published: October 2011

Objective:

To retrospectively assess, in a pediatric multicenter cohort, guidelines for the management of familial adenomatous polyposis (FAP).

Methods:

Ten centers from the French‐speaking Pediatric Gastroenterology Hepatology and Nutrition Group provided follow‐up data on patients up to 18 years of age. Clinical records, genetic test results, endoscopy with histopathology examination, and therapeutic modalities were reviewed.

Results:

A total of 70 children from 47 families were included. When initial consultation resulted from a surveillance program because of an affected family member, 12 of 59 children were already symptomatic. Among 11 patients whose initial consultation was based only on symptoms, families were unaware at the time of a familial FAP history for 7 children, whereas only 4 cases were sporadic. A panel of 27 different pathogenic adenomatous polyposis coli (APC) germ‐line mutations and large genomic deletions were identified in 43 families. Extracolonic manifestations were found in half of the patients. As part of the standard practice for initial screening, the entire cohort underwent colonoscopy, which revealed adenoma above an intact rectosigmoid in 8 cases. Prophylactic colectomy was performed in 42 cases; high‐grade dysplastic adenoma and 1 invasive carcinoma were detected in 6 children. For timing of surgery, indications were in accordance with recent international guidelines.

Conclusions:

Defining optimal screening and therapeutic modalities in pediatric FAP cohorts is a challenge. Specific advice for genetic screening, endoscopy surveillance, and type of surgery based on recent guidelines is recommended.
European Society for Pediatric Gastroenterology, Hepatology, and Nutrition Guidelines for the Diagnosis of Coeliac Disease
Authors: Husby S. , Koletzko S. , Korponay‐Szabó I.R. , Mearin M.L. , Phillips A. , Shamir R. , Troncone R. , Giersiepen K. , Branski D. , Catassi C. , Lelgeman M. , Mäki M. , Ribes‐Koninckx C. , Ventura A. , Zimmer K.P. ,   ESPGHAN Working Group on Coeliac Disease Diagnosis,   ESPGHAN Gastroenterology Committee
Published: October 2011

Objective:

Diagnostic criteria for coeliac disease (CD) from the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) were published in 1990. Since then, the autoantigen in CD, tissue transglutaminase, has been identified; the perception of CD has changed from that of a rather uncommon enteropathy to a common multiorgan disease strongly dependent on the haplotypes human leukocyte antigen (HLA)‐DQ2 and HLA‐DQ8; and CD‐specific antibody tests have improved.

Methods:

A panel of 17 experts defined CD and developed new diagnostic criteria based on the Delphi process. Two groups of patients were defined with different diagnostic approaches to diagnose CD: children with symptoms suggestive of CD (group 1) and asymptomatic children at increased risk for CD (group 2). The 2004 National Institutes of Health/Agency for Healthcare Research and Quality report and a systematic literature search on antibody tests for CD in paediatric patients covering the years 2004 to 2009 was the basis for the evidence‐based recommendations on CD‐specific antibody testing.

Results:

In group 1, the diagnosis of CD is based on symptoms, positive serology, and histology that is consistent with CD. If immunoglobulin A anti‐tissue transglutaminase type 2 antibody titers are high (>10 times the upper limit of normal), then the option is to diagnose CD without duodenal biopsies by applying a strict protocol with further laboratory tests. In group 2, the diagnosis of CD is based on positive serology and histology. HLA‐DQ2 and HLA‐DQ8 testing is valuable because CD is unlikely if both haplotypes are negative.

Conclusions:

The aim of the new guidelines was to achieve a high diagnostic accuracy and to reduce the burden for patients and their families. The performance of these guidelines in clinical practice should be evaluated prospectively.
Detection of Pepsinogen in the Neonatal Lung and Stomach by Immunohistochemistry
Authors: Elabiad Mohamad T. , Zhang Jie
Published: October 2011

Objective:

Evaluate the hypothesis that the same pepsinogen C molecule produced in the stomach is also produced by the lung.

Patients and Methods:

Pulmonary and gastric tissues collected postmortem were immunohistochemically stained for pepsinogen C and pepsinogen A.

Results:

Sixteen patients with diverse causes of death were evaluated. Gestational age at birth ranged between 21 and 37 weeks. Pepsinogen A was detected in 12 of the 13 stomach sections, mainly in the chief cells, but not in any lung sections. Pepsinogen C was detected in all stomach sections in chief and mucus cells and in 9 of the 16 lung sections, mainly in type II pneumocytes. Pepsinogen C was not detected in the 3 lung cases with a gestational age <23 weeks.

Conclusions:

The same pepsinogen C molecule is produced in the stomach and in the lung. These findings potentially affect previous study results that used an enzymatic pepsin detection assay to evaluate for and associate gastroesophageal reflux disease with other morbidities.
Multicomponent School‐initiated Obesity Intervention in a High‐risk, Hispanic Elementary School
Authors: Klish William J. , Karavias Kellie E. , White Katie S. , Balch Angela J. , Fraley J. Kennard , Mikhail Carmen , Abrams Stephanie H. , Terrazas Norma L. , Smith E. O'Brian , Wong William W.
Published: October 2011

The aim of the study was to determine the effectiveness of a school‐initiated cognitive and behavioral program to reduce childhood obesity. Height, weight, body mass index (BMI), and BMI z scores were obtained at the beginning and end of the school year at an intervention school (n = 1022) and at a control school (n = 692). The prevalence of overweight and obesity was 18.9% and 30.4% versus 19% and 30.2%, respectively, in the intervention and control schools. The incidence of overweight increased in the control school, but the incidence of obesity, weight, and BMI z scores increased significantly in the intervention school, suggesting that implementation of any school‐based obesity intervention programs requires careful planning to achieve goals.
Neutrophil Transintestinal Epithelial Migration to CXCR2 Ligands Is Regulated by Adenosine
Authors: Stadnyk Andrew W. , Carrigan Svetlana O. , Otley Anthony R.
Published: October 2011

Objectives:

Polymorphonuclear leukocytes (PMN) feature prominently in the mucosa, including in crypt abscesses, of patients with inflammatory bowel disease, yet the mediators that are responsible for this migration are unknown. We discovered that CXCR2 chemokines (reportedly elevated in the mucosa) have reduced potency recruiting PMN across epithelial cell monolayers versus acellular filters, so the objective was to determine what molecules modify transepithelial PMN migration to CXCR2 chemokines.

Methods:

Transwells with T84 colon carcinoma monolayers or no epithelium were used with adolescent patient peripheral blood PMN and CXCL8 (interleukin‐8 [IL‐8], binds CXCR1 and CXCR2), CXCL5 (epithelial‐derived neutrophil chemoattractant‐78 [ENA‐78]), or CXCL1 (Gro‐α, both bind CXCR2) as chemoattractants.

Results:

IL‐8 was equally potent at recruiting PMN across filters and T84 monolayers growing on the filters. In contrast, ENA‐78 and Gro‐α were significantly less potent at recruiting PMN across monolayers than across bare filters. Blocking CXCR1 reduced PMN migration across monolayers to IL‐8. We ruled out superoxide radicals possibly enhancing migration to IL‐8 by using PMN from a patient with chronic granulomatous disease. PMN constitutively produce adenosine, so we added adenosine deaminase to the transwell assays and observed increased migration to ENA‐78 across T84 monolayers. The level of migration was further enhanced by pretreating PMN with adenosine before adding the cells to the assay in the presence of the deaminase.

Conclusions:

PMN migration mediated by CXCR2 through the epithelium is regulated by adenosine. Adenosine appears to reduce transepithelial migration by influencing β2 integrin use on the PMN.
Comparison of Quick Point‐of‐Care Test for Small‐bowel Hypolactasia With Biochemical Lactase Assay in Children
Authors: Rao Prithviraj , Rao Nagendra , Jordinson Matthew , Scott Camilla , Hinchcliffe Carol , Campbell David
Published: October 2011

Aim:

The aim of the present study was to compare the Biohit Lactose Intolerance Quick Test (BLIQT) to the criterion standard biochemical duodenal lactase (DL) activity assay in the paediatric population using standard statistical comparative tests.

Methods:

Using standard Olympus endoscopes, 2 postbulbar duodenal biopsies were taken from 38 prospective children (0–16 years) from June 2008–May 2009 at a single tertiary paediatric gastroenterology unit. The biopsies were used for the BLIQT and for biochemical disaccharides assay.

Results:

Thirty‐eight children (19 boys) of median age 5.45 years (0.3–14.8 years) underwent the combined BLIQT and disaccharidase testing. We subdivided the group into those who had biopsies with a larger endoscope (XQ, n = 26) and those who had a smaller endoscope (XP, n = 12) and thus a smaller biopsy forcep. When using a larger endoscope, the BLIQT showed a sensitivity of 100%, specificity of 86%, and positive and negative predictive value of 57.1% and 100%, respectively, on comparing it with DL. With a smaller endoscope, the BLIQT had a sensitivity of 100%, specificity of 80%, positive predictive value of 50%, and a negative predictive value of 100%.

Conclusions:

As in adult studies, the sensitivity and negative predictive value of the BLIQT was 100%. The specificity too appears to be high but variable, probably because of smaller biopsies obtained, and may warrant the need for 2 biopsies. The high sensitivity, specificity, and negative predictive value of the BLIQT for indicating hypolactasia make it an effective point‐of‐care test for paediatric hypolactasia.
Are Immunoglobulin A Anti‐gliadin Antibodies Helpful in Diagnosing Coeliac Disease in Children Younger Than 2 Years?
Authors: Foucher Barbara , Johanet Catherine , Jégo‐Desplat Sophie , Sanmarco Marielle , Dubucquoi Sylvain , Fily‐Nalewajk Sandrine , Olsson Nils‐Olivier , Lakomy Daniela , Escande Andrée , Chrétien Pascale , Fortenfant Françoise , Chevailler Alain , André Chantal , Goetz Joëlle , Humbel René‐Louis , Monier Jean‐Claude , Sibilia Jean , Taillefer Marie‐France , Abreu Isabelle , Fabien Nicole
Published: October 2011

The usefulness of immumoglobulin (Ig) A antibodies to gliadin (AGA‐IgA) in addition to IgA anti‐endomysium and tissue transglutaminase antibodies was evaluated in 4122 children younger than 2 years with a suspicion of coeliac disease (CD). Eight percent (312/4122) displayed IgA anti‐endomysium and/or IgA anti‐tissue transglutaminase, whereas 2.1% (85/4122) displayed only AGA‐IgA. Clinical data were obtained for 62 of 85 children with isolated AGA‐IgA, and 33 children underwent a duodenal biopsy. Histologically proven CD was established for 5 patients, whereas 57 children were diagnosed to experience other diseases. The systematic detection of AGA‐IgA using native gliadin conferred no additional diagnostic benefit for the diagnosis of CD in children younger than 2 years of age, except for rare cases.
Monitoring of Anti‐transglutaminase Autoantibodies in Pediatric Celiac Disease Using a Sensitive Radiobinding Assay
Authors: Candon Sophie , Mauvais François‐Xavier , Garnier‐Lengliné Hélène , Chatenoud Lucienne , Schmitz Jacques
Published: October 2011

Objectives:

The diagnosis of celiac disease (CD) is based on the histological identification of gluten‐sensitive enteropathy and detection of anti‐tissue transglutaminase antibodies (tTGA) and/or endomysial antibodies. Serial measurements of tTGA are now recommended as a follow‐up strategy to monitor compliance with a gluten‐free diet (GFD). We evaluated the performances of a quantitative radiobinding assay (RBA) of tTGA immunoglobulin A at diagnosis and during monitoring of GFD in pediatric CD.

Methods:

Eighty children with confirmed CD were selected. Levels of serum tTGA measured by RBA and a commercial enzyme‐linked immunosorbent assay (ELISA) were compared at diagnosis. The relation between RBA‐tTGA levels and histological damage was analyzed, as well as the time course of tTGA clearance during GFD.

Results:

Both RBA and ELISA showed high sensitivity and specificity for tTGA detection at diagnosis. There was no relation between RBA‐tTGA levels at diagnosis and severity of mucosal damage. Upon initiation of GFD, the rate of RBA‐tTGA positivity declined slower than that of endomysial antibodies positivity, with >50% of the children still tTGA positive at year 5; however, tTGA levels decreased rapidly during the first year of GFD and more slowly thereafter. Children who seroreverted had lower tTGA levels at diagnosis (2080±1554 cpm) than those who remained tTGA positive throughout follow‐up (3688±1435 cpm).

Conclusions:

The high sensitivity of RBA is likely responsible for higher tTGA positivity rates during GFD than previously reported with ELISA. A decreasing trend for tTGA levels may represent a better surrogate marker of compliance with GFD than absolute normal tTGA levels.
MYO5B Mutations in Patients With Microvillus Inclusion Disease Presenting With Transient Renal Fanconi Syndrome
Authors: Golachowska Magdalena R. , van Dael Carin M.L. , Keuning Hilda , Karrenbeld Arend , Hoekstra Dick , Gijsbers Carolien F.M. , Benninga Marc A. , Rings Edmond H.H.M. , van IJzendoorn Sven C.D.
Published: October 2011

Background and Objective:

Microvillus inclusion disease (MVID) is a rare congenital enteropathy associated with brush border atrophy and reduced expression of enzymes at the enterocytes' apical surface. MVID is associated with mutations in the MYO5B gene, which is expressed in all epithelial tissues. Whether organs other than the intestine are affected in MVID is unclear. We report 2 patients with MVID that developed renal Fanconi syndrome while receiving total parenteral nutrition. Renal Fanconi syndrome has been correlated to apical plasma membrane defects in kidney proximal tubular epithelial cells. The aim of the present study was to determine whether MYO5B mutations in these patients correlate with similar apical plasma membrane defects in renal tubular epithelial cells as observed in the intestine.

Methods:

Biopsies from kidney, duodenum, ileum, jejunum, and colon of 2 patients with MVID carrying MYO5B mutations and of age‐matched controls were fixed in paraffin and analyzed with immunohistochemistry and transmission electron microscopy.

Results:

Structural defects of the brush border and apical recycling endosome organization are observed in enterocytes of all of the segments of the small intestine and colon. MYO5B mutations in patients with MVID with renal Fanconi syndrome do not correlate with aberrant apical plasma membrane morphology or altered apical recycling endosome organization in renal tubular epithelial cells.

Conclusions:

MYO5B mutations have divergent effects on the apical membrane system in kidney and intestinal epithelial cells. Epithelial defects presented in MVID are therefore likely triggered by intestine‐specific factors, the identification of which may provide new targets and open avenues for the development of alternative therapeutic strategies to combat this devastating disease.
New Prebiotic Blend of Polydextrose and Galacto‐oligosaccharides Has a Bifidogenic Effect in Young Infants
Authors: Scalabrin Deolinda M.F. , Mitmesser Susan H. , Welling Gjalt W. , Harris Cheryl L. , Marunycz John D. , Walker D. Carey , Bos Nico A. , Tölkkö Satu , Salminen Seppo , Vanderhoof Jon A.
Published: October 2011

Objective:

The aim of the study was to evaluate the effect of infant formula with polydextrose (PDX) and galacto‐oligosaccharides (GOS) on fecal microbiota and secretory IgA (sIgA).

Materials and Methods:

In the present double‐blind, randomized study, term infants received control (Enfamil Lipil) or the same formula with PDX/GOS (4 g/L, 1:1 ratio; PDX/GOS) for 60 days; a reference breast‐fed group was included. Formula intake, tolerance, and stool characteristics were collected via electronic diary and analyzed by repeated measures analysis of variance. Anthropometric measurements and stool samples were obtained at baseline and after 30 and 60 days of feeding. Fecal sIgA was measured by enzyme‐linked immunosorbent assay and fecal bacteria by fluorescent in situ hybridization and quantitative real‐time polymerase chain reaction (qPCR); both were analyzed by Wilcoxon rank sum test.

Results:

Two hundred thirty infants completed the study. Infants consuming PDX/GOS had softer stools than control at all times (P < 0.001). Using qPCR, counts in PDX/GOS were closer to the breast‐fed group, tended to be higher than control for total bifidobacteria (P = 0.069) and Bifidobacterium longum (P = 0.057) at 30 days, and were significantly higher for total bifidobacteria and B longum at 60 days and B infantis at 30 days (P = 0.002). No significant differences were detected between PDX/GOS and control in changes from baseline to 30 or 60 days for sIgA or total bifidobacteria by fluorescent in situ hybridization or qPCR; however, significantly higher changes from baseline were detected between PDX/GOS and control for B infantis at 30 days and B longum at 60 days (P ≤ 0.035).

Conclusions:

Infant formula with PDX/GOS produces soft stools and a bifidogenic effect closer to breast milk than formula without PDX/GOS.
Changes in Inflammation and QoL After a Single Dose of Infliximab During Ongoing IBD Treatment
Authors: DeBoer Mark D. , Barnes Barrett H. , Stygles Nicholas A. , Sutphen James L. , Borowitz Stephen M.
Published: October 2011

Background and Objectives:

Infliximab is used increasingly as maintenance therapy for inflammatory bowel disease (IBD); however, the effects of a single maintenance dose of infliximab are unclear with respect to the quality of life and hormones related to growth and puberty. The aim of the present study was to determine the time course of inflammatory, hormonal, and quality‐of‐life changes following a single dose of infliximab in the context of ongoing therapy, as related to presence of IBD symptoms at time of administration.

Methods:

Children and adolescents with IBD receiving ongoing therapy with infliximab for clinical indications were recruited. The Pediatric Crohn's Disease Activity Index was determined at baseline and laboratory measures of high‐sensitivity C‐reactive protein (hsCRP) and hormones of growth and puberty were determined on days 0, 2, and 14. IBD‐related quality of life (IMPACT III questionnaire) was tested on days 0 and 14. Subjects who had symptoms of IBD were compared with asymptomatic subjects.

Results:

Subjects overall and in the symptomatic group exhibited improved hsCRP by day 2 following treatment. Symptomatic subjects had higher Pediatric Crohn's Disease Activity Index scores and lower quality‐of‐life scores than asymptomatic subjects on day 0, whereas at day 14 there were no significant differences in quality‐of‐life scores between the 2 groups.

Conclusions:

Even in the context of ongoing treatment, a single dose of infliximab results in decreased hsCRP, an improvement that is particularly noted among subjects who are symptomatic at the time of treatment. Although randomized trials are needed, these observational data may assist clinicians, patients, and families regarding expectations about timing and extent of these changes following a single treatment dose.
Neural circuitry and plasticity mechanisms underlying delay eyeblink conditioning
Authors: Freeman John H. , Steinmetz Adam B.
Published: October 2011

Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of parallel fiber synapses on Purkinje cells and long-term potentiation of mossy fiber synapses on neurons in the anterior interpositus nucleus. Conditioned stimulus and unconditioned stimulus inputs arise from the pontine nuclei and inferior olive, respectively, converging in the cerebellar cortex and deep nuclei. Projections from subcortical sensory nuclei to the pontine nuclei that are necessary for eyeblink conditioning are beginning to be identified, and recent studies indicate that there are dynamic interactions between sensory thalamic nuclei and the cerebellum during eyeblink conditioning. Cerebellar output is projected to the magnocellular red nucleus and then to the motor nuclei that generate the blink response(s). Tremendous progress has been made toward determining the neural mechanisms of delay eyeblink conditioning but there are still significant gaps in our understanding of the necessary neural circuitry and plasticity mechanisms underlying cerebellar learning.
Disentangling ribbon worm relationships: multi‐locus analysis supports traditional classification of the phylum Nemertea
Authors: Andrade Sónia C. S. , Strand Malin , Schwartz Megan , Chen Haixia , Kajihara Hiroshi , von Döhren Jörn , Sun Shichun , Junoy Juan , Thiel Martin , Norenburg Jon L. , Turbeville James M. , Giribet Gonzalo , Sundberg Per
Published: October 2011

The phylogenetic relationships of selected members of the phylum Nemertea are explored by means of six markers amplified from the genomic DNA of freshly collected specimens (the nuclear 18S rRNA and 28S rRNA genes, histones H3 and H4, and the mitochondrial genes 16S rRNA and cytochrome c oxidase subunit I). These include all previous markers and regions used in earlier phylogenetic analyses of nemerteans, therefore acting as a scaffold to which one could pinpoint any previously published study. Our results, based on analyses of static and dynamic homology concepts under probabilistic and parsimony frameworks, agree in the non‐monophyly of Palaeonemertea and in the monophyly of Heteronemerta and Hoplonemertea. The position of Hubrechtella and the Pilidiophora hypothesis are, however, sensitive to analytical method, as is the monophyly of the non‐hubrechtiid palaeonemerteans. Our results are, however, consistent with the main division of Hoplonemertea into Polystilifera and Monostilifera, the last named being divided into Cratenemertea and Distromatonemertea, as well as into the main division of Heteronemertea into Baseodiscus and the remaining species. The study also continues to highlight the deficient taxonomy at the family and generic level within Nemertea and sheds light on the areas of the tree that require further refinement.

© The Willi Hennig Society 2011.
Complications associated with peripheral or central routes for central venous cannulation
Authors: Pikwer A. , Åkeson J. , Lindgren S.
Published: October 2011

We undertook a review of studies comparing complications of centrally or peripherally inserted central venous catheters. Twelve studies were included. Catheter tip malpositioning (9.3% vs 3.4%, p = 0.0007), thrombophlebitis (78 vs 7.5 per 10 000 indwelling days, p = 0.0001) and catheter dysfunction (78 vs 14 per 10 000 indwelling days, p = 0.04) were more common with peripherally inserted catheters than with central catheter placement, respectively. There was no difference in infection rates. We found that the risks of tip malpositioning, thrombophlebitis and catheter dysfunction favour clinical use of centrally placed catheters instead of peripherally inserted central catheters, and that the two catheter types do not differ with respect to catheter‐related infection rates.
The influence of patient position on withdrawal force of thoracic epidural catheters*
Authors: Sim W. S. , Choi J. W. , Lee C. J. , Nahm F. S. , Lee S. H. , Shin B. S. , Cho H. S.
Published: October 2011

We investigated the forces required to remove thoracic epidural catheters to determine the effect of patient position on removal. Eighty‐four patients undergoing open thoracotomy and thoracic patient‐controlled epidural analgesia were enrolled. Catheterisation was performed under fluoroscopic guidance before surgery, and the patients were allocated to one of three position groups for removal: prone; sitting; and lateral. On the third postoperative day, the peak tension during withdrawal in the assigned position was measured. No differences in mean (SD) forces were found between groups: prone 1.61 (0.39) N, supine 1.62 (0.61) N and lateral 1.36 (0.56) N (p = 0.140). The withdrawal forces required to remove thoracic epidural catheters were not affected by the position. Thus, the position for removal can be determined by patient’s choice and clinical judgement.
Twenty‐four‐hour profiles of plasma glucose, insulin, C‐peptide and free fatty acid in subjects with varying degrees of glucose tolerance following short‐term, medium‐dose prednisone (20 mg/day) treatment: evidence for differing effects on insulin secretion and action
Authors: Yuen Kevin C. J. , McDaniel Patricia A. , Riddle Matthew C.
Published: October 2011

Objective  To determine the time course and prandial effects of short‐term, medium‐dose prednisone on 24‐h metabolic patterns under standardized conditions.

Context  Glucocorticoids (GCs) adversely affect glucose homoeostasis but 24‐h profiles of glucose, insulin, C‐peptide and free fatty acids (FFAs) following short‐term, medium‐dose prednisone treatment in persons with varying degrees of glucose tolerance are not well defined.

Design  An open‐label cross‐sectional interventional study.

Subjects  Three groups were prospectively studied: persons with type 2 diabetes (T2DM; n = 7), persons ‘at risk’ for T2DM (AR; n = 8) and persons with normal glucose tolerance (NGT; n = 5).

Methods  Before and after 3‐day treatment with prednisone 20 mg each morning, subjects underwent 24‐h frequent blood sampling. Eucaloric mixed meals were provided at 08:00, 12:00 and 18:00 h. Insulin/glucose ratio provided an estimate of β‐cell response to meal stimuli.

Measurements  Plasma glucose, insulin, C‐peptide, haemoglobin A1c and FFA.

Results  Prednisone induced greater increases in glucose levels from midday (P = 0·001) to midnight (P = 0·02) in the T2DM than the AR and NGT groups. In contrast, insulin (P = 0·03) and C‐peptide (P = 0·04) levels decreased postbreakfast in the T2DM group, whereas no changes in the morning but higher C‐peptide levels (P = 0·03) from midday to midnight were observed in the AR group. In the T2DM group, insulin/glucose ratio decreased postbreakfast (P = 0·04) and increased postdinner (P = 0·03). Fasting glucose, insulin and C‐peptide levels were unchanged in all groups, and FFA levels modestly increased postdinner (P = 0·03) in the NGT group.

Conclusion  Short‐term, medium‐dose prednisone treatment induces postprandial hyperglycaemia in T2DM and AR predominantly from midday to midnight because of suppression of insulin secretion followed by decreased insulin action that dissipates overnight. Effective treatment of prednisone‐induced hyperglycaemia should target both rapid onset relative insulin deficiency and a less than 24‐h total duration of effect.