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Biomedical subjects

R B Scott

Publications and source records attributed to R B Scott.

At least 19 recordsLinked to original sources
PubMed2003

Post-operative progress of dystonia patients following globus pallidus internus deep brain stimulation.

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.

Adult↗
PubMed2001

Dose response of carboplatin-induced hearing loss in rats: antioxidant defense system.

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.

Animals↗
PubMed2001

Lateralized cognitive deficits in children following cerebellar lesions.

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.

Cerebellar Neoplasms↗
PubMed2001

Prevalence of IgA-antiendomysial antibody in asymptomatic low bone mineral density.

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.

Absorptiometry, Photon↗
PubMed2001

Intractable diarrhea in a newborn infant: microvillous inclusion disease.

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.

Diagnosis, Differential↗
PubMed2001

Targeting the subthalamic nucleus.

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.

Electric Stimulation Therapy↗
PubMed2000

Effect of splanchnectomy on jejunal motility and fos expression in brain stem after intestinal anaphylaxis in rat.

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.

Anaphylaxis↗
PubMed1999

Undernournishment and Yersinia enterocolitica enterocolitis alter intestinal contractility in the rabbit: role of smooth muscle contractile protein content.

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.

Analysis of Variance↗
PubMed1999

Dose response of ethanol ingestion on antioxidant defense system in rat brain subcellular fractions.

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.

Animals↗
PubMed1998

Brain biochemistry in Duchenne muscular dystrophy: a 1H magnetic resonance and neuropsychological study.

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.

Age Factors↗
PubMed1998

Effect of the prokinetic agent, erythromycin, in the Richardson ground squirrel model of cholesterol gallstone disease.

Impaired gallbladder motility and delayed intestinal transit contribute to cholesterol gallstone formation by impeding the enterohepatic circulation of bile salts and causing gallbladder stasis. The therapeutic value of erythromycin, a prokinetic motilin analog, was evaluated in an animal model of gallstone formation. Eighty ground squirrels were fed either a trace- (control) or a high- (1%) cholesterol diet. Half of each diet group received either erythromycin stearate or placebo orally twice daily for 4 weeks. Biliary lipid secretion and bile salt pool size were determined via common duct cannulation. Gallbladder contractile response to cholecystokinin (CCK) was studied in vitro. Intestinal transit was evaluated in vivo by 51Cr marker. In the placebo-treated group, fed the high- versus the trace-cholesterol diet, bile salt secretion decreased (trace-cholesterol + placebo, 21.0 +/- 1.8 nmol/min/g liver vs. high-cholesterol + placebo, 9.3 +/- 1.4 nmol/min/g liver), cholesterol saturation index (CSI) doubled (trace-cholesterol + placebo, 0.61 +/- 0.06 vs. high-cholesterol + placebo, 1.30 +/- 0.04), nucleation time shortened (trace-cholesterol + placebo, > 21 days vs. high-cholesterol + placebo, 6.4 +/- 1.0 days), cholesterol crystals formed, gallbladder contractility diminished, and intestinal transit was delayed (each P < .05). Erythromycin treatment of animals on the high-cholesterol diet restored gallbladder contractility and intestinal transit to control levels, increased bile salt secretion, reduced the total bile salt pool, lowered the cholesterol saturation of bile, lengthened the nucleation time, and so reduced crystal formation (each P < .05). Erythromycin enhances gallbladder motility and hastens intestinal transit, promoting more rapid enterohepatic cycling of bile salts. This increases bile salt secretion, improves cholesterol solubility, and reduces crystal development.

Animals↗
PubMed1998

Plasma L-arginine concentration, oxygenation index, and systemic blood pressure in premature infants.

OBJECTIVE: To determine the relationships between plasma L-arginine concentrations and the severity of respiratory distress syndrome (RDS) or systemic blood pressure in premature infants. DESIGN: Prospective, observational study. SETTING: Neonatal intensive care, tertiary referral hospital. SUBJECTS: Fifty-three premature infants. INTERVENTIONS: We measured arginine and nutritional intake, plasma arginine concentration, total amino acid concentrations, and blood pressure on days 3, 7, 14, and 21 of life. In 33 infants who received assisted ventilation, oxygenation index could be calculated to reflect the severity of RDS. The relationships between plasma arginine and oxygenation index or blood pressure were analyzed using multiple linear regression. MEASUREMENTS AND MAIN RESULTS: On day 3, plasma arginine concentrations were decreased compared with normal published values. Arginine concentrations increased with the day of life of measurement (p < .001) and with arginine intake (p < .001). After adjusting for arginine intake and day of life, an inverse relationship was found between oxygenation index and plasma arginine concentrations: (p = .025). No similar relationship was found between oxygenation index and the concentration of total amino acids. A weak positive relationship was found between plasma arginine concentration and systemic blood pressure. CONCLUSIONS: Increments in the oxygenation index, reflective of an increased severity of RDS, are associated with a decrease in plasma arginine concentration. This finding may reflect arginine consumption by the nitric oxide synthase pathway in the lungs of premature infants with RDS, or may be explained by increased arginine catabolism. The lack of a similar relationship between total plasma amino acids and oxygenation index supports the first interpretation.

Amino Acids↗
PubMed1998

Altered migrating myoelectrical complex in an animal model of cholesterol gallstone disease: the effect of erythromycin.

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.

Animals↗
PubMed1998

Anaphylaxis-induced alterations in intestinal motility: role of extrinsic neural pathways.

The roles of mast cells and extrinsic and vagal neural pathways in the anaphylaxis-induced alterations in motility observed at sites remote from antigen exposure were explored. Rats were sensitized to egg albumin (EA) and prepared with 1) electrodes to monitor intestinal myoelectric activity, 2) an isolated intestinal loop, and 3) either intact vagal innervation or a subdiaphragmatic vagotomy. Fasting myoelectric activity was recorded before and after challenge of the jejunum in continuity or the isolated loop with EA or BSA. Intestinal segments and the brain stems were processed for mast cell identification (intestine) or Fos immunoreactivity (brain stem). EA but not BSA challenge of the jejunum or the isolated loop induced altered motility at both sites and diarrhea. Granulated mast cells were significantly reduced at the site local to but not remote from challenge. Vagotomy did not inhibit antigen-induced alterations in motility or diarrhea. The number of Fos-immunoreactive nuclei in vagal sensory or motor nuclei was not significantly altered by vagotomy. Thus antigen challenge of sensitized animals causes mast cell degranulation only at the site of direct challenge but alters motility at sites local and remote from challenge. The remote response requires intact extrinsic but not necessarily vagal neural pathways.

Anaphylaxis↗
PubMed1998

GLP-2 augments the adaptive response to massive intestinal resection in rat.

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.

Adaptation, Physiological↗
PubMed1998

Anaphylaxis-induced mesenteric vascular permeability, granulocyte adhesion, and platelet aggregates in rat.

This study investigates the response of small venules to IgE-dependent, antigen-mediated mast cell activation. Intravital microscopy was utilized to visualize 25- to 40-micron mesenteric venules, mast cell degranulation (on-line detection), vascular permeability changes (albumin leakage), leukocyte adhesion, and the formation of platelet aggregates in rats sensitized with 10 microg of intraperitoneal egg albumin (EA) in saline- or sham-sensitized (saline alone) rats. Sensitized rats challenged with EA (1 mg/ml superfusing mesentery), but not sensitized rats challenged with BSA or sham-sensitized rats challenged with EA, exhibited mast cell degranulation with significant time-dependent increases in vascular permeability (inhibited by diphenhydramine, salbutamol, and indomethacin), leukocyte adhesion (inhibited by Web-2086), and the formation of cellular aggregates (platelet), which were associated with intermittent obstruction of venular flow. Anti-platelet antibody, but not anti-neutrophil antibody or fucoidin (selectin antagonist), prevented platelet aggregate formation. Compound 48/80-induced mast cell degranulation caused similar changes in permeability (via different mediators) and leukocyte adhesion but did not induce platelet aggregation. EA-induced platelet aggregation was not inhibited by any of the mediators tested, and platelets isolated from sensitized rats failed to aggregate in response to direct EA challenge, suggesting release of an unidentified inflammatory mediator as the factor initiating platelet aggregation.

Albuterol↗
PubMed1998

Catch-up growth in children treated with home enteral nutrition.

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.

Adolescent↗