Biomedical subjects

R Shaker

Publications and source records attributed to R Shaker.

At least 19 recordsLinked to original sources

PubMed2006

Radial asymmetry of the upper oesophageal sphincter pressure profile: fact or artefact.

Radial asymmetry of the upper oesophageal sphincter high-pressure zone (UESHPZ) is an accepted notion based on manometric studies. Our aim was to evaluate the effect of the catheter diameter and configuration on the resting pressure profile of the UES. We studied 14 young (30 +/- 2 years) and 14 healthy elderly volunteers (77 +/- 2 years) using the station pull-through technique. We used a specially designed water perfused manometric assembly that incorporated a proximal round cross-section (4.8 mm) and a distal flat cross-section (4.8 x 1.2 mm). Anterior and posterior manometric sites on the round catheter measured significantly higher pressure values than did the sites oriented laterally at the same level (P < 0.001) in both young and elderly. In contrast, the flat-shaped catheter measured statistically indistinguishable pressures from all four orientations in both age groups. In both young and elderly the anterio-posterior, but not lateral pressures by the round catheter were significantly higher (P < 0.001) than those of the flat catheter. An exaggerated anteriorly and posteriorly oriented pressure may be recorded compared with lateral pressures depending on the diameter and non-conforming shape of the recording catheter with respect to the UES producing the appearance of radial asymmetry in the UESHPZ.

Adult↗

PubMed2005

Response properties of the brainstem neurons of the cat following intra-esophageal acid-pepsin infusion.

Studies in humans have documented that acute acid infusion into the esophagus leads to decrease in threshold for sensations to mechanical distension of the esophagus. It is not known whether acid infusion leads to sensitization of brainstem neurons receiving synaptic input from vagal afferent fibers innervating the esophagus. The aim of this study was to investigate the correlation of responses of vagal afferents and brainstem neurons after acute infusion of acid (0.1 N HCl)+pepsin (1 mg/ml) into the esophagus of cats. The vagal afferent fibers (n=20) exhibited pressure-dependent increase in firing to graded esophageal distension (5-80 mm Hg). Infusion of acid+pepsin into the esophagus produced a significant increase in ongoing resting firing of five of 16 fibers (31%) tested. However, their responses to graded esophageal distension did not change when tested 30 min after infusion. Pepsin infusion did not change the resting firing and response to esophageal distension (n=4). Twenty-one brainstem neurons were recorded that responded in an intensity-dependent manner to graded esophageal distension. Responses of 12 excited neurons were tested after intra-esophageal acid+pepsin infusion. Neurons exhibited a decrease in threshold for response to esophageal distension and increase in firing after acid+pepsin infusion. The sensitization of response after intra-esophageal acid remained unaffected after cervical (C1-C2) spinal transection (n=3). Results indicate that the esophageal distension-sensitive neurons in the brainstem exhibit sensitization of response to esophageal distension after acute acid+pepsin exposure. The sensitization of brainstem neurons is possibly initiated by increased spontaneous firing of the vagal afferent fibers to acid+pepsin, but not to sensitized response of vagal distension-sensitive afferent fibers to esophageal distension. Results also indicate that spinal pathway does not contribute to sensitization of brainstem neurons.

Animals↗

PubMed2005

Feasibility and safety of endoscopic evaluation of gastric emptying.

BACKGROUND AND STUDY AIMS: Scintigraphy is the currently accepted method for evaluation of gastric emptying. Although quantitative, this method is complicated, time-consuming, and costly. If a simple endoscopic technique was available for those instances when quantification of an emptying abnormality is not needed, the same clinical information could be obtained in less time and with resource savings. Our aims in this study were therefore to assess the technical feasibility, tolerability, and safety of unsedated transnasal esophagogastroscopy (T-EG) as a technique for qualitative assessment of gastric emptying. METHODS: The study was done in two phases. In the first phase, 18 volunteers (ten men, eight women) underwent T-EG at 4 hours, 5 hours, or 6 hours after ingestion of a standard meal used for scintigraphic evaluation of gastric emptying without radiolabeling. In the second phase, ten volunteers underwent T-EG after scintigraphic imaging had demonstrated complete gastric emptying. RESULTS: Subjects in both phases tolerated the procedure well and completed the study. In the first phase, 13 of 15 volunteers exhibited complete gastric emptying at 6 hours (87%), while two (13%) revealed some particulate matter in the stomach at that time. In the second phase, one of the ten volunteers exhibited a small amount of solid food residue in the stomach despite documentation of scintigraphic complete emptying. CONCLUSIONS: Evaluation of gastric emptying by unsedated T-EG is both feasible and safe. In healthy, asymptomatic individuals, complete gastric emptying of solid food may take as long as 6 hours.

Adult↗

PubMed2005

Characteristics of upper oesophageal sphincter and oesophageal body during maturation in healthy human neonates compared with adults.

We evaluated the upper oesophageal sphincter (UOS) relationship with oesophageal body during primary peristalsis (PP) sequences in healthy human neonates during maturation and compared with that of healthy adult volunteers. Forty-nine studies were performed using a water perfusion manometry system and a specially designed oesophageal catheter with a UOS sleeve concurrent with submental electromyogram in 31 subjects in supine position (18 preterm neonates, 29.9 +/- 2.5 weeks gestation; four full-term neonates, 39.3 +/- 1.0 weeks gestation; and nine adults, 18-65 years). The preterm neonates were studied longitudinally at 33 and 36 weeks postmenstrual age (PMA) and full-term born at 40 weeks PMA. Data were compared between the groups to recognize the effects of gestation, postnatal age and ageing. We evaluated 403 consecutive spontaneous solitary swallows during maturation (preterm at time-1 vs time-2) and growth (preterm and full-term vs adults) and observed significant (P < 0.05) differences in the basal UOS resting pressure, UOS relaxation characteristics, proximal and distal oesophageal body amplitude, duration, propagation and peristaltic velocity. Characteristics of UOS and PP are well-developed by 33 weeks PMA and undergo further maturation during the postnatal period, and are significantly different from that of adult.

Adult↗

PubMed2005

BioMediator data integration: beyond genomics to neuroscience data.

The BioMediator system developed at the University of Washington (UW) provides a theoretical and practical foundation for data integration across diverse biomedical research domains and various data types. In this paper we demonstrate the generalizability of its architecture through its application to the UW Human Brain Project (HBP) for understanding language organization in the brain. We first describe the system architecture and the characteristics of the four data sources developed by the UW HBP. Second we present the process of developing the application prototype for HBP neuroscience researchers posing queries across these semantically and syntactically heterogeneous neurophysiologic data sources. Then we discuss the benefits and potential limitations of the BioMediator system as a general data integration solution for different user groups in genomic and neuroscience research domains.

Brain↗

PubMed2005

Integration of data for gene annotation using the BioMediator system.

Gene annotation requires integration of data from multiple sources in order to functionally classify genes. We are using BioMediator, a general purpose data-integration solution, to develop a gene annotation system to automate the process of collecting data from disparate genomic databases. Integration of annotation data from multiple sources into a single format will facilitate use of analytic tools for the proper functional classification of genes.

Base Sequence↗

PubMed2004

Response properties of antral mechanosensitive afferent fibers and effects of ionotropic glutamate receptor antagonists.

The ionotropic glutamate receptors N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are present peripherally in the primary sensory afferent neurons innervating the viscera. Multiple studies have reported roles of glutamate receptors in gastric functions. However, no study has previously shown the direct influence of ionotropic glutamate receptor antagonist on vagal sensory neurons. The objective of this study was to investigate the effects of NMDA and AMPA receptor antagonists on mechanotransduction properties of vagal afferent fibers innervating the rat stomach. Action potentials were recorded from the hyponodal vagus nerve innervating the antrum of the Long-Evans rats. For antral distension (AD), a small latex balloon was inserted into the stomach and positioned in the antrum. The antral contractions were recorded with solid-state probe inserted into the water-filled balloon. Antral units were identified to isovolumic (0.2-1 ml) or isobaric AD (5-60 mm Hg). NMDA and AMPA receptor antagonists were injected in a cumulative fashion (1-100 micromol/kg, i.v.). After the conclusion of experiment, the abdomen was opened and receptive field was mapped by probing the serosa of the stomach. Thirty-two fibers were identified to AD. The receptive fields of 26 fibers were located in the posterior part of the antrum. All fibers exhibited spontaneous firing (mean: 7.00+/-0.97 impulses/s). Twenty fibers exhibited a rhythmic firing that was in phase with antral contractions, whereas 12 fibers exhibited non-rhythmic spontaneous firing unrelated to spontaneous antral contraction. Both groups of fibers exhibited a linear increase in responses to graded isovolumic or isobaric distensions. NMDA (memantine HCl and dizocilpine (MK-801)) and AMPA/kainate (6-cyano-7-nitroquinoxaline 2,3-dione; CNQX) receptor antagonists dose-dependently attenuated the mechanotransduction properties of these fibers to AD. However, competitive NMDA antagonist dl-2-amino-5 phosphopentanoic acid (AP-5) had no effect. The study documents that glutamate receptor antagonists can attenuate responses of gastric vagal sensory afferent fibers innervating the distal stomach, offering insight to potential pharmacological agents in the treatment of gastric disorders.

Action Potentials↗

PubMed2004

Review article: impact of night-time reflux on lifestyle - unrecognized issues in reflux disease.

Gastro-oesophageal reflux disease (GERD), manifesting with symptoms including heartburn and regurgitation, affects people during both daytime and nocturnal hours. Night-time GERD has been reported to have a greater impact on a patient's life than daytime GERD due to prolonged oesophageal acid exposure time per reflux episode. To further understand this issue, it is important to implement quality of life (QOL) measures. QOL studies are becoming increasingly important to physicians in making clinical decisions, and generic and disease-specific health-related QOL (HRQL) tools have been developed to measure a wide variety of topics. There are currently no universally accepted guidelines on how to best measure HRQL in GERD patients. It is important to note that these surveys may not yield accurate results because many GERD sufferers may feel that their symptoms are not serious enough to seek treatment. Some surveys include the GERD-HRQL assessment, the Short Form Health Survey (SF-36), and the Gallup survey. When compared with daytime GERD patients, night-time GERD patients may suffer from sleep deprivation, which in turn leads to physical and emotional problems and a poor overall QOL. Studies indicate that the prevalence and impact of night-time heartburn have been underestimated and that adequate treatment of symptoms is often not achieved. In addition, GERD greatly affects work productivity and leads to a significant economic burden on society. Although limited studies are available on the impact of pharmacological treatment on GERD QOL, recent findings indicate that proton pump inhibitors are more effective than H(2)-receptor antagonists for the improvement of overall QOL.

Absenteeism↗

PubMed2003

Modulation of oesophago-UOS contractile reflex: effect of proximal and distal esophageal distention and swallowing.

Upper oesophageal sphincter (UOS) tone is influenced by intraoesophageal pressure events. Our aim was to test the hypothesis that UOS tone is responsive to simultaneous inhibitory and stimulatory signals originating from the oesophagus and compare effect of proximal and distal oesophageal air distention on oesophageal balloon-stimulated UOS contraction. We studied 16 healthy volunteers, ages 19-80 years in two stages. We induced UOS contraction by distending various size balloons intraoesophageally and studied response of contracted UOS to oesophageal air distentions and swallowing. Intraoesophageal injections of 60-ml room air resulted in UOS pressure augmentation (31%), relaxation (64%) and no effect in the remaining 5% of instances. The majority of air injections into the oesophageal segment proximal to the distended balloon were followed by relaxation of the contracted UOS, whereas, the majority of oesophageal air distentions distal to the balloon resulted in augmentation of UOS contraction (P < 0.01). Swallowing resulted in complete relaxation of the UOS. In conclusion, UOS contractile response to oesophageal balloon distention is overridden by further augmentation or relaxation as a result of oesophageal air distention and swallowing. Contractile and inhibitory responses of the contracted UOS to generalized oesophageal distention is region-specific.

Adult↗

PubMed2003

Resistance of the pulmonary epithelium to movement of buffer ions.

Exposure of the apical surfaces of alveolar monolayers to acidic and alkaline solutions has been reported to have little influence on intracellular pH compared with basolateral challenges (Joseph D, Tirmizi O, Zhang X, Crandall ED, and Lubman RL. Am J Physiol Lung Cell Mol Physiol 282: L675-L683, 2002). We have used fluorescent pH indicators and a trifurcated optical bundle to determine whether the apical surfaces are less permeable to ionized buffers than the membranes that separate the vasculature from the tissues in intact rat lungs. In the first set of experiments, the air spaces were filled with perfusate containing FITC-dextran (mol wt 60000) or 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Air space pH fell progressively from 7.4 to 6.61 +/- 0.03 (mean +/- SE, n = 11, air space buffers at 10 mM). Perfusion for 2 min with 2 mM NH4Cl increased air space pH by 0.142 +/- 0.019 unit, without a subsequent acidic overshoot. Infusions of NaHCO3 and sodium acetate reduced pH without a subsequent alkaline overshoot. In the second set of experiments, cellular pH was monitored in air-filled lungs after perfusion with BCECFAM. Injections of NH4Cl caused a biphasic response, with initial alkalinization of the cellular compartment followed by acidification after the NH4Cl was washed from the lungs. Subsequent return of pH to normal was slowed by infusions of 1.0 mM dimethyl amiloride. These studies suggest that lung cells are protected from air space acidification by the impermeability of the apical membranes to buffer ions and that the cells extrude excess H+ through basolateral Na+/H+ exchangers.

Acid-Base Equilibrium↗

PubMed2003

Expression array annotation using the BioMediator biological data integration system and the BioConductor analytic platform.

This paper presents the implementation of a model for expression array annotation (EAA) using the BioMediator biological data integration system along with BioConductor, an analytic tools platform. The model presented addresses the need for annotation sources identified during BioConductor inverted exclamation mark s development. Annotation provides us with well-curated genomic background knowledge for expression array analysis and interpretation. Annotation requests are constructed and posted to the query interface of the EAA package (the EAA model implemented as a component of BioConductor). The software enumerates all possible annotation paths for queries. These are then transformed to PQL queries and processed by BioMediator. Annotation entities returned from the EAA package answer the annotation request.

Computational Biology↗

PubMed2002

Effect of chronic and acute cigarette smoking on the pharyngoglottal closure reflex.

BACKGROUND: Injection of water into the pharynx at a threshold volume induces vocal cord adduction--the pharyngoglottal closure reflex (PGCR). This reflex together with other supraoesophageal reflexes may be helpful in preventing aspiration. Cigarette smoking has an adverse affect on the pharyngo-upper oesophageal sphincter contractile reflex and reflexive pharyngeal swallow. The effect of smoking on PGCR has not been studied previously. AIMS: To elucidate the effect of chronic and acute cigarette smoking on PGCR. SUBJECTS: We studied 10 chronic smokers and 10 non-smokers before and after real/simulated smoking, respectively. METHODS: Using concurrent recordings, glottal function was monitored by video endoscopy, swallowing by electromyography, and PGCR was triggered by rapid and slow pharyngeal water injections. RESULTS: The threshold volume to trigger PGCR during rapid injection was significantly higher in chronic smokers (non-smoker 0.20 (SEM 0.02) ml, smoker 0.36 (0.02) ml; p<0.001). In six of 10 smokers, acute smoking abolished this reflex during slow water injection. CONCLUSIONS: Smoking adversely affects stimulation of PGCR. This finding may have implications in the development of reflux related respiratory complications in smokers.

Adult↗

PubMed2002

PQL: a declarative query language over dynamic biological schemata.

We introduce the PQL query language (PQL) used in the GeneSeek genetic data integration project. PQL incorporates many features of query languages for semi-structured data. To this we add the ability to express metadata constraints like intended semantics and database curation approach. These constraints guide the dynamic generation of potential query plans. This allows a single query to remain relevant even in the presence of source and mediated schemas that are continually evolving, as is often the case in data integration.

Computational Biology↗

PubMed2002

A rule driven bi-directional translation system for remapping queries and result sets between a mediated schema and heterogeneous data sources.

As the number of online biomedical data sources increases, so too do the number of ways to access such data. The research described herein focuses on creating a data access system that provides bi-directional translation and mapping of data between heterogeneous databases and a mediated schema. Semantic mapping rules stored in a knowledge base are used by our generalized software to convert XML query results obtained from each data source to a common schema representing a single ontology. We apply this approach to the domain of online genetic databases, demonstrating the system's scalability and integratability.

Databases as Topic↗

PubMed2001

Medical treatment of supraesophageal complications of gastroesophageal reflux disease.

A growing number of bronchopulmonary, laryngopharyngeal, and oral cavity disorders are suspected of being caused by gastroesophageal refluxate traveling from the esophageal body. Although diagnostic methods have not been developed to positively identify the etiology of these conditions as being related to refluxate, many patients with these supraesophageal manifestations of gastroesophageal reflux disease (SeGERD) respond to empiric antireflux therapy with proton pump inhibitors (PPIs). When used in an appropriate dose (twice daily) and for an appropriate duration (12 weeks or longer), PPIs can be effective in relieving SeGERD symptoms. Economic issues and outcome studies are needed to help further define the role of PPIs in SeGERD.

Gastroesophageal Reflux↗

PubMed2001

Esophageal and upper esophageal sphincter motor function in babies.

The incidence of concomitant feeding and airway-related disorders is high among premature infants and babies with congenital anomalies. The cause of these disorders is commonly attributed to foregut dysfunction, and the approach to diagnosis and management is largely empiric. Management strategies usually are based on the failure to improve feeding tolerance with advancing maturation and the presence of supraesophageal complications of reflux disease. Very little information exists about the functional development of deglutitive and airway-protective mechanisms in neonates. The purpose of this article is to review the available information on esophageal and upper esophageal sphincter (UES) motor function in human infants. Understanding the maturation of the motor functions of the pharynx-UES and esophagus and related airway-protection responses is essential for determining the pathophysiologic basis of feeding-related airway disorders.

Child Development↗

PubMed2001

Unsedated transnasal laryngo-esophagogastroduodenoscopy: an alternative to conventional endoscopy.

The introduction, refinement, and subsequent widespread use of flexible fiberoptic endoscopes have revolutionized the diagnosis and management of upper gastrointestinal (GI) disorders. There has been a simultaneous increase in the cost of managing upper GI disorders, which is in part attributed to the high price of endoscopy. Unfortunately, in the current cost-conscious health-care environment, the high cost of endoscopy has resulted in the underuse of this valuable clinical tool. Unsedated transnasal laryngo-esophagogastroduodenoscopy (T-EGD) is a new technique for upper endoscopy that uses an ultrathin endoscope and has a comparable yield to conventional upper endoscopy but obviates the need for conscious sedation because it is better tolerated. Studies have found that T-EGD is a feasible alternative to conventional endoscopy in terms of safety, efficacy, and cost containment. This article reviews these factors, the technique of T-EGD, patient and endoscopist considerations, tissue sampling, and the characteristics of ultrathin endoscopes used for T-EGD.

Procedural Sedation↗

PubMed2001

Choline acetyltransferase activity parallels the pressure gradient in the feline pharyngo-esophageal region.

Pressures generated by the pharyngeal constrictor muscles and proximal esophagus involve acetylcholine-induced muscle contractions. We hypothesized that the pharyngo-esophageal pressure gradient is related to choline acetyltransferase activity. In nine anesthetized cats, hypopharyngeal pressure and proximal esophageal pressure were recorded with a solid state transducer assembly. Enzymatic activities in the thyropharyngeus, cricopharyngeus, and proximal esophageal muscles were measured. Hypopharyngeal pressure was higher than the proximal esophagus (p < 0.01), and choline acetyltransferase activity was higher in the cricopharyngeus compared to the proximal esophagus ( p < 0.05). The pressure gradient between the hypopharynx and proximal esophagus may be influenced by the activity of choline acetyltransferase.

Acetylcholinesterase↗