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Biomedical subjects

Reza Shaker

Publications and source records attributed to Reza Shaker.

At least 55 records · Page 3Linked to original sources
PubMed2003

Cerebral cortical representation of external anal sphincter contraction: effect of effort.

The external anal sphincter (EAS) plays a critical role in maintaining fecal continence; however, cerebral cortical control of voluntary EAS contraction is not completely understood. Our aims were to determine the cortical areas associated with voluntary EAS contraction and to determine the effect of two levels of sphincter contraction effort on brain activity. Seventeen asymptomatic adults (ages 21-48, 9 male) were studied using functional magnetic resonance imaging (fMRI) to detect brain activity. Studies were done in two stages. In stage 1 (10 subjects, 5 male), anal sphincter pressure was monitored from a catheter-affixed bag. Subjects performed maximal and submaximal EAS contractions during two fMRI scanning sessions consisting of alternating 10-s intervals of sustained contraction and rest. In stage 2 studies, seven subjects (4 male) performed only maximum effort sphincter contractions without a catheter. EAS contraction was associated with multifocal fMRI activity in sensory/motor, anterior cingulate, prefrontal, parietal, occipital, and insular regions. Total cortical activity volume was significantly larger (P < 0.05) for maximal (5,175 +/- 720 microl) compared with submaximal effort contractions (2,558 +/- 306 microl). Similarly, percent fMRI signal change was significantly higher (P < 0.05) for maximal (4.8 +/- 0.1%) compared with submaximal effort contractions (2.2 +/- 0.1%). Cortical region-of-interest analysis showed the incidence of insular activation to be more common in women compared with men. Other cortical regions showed no such gender differences. fMRI activity detected in stage 2 showed similar regions of cortical activation to those of the stage 1 study. Willful contraction of the EAS is associated with multifocal cerebral cortical activity. The volume and intensity of cerebral cortical activation is commensurate with the level of contractile effort.

Adult↗
PubMed2003

A simple method for estimating respiratory solute dilution in exhaled breath condensates.

Exhaled breath condensates have been widely used to detect inflammatory mediators in the fluid that covers airway surfaces of patients with inflammatory lung disorders. This approach is much less invasive than bronchoalveolar lavage, but respiratory droplets are markedly diluted by large and variable amounts of water vapor. We estimated the dilution of respiratory droplets by comparing concentrations of nonvolatile, reference indicators (total nonvolatile cations, urea or conductivity) in 18 normal subjects with normal plasma concentrations by assuming similar concentrations in the respiratory fluid and plasma. The volatile cation, NH4+ (most of which is delivered as NH3 gas from the mouth), represented 93 +/- 3% (SEM) of the condensate cations. More than 99% of the NH4+ was removed by lyophilization, making it possible to use conductivity to estimate total nonvolatile ionic concentrations and facilitating analysis of urea. Conductivity was significantly correlated with electrolyte and urea concentrations. Estimates of dilution based on total cations, conductivity, and urea were not significantly different (cations: 20,472 +/- 2,516; conductivity: 21,019 +/- 2,427; and urea: 18,818 +/- 2,402). These observations suggest that the conductivity of lyophilized samples can be used as an inexpensive, simple, and reliable method for estimating dilution of nonvolatile, hydrophilic mediators in condensates.

Adult↗
PubMed2003

Normal physiology of the aerodigestive tract and its effect on the upper gut.

There is a close functional relation between the aerodigestive tract and the upper gastrointestinal tract. The pharynx and larynx are involved in respiration, speech, and deglutition. This article reviews the effects of reflexes emanating from the pharynx and larynx on the esophagus and its sphincters, as well as the effects of reflexes emanating from the esophagus on the larynx. Principally, reciprocal reflexes within these 2 regions result in protection of the airway against aspiration from above and below, either by swallowed or refluxed material. However, other reflexes appear to facilitate reflux of gastric content into the esophagus and inhibit esophageal motor function.

Cough↗
PubMed2003

Exhaled breath condensates: a potential novel technique for detecting aspiration.

There is an urgent need for diagnostic procedures that can detect aspiration of oral and gastrointestinal (GI) secretions into the respiratory tract. Current approaches are limited by poor sensitivity and specificity. These techniques include (1) adding indicators to feedings; (2) recovery of lipid-filled macrophages in respiratory secretions; (3) measurement of changes in the pH of the upper GI and respiratory tracts; (4) endoscopic visualization of reflux events; and (5) measurement of increased glucose concentrations in respiratory secretions. Ideally, specific markers from various sites in the oral and GI tracts might be discovered in respiratory secretions, but conventional bronchoalveolar lavage for sampling respiratory secretions is not practical and involves some risk. Noninvasive measurements of indicators in the exhaled breath condensates could be used to detect aspiration, but a number of theoretical and practical aspects of such studies must be considered before this approach can be applied to the problem of aspiration.

Breath Tests↗
PubMed2003

A critical review of endoscopic therapy for gastroesophageal reflux disease.

The US Food and Drug Administration has approved 2 endoscopic devices for treating gastroesophageal reflux disease, and several thousand procedures have been performed to date. At least 6 other endoscopic devices designed to treat gastroesophageal reflux are in various stages of testing and may soon obtain approval for clinical use. Short-term follow-up studies uniformly report improvement in heartburn symptoms and quality-of-life scores, as well as decreases in use of antisecretory medications. However, esophageal acid reflux is not normalized after these treatments, nor is esophagitis improved. Although troubling efficacy and safety issues are currently unresolved, these techniques are becoming routine clinical procedures outside of clinical trials. Unless there is rigorous attention to scientific validation of these techniques, including comparative trials versus conventional treatments, there will remain a cloud of doubt and concern about their role and usefulness in clinical medicine. The rapid incursion of these devices into the clinical marketplace before they have undergone critical scientific scrutiny magnifies the urgency of addressing these issues.

Cost-Benefit Analysis↗
PubMed2003

Isolation and characterization of human esophageal microvascular endothelial cells: mechanisms of inflammatory activation.

Gastroesophageal reflux disease is the most common malady of the esophagus, affecting 7% of the United States population. Histological assessment demonstrates classic inflammatory mechanisms including selective leukocyte recruitment and hemorrhage, suggesting a prominent role for the microvasculature. We isolated and characterized human esophageal microvascular endothelial cells (EC) (HEMEC), examined inflammatory activation in response to cytokines, LPS, and acidic pH exposure, and identified signaling pathways that underlie activation. HEMEC displayed characteristic morphological and phenotypic features including acetylated LDL uptake. TNF-alpha/LPS activation of HEMEC resulted in upregulation of the cell adhesion molecules (CAM) ICAM-1, VCAM-1, E-selectin, and mucosal addressin CAM-1 (MAdCAM-1), increased IL-8 production, and enhanced leukocyte binding. Both acid and TNF-alpha/LPS activation lead to activation of SAPK/JNK in HEMEC that was linked to VCAM-1 expression and U-937 leukocyte adhesion. Expression of constitutive inducible nitric oxide synthase in HEMEC was in marked contrast to intestinal microvascular endothelial cells. In this study, we demonstrate that HEMECs are phenotypically and functionally distinct from lower gut-derived endothelial cells and will facilitate understanding of inflammatory mechanisms in esophageal inflammation.

Cell Adhesion↗
PubMed2003

Relative contribution of various airway protective mechanisms to prevention of aspiration during swallowing.

Deglutitive airway protective mechanisms include glottal closure, epiglottal descent, and anterosuperior displacement of the larynx. Aspiration of swallowed material may occur during the pre-, intra-, or postpharyngeal phase of swallowing. Our objectives were to determine the relative contribution of the airway protective mechanisms during each phase of swallow in 14 decerebrated cats before and after suprahyoid myotomy, epiglottectomy, and unilateral cordectomy. After myotomy, superior excursions of the hyoid, thyroid, and cricoid cartilages and anteroposterior diameter of maximum upper esophageal spincter (UES) opening were significantly diminished, but the incidence of pharyngeal residue significantly increased (P < 0.05). No aspiration was observed in the predeglutitive period. After myotomy, the incidence of aspiration significantly increased in both intra- and postdeglutitive periods. Epiglottectomy did not alter aspiration incidence, but unilateral cordectomy resulted in a 100% incidence of intra- and postdeglutitive aspiration. In conclusion, glottal closure constitutes the primary mechanism for prevention of intra- and postdeglutitive aspiration, but laryngeal elevation may assist this function. Bolus pulsion without laryngeal distraction can open the UES, but at risk of aspiration due to decreased pharyngeal clearance. The epiglottis provides no apparent airway protection during any phase of swallowing.

Animals↗
PubMed2003

Esophageal body and upper esophageal sphincter motor responses to esophageal provocation during maturation in preterm newborns.

OBJECTIVES: We studied the maturation of esophageal body and upper esophageal sphincter (UES) motor responses that protect against reflux in newborns. STUDY DESIGN: The responses of esophageal body and UES on midesophageal provocation were quantified using a micromanometric water perfusion system and a specially designed catheter with a UES sleeve and 5 side-hole recording sites. Eighteen healthy premature infants were studied twice, at 33.4 weeks' and 35.7 weeks' mean postmenstrual ages (PMAs). RESULTS: Mean threshold volumes and the distribution of responses including secondary peristalsis, UES pressure increase, and primary peristalsis were similar for air and liquids. Secondary peristalsis and UES pressure increases were volume dependent for both studies, but their characteristics changed as PMA increased in that (1) completely propagated secondary peristalsis with liquids increased; (2) proximal esophageal contraction duration was shorter for air and liquids; and (3) propagating velocity for liquids was faster. CONCLUSIONS: Esophageal and UES motor responses to abrupt midesophageal provocation are present as early as 33 weeks' PMA, and the response-characteristics improve during development. Reflexes that may facilitate esophageal clearance include (1) secondary peristalsis; (2) esophago-UES-contractile reflex; and (3) esophago-deglutition response.

Deglutition Disorders↗
PubMed2003

Intrapharyngeal distribution of gastric acid refluxate.

OBJECTIVES/HYPOTHESIS: Determination of intrapharyngeal distribution of gastric acid refluxate is needed to better understand the pathogenesis of reflux-attributed aerodigestive tract disorders. The aims of the study were to determine intrapharyngeal distribution of gastric acid refluxate and to determine whether this distribution can better differentiate patients from control subjects compared with data obtained from a single hypopharyngeal site. METHODS: We prospectively studied 10 healthy volunteers, 12 patients with reflux laryngitis, and 15 patients with vasomotor rhinitis using a concurrent dual pharyngeal/dual esophageal pH recording technique. We determined the hypopharyngeal and oropharyngeal pH profile, including number, duration, and distribution of reflux events irrespective of and in correlation with intraesophageal pH profile using four different pH thresholds. RESULTS: Few drops in pharyngeal pH were found to be true reflux events based on their correlation with esophageal pH events. For the pharyngeal pH threshold criterion of a drop to 4.0 or less, 6 of 12 patients with reflux laryngitis, 5 of 15 patients with vasomotor rhinitis, and 2 of 10 normal control subjects exhibited a total of 25 (range, 1-5) distal pharyngeal acid reflux events. Overall, 34% of these events reached the oropharyngeal pH recording site. Between-group comparison for all levels of pH threshold criteria did not show any significant difference of reflux parameters in the hypopharyngeal or in the oropharyngeal sites among the studied groups. CONCLUSIONS: Reflux of gastric acid into the pharynx may extend to the region of the oropharynx in both patients and control subjects. Overall distribution of acid refluxate to the oropharynx is low but as groups is similar between healthy individuals and patients with reflux laryngitis and those with vasomotor rhinitis. Parameters of oropharyngeal acid reflux such as number and duration do not differentiate patients from control subjects.

Gastric Acid↗
PubMed2003

Nighttime heartburn is an under-appreciated clinical problem that impacts sleep and daytime function: the results of a Gallup survey conducted on behalf of the American Gastroenterological Association.

OBJECTIVE: Although a large body of information exists about the prevalence of gastroesophageal reflux disease (GERD) in general, available data specifically addressing nocturnal reflux are limited. Because nocturnal acid reflux is reported to be associated with more severe injuries such as esophagitis and stricture, as well as adenocarcinoma of the esophagus, a better understanding of the prevalence and impact of nighttime heartburn as a sign of nocturnal acid reflux events can have significant potential management implications. The aims of this study were to determine the prevalence of nighttime heartburn and reflux-attributed supraesophageal symptoms among patients with GERD; and the impact of nighttime heartburn on sleep and several activities of daily living that could affect quality of life. METHODS: A nationwide telephone survey of 1000 adults experiencing heartburn at least once a week was conducted by the Gallup Organization on behalf of the American Gastroenterological Association. RESULTS: Altogether, 79% of respondents reported experiencing heartburn at night. Among those, 75% reported that symptoms affected their sleep, 63% believed that heartburn negatively affected their ability to sleep well, and 40% believed that nocturnal heartburn impaired their ability to function the following day. Of the 791 respondents with nighttime heartburn, 71% reported taking over-the-counter medicine for it, but only 29% of these rated this approach extremely effective. Forty-one percent reported trying prescription medicines, and 49% of these rated this approach extremely effective. CONCLUSIONS: Nighttime heartburn occurs in a large majority of adults with GERD, resulting in sleeping difficulties and impaired next-day function. The expected result from implemented therapy for heartburn is not achieved by a sizable percentage of patients.

Activities of Daily Living↗
PubMed2003

Medical management of nocturnal symptoms of gastro-oesophageal reflux disease in the elderly.

Elderly patients with nocturnal symptoms of gastro-oesophageal reflux disease (GORD) usually experience a more aggressive and complicated disease course compared with younger patients, resulting in impaired quality of life. The severity of disease and possible complications should be evaluated with upper endoscopy once the diagnosis is suspected. Elderly patients with nocturnal symptoms of GORD and evidence of endoscopic complications (oesophagitis, Barrett's oesophagus, etc.) and those with severe endoscopically negative reflux disease (ENRD) should be treated with proton pump inhibitors. Histamine H(2) receptor antagonists are suitable for mild-to-moderate ENRD. Antacids and lifestyle modifications may be incorporated into the management as adjuncts to more potent and durable therapeutic agents. Effective treatment of nocturnal GORD symptoms in the elderly will result in relief of symptoms, healing of oesophagitis and improved quality of life, and should be maintained indefinitely to prevent relapses of the disease.

Aged↗
PubMed2002

Effect of GABA(B) receptor agonist on distension-sensitive pelvic nerve afferent fibers innervating rat colon.

Spinal afferents innervating the gastrointestinal tract are the major pathways for visceral nociception. Many centrally acting analgesic drugs attenuate responses of visceral primary afferent fibers by acting at the peripheral site. Gamma-amino butyric acid (GABA), a major inhibitory neurotransmitter, acts via metobotropic GABA(B) and ionotropic GABA(A)/GABA(C) receptors. The aim of this study was to test the peripheral effect of selective GABA(B) receptor agonist baclofen on responses of the pelvic nerve afferent fibers innervating the colon of the rat. Distension-sensitive pelvic nerve afferent fibers were recorded from the S(1) sacral dorsal root in anesthetized rats. The effect of baclofen (1-300 micromol/kg) was tested on responses of these fibers to colorectal distension (CRD; 60 mmHg, 30 s). A total of 21 pelvic nerve afferent fibers was recorded. Mechanosensitive properties of four fibers were also recorded before and after bilateral transections of T(12)-S(3) ventral roots (VR). Effect of baclofen was tested on 15 fibers (7 in intact rats, 4 in rats with transected VR, and 4 in rats pretreated with CGP 54626). In nine fibers (5/7 in intact and 4/4 in VR transected rats), baclofen produced dose-dependent inhibition of response to CRD. Pretreatment with selective GABA(B) receptor antagonist CGP 54626 (1 micromol/kg) reversed the inhibitory effect of baclofen. Results suggest a peripheral role of GABA(B) receptors in the inhibition of mechanotransduction property of distension-sensitive pelvic nerve afferent fibers.

Afferent Pathways↗
PubMed2002

Vocal cord closure pressure during volitional swallow and other voluntary tasks.

Our goal was to determine and compare vocal cord (VC) closure pressure and its associated intratracheal pressure during several physiological events such as swallowing, coughing, straining, and phonation. We studied 11 healthy subjects (age 41 +/- 2 years) with no current or previous history of laryngeal or pulmonary diseases. VC closure pressure during the above-mentioned tasks was studied using a concurrent manometric and endoscopic technique. VC closure pressure during dry swallows averaged 298 +/- 23 mm Hg, while intratracheal pressures exhibited a biphasic pattern ranging from -4 +/- 0.5 to +6 +/- 0.8 mm Hg. Average VC closure pressure during cough was 280 +/- 20 mm Hg, during straining/valsalva maneuver it averaged 330 +/- 45 mm Hg, during phonation it produced an initial rapidly rising spike like pressure (222 +/- 25 mm Hg) followed by a sustained minimally positive pressure during continued phonation of two tested vowel sounds (15-25 mm Hg). Between-group comparison showed that for all studied tasks, the in-' tercordal pressures were significantly higher than those of respective intratracheal pressures (p < 0.05). The vocal cords generate closure pressures that vary depending on the performed function.

Adult↗
PubMed2002

Radiographic evaluation of complex dysphagic patients: comparison with videoendoscopic technique.

Swallowing is a highly coordinated sequence of physiologic events. Many disease processes affect the patient's ability to have a functional swallow. The traditional videofluoroscopic swallowing study is an effective and established method for evaluating these patients and is the current examination of choice. Videoendoscopic evaluation is a safe and affordable procedure that can be used in an outpatient or office setting. It can also be a complementary technique, allowing direct visualization of pharyngeal structures and aspiration. We discuss the use of both techniques.

Deglutition Disorders↗
PubMed2002

Peripheral mechanisms affecting the lower esophageal sphincter tone.

LES tone is influenced by central and peripheral mechanisms. Peripheral factors influencing the LES tone include inhibitory reflexes originating from the stomach, esophagus, pharynx, and larynx. Although the role of LES relaxation and its associated reflux events induced by gastric distention has been extensively studied, the LES relaxations triggered by stimulation of the aerodigestive tract have only recently been the focus of systematic investigation and have resulted in documentation of the intricate reflex relationship between the upper gastrointestinal tract and the aerodigestive tract.

Animals↗
PubMed2002

Cerebral cortical registration of subliminal visceral stimulation.

BACKGROUND & AIMS: Although brain registration of subliminal somatic stimulations such as masked visual stimuli and their influence on electrical and hemodynamic measures of cerebral activity have been reported previously, there have been no reports on cerebral cortical registration of subliminal visceral stimulation. Because studies evaluating the consequences of subliminal somatic stimulation have shown that subliminal stimulation can effect behavior, it is conceivable that such subliminal messages from the intestine could potentially influence intestinal sensory/motor function or effect the perception/interpretation of sensory signals originating from the gut. METHODS: We studied the cerebral cortical functional magnetic resonance imaging (fMRI) response to subliminal, liminal, and supraliminal rectal distention in healthy volunteers. RESULTS: Study findings indicate that subliminal afferent signals originating from the gut are registered in the cerebral cortex without reaching the level of awareness. Locations of cortical activity caused by intestinal subliminal stimulation are similar to those of liminal and supraliminal stimulation but their intensity and volume are significantly lower (P < 0.05). CONCLUSIONS: Subliminal afferent signals originating from the gut are registered in the cerebral cortex and induce changes in measures of brain activity, such as hemodynamic changes detectable by fMRI.

Adult↗
PubMed2002

Rehabilitation of swallowing by exercise in tube-fed patients with pharyngeal dysphagia secondary to abnormal UES opening.

BACKGROUND & AIMS: We evaluated the effect of a novel rehabilitative exercise on restoration of deglutition in a group of patients with deglutitive failure caused by abnormal upper esophageal sphincter (UES) opening manifested by postswallow residue and aspiration necessitating percutaneous tube feeding. METHODS: We studied a total of 27 patients by videofluoroscopy and functional assessment of swallowing scores before and after 6 weeks of a head-raising exercise program. Seven of 27 patients, assigned randomly, participated in a sham exercise before entering the tested exercise program. Eleven of 27 were randomized to the real exercise program. RESULTS: Although there was no change in swallow function and biomechanics after the sham exercise, following 6 weeks of real exercise, all 11 patients exhibited a significant improvement in their UES opening, anterior laryngeal excursion (P < 0.01), as well as resolution of postdeglutitive aspiration and were able to resume oral feeding. Similar results were found when the 7 patients in the sham group were crossed over to the real exercise group. Comparison of before and after exercise values for anteroposterior UES opening (P < 0.01) and laryngeal anterior excursion (P < 0.05), as well as functional outcome assessment of swallowing (P < 0.05) in the entire group of 27 patients also showed significant improvement. Etiology and duration of dysphagia did not affect the outcome. CONCLUSIONS: The proposed suprahyoid muscle strengthening exercise program is effective in restoring oral feeding in some patients with deglutitive failure because of abnormal UES opening.

Aged↗