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Biomedical subjects

R B Scott

Publications and source records attributed to R B Scott.

At least 37 records · Page 2Linked to original sources
PubMed1998

Use of immunoglobulin A-antiendomysial antibody to screen for celiac disease in North American children with type 1 diabetes.

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.

Adolescent↗
PubMed1997

Plasma L-arginine concentrations in premature infants with necrotizing enterocolitis.

OBJECTIVE: To determine whether L-arginine concentrations (the substrate for nitric oxide synthesis) are lower in premature infants in whom necrotizing enterocolitis (NEC) develops than in unaffected infants. METHODS: We measured arginine and nutritional intake, plasma arginine, glutamine, total amino acids, and ammonia concentrations in 53 premature infants (mean gestational age +/- SD: 27 +/- 1.7 weeks) at risk of NEC. Measurements were done on days 3, 7, 14 and 21 and just before treatment in infants with NEC. RESULTS: Necrotizing enterocolitis developed in 11 infants between postnatal days 1 and 26. On day 3, plasma arginine concentrations were decreased compared with normal published values (mean +/- SE, 41 mumol/L +/- 4). Arginine concentrations increased with day of life of measurement (p < 0.001) and arginine intake (p < 0.001). Plasma arginine concentrations were significantly lower at the time of diagnosis in infants with NEC compared with control subjects, even after adjusting for arginine intake and day of life (p = 0.032). Plasma glutamine and total amino acid concentrations were not significantly different in infants with NEC compared with control subjects. Plasma ammonia concentrations were elevated on day 3 (mean +/- SE, 72 +/- 3.3 mumol/L) and decreased with postnatal age (p < 0.001) and increasing plasma arginine concentrations (p < 0.001). CONCLUSION: Plasma arginine concentrations are decreased at the time of diagnosis in premature infants with NEC. The potential benefit of arginine supplementation in the prevention of the disease deserves evaluation.

Age Factors↗
PubMed1997

Mitochondrial abnormalities of liver in two children with citrullinaemia.

Citrullinaemia is a rare inborn error of urea-cycle metabolism. Two affected children are reported in whom progressive metabolic instability suggested the possibility of hepatopathy or an ongoing hepatic mitochondrial injury. A percutaneous liver biopsy was performed in each patient. Electron-microscopic findings were similar in both cases. Approximately 20% of the mitochondria were abnormally enlarged with paracrystalline inclusions and electron-dense bodies of different sizes and shapes present in the matrix. The specificity of these findings is discussed in the context of previous reports of ultrastructural abnormalities in the hepatocytes of patients with inborn errors of the urea cycle. It is speculated that the mitochondrial abnormalities in citrullinaemia may be related to the accumulation of citrulline in the mitochondria which may eventually manifest as metabolic instability.

Cell Nucleus↗
PubMed1997

Effects of Giardia lamblia infection on gastrointestinal transit and contractility in Mongolian gerbils.

To determine if Giardia lamblia infection is associated with altered gastrointestinal transit and smooth muscle contractile function, Mongolian gerbils were infected orogastrically with 2 x 10(5) trophozoites (infected) or vehicle (uninfected controls). At the time of peak colonization, control and infected animals were infused either orogastrically or intraduodenally with 51Cr. Gastric emptying of isotope and intestinal transit (measured by the geometric center of distribution of intestinal 51Cr transit) were significantly (P < 0.05) greater in the infected compared to control animals in both the fasted and the fed states. Then, to determine whether Giardia lamblia has an effect on the contractility of longitudinal and circular smooth muscle, isometric tension of jejunal segments was recorded. The development of active tension with stretch and the dose-response curve to bethanechol were significantly increased in the longitudinal muscle of infected animals compared to controls. However, the circular smooth muscle did not show a similar increase in contractility. These findings suggest that an altered gastrointestinal transit and smooth muscle contractility may be involved in the pathophysiology of giardiasis.

Animals↗
PubMed1997

Colonic and jejunal motor disturbances after colonic antigen challenge of sensitized rat.

BACKGROUND & AIMS: Inflammation in the colon may alter motility in the proximal gut and potentiate clinical symptoms. The aim of this study was to characterize the effect of colonic anaphylaxis on local (colonic) and remote (small intestinal) motility and identify the mechanism and mediators involved. METHODS: Rats were sensitized by intraperitoneal injection of 10 microg egg albumin and surgically prepared with electrodes in jejunum and colon and a colostomy tube. Colonic and jejunal myoelectric activity were recorded in fasted animals before and after colonic antigen challenge without and then after pretreatment with specific antagonists. RESULTS: Colonic antigen challenge of sensitized rats was associated with significant (1) increase in colonic myoelectric spike activity, (2) disruption of fasting jejunal motility and initiation of aborally propagating spike complexes, and (3) increase in plasma rat mast cell protease II levels with a decrease in granulated mast cells in colon but not jejunum. The myoelectric disturbance in both colon and jejunum was inhibited significantly by pretreatment with atropine and hexamethonium, doxantrazole, cyclooxygenase, and lipoxygenase inhibitors. Methysergide inhibited only the jejunal disturbance. CONCLUSIONS: Colonic antigen challenge of sensitized animals results in local mast cell activation and the release of mediators that modulate neural pathways to initiate both a local colonic and a remote jejunal myoelectric disturbance.

Albumins↗
PubMed1997

Cisapride in pediatric gastroesophageal reflux.

BACKGROUND: Gastroesophageal reflux is a common condition that in infants may lead to serious complication. This study assessed the efficacy and safety of oral cisapride suspension in the treatment of children 6 weeks to 2 years old with daily regurgitant reflux. METHODS: A randomized, prospective, double-blind, placebo-controlled clinical trial was conducted at three study sites. After a 1 week baseline assessment, 45 infants 6 weeks to 2 years old were randomized to a double-blind trial in which they received a 6 week course of cisapride (0.2 mg/kg q6h) or a placebo suspension. Efficacy was assessed with 24 hour esophageal pH monitoring, esophageal manometry, and esophageal biopsy before and after the treatment period. A diary of regurgitation frequency and severity was kept by the parents. Safety was assessed by adverse event monitoring and standard laboratory measurements. RESULTS: Compared with placebo, cisapride significantly (p < 0.05) reduced the mean duration of upright and supine reflux episodes. Compared to baseline, cisapride significantly reduced the mean duration of the longest reflux episode, and placebo increased the mean number of reflux episodes longer than 5 minutes. Cisapride was not significantly different from placebo for the following mean measurements: percent of total time pH < 4, number of reflux episodes, lower esophageal sphincter pressure, swallow pressure, regurgitation frequency or global evaluation scores. CONCLUSIONS: Cisapride is a safe, well tolerated prokinetic agent that improves the esophageal clearance of refluxed gastric acid in children under the age of 2 years.

Biopsy↗
PubMed1997

Intestinal anaphylaxis induces Fos immunoreactivity in myenteric plexus of rat small intestine.

Fos immunohistochemistry was used to identify myenteric neurons activated as a consequence of intestinal anaphylaxis in Hooded-Lister rats sensitized to egg albumin (EA 10 micrograms ip). After incubation in test solutions, or after in vivo challenge, jejunal tissues were processed for immunohistochemistry with an anti-Fos antibody (1:500, TF161). The neuronal identity of the Fos-labeled nuclei was confirmed by double labeling with neuron-specific enclose (1:1,000). In in vitro studies, exposure of control tissue to 50 mM K(+)-Krebs-EA (2 x 10(-5) M) solutions significantly increased Fos immunoreactivity in the myenteric plexus, whereas a basal level of Fos was seen in control tissue incubated in Krebs solution, sham-sensitized tissue exposed to bovine serum albumin (BSA, 2 x 10(-5) M), or EA and sensitized tissue exposed to BSA. Pretreatment of sensitized tissue with doxantrazole (10(-4) M) markedly reduced Fos immunoreactivity observed after EA exposure. In in vivo studies, there was negligible Fos immunoreactivity in the myenteric plexus of control, sham-sensitized, or sensitized rats challenged with saline. A low level of Fos was seen in neurons of sham-sensitized rats challenged with BSA or EA and in sensitized rats challenged with BSA. Significantly greater levels of Fos were observed in the myenteric plexus of sensitized animals challenged with EA, even after pretreatment with capsaicin (125 mg/kg). These results suggest a role for myenteric neurons in intestinal anaphylaxis. In sensitized rats, activation of myenteric neurons is dependent on antigen-induced mast cell activation and occurs independently of capsaicin-sensitive afferent nerves.

Anaphylaxis↗
PubMed1996

Is pH a biochemical marker of IQ?

We have measured intracellular brain pH in vivo in 42 boys and found a significant correlation between this biochemical parameter and samples of intelligent behaviour. To the best of our knowledge this is the first reported relation between a biochemical marker which is within normal physiological values and intellectual ability. pH is one of the most accurate parameters that can be measured by 31P magnetic resonance spectroscopy and it reflects sensitively cellular ionic status and metabolic activity. The observed correlation, although not implying a causal relation, raises the possibility that intelligent behaviour may be influenced by the ionic status of brain tissue, or vice versa.

Brain↗
PubMed1996

Slow intestinal transit: a motor disorder contributing to cholesterol gallstone formation in the ground squirrel.

Impaired gallbladder motility is an established factor in cholesterol gallstone formation. We assessed whether altered small intestinal smooth muscle contractility with slow transit might potentiate gallstone formation by further impeding enterohepatic cycling of bile acids. Ground squirrels were fed a 1% or a trace (controls) cholesterol diet. Small intestinal transit was evaluated from 51Cr distribution in conscious, fasted animals 20 minutes after infusion into the proximal jejunum. Small intestinal and gallbladder smooth muscle contractility was determined in vitro. Biliary lipid secretion was measured from the cannulated common duct and the bile salt pool size calculated by isotope dilution. Gas-liquid chromatography (GLC) assessed bile salt profile. In animals on the 1% cholesterol diet, aboral transit was significantly delayed, the maximal contractile response to bethanechol was markedly increased (P <.05) with no change in median effective concentration in either circular or longitudinal muscle strips from both the jejunum and ileum, and the gallbladder contractile responses to bethanechol and cholecystokinin (CCK) were decreased. Cholesterol saturation index and the fraction of deoxycholic acid in the pool doubled, whereas the total bile salt pool size remained unchanged in cholesterol-fed animals. In this model, a high-cholesterol diet is associated with altered small intestinal smooth muscle contractility and prolonged small intestinal transit, in addition to diminished gallbladder contractility. The resulting sluggish enterohepatic cycling of bile salts, associated with expanded deoxycholate pool, contributes to cholesterol gallstone formation.

Animals↗
PubMed1996

Colonic motor response to IgE-mediated mast cell degranulation in the Hooded-Lister rat.

After challenge of sensitized individuals, food protein-induced colonic anaphylaxis may contribute to the symptom of diarrhoea. The aim of this study was to characterize the effect of food protein-induced anaphylaxis on colonic circular muscle in vitro, identify the mediators involved, and then evaluate the effect of antigen challenge on colonic transit in vivo. Hooded-Lister rats were sensitized by intraperitoneal injection of egg albumin and controls were sham-sensitized with saline. Rings of distal colonic tissue were suspended in standard tissue baths (mucosa intact) and circular muscle contractility was measured in response to antigen or other agents on day 14. In conscious animals, Na2(51)CrO4 was instilled alone, or with antigen, via proximal colostomy and the geometric centre of distribution of51Cr calculated. Following antigen challenge, a contractile response occurred only in animals that were sensitized (specific IgE antibody levels > or = 1:64), and was specific for the sensitizing antigen. Mast cell involvement was suggested when (1) concanavalin A (a degranulator of both mucosal and connective tissue mast cells) mimicked the antigen-induced response, and (2) Ag-induced contraction was significantly inhibited by mast cell stabilizers. The Ag-induced response was significantly and independently inhibited by a lipo-oxygenase enzyme inhibitor and by LTD4 and platelet activating factor receptor antagonists. The antigen-induced response was resistant to histamine and 5-hydroxytryptamine receptor antagonists, indomethacin, atropine and tetrodotoxin. The geometric centre of distribution of 51Cr was significantly more distal in sensitized animals challenged with antigen rather than placebo, and only sensitized animals challenged with antigen developed diarrhoea. These results suggest that colonic antigen challenge of sensitized rats is associated with IgE-mediated mast cell activation, the release of membrane derived mediators which, in vitro, act directly on smooth muscle to induce contraction, and in vivo result in an increased rate of aboral transit and diarrhoea.

Albumins↗
PubMed1996

Effect of combination therapy with ciprofloxacin and clarithromycin on theophylline pharmacokinetics in healthy volunteers.

Five adults completed this four-way randomized crossover study to compare the effects of oral treatment with ciprofloxacin, clarithromycin, and a combination of the two drugs on theophylline pharmacokinetics. The area under the concentration-time curve for theophylline during combination therapy was not different from that for ciprofloxacin alone. Beta error may explain this finding, but any real effect from combination treatment appears to be clinically unimportant.

Adult↗
PubMed1996

Depressed smooth muscle contractility after massive intestinal resection in rat: role of alterations in muscarinic receptor status or source of calcium for excitation-contraction coupling.

Following massive intestinal resection (removal of 75% of the mid-jejunoileum) in the rat, there is a significant reduction in the in vitro tonic contractile response of the remaining jejunal circular smooth muscle in response to stimulation with the muscarinic agonist bethanechol. The aim of these experiments was to determine if this alteration is specific to muscarinic excitation and occurs as a result of changes in the source and availability of calcium required for excitation-contraction coupling, or reflects changes in muscarinic receptor number and (or) affinity. The contractile response of proximal jejunal circular muscle strips from sham-operated and resected rats was studied in vitro in response to electrical field stimulation, serotonin, and bethanechol, the later under conditions where extracellular calcium was absent or entry was excluded. In contrast with the significant reduction in tonic contractile response to muscarinic excitation of tissues from resected animals, there was an equivalent or enhanced response of these tissues to electrical field stimulation and serotonin, respectively. While sham-operated and resected groups showed similar dependency upon or availability of intracellular and extracellular calcium, the data indicate distinct pathways of calcium mobilization for tonic versus phasic contractile activity. Muscarinic receptor number and affinity were assessed by 1-quinuclidinyl[pheny1-4-3H]benzilate ([3H]QNB) binding to isolated smooth muscle cells and showed a significant increase in Bmax, with no change in Kd after resection. Thus, the reduced contractility of the circular muscle of the remnant jejunum after massive intestinal resection is a specific even associated with muscarinic receptor activation, but it is not the result of either an alteration in the source or availability of calcium required for excitation-contraction coupling or a reduction in the number and (or) affinity of muscarinic receptors.

Action Potentials↗
PubMed1996

Elevated aminotransferase activity as an indication of muscular dystrophy: case reports and review of the literature.

Five male children are reported in whom incidental recognition of elevated serum alanine aminotransferase (ALT) activity initiated investigation to identity the cause of suspected hepatocellular injury. All five were later diagnosed with X chromosome-linked muscular dystrophy. The serum level of ALT, generally considered to be specific for hepatocellular injury, was increased two to 25 times above normal in all the reported cases. Paradoxically, the increase in ALT activity was greater than that of serum aspartate aminotransferase (three to 16 times normal), an enzyme whose elevation is generally recognized as being less specific and indicative of muscle, cardiac, kidney, pancreatic, red blood cell or hepatic injury. At presentation to the gastrointestinal service, one case, age 2.5 months, had no symptoms or signs of neuromuscular dysfunction, while the other four had previously unrecognized hypertrophy of the calves, proximal limb weakness, positive Gower's sign or delayed gross motor skills. All five patients had marked elevation of serum creatine kinase activity and histopathologically confirmed muscular dystrophy. The practical clinical implication of this report is that children with elevated serum ALT, in the absence of other signs and symptoms of hepatic injury, may have occult muscular disease--most frequently muscular dystrophy. Although the clinical signs of muscular dystrophy may be subtle or absent, early determination of creatine kinase will suggest the correct diagnosis and minimize extensive and invasive investigation focusing on hepatic injury.

Adolescent↗
PubMed1996

Contractility of longitudinal smooth muscle after massive intestinal resection in rat.

To determine whether functional changes in contractility of jejunal longitudinal smooth muscle in vitro accompany the adaptive structural changes after massive intestinal resection, the investigators subjected rats either to surgical resection of 75% of the mid-jejuno-ileum or to a sham operation. The development of isometric tension in strips of jejunal tissue was measured 10, 20, 30 or 40 days after surgery. Basal stress in response to stretch was similar for both groups at all of the post-operative times. The optimal length (Lo) needed for the generation of maximal stress (130% of initial resting length) did not differ between the group that had undergone a sham operation and the group that had undergone resection. Concentration-response curves to the muscarinic agonist bethanechol had similar values for the estimated concentration at which the response is half-maximal (EC50) and maximal active stress in both groups. However, significant increases were observed in the frequency and amplitude of spontaneous and bethanechol-stimulated phasic contractions of jejunal tissues obtained from resected rats. The presence of tetrodotoxin (10(-6) mol/L) did not alter the active contractile response (tonic stress, phasic frequency and amplitude) of resected tissues. Thus, after massive intestinal resection, longitudinal smooth muscle shows no adaptive change with respect to basal or active stress but does exhibit an increase in phasic contractile activity. This altered response is non-neural; it may reflect changes in the smooth muscle itself or, alternatively, modulation of myogenic activity by prejunctional effects or by the activity of the interstitial cells of Cajal.

Adaptation, Physiological↗
PubMed1996

Mediation of altered motility in food protein induced intestinal anaphylaxis in Hooded-Lister rat.

In the Hooded-Lister rat model, food protein induced intestinal anaphylaxis disrupts the migrating motor complex (MMC) and causes an increased frequency of migrating clusters of contractions (MCCs, including giant migrating contractions (GMCs)) and diarrhea. To determine whether mast cell mediators act on enteric neurons to initiate these alterations in motility, rats were sensitized by intraperitoneal injection of 10 micrograms egg albumin (antigen (Ag)). Seven days later two jejunal manometry catheters were implanted 2.5 cm apart. On day 14, motility was recorded in fasted rats before and after intraluminal challenge with 10 mg Ag in 0.5 mL saline, both without and after pretreatment by specific antagonists. Ag challenge of sensitized animals disrupted MMCs and caused an increase in total MCCs (including GMCs) and diarrhea. Atropine or hexamethonium abolished all intestinal motility, including Ag-induced MCCs, GMCs, and diarrhea. At higher doses, agents that inhibit mast cell degranulation, cromoglycate, doxantrazole, and quercetin, did inhibit Ag-induced MCCs, GMCs, and diarrhea, but at the expense of inhibiting normal intestinal motility. Cimetidine and diphenhydramine together inhibited normal cycling of the MMC, but did not abolish Ag-induced MCCs, GMCs, and diarrhea. Methysergide was ineffective, but cinanserin and WAY 100,289 significantly inhibited, and indomethacin most effectively blocked, the Ag-induced disruption of MMCs and the increase in MCCs, GMCs, and diarrhea. Thus, the altered motility and the diarrhea observed after food protein induced luminal challenge of sensitized rats is dependent upon myenteric neuronal circuitry. The mast cell stabilizers doxantrazole and quercetin block the response because of a nonspecific anticholinergic effect. Cinanserin and WAY 100,289 partially inhibit, and indomethacin most effectively blocks, the response, suggesting that activated mast cells release prostaglandins and perhaps 5-hydroxytryptamine, which stimulate the neuronal pathway.

Anaphylaxis↗
PubMed1995

Brain abnormalities in Duchenne muscular dystrophy: phosphorus-31 magnetic resonance spectroscopy and neuropsychological study.

Duchenne muscular dystrophy (DMD) is one of a range of muscular dystrophies caused by abnormalities of the short arm of the X chromosome (Xp21), which often cause mental retardation in addition to progressive muscular weakness. Normal dystrophin expression is lacking in both skeletal muscle and brain of affected subjects. Phosphorus-31 magnetic resonance spectroscopy has shown several abnormalities in skeletal muscle in DMD. We looked for similar abnormalities in brain in patients with DMD and related the findings to neuropsychological test results. We studied by magnetic resonance spectroscopy 19 boys (aged 76-167 months) diagnosed as having DMD and 19 control boys of similar age (87-135 months). Intelligence quotient (IQ) was assessed with the Wechsler Intelligence Scale for children. The DMD patients had significantly higher values than the controls in the brain ratios of inorganic phosphate to adenosine triphosphate (mean 0.53 [SD 0.21] vs 0.36 [0.09], p = 0.003), to phosphomonoesters (0.40 [0.07] vs 0.29 [0.07], p = 0.0001), and to phosphocreatine (0.44 [0.10] vs 0.37 [0.08], p = 0.02). There were significant differences between the DMD patients and the controls in full-scale IQ (76 [16] vs 101 [16], p = 0.0001), performance IQ (78 [17] vs 94 [14], p = 0.003), and verbal IQ (78 [17] vs 106 [17], p = 0.0001). These altered metabolite ratios parallel the findings in dystrophic muscle and suggest bioenergetic similarities in tissues that lack dystrophin.

Adenosine Triphosphate↗
PubMed1995

Post-traumatic morbidity in a civilian community of litigants: a follow-up at 3 years.

This paper examines post-traumatic morbidity in a community sample who had claimed compensation and been assessed 10-14 months after the Lockerbie Disaster. At 36 months 25 residents were reassessed by clinical interview and 35 by questionnaire. A chronic pattern of morbidity was found in 56% of this sample with the most frequent diagnoses being post traumatic stress disorder and depression, followed by other anxiety disorders. Only six cases were found to have "recovered" and there was only one case of delayed onset morbidity between 12 and 36 months. No unequivocal predictors of the presence of diagnosis or questionnaire scores were found.

Accidents, Aviation↗