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1.
Biol Psychol ; 173: 108398, 2022 09.
Article in English | MEDLINE | ID: mdl-35907511

ABSTRACT

An important, yet under-explored area of interpretation bias research concerns the examination of potential physiological correlates and sequalae of this bias. Developing a better understanding of the physiological processes that underpin interpretation biases will extend current theoretical frameworks underlying interpretation bias, as well as optimise the efficacy of cognitive bias modification for interpretation (CBM-I) interventions aimed at improving symptoms of emotional disorders. To this end, systematic searches were conducted across the Web of Science, PsycInfo and Pubmed databases to identify physiological markers of interpretation bias. In addition, grey literature database searches were conducted to compliment peer-reviewed research and to counter publication bias. From a combined initial total of 898 records, 15 studies were included in qualitative synthesis (one of which was obtained from the grey literature). Eligible studies were assessed using a quality assessment tool adapted from the Quality Checklist for Healthcare Intervention Studies. The searches revealed seven psychophysiological correlates of interpretation bias, namely event-related potentials, heart rate and heart rate variability, respiratory sinus arrythmia, skin conductance response, pupillometry, and electromyography. The respective theoretical and practical implications of the research are discussed, followed by recommendations for future research.


Subject(s)
Bias , Humans
2.
Cognition ; 208: 104546, 2021 03.
Article in English | MEDLINE | ID: mdl-33360281

ABSTRACT

Instrumental conditioning is a crucial substrate of adaptive behaviour, allowing individuals to selectively interact with the stimuli in their environment to maximise benefit and minimise harm. The extent to which complex forms of learning, such as instrumental conditioning, are possible without conscious awareness is a topic of considerable importance and ongoing debate. In light of recent theoretical and empirical contributions casting doubt on the early demonstrations of unconscious instrumental conditioning, we revisit the question of its feasibility in two modes of conditioning. In Experiment 1, we used trace conditioning, following a prominent paradigm (Pessiglione et al., 2008) and enhancing its sensitivity. Success in this task requires participants to learn to approach reward-predictive stimuli and avoid punishment-predictive stimuli through monetary reinforcement. All stimuli were rendered unconscious using forward-backward masking. In Experiment 2, we used delay conditioning to shorten the stimulus-outcome delay, retaining the structure of the original task but presenting the stimuli under continuous flash suppression to allow for an overlap of the stimulus, action, and outcome, as well as replacing monetary reinforcement with primary appetitive reinforcement. In both experiments, we found evidence for absence of unconscious instrumental conditioning, showing that participants were unable to learn to adjust their behaviour to approach positive stimuli and avoid negative ones. This result is consistent with evidence that unconscious stimuli fail to bring about long-term behavioural adaptations, and provides empirical evidence to support theoretical proposals that consciousness might be necessary for adaptive behaviour, where selective action is required.


Subject(s)
Conditioning, Operant , Consciousness , Awareness , Humans , Learning , Reinforcement, Psychology , Reward
3.
Nat Commun ; 11(1): 4853, 2020 09 25.
Article in English | MEDLINE | ID: mdl-32978377

ABSTRACT

In hypnotic responding, expectancies arising from imaginative suggestion drive striking experiential changes (e.g., hallucinations) - which are experienced as involuntary - according to a normally distributed and stable trait ability (hypnotisability). Such experiences can be triggered by implicit suggestion and occur outside the hypnotic context. In large sample studies (of 156, 404 and 353 participants), we report substantial relationships between hypnotisability and experimental measures of experiential change in mirror-sensory synaesthesia and the rubber hand illusion comparable to relationships between hypnotisability and individual hypnosis scale items. The control of phenomenology to meet expectancies arising from perceived task requirements can account for experiential change in psychological experiments.


Subject(s)
Hand , Hypnosis/methods , Illusions/physiology , Pain Management/methods , Synesthesia/therapy , Adolescent , Adult , Female , Humans , Imagination , Male , Middle Aged , Pain , Suggestion , Young Adult
4.
Psychol Res ; 84(5): 1460-1471, 2020 Jul.
Article in English | MEDLINE | ID: mdl-30834966

ABSTRACT

Hypnosis and hypnotic suggestions are gradually gaining popularity within the consciousness community as established tools for the experimental manipulation of illusions of involuntariness, hallucinations and delusions. However, hypnosis is still far from being a widespread instrument; a crucial hindrance to taking it up is the amount of time needed to invest in identifying people high and low in responsiveness to suggestion. In this study, we introduced an online assessment of hypnotic response and estimated the extent to which the scores and psychometric properties of an online screening differ from an offline one. We propose that the online screening of hypnotic response is viable as it reduces the level of responsiveness only by a slight extent. The application of online screening may prompt researchers to run large-scale studies with more heterogeneous samples, which would help researchers to overcome some of the issues underlying the current replication crisis in psychology.


Subject(s)
Hypnosis , Suggestion , Female , Humans , Internet , Male
5.
Clin Transl Sci ; 10(1): 35-41, 2017 01.
Article in English | MEDLINE | ID: mdl-27863029

ABSTRACT

Anastomotic leaks are a serious complication associated with Ivor Lewis esophagectomies. Endoluminal negative pressure vacuum devices create a possible treatment alternative to conventional surgical intervention. Ten pigs had an intrathoracic esophageal anastomosis with a 1-cm defect. The experimental group had the device placed intraoperatively across the defect, whereas the control group did not. Once treatment was completed, a contrast fluoroscopic study and necropsy was performed. All control pigs had contrast extravasation on fluoroscopy and contamination on necropsy. The experimental group had no radiologic leak and no contamination on necropsy. The P value for leak is 0.03. This study demonstrated that endoluminal negative pressure vacuum therapy is tolerated in the swine model and is successful in facilitating the healing of anastomotic leaks. Endoluminal negative pressure vacuum therapy has potential clinical benefits, including decreased morbidity and length of hospital stay.


Subject(s)
Anastomotic Leak/therapy , Vacuum , Animals , Disease Models, Animal , Esophagus/diagnostic imaging , Esophagus/pathology , Fluoroscopy , Pilot Projects , Swine
6.
Eur J Neurol ; 10(3): 239-47, 2003 May.
Article in English | MEDLINE | ID: mdl-12752397

ABSTRACT

In the current era of functional surgery for movement disorders, deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favoured intervention for patients with dystonia. Here we report our results in 20 patients with medically intractable dystonia treated with GPi stimulation. The series comprised 14 patients with generalized dystonia and six with spasmodic torticollis. Although comparisons were limited by differences in their respective neurological rating scales, chronic DBS clearly benefited both patient groups. Data conveying the rate of change in neurological function following intervention are also presented, demonstrating the gradual but progressive and sustained nature of improvement following stimulation of the GPi in dystonic patients.


Subject(s)
Dystonia/surgery , Electric Stimulation Therapy/methods , Globus Pallidus/surgery , Postoperative Care , Torticollis/surgery , Adult , Aged , Child , Chronic Disease , Disability Evaluation , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neurologic Examination , Neurosurgical Procedures/methods , Regression, Psychology , Severity of Illness Index , Time Factors , Treatment Outcome
7.
Dev Med Child Neurol ; 43(10): 685-91, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11665825

ABSTRACT

The aim of this preliminary study was to examine the developing cognitive profiles of children with cerebellar tumours in a consecutive series of clinical patients. MRI and longitudinal intellectual profiles were obtained on seven children (two females, five males; mean age 3 years at diagnosis; mean age 7 years at first assessment). Tumours in three of the children were astrocytomas; of the remaining tumours, two were medulloblastomas, one low-grade glioma, and one ependymoma. In right-handed children, we observed an association between greater damage to right cerebellar structures and a plateauing in verbal and/or literacy skills. In contrast, greater damage to left cerebellar structures was associated with delayed or impaired non-verbal/spatial skills. Long-term cognitive development of the children studied tentatively supports a role for the cerebellum in learning/development. These findings suggest that lateralized cerebellar damage may selectively impair the development of cognitive functions subserved by the contralateral cerebral hemisphere and, in addition, that all children with cerebellar lesions in early childhood should routinely undergo long-term monitoring of their intellectual development.


Subject(s)
Cerebellar Neoplasms/complications , Cerebellar Neoplasms/physiopathology , Cognition Disorders/etiology , Cognition Disorders/physiopathology , Functional Laterality/physiology , Glioma/complications , Glioma/physiopathology , Cerebellar Neoplasms/pathology , Cerebellum/pathology , Cerebellum/physiopathology , Child , Child Development/physiology , Child, Preschool , Cognition Disorders/pathology , Dyslexia/etiology , Dyslexia/pathology , Dyslexia/physiopathology , Female , Glioma/pathology , Humans , Intelligence Tests , Male , Memory Disorders/etiology , Memory Disorders/pathology , Memory Disorders/physiopathology , Neuronal Plasticity/physiology , Neuropsychological Tests , Speech Disorders/etiology , Speech Disorders/pathology , Speech Disorders/physiopathology
8.
Am J Gastroenterol ; 96(1): 120-5, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11197240

ABSTRACT

OBJECTIVE: Celiac disease (CD) is a relatively common gastrointestinal disorder that can be asymptomatic. However, even among asymptomatic patients a long-term reduction in bone mineral density (BMD) is found. Excellent noninvasive screening tests for CD are now available. Studies using older screening techniques have suggested a 10-fold increased prevalence of CD among patients with low BMD, but this has not been confirmed with current testing methodology. We set out to confirm these prevalence estimates using antiendomysial antibody testing. METHODS: A total of 100 consecutive patients referred to our outpatient endocrinology clinic for evaluation of idiopathic low BMD were studied. In addition to the routine evaluation, patients completed a symptom questionnaire and underwent serological testing for the presence of the IgA antiendomysial antibody (EMA). All patients with a positive EMA underwent small bowel biopsy and permeability studies. RESULTS: EMA results were available on 96 patients; 78/96 patients were female and the mean age was 57 yr (range 18-86 yr). Seven of 96 (7.3% [95% CI 2.1-12.5%]) were EMA-positive, but all tests were low titer (< or = 1:20). However, none of the biopsies showed any histopathological features of CD, nor did EMA status correlate with any of the clinical or laboratory features assessed. CONCLUSIONS: Despite a high rate of weakly positive antibody tests, our data do not support an increased prevalence of CD among asymptomatic patients referred for evaluation of low BMD. Without an increase over the background prevalence, the high cost of EMA testing argues against routine use of this test for screening of this population.


Subject(s)
Antibodies, Antinuclear/analysis , Celiac Disease/diagnosis , Celiac Disease/epidemiology , Immunoglobulin A/analysis , Osteoporosis/diagnosis , Osteoporosis/epidemiology , Absorptiometry, Photon/methods , Adult , Aged , Biomarkers/analysis , Bone Density/immunology , Celiac Disease/immunology , Comorbidity , Confidence Intervals , Female , Fluorescent Antibody Technique , Humans , Male , Middle Aged , Osteoporosis/immunology , Prevalence , Probability , Prospective Studies , Sensitivity and Specificity , Severity of Illness Index , Statistics, Nonparametric
9.
Can J Gastroenterol ; 15(1): 61-4, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11173328

ABSTRACT

A newborn male presented with watery diarrhea, dehydration and metabolic acidosis. Severe secretory diarrhea of variable magnitude persisted when the patient was on parenteral nutrition with no oral intake. Initial light microscopic evaluation of a small intestinal mucosal biopsy showed partial villous atrophy and crypt hypoplasia. Ultrastructural studies of the villous enterocyte revealed internalized inclusions of microvilli, typical of microvillous inclusion disease. Presented are a case report and a discussion of the differential diagnosis of watery diarrhea in the neonate, as well as a short review of microvillous inclusion disease.


Subject(s)
Diarrhea, Infantile/etiology , Intestinal Diseases/complications , Intestinal Diseases/diagnosis , Diagnosis, Differential , Failure to Thrive/etiology , Fatal Outcome , Humans , Infant, Newborn , Intestinal Diseases/pathology , Jejunum/ultrastructure , Male , Microvilli
10.
Hear Res ; 151(1-2): 71-78, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11124453

ABSTRACT

Carboplatin, a platinum-containing anticancer drug, is currently being used against a variety of cancers. However, a single high dose of carboplatin is ototoxic in cancer patients. This is the first study to show carboplatin-induced hearing loss in a rat model. Male Wistar rats were divided into five groups and treated as follows: (1) control (saline, intraperitoneally (i.p.)); (2) carboplatin (64 mg/kg, i.p.); (3) carboplatin (128 mg/kg i.p.); (4) carboplatin (192 mg/kg, i.p.) and (5) carboplatin (256 mg/kg, i.p.). Animals in all groups were sedated with ketamine/xylazine and auditory brain-evoked responses (ABRs) were recorded before and 4 days after treatments. The animals were sacrificed on the fourth day and cochleae were harvested and analyzed. Carboplatin dose-dependently decreased body weight. However, at higher doses of carboplatin (192 and 256 mg/kg), there was a significant elevation of hearing threshold shifts at clicks, 4, 8, 16 and 32 kHz tone burst stimuli. The higher doses of carboplatin (192 and 256 mg/kg) significantly increased cochlear lipid peroxidation (132 and 146% of control) and depleted cochlear glutathione levels (66 and 63% of control), respectively. The antioxidant enzyme activities such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase (GST) depressed significantly at higher doses of carboplatin. The data suggest that higher doses of carboplatin (above 128 mg/kg) induce hearing loss as evidenced by significant changes in ABRs, lipid peroxidation and antioxidants in the cochlea of rats.


Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/toxicity , Antioxidants/metabolism , Carboplatin/administration & dosage , Carboplatin/toxicity , Deafness/chemically induced , Animals , Auditory Threshold/drug effects , Catalase/antagonists & inhibitors , Cochlea/drug effects , Cochlea/metabolism , Cochlea/physiopathology , Deafness/metabolism , Deafness/physiopathology , Dose-Response Relationship, Drug , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/toxicity , Evoked Potentials, Auditory, Brain Stem/drug effects , Glutathione/metabolism , Glutathione Peroxidase/antagonists & inhibitors , Glutathione Reductase/antagonists & inhibitors , Glutathione Transferase/antagonists & inhibitors , Humans , Lipid Peroxidation/drug effects , Male , Malondialdehyde/metabolism , Rats , Rats, Wistar , Superoxide Dismutase/antagonists & inhibitors
11.
Stereotact Funct Neurosurg ; 77(1-4): 87-90, 2001.
Article in English | MEDLINE | ID: mdl-12378062

ABSTRACT

The small size and surrounding neuronal structures and fibre tracts make the STN a difficult stereotactic target. In this article we present the technique used by us to target the STN. Our combined experience from two centres comprises 18 lesions and 27 stimulator implants in the STN. Our criteria for patient selection and the use of MRI, frame-on CT and volumetric image fusion are presented. The role of a movement disorder specialist neurologist in the operating theatre, local field potential recording, impedance monitoring, macrostimulation, post-operative CT/MRI and test stimulation are detailed.


Subject(s)
Electric Stimulation Therapy/methods , Electrocoagulation/methods , Parkinson Disease/therapy , Stereotaxic Techniques , Subthalamic Nucleus , Electric Stimulation Therapy/instrumentation , Electrocoagulation/instrumentation , Electrodes, Implanted , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Monitoring, Intraoperative , Parkinson Disease/surgery , Recurrence , Retrospective Studies , Subthalamic Nucleus/physiopathology , Subthalamic Nucleus/surgery , Tomography, X-Ray Computed , Treatment Outcome
12.
Am J Physiol Gastrointest Liver Physiol ; 279(5): G990-7, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11052996

ABSTRACT

This study was to determine whether alterations in jejunal motility observed after antigen challenge of sensitized rats occurred after extirpation of the celiac-superior mesenteric ganglia. Hooded-Lister rats were prepared with an intact or extirpated celiac-superior mesenteric ganglion, an isolated Thiry-Vella loop of ileum for instillation of antigen, and jejunal electrodes for myoelectric recording. Animals were sensitized by injection of 10 microg egg albumin (EA, ip), and specific anti-EA IgE titers were determined to be >1:64. In both control and splanchnectomized rats, normal fasting migrating myoelectric complexes (MMC) were observed before challenge with EA. MMCs were disrupted, and diarrhea was observed immediately after EA challenge of control but not splanchnectomized animals. Brain stems were removed and processed for Fos immunoreactivity. The absence of perivascular neuropeptide Y immunoreactivity in the submucosa was used to confirm the success of splanchnectomy. The number of Fos-immunoreactive neuronal nuclei was significantly reduced in the brain stem after splanchnectomy. Thus the mesenteric sympathetic ganglia are an integral part of the extramural neuronal pathways required for altered motility in this model of intestinal anaphylaxis.


Subject(s)
Anaphylaxis/physiopathology , Gastrointestinal Motility/immunology , Jejunum/physiology , Proto-Oncogene Proteins c-fos/biosynthesis , Solitary Nucleus/metabolism , Splanchnic Nerves/surgery , Animals , Disease Models, Animal , Immunoglobulin E/immunology , Jejunum/innervation , Mast Cells/immunology , Motor Neurons/physiology , Proto-Oncogene Proteins c-fos/analysis , Rats , Rats, Inbred Strains , Solitary Nucleus/chemistry , Splanchnic Nerves/cytology , Splanchnic Nerves/immunology , Sympathectomy
13.
Can J Gastroenterol ; 13(4): 319-24, 1999 May.
Article in English | MEDLINE | ID: mdl-10360992

ABSTRACT

Previous studies have demonstrated that the longitudinal smooth muscle of rabbits infected with Yersinia enterocolitica and undernourished because of reduced food intake exhibit a significantly reduced ability to develop tension in response to carbachol compared with pair-fed animals, which are uninfected but equivalently undernourished. To determine whether the alteration in smooth muscle contractility results from changes in cell number (hypo- or hyperplasia), or in contractile protein content or isoform distribution, New Zealand White rabbits (600 to 1000 g) were randomly assigned to one of three treatment groups: infected, pair-fed or control. Tissue contractility was measured, morphometric studies were performed and immunoassays were developed for the measurement of total actin, gamma-enteric and alpha-vascular isoactins, and myosin heavy chain. Consistent with what was found in previous reports, the contractility of longitudinal smooth muscle in response to carbachol was found to increase in pair-fed animals and to decrease in Y enterocolitica-infected animals. There was no significant change in the proportional thickness of the ileal longitudinal smooth muscle coat, and the number of cross-sectioned longitudinal smooth muscle cells/mm2 was not significantly different in infected, pair-fed or control tissues. Immunoassay indicated that the proportion of each specific contractile protein, relative to total protein content in the muscularis propria, was unaffected by Y enterocolitica infection or by pair-feeding. Thus, the alterations in intestinal longitudinal smooth muscle function observed after Y enterocolitica infection were concluded not to be associated with tissue hypo- or hyperplasia, or changes in the total content or isoform distribution of contractile proteins in the muscularis propria.


Subject(s)
Enterocolitis/physiopathology , Muscle Proteins/metabolism , Muscle, Smooth/physiology , Yersinia Infections/physiopathology , Yersinia enterocolitica , Analysis of Variance , Animals , Disease Models, Animal , Enterocolitis/microbiology , Enterocolitis/pathology , Gastrointestinal Motility/physiology , Ileum/physiology , Muscle Contraction/physiology , Muscle Proteins/analysis , Muscle, Smooth/metabolism , Nutritional Status , Rabbits , Radioimmunoassay , Random Allocation , Reference Values , Yersinia Infections/pathology
14.
Can J Gastroenterol ; 13(1): 31-6, 1999.
Article in English | MEDLINE | ID: mdl-10099814

ABSTRACT

BACKGROUND: Members of a subset of first-degree relatives of adults with Crohn's disease have been shown to have an increased baseline intestinal permeability and/or an exaggerated increase in intestinal permeability after the administration of acetylsalicylic acid. PURPOSE: To determine intestinal permeability in unaffected first-degree relatives of children with Crohn's disease before and after the administration of an ibuprofen challenge. METHODS: Lactulose-mannitol ratios, a measure of intestinal permeability, were determined in 14 healthy control families (41 subjects) and 14 families with a child with Crohn's disease (36 relatives, 14 probands) before and after ingestion of ibuprofen. An upper reference limit was defined using the control group as mean +/- 2 SD. RESULTS: The proportion of healthy, first-degree relatives with an exaggerated response to ibuprofen (20%, 95% CI 7% to 33%) was significantly higher than controls (P = 0.003). The exaggerated response was more common among siblings than among parents of pediatric probands. CONCLUSIONS: Members of a subset of first-degree relatives of children with Crohn's disease have an exaggerated increase in intestinal permeability after ibuprofen ingestion. These findings are compatible with there being a genetic link between abnormalities of intestinal permeability and Crohn's disease.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Crohn Disease/genetics , Ibuprofen/pharmacology , Intestinal Absorption/drug effects , Adolescent , Adult , Crohn Disease/physiopathology , Female , Humans , Intestinal Absorption/genetics , Lactulose , Male , Mannitol , Permeability
15.
Neurotoxicology ; 20(6): 977-87, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10693979

ABSTRACT

This study investigated the response of the antioxidant defense system in brain subcellular fractions after oral graded doses of ethanol to rat. Four groups of male Fischer-344 rats were orally administered saline, ethanol 2 g, 4 g, and 6 g/kg, respectively, and sacrificed 1 hour post treatment. Brain cytosol, synaptosomes, microsomes and mitochondria were separated by density gradient differential centrifugation and assayed for antioxidant system. A significant and dose-dependent-decrease in superoxide dismutase (SOD) activity was observed in all brain subcellular fractions. Catalase (CAT) activity was significantly decreased in brain mitochondria (67% and 80% of control) at higher doses of ethanol; whereas, CAT activity was significantly increased in cytosol, synaptosomes and microsomes. Glutathione peroxidase (GSH-Px) activity was significantly increased in all brain subcellular fractions except in cytosol at higher dose of ethanol. Malondialdehyde (MDA) content was significantly increased in all brain subcellular fractions showing dose response of ethanol-induced oxidative stress. The increase in MDA levels in the brain synaptosomes and microsomes were higher at 6 g dose of ethanol (155% and 163% of control) when compared to mitochondria and cytosol. Glutathione (GSH) levels were significantly increased in brain cytosol and microsomes at higher dose of ethanol (164% and 159% of control); whereas, the GSH concentration was significantly decreased in brain synaptosomes and mitochondria. The antioxidant enzyme (AOE) activity ratios (GSH-Px/SOD and GSH-Px + CAT/SOD) were dose dependently increased in all brain subcellular fractions, particularly in synaptosomes. The GSH/GSSG ratio was dose dependently increased in brain microsomes. The perturbations in the antioxidant defense system and enhanced lipid peroxidation following graded doses of ethanol ingestion indicate a dose-dependent-oxidative 2133stress response in brain subcellular compartments of rats.


Subject(s)
Brain/drug effects , Ethanol/toxicity , Glutathione/metabolism , Lipid Peroxidation/drug effects , Malondialdehyde/metabolism , Animals , Brain/enzymology , Brain/ultrastructure , Catalase/metabolism , Cytosol/enzymology , Dose-Response Relationship, Drug , Glutathione Peroxidase/metabolism , Male , Microsomes/enzymology , Mitochondria/enzymology , Random Allocation , Rats , Rats, Inbred F344 , Superoxide Dismutase/metabolism , Synaptosomes/enzymology
16.
J Neurol Sci ; 160(2): 148-57, 1998 Oct 08.
Article in English | MEDLINE | ID: mdl-9849797

ABSTRACT

Duchenne muscular dystrophy (DMD) is a progressive muscle disorder associated with an intellectual deficit which is non-progressive. We obtained localised 1H magnetic resonance spectra from the left frontal lobe and left cerebellum of 15 boys with DMD (mean age 106 months+/-32) and 15 similarly aged control boys (mean age 115 months+/-31); all boys underwent a battery of neuropsychological tests. We found a significant (P<0.01) increase in the ratio of choline-containing compounds to N-acetylaspartate (Cho/NA) in the left cerebellum in boys with DMD compared with control boys. There was no change in the creatine/NA ratio and a significant increase (P=0.03) in the Cho/creatine ratio, suggesting that the change in Cho/NA ratio was due to an increase in choline-containing compounds; this increase has been previously observed in the brain of the murine model of DMD, the mdx mouse. No significant changes were observed in spectra obtained from left frontal lobe in DMD compared to controls. We also observed a significant association between Cho/NA in the left cerebellum, and the performance of DMD boys on the Matrix Analogies Test (MAT). The MAT is a test of visuo-spatial ability and non-verbal reasoning which requires neither manual dexterity nor a verbal response for an adequate performance. A comparison of DMD boys whose cerebellar Cho/NA fell within 2 standard deviations of the control norm (0.56+/-0.24) with DMD boys whose cerebellar Cho/NA was outside this range (i.e. >0.80) revealed a significant difference in ability on the MAT (P<0.05). DMD boys whose Cho/NA ratio is more than two standard deviations higher than controls perform significantly better on the MAT than DMD boys whose Cho/NA ratio is within the normal range. This finding suggests that the observed elevation in Cho/NA and Cho/creatine is not associated with intellectual deficit (as sampled by the MAT), and may represent a compensatory mechanism. The possible interpretations of these metabolic changes are discussed.


Subject(s)
Brain/metabolism , Cerebellum/metabolism , Muscular Dystrophies/metabolism , Muscular Dystrophies/psychology , Age Factors , Aspartic Acid/analogs & derivatives , Aspartic Acid/metabolism , Child , Choline/metabolism , Cognition , Creatine/metabolism , Humans , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Male , Neuropsychological Tests
17.
Am J Physiol ; 275(5): G911-21, 1998 11.
Article in English | MEDLINE | ID: mdl-9815019

ABSTRACT

To determine whether treatment with a potent protease-resistant analog of human glucagon-like peptide 2 (GLP-2) might augment the adaptive response to massive intestinal resection, rats were divided into resected, which had 75% of the midjejunoileum removed, sham-resected, and nonsurgical groups. Within each group, animals were assigned to 21 days of treatment with the drug (0.1 micrograms/g of the GLP-2 analog in phosphate-buffered saline) or vehicle alone subcutaneously twice daily. Food intake; weight gain; jejunal and ileal diameters, total and mucosal wet weights per centimeter, crypt depths, and villus heights; mucosal sucrase activity, milligrams of protein per centimeter, and micrograms of DNA per centimeter; and D-xylose absorption were measured. There was a significant increase in diameter, total and mucosal wet weights per centimeter, crypt-villus height, sucrase activity, milligrams of protein per centimeter and micrograms of DNA per centimeter in both the jejunum and ileum in response to resection and a significant additive response to the GLP-2 analog in the jejunum but not in the ileum. The ratio of milligrams of protein per centimeter to micrograms of DNA per centimeter of mucosa was not different among groups, consistent with hyperplasia. D-Xylose absorption was significantly reduced in response to resection; however, the GLP-2 analog enhanced the absorptive capacity in control animals and restored the absorptive capacity in resected animals. Thus the GLP-2 analog induces mucosal hyperplasia and enhances the rate and magnitude of the proximal intestinal adaptive response to massive resection.


Subject(s)
Adaptation, Physiological/drug effects , Ileum/physiology , Ileum/surgery , Intestinal Mucosa/physiology , Jejunum/physiology , Jejunum/surgery , Peptides/pharmacology , Anastomosis, Surgical , Animals , Body Weight/drug effects , DNA/metabolism , Energy Intake , Gastrointestinal Hormones/pharmacology , Glucagon-Like Peptide 2 , Glucagon-Like Peptides , Humans , Intestinal Mucosa/drug effects , Intestinal Mucosa/surgery , Organ Size , Permeability , Proteins/metabolism , Rats , Rats, Sprague-Dawley , Sucrase/metabolism
18.
Gut ; 43(6): 817-22, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9824610

ABSTRACT

BACKGROUND: The ground squirrel on a high cholesterol diet exhibits prolonged intestinal transit, a pathogenetic factor in cholesterol gallstone formation. AIMS: To examine the effect of a high cholesterol diet on the characteristics of the migrating myoelectrical complex (MMC) and the potential benefit of erythromycin. METHODS: Twenty four animals received either a trace (controls) or a 1% (high) cholesterol diet. After four weeks, five bipolar jejunal and terminal ileal electrodes were implanted. Seven days later, myoelectric activity was measured in conscious, fasted animals before and after treatment with erythromycin. Biliary lipid composition was assessed. RESULTS: Compared with controls, animals fed the high cholesterol diet exhibited a prolonged MMC cycle period (70 (6) versus 83 (3) minutes; p<0.05), whereas MMC migration velocity and the proportions of the MMC represented by phases I, II, and III were unchanged. Oral erythromycin significantly shortened the MMC cycle period in animals on the control and high cholesterol diet by 59% and 54% respectively, and increased the proportion of the cycle period occupied by phase III of the MMC in both dietary groups. Gall bladder bile became saturated with cholesterol and crystals developed in nine of 12 animals on the high cholesterol diet; controls had none. CONCLUSION: Animals fed a high cholesterol diet had a prolonged MMC cycle period. This, along with diminished gall bladder motility, impairs the enterohepatic cycling of bile salts and reduces their hepatic secretion, contributing to the formation of abnormal bile. Erythromycin initiated more frequent cycling of the MMC. Its therapeutic value in cholesterol gallstone formation warrants further evaluation.


Subject(s)
Bile/chemistry , Cholelithiasis/chemistry , Cholesterol, Dietary/administration & dosage , Erythromycin/pharmacology , Gastrointestinal Agents/pharmacology , Intestines/physiology , Lipid Metabolism , Myoelectric Complex, Migrating/physiology , Animals , Cholelithiasis/etiology , Myoelectric Complex, Migrating/drug effects , Sciuridae
19.
Diabetes Care ; 21(11): 1985-9, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9802755

ABSTRACT

OBJECTIVE: Our objective was to determine if a serological marker, the immunoglobulin A antiendomysial antibody (IgA-EMA), can be used to screen for celiac disease in North American children with type 1 diabetes. RESEARCH DESIGN AND METHODS: Subjects included 236 diabetes clinic patients and 56 gastrointestinal clinic patients who underwent intestinal biopsy for suspected malabsorption. Total IgA and IgA-EMA assays were performed. Diabetic patients who were positive for IgA-EMA were asked to undergo biopsy. RESULTS: Of 236 diabetic patients tested, none were IgA deficient and 19 were positive for IgA-EMA (8%). Of 17 patients biopsied, 12 had celiac disease and 3 were symptomatic. The estimated prevalence of celiac disease was 5.1%, consistent with data from European diabetic clinics. Of the 56 gastrointestinal clinic patients, the 3 who were IgA-EMA positive had biopsies diagnostic of celiac disease. Three were found to be IgA deficient, one of whom had celiac disease. Of the 50 IgA-sufficient and IgA-EMA-negative patients, 1 had celiac disease and 49 did not. The IgA-EMA test had a sensitivity of 94% and a specificity of 91% for IgA-sufficient biopsied patients. CONCLUSIONS: IgA-EMA is an appropriate tool for demonstrating an increased prevalence of celiac disease in a North American pediatric diabetic population. Positive testing should be confirmed by intestinal biopsy, and false-positive results require serial follow-up. Symptomatic children require biopsy regardless of their IgA-EMA status.


Subject(s)
Antibodies, Anti-Idiotypic/analysis , Autoantibodies/analysis , Celiac Disease/complications , Celiac Disease/diagnosis , Diabetes Mellitus, Type 1/complications , Immunoglobulin A/immunology , Adolescent , Biomarkers , Biopsy , Celiac Disease/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Intestines/immunology , Intestines/pathology , Male , Mass Screening , North America/epidemiology , Prevalence , Prospective Studies
20.
Pediatrics ; 102(4 Pt 1): 951-5, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9755271

ABSTRACT

OBJECTIVE: This study was designed to determine the effect of home enteral nutrition on the outcomes of growth and the relationship between growth and entrance anthropometric criteria. METHODS: We reviewed the medical records of 78 consecutive children (median age, 20 months) who were enrolled in the home enteral feeding program at the Alberta Children's Hospital (Calgary, Alberta, Canada) between 1993 and 1995. Weights, heights, and weight-for-heights were expressed as Z scores, using the Centers for Disease Control and Prevention anthropometric growth curve software. To evaluate growth outcome, the total group was further subdivided using anthropometric criteria into appropriate, wasted, or stunted at the time of entry to the program. In a subgroup of 36 children on whom anthropometric data was available for a median length of 5.7 months, Z scores were compared at 3 points in time: before entry, at time of entry, and last follow-up. RESULTS: Patients were classified into five main groups: 11 (14%) had pulmonary disease, 26 (33%) had a gastrointestinal disorder, 21 (27%) had congenital defects, 10 (13%) had a neurologic disorder, and the remaining 10 (13%) had a variety of other illnesses, including malignancies and metabolic disorders. Patients were on the program for a median duration of 8.9 months. It was found that during the period of support within the program, enteral feeding was successful in improving weight-for-age Z scores by 0.42 standard deviations but the effect on height-for-age Z scores and weight-for-height Z scores did not reach significance for this population. The subgroup of 36 children on whom longitudinal anthropometric data was available before entering the program was found to have had a significant drop in weight Z scores between the time before program entry (median length of time, 5.7 months) and the time of program entry, which indicates that these children were falling off the growth curve before commencing enteral feeding. To evaluate growth outcome, the total group was further subdivided using anthropometric criteria into appropriate, wasted, or stunted at the time of entry to the program. In the group of appropriate growth patients, while in the program, 50% had catch-up growth for weight (positive change in Z scores) and 33% for height. In the wasted patients, 92% improved their weight percentile and 75% their height percentile. In the stunted group, 71% had catch-up growth for weight and 74% for height. CONCLUSION: We concluded that the enteral feeding program was able to promote catch-up growth or maintain growth along percentiles in the majority of children.


Subject(s)
Enteral Nutrition , Growth , Adolescent , Body Height , Body Weight , Child , Chronic Disease/therapy , Enteral Nutrition/adverse effects , Female , Humans , Infant , Infant, Newborn , Longitudinal Studies , Male , Nutritional Status , Weight Gain
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